Science.gov

Sample records for drug reactions induced

  1. Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions

    PubMed Central

    Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

    2015-01-01

    Objective We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Methods Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Results Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). Conclusions We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse

  2. A systematic review of drug induced ocular reactions in diabetes

    PubMed Central

    Hampson, J; Harvey, J

    2000-01-01

    AIMS—To conduct a systematic review of drug induced adverse ocular effects in diabetes to determine if this approach identified any previously unrecognised adverse drug effects; to make a preliminary assessment of the feasibility of this approach in identifying adverse drug reactions; and to assess the current accessibility of this information to prescribing physicians.
METHODS—Literature search of online biomedical databases. The search strategy linked eye disorders with adverse drug reactions and diabetes. Source journals were classified as medical, pharmaceutical, diabetes related, or ophthalmological. It was determined whether the reactions identified were recorded in drug datasheets and the British National Formulary.
RESULTS—63 references fulfilled the selection criteria, of which 45 were considered to be relevant to the study. The majority of these were case reports but cross sectional surveys, case-control and cohort studies, and review articles were also identified. 61% of the reactions were not recorded in the British National Formulary and 41% were not recorded in the datasheets. 55% appeared in specialist ophthalmology journals.
CONCLUSIONS—This is a feasible approach to the identification of adverse drug reactions. Adverse reactions not listed in the most commonly used reference sources were found. The majority were published in specialist ophthalmology journals which might not be seen by prescribing physicians.

 PMID:10655188

  3. Levetiracetam Induced Drug Reaction with Eosinophilia and Systemic Symptom Syndrome

    PubMed Central

    Dar, Waseem Raja; Sofi, Najeebullah; Latief, Muzamil; Dar, Imtiyaz Ahmad; Kasana, Basharat Ahmad

    2016-01-01

    Drug reaction with eosinophilia and systemic symptom syndrome (DRESS) is a hypersensitivity drug reaction, most frequently associated with antiepileptic drugs, characterized by skin rash, fever, pharyngitis, lymphadenopathy, and visceral organ involvement, typically presenting within 8 weeks of initiation of therapy. Management involves prompt withdrawal of the offending drug and use of systemic corticosteroids. We here present a rare case of DRESS secondary to levetiracetam. Only few case reports of DRESS secondary to levetiracetam have been published so far. PMID:27057042

  4. Levetiracetam Induced Drug Reaction with Eosinophilia and Systemic Symptom Syndrome.

    PubMed

    Dar, Waseem Raja; Sofi, Najeebullah; Latief, Muzamil; Dar, Imtiyaz Ahmad; Kasana, Basharat Ahmad

    2016-01-01

    Drug reaction with eosinophilia and systemic symptom syndrome (DRESS) is a hypersensitivity drug reaction, most frequently associated with antiepileptic drugs, characterized by skin rash, fever, pharyngitis, lymphadenopathy, and visceral organ involvement, typically presenting within 8 weeks of initiation of therapy. Management involves prompt withdrawal of the offending drug and use of systemic corticosteroids. We here present a rare case of DRESS secondary to levetiracetam. Only few case reports of DRESS secondary to levetiracetam have been published so far. PMID:27057042

  5. Ciprofloxacin induced bullous fixed drug reaction: three case reports

    PubMed Central

    Nair, Pragya A.

    2015-01-01

    Cutaneous adverse drug reactions (ADRs) are seen in about 1–2% cases. Fixed drug reaction (FDR) is responsible for about 10% of all ADRs. It is a delayed type of hypersensitivity reaction that occurs as lesions recurs at the same skin site due to repeated intake of an offending drug. The most common drugs causing fixed drug eruption (FDE) are analgesics, antibiotics, muscle relaxants and anticonvulsants. FDE due to ciprofloxacin has been reported earlier also, but bullous variant of FDR is rare. We hereby report three case reports of bullous FDR caused due to ciprofloxacin. PMID:25949980

  6. Drug Reactions

    MedlinePlus

    ... using any of these products. Some types of food may also cause adverse drug reactions. For example, grapefruit and grapefruit juice, as well as alcohol and caffeine, may affect how drugs work. Every time your doctor ... interactions with any foods or beverages. What about medicines I've used ...

  7. Pharmacoepidemiological characterization of drug-induced adverse reaction clusters towards understanding of their mechanisms.

    PubMed

    Mizutani, Sayaka; Noro, Yousuke; Kotera, Masaaki; Goto, Susumu

    2014-06-01

    A big challenge in pharmacology is the understanding of the underlying mechanisms that cause drug-induced adverse reactions (ADRs), which are in some cases similar to each other regardless of different drug indications, and are in other cases different regardless of same drug indications. The FDA Adverse Event Reporting System (FAERS) provides a valuable resource for pharmacoepidemiology, the study of the uses and the effects of drugs in large human population. However, FAERS is a spontaneous reporting system that inevitably contains noise that deviates the application of conventional clustering approaches. By performing a biclustering analysis on the FAERS data we identified 163 biclusters of drug-induced adverse reactions, counting for 691 ADRs and 240 drugs in total, where the number of ADR occurrences are consistently high across the associated drugs. Medically similar ADRs are derived from several distinct indications for use in the majority (145/163=88%) of the biclusters, which enabled us to interpret the underlying mechanisms that lead to similar ADRs. Furthermore, we compared the biclusters that contain same drugs but different ADRs, finding the cases where the populations of the patients were different in terms of age, sex, and body weight. We applied a biclustering approach to catalogue the relationship between drugs and adverse reactions from a large FAERS data set, and demonstrated a systematic way to uncover the cases different drug administrations resulted in similar adverse reactions, and the same drug can cause different reactions dependent on the patients' conditions. PMID:24534381

  8. Drug Reactions

    MedlinePlus

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  9. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  10. Propranolol-induced gingival hyperplasia with Nager syndrome: A rare adverse drug reaction

    PubMed Central

    Raheel, Syed Ahamed; Kujan, Omar Bashar; Tarakji, Bassel; Umar, Dilshad; Ibrahim, Salah

    2016-01-01

    Drug reactions are a group of reactionary lesions generally show their manifestations in the oral cavity. The drug reactions may vary from local rashes to well-developed swellings in the oral cavity especially involving the gingiva. Most of the drug reactions are asymptomatic and commonly triggered from the active metabolite of a drug used for a long time. Nager syndrome is a group of acrofacial dysostosis that usually results in craniofacial and limb malformations. The craniofacial defects are very similar to the mandibulofacial dysostosis. A very early intervention is needed for the habilitation of the patient especially when it is concerned with speech and language development. This paper reports a case of a 32-year-old female with craniofacial, limb, and skeletal abnormalities along with a drug-induced gingival hyperplasia. PMID:27144155

  11. A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives.

    PubMed

    Kim, Mi-Yeong; Jo, Eun-Jung; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up; Kim, Sae-Hoon

    2013-10-01

    Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient. PMID:24260733

  12. A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives

    PubMed Central

    Kim, Mi-Yeong; Jo, Eun-Jung; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up

    2013-01-01

    Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient. PMID:24260733

  13. Drug Reactions

    MedlinePlus

    Most of the time, medicines make our lives better. They reduce aches and pains, fight infections, and control problems such as high blood pressure or diabetes. But medicines can also cause unwanted reactions. One problem is ...

  14. Practice Gaps: Drug Reactions.

    PubMed

    Wolverton, Stephen E

    2016-07-01

    The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions. PMID:27363888

  15. Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine

    PubMed Central

    Massot, Andreu; Gimenez-Arnau, Ana

    2014-01-01

    Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

  16. Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine.

    PubMed

    Massot, Andreu; Gimenez-Arnau, Ana

    2014-10-01

    Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

  17. Drug-induced anaphylactic reactions in Indian population: A systematic review

    PubMed Central

    Patel, Tejas K.; Patel, Parvati B.; Barvaliya, Manish J.; Tripathi, C. B.

    2014-01-01

    Background: Epidemiological data on drug-induced anaphylactic reactions are limited in India and are largely depending on studies from developed countries. Aim: The aim was to analyze the published studies of drug-induced anaphylaxis reported from India in relation with causative drugs and other clinical characteristics. Materials and Methods: The electronic databases were searched for Indian publications from 1998 to 2013 describing anaphylactic reactions. The information was collected for demographics, set up in which anaphylaxis occurred, causative drugs, incubation period, clinical features, associated allergic conditions, past reactions, co-morbid conditions, skin testing, IgE assays, therapeutic intervention and mortality. Reactions were analyzed for severity, causality, and preventability. Data were extracted and summarized by absolute numbers, mean (95% confidence interval [CI]), percentages and odds ratio (OR) (95% CI). Results: From 3839 retrieved references, 52 references describing 54 reactions were included. The mean age was 35.31 (95% CI: 30.52–40.10) years. Total female patients were 61.11%. Majority reactions were developed in perioperative conditions (53.70%), ward (20.37%) and home (11.11%). The major incriminated groups were antimicrobials (18.52%), nonsteroidal antiinflammatory drugs-(NSAIDs) (12.96%) and neuromuscular blockers (12.96%). Common causative drugs were diclofenac (11.11%), atracurium (7.41%) and β-lactams (5.96%). Cardiovascular (98.15%) and respiratory (81.48%) symptoms dominated the presentation. Skin tests and IgE assays were performed in 37.03% and 18.52% cases, respectively. The fatal cases were associated with complications (OR =5.04; 95% CI: 1.41–17.92), cerebral hypoxic damage (OR =6.80; 95% CI: 2.14–21.58) and preventable reactions (OR =14.33; 95% CI: 2.33–87.97). Conclusion: Antimicrobials, NSAIDs, and neuromuscular blockers are common causative groups. The most fatal cases can be prevented by avoiding allergen

  18. HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese

    PubMed Central

    Chu, Hieu Chi; Nguyen, Doan Van; Phan, Minh Hong; Craig, Timothy; Baumgart, Karl; van Nunen, Sheryl

    2015-01-01

    Background In Vietnam, we observed a high incidence of carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs)-Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity rash with eosinophilia and systemic symptoms (DRESS). In other Asian countries, HLA-B*1502 is an established risk factor for SCARs. Objective The aim of our study was to determine the frequency of HLA-B*1502 in SCARs patients at a large University Medical Center in Hanoi, Vietnam. Methods Thirty-eight cases of SCARs caused by CBZ and 25 patients with epilepsy tolerating CBZ were enrolled in a case-controlled study. Clinical manifestations and laboratory findings were recorded for each subject. Genomic DNA was isolated using the QIAamp DNA purification system. The combination of polymerase chain reaction and sequence specific oligonucleotide probes with the Luminex 100×MAP flow cytometry dual laser system was then used to quantitate fluorescently labelled oligonucleotides attached to colour-coded microbeads. Results Cases comprised 20 SJS (52.6%), 7 TEN (18.4%), 8 overlap syndrome (21.1%), and 3 DRESS patients (7.9%). A strong association between HLA B*1502 and bullous skin reactions such as SJS/TEN and overlap was confirmed with an odds ratio (OR) of 33.78 (95% confidence interval [CI], 7.55-151.03), p < 0.0001, Sensitivity 91.4%, Specificity 76.0%, positive predictive value 84.2%, and negative predictive value 86.4%. We did not, however, observe any correlation between the presence of this allele and CBZ-induced nonbullous skin reactions (DRESS) (OR, 6.33; 95% CI, 0.48-82.74; p = 0.1592). Conclusion Our results indicate the presence of HLA-B*1502 in Vietnamese is a pharmacogenetic risk factor for developing CBZ-induced SJS/TEN. PMID:25938071

  19. Analysis of the adverse reactions induced by natural product-derived drugs

    PubMed Central

    Zeng, Zhi-Ping; Jiang, Jian-Guo

    2010-01-01

    Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209

  20. Relationship between serum acetaminophen concentration and N-acetylcysteine-induced adverse drug reactions.

    PubMed

    Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Khan, Halilol Rahman Mohamed; Sawalha, Ansam F; Sweileh, Waleed M; Al-Jabi, Samah W

    2010-09-01

    Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR. PMID:20374238

  1. [Analysis on 315 cases of clinical adverse drug reaction/event induced by gastrodin].

    PubMed

    Zheng, Yang-yang; Dong, Zhi; Lu, Xiao-qin; Xia, Yong-peng; Zhu, Shu-bing

    2015-05-01

    With patients' general situation, medication use, occurrence time of adverse drug reaction/event (ADR/ADE), clinical manifestations and prognosis as reference items, a retrospective study was made for 315 cases with ADR/ADE induced by Gastrodin in Chongqing from January 2008 to June 2014, in order to analyze the characteristics of ADR/ADE and provide reference for rational clinical medication. The results showed that among the 315 cases with ADR/ADE, 143 cases (45.4%) were males and 172 cases (54.6%) were females, most of them (74.9%) were aged above 45; 60 cases (19.0%) with ADE were caused by off-label indications and 66 cases (21.0%) with ADE were caused by over dosage; ADR/ADE cases induced by intravenous drip mainly happened within 30 min (85.5%), ADR/ADE cases induced by oral administration mainly happened within 2 h (74.4%), and all of ADR/ ADE cases induced by intramuscular injection happened within 10 min. Totally 593 ADR/ADE cases were reported, which were mainly damages in gastrointestinal system, skin and its adnexa; And 61.9% of ADR/ADE cases were newly reported. It is suggested that medical workers shall learn about the regularity and characteristics of ADR/ADE induced by gastrodin, apply it in clinic with standards, pay close attention to changes of patients' situations and attach importance to the monitoring of ADR/ADE, so as to enhance the safety of medication. PMID:26390669

  2. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  3. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  4. Drug-induced Photosensitivity.

    PubMed

    Zuba, Ewelina Bogumiła; Koronowska, Sandra; Osmola-Mańkowska, Agnieszka; Jenerowicz, Dorota

    2016-04-01

    Ultraviolet radiation is considered the main environmental physical hazard to the skin. It is responsible for photoaging, sunburns, carcinogenesis, and photodermatoses, including drug-induced photosensitivity. Drug-induced photosensitivity is an abnormal skin reaction either to sunlight or to artificial light. Drugs may be a cause of photoallergic, phototoxic, and photoaggravated dermatitis. There are numerous medications that can be implicated in these types of reactions. Recently, non-steroidal anti-inflammatory drugs have been shown to be a common cause of photosensitivity. As both systemic and topical medications may promote photosensitive reactions, it is important to take into consideration the potential risk of occurrence such reactions, especially in people chronically exposed to ultraviolet radiation. PMID:27149132

  5. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    SciTech Connect

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  6. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  7. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review.

    PubMed

    Oussalah, A; Mayorga, C; Blanca, M; Barbaud, A; Nakonechna, A; Cernadas, J; Gotua, M; Brockow, K; Caubet, J-C; Bircher, A; Atanaskovic, M; Demoly, P; K Tanno, L; Terreehorst, I; Laguna, J J; Romano, A; Guéant, J-L

    2016-04-01

    Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. PMID:26678823

  8. Identification of risk factors for carbamazepine-induced serious mucocutaneous adverse reactions: A case-control study using data from spontaneous adverse drug reaction reports

    PubMed Central

    Bertulyte, Ilma; Schwan, Sofie; Hallberg, Pär

    2014-01-01

    Objectives: To identify risk factors other than genetic for severe carbamazepine-induced mucocutaneous reactions, that is, SJS, TEN, and exfoliative dermatitis (ED). Materials and Methods: We did a case-control study using data from the Swedish national database of spontaneously reported adverse drug reactions (ADRs). We selected all patients who had been reported from January 1, 1965 to March 31, 2010 as having experienced SJS (n = 78), TEN (n = 6), or ED (n = 8), and assessed as at least possibly related to carbamazepine. We also included diagnoses possibly representative of early signs of these serious conditions, that is, erythema multiforme (EM, n = 34) and scaly rash (n = 13). We compared data on demographics, drug treatment, and clinical features for these patients (cases, n = 139) with those from patients who had experienced any other type of ADR from carbamazepine during the same time period (controls, n = 887). Results: After adjustment for multiple comparisons, alcohol abuse was statistically significantly more common among cases than controls (34.5% vs 8.7%, odds ratio 5.5 [95% confidence interval 3.6-8.4], P = 3.14 × 10-14 ). The same was seen for SJS and EM individually. Conclusion: Alcohol abuse is a possible risk factor for serious carbamazepine-induced mucocutaneous reactions. PMID:24799813

  9. Medications and Drug Allergic Reactions

    MedlinePlus

    ... Drug Guide Conditions Dictionary Just for Kids Library School Tools Videos Virtual Allergist Education & Training Careers in ... reaction to a medication. These include: genetics, body chemistry, frequent drug exposure or the presence of an ...

  10. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  11. A rare adverse reaction to ethambutol: drug-induced haemolytic anaemia.

    PubMed

    Nicolini, A; Perazzo, A; Gatto, P; Piroddi, I M G; Barlascini, C; Karamichali, S; Strada, P

    2016-05-01

    Anti-tuberculosis drugs seldom cause serious haematological side effects. However, among these drugs, isoniazid and rifampicin, especially when administered intermittently, may very rarely be linked to acute autoimmune haemolytic anaemia. Ethambutol (EMB) can cause dose-related retrobulbar neuritis. In this paper, we present the first reported case of acute fatal autoimmune haemolytic anaemia due to EMB. PMID:27084828

  12. HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand

    PubMed Central

    Sukasem, Chonlaphat; Jantararoungtong, Thawinee; Kuntawong, Parnrat; Puangpetch, Apichaya; Koomdee, Napatrupron; Satapornpong, Patompong; Supapsophon, Patcharin; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha

    2016-01-01

    Background: The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B*58:01 in a Thai population. Methods: This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system. Results: Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for HLA-B*58:01, compared to only 4.0% in allopurinol-tolerant patients (p < 0.001). Odds ratio (OR) for the association of HLA-B*58:01 with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8–6475.0). The HLA-B*58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5–11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6–8958.9, p < 0.001). Additionally, OR of HLA-B*58:01 was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9–1497.0, p < 0.001). Conclusion: In this study we confirmed the association between HLAB*58:01 and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between HLA-B*58:01 and allopurinol-induced DRESS and MPE in this population. Therefore, HLA-B*58:01 can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for HLA-B*58:01 alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients. Summary Regardless of

  13. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  14. Drug-induced hypoglycemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000310.htm Drug-induced hypoglycemia To use the sharing features on this page, please enable JavaScript. Drug-induced hypoglycemia is low blood sugar that results from medication. ...

  15. New approaches for predicting T cell-mediated drug reactions: A role for inducible and potentially preventable autoimmunity.

    PubMed

    Michels, Aaron W; Ostrov, David A

    2015-08-01

    Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacologic target (type A ADR) or an unintended target (type B ADR). Immunologically mediated type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms syndrome, and Stevens-Johnson syndrome/toxic epidermal necrolysis, can be severe and result in a diverse set of clinical manifestations that include fever and rash, as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell-mediated ADRs are strikingly similar to those displayed by patients with autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for immunologically mediated type B ADRs. Because methods to predict type 1 diabetes by using genetic and immunologic biomarkers have been developed to a high level of accuracy (predicting 100% of subjects likely to progress), new research strategies based on these methods might also improve the ability to predict drug hypersensitivity. PMID:26254052

  16. Immediate-type hypersensitivity drug reactions

    PubMed Central

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-01-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. PMID:24286446

  17. Drug-Induced Itch Management.

    PubMed

    Ebata, Toshiya

    2016-01-01

    Drugs may cause itching as a concomitant symptom of drug-induced skin reactions or in the form of pruritus without skin lesions. Drug-induced itch is defined as generalized itching without skin lesions, caused by a drug. Itching associated with drug-induced cholestasis is among the common dermatologic adverse events (dAEs) that induce itching. Some drugs such as opioids, antimalarials, and hydroxyethyl starch are known to induce itching without skin lesions. The clinical features and underlying proposed mechanisms of itching caused by these drugs have been specifically investigated. The recent application of targeted anticancer drugs has increased the survival rate of cancer patients. These new agents cause significant dAEs such as acneiform rashes, dry skin, hand-foot syndrome, paronychia, and itching. Itching is a common side effect of epidermal growth factor receptor inhibitors. Though not life-threatening, these dAEs have a negative impact on a patient's quality of life, leading to dose reduction and possibly less effective cancer therapy. It is important to provide an effective supportive antipruritic treatment without interruption of the administration of these drugs. This chapter concludes by describing basic measures to be taken for diagnosis and treatment of drug-induced itch. The principle of treatment is discontinuation of suspected causative drugs in general except for anticancer medications. In case itching lasts long after drug withdrawal or the causative drug cannot be stopped, vigorous symptomatic antipruritic treatment and specific therapies for different types of drug-induced itch should be undertaken. PMID:27578085

  18. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  19. Drug-induced nightmares.

    PubMed

    2000-12-01

    (1) A wide variety of drugs have been implicated in nightmares, often on inadequate evidence. (2) Recurrent nightmares can be induced by many drugs, and not only agents with psychotropic or neurological effects. PMID:11475499

  20. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  1. Tenofovir induced lichenoid drug eruption

    PubMed Central

    Gupta, Mrinal; Gupta, Heena; Gupta, Anish

    2015-01-01

    Cutaneous adverse reactions are a common complication of anti-retroviral therapy. Tenofovir is a newer anti-retroviral drug belonging to the nucleotide reverse transcriptase inhibitor group. Systemic adverse effects like nausea, vomiting, diarrhea, hepatotoxicity and renal toxicity are common with tenofovir but cutaneous adverse effects are rare. Lichenoid drug eruptions are a common adverse effect seen with a large variety of drugs including antimalarials, antihypertensives, nonsteroidal anti-inflammatory drugs and diuretics. Lichenoid drug eruption is a rare cutaneous adverse effect of tenofovir with only a single case reported till date. Here, we report a case of tenofovir induced lichenoid drug eruption in a 54-year-old human immunodeficiency virus affected male who presented with generalized lichenoid eruption after 6 weeks of initiation of tenofovir and complete clearance on cessation of the drug. PMID:26229762

  2. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

    Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

  3. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  4. Drug-induced panniculitides.

    PubMed

    Borroni, G; Torti, S; D'Ospina, R M; Pezzini, C

    2014-04-01

    A substantial number of all panniculitides fails to recognize a specific etiology, and that is true also for a relatively frequent type of panniculitis, such as erythema nodosum (EN). Between the recognized causative factors of panniculitides, infectious, physical agents, autoimmune mechanisms and neoplastic disorders are well known. On the contrary, the role of drugs as inducers of panniculitides is marginally considered, and their report limited to anecdotal observations, often without due histopathological support. Since the clinical and histopathological features of drug-induced panniculitides are indistinguishable from those caused by other agents, the causative relationship may be demonstrated by the history of previous drug intake and by clinical improvement after drug discontinuation. We reviewed the currently reported descriptions of drug-induced panniculitis, including a few exemplificative original observations. EN results as the most frequently reported drug-induced panniculitis. Among the causative drugs of EN a variety of medications, with disparate, or even opposite, mechanisms of action are reported, thus limiting the understanding of the pathogenesis. Common causative drugs include oral contraceptives, nonsteroidal anti-inflammatory drugs, antiobiotics and leukotriene-modifying agents. Unfortunately, in several cases, the diagnosis of drug-induced EN is done on clinical findings alone. In those cases, the lack of histopathological support does not allow to define a precise clinicopathological correlation on etiologic grounds. Drug-induced lobular and mixed panniculitides, including eosinophilic panniculitis, are even more rarely described. Reported causative agents are glatiramer acetate, interferon beta and heparin (at sites of injections), and systemic steroids, tyrosine kinase inhibitors and BRAF with subcutaneous fat involvement at distance. In view of the recent introduction of new classes of drugs, attention should be paid to disclose their

  5. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia. PMID:25047526

  6. Clindamycin-induced hypersensitivity reaction.

    PubMed

    Bulloch, Marilyn N; Baccas, Jonathan T; Arnold, Scott

    2016-06-01

    Drug-induced anaphylaxis is an unpredictable adverse reaction. Although it may occur with any medication, antibiotics induce more cases of anaphylaxis than any other medication class with most cases being induced by β-lactam antibiotics. Clindamycin is an antibiotic with good gram-positive and anaerobe coverage which is often used in patients with β-lactam allergies. We report the case of a 46-year-old female who experienced anaphylaxis after a dose of intravenous (IV) clindamycin. Following treatment with methylprednisolone, epinephrine, diphenhydramine, and albuterol, the patient stabilized. The patient's score on the Naranjo's algorithm was 8 (probable); a score of 9 (definite) limited only by absence of drug re-challenge. To our knowledge, this is the first report of a clindamycin-induced anaphylaxis where the patient was not exposed to any other agent that may have triggered the response, the first case in the United States, and only the third documented case in the literature. Clinicians should be aware of the potential for drug-induced anaphylaxis in all medications. PMID:26216470

  7. The Genetics of Drug Hypersensitivity Reactions.

    PubMed

    Cornejo-García, J A; Jurado-Escobar, R; Doña, I; Perkins, J R; Agúndez, J A; García-Martín, E; Viguera, E; Blanca-López, N; Canto, G; Blanca, M

    2016-01-01

    DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice. PMID:27375032

  8. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  9. Vitiligo, drug induced (image)

    MedlinePlus

    ... drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally occurs as a result of medications, as is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains the normal skin texture.

  10. DRUG INDUCED CHOLESTASIS

    PubMed Central

    Padda, Manmeet S.; Sanchez, Mayra; Akhtar, Abbasi J.; Boyer, James L.

    2011-01-01

    Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug induced cholestasis. This review summarizes their variable clinical presentations, examines the, role of transport proteins in hepatic drug clearance and toxicity and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. PMID:21480339

  11. Adverse drug reactions and organ damage: The skin.

    PubMed

    Marzano, Angelo V; Borghi, Alessandro; Cugno, Massimo

    2016-03-01

    Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens-Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. PMID:26674736

  12. Association Study of a Functional Variant on ABCG2 Gene with Sunitinib-Induced Severe Adverse Drug Reaction

    PubMed Central

    Low, Siew-Kee; Fukunaga, Koya; Takahashi, Atsushi; Matsuda, Koichi; Hongo, Fumiya; Nakanishi, Hiroyuki; Kitamura, Hiroshi; Inoue, Takamitsu; Kato, Yoichiro; Tomita, Yoshihiko; Fukasawa, Satoshi; Tanaka, Tomoaki; Nishimura, Kazuo; Uemura, Hirotsugu; Hara, Isao; Fujisawa, Masato; Matsuyama, Hideyasu; Hashine, Katsuyoshi; Tatsugami, Katsunori; Enokida, Hideki; Kubo, Michiaki; Miki, Tsuneharu; Mushiroda, Taisei

    2016-01-01

    Sunitinib is a tyrosine kinase inhibitor and used as the first-line treatment for advanced renal cell carcinoma (RCC). Nevertheless, inter-individual variability of drug’s toxicity was often observed among patients who received sunitinib treatment. This study is to investigate the association of a functional germline variant on ABCG2 that affects the pharmacokinetics of sunitinib with sunitinib-induced toxicity of RCC patients in the Japanese population. A total of 219 RCC patients were recruited to this pharmacogenetic study. ABCG2 421C>A (Q141K) was genotyped by using PCR-Invader assay. The associations of both clinical and genetic variables were evaluated with logistic regression analysis and subsequently receiver operating characteristic (ROC) curve was plotted. About 43% (92/216) of RCC patients that received sunitinib treatment developed severe grade 3 or grade 4 thrombocytopenia according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 3.0, the most common sunitinib-induced adverse reaction in this study. In the univariate analysis, both age (P = 7.77x10-3, odds ratio (OR) = 1.04, 95%CI = 1.01–1.07) and ABCG2 421C>A (P = 1.87x10-2, OR = 1.71, 95%CI = 1.09–2.68) showed association with sunitinib-induced severe thrombocytopenia. Multivariate analysis indicated that the variant ABCG2 421C>A is suggestively associated with severe thrombocytopenia (P = 8.41x10-3, OR = 1.86, 95% CI = 1.17–2.94) after adjustment of age as a confounding factor. The area under curve (AUC) of the risk prediction model that utilized age and ABCG2 421C>A was 0.648 with sensitivity of 0.859 and specificity of 0.415. Severe thrombocytopenia is the most common adverse reaction of sunitinib treatment in Japanese RCC patients. ABCG2 421C>A could explain part of the inter-individual variability of sunitinib-induced severe thrombocytopenia. PMID:26914831

  13. [Designer drug induced psychosis].

    PubMed

    Fullajtar, Mate; Ferencz, Csaba

    2012-06-01

    3,4-methylene-dioxy-pyrovalerone (MDPV) is a popular designer drug in Hungary, known as MP4. We present a case of a 34-year-old man, whose first psychotic episode was observed in the presence of MP4 use. The paranoid ideas of reference and the dereistic thinking could be the consequence of drug-induced psychosis. Within 24 hours after the intoxication was over delirium set in. The patient's history included only the use of MP4, use of other kinds of drugs was negated. The drug tests were negative, amphetamine derivates were not detectable in the urine sample. It is most likely that the MP4 pill contained an amount of MDPV less than detectable. In conclusion we suggest that the clinical picture could be the consequence of regular MDPV use. PMID:22710853

  14. Laser induced nuclear reactions

    SciTech Connect

    Ledingham, Ken; McCanny, Tom; Graham, Paul; Fang Xiao; Singhal, Ravi; Magill, Joe; Creswell, Alan; Sanderson, David; Allott, Ric; Neely, David; Norreys, Peter; Santala, Marko; Zepf, Matthew; Watts, Ian; Clark, Eugene; Krushelnick, Karl; Tatarakis, Michael; Dangor, Bucker; Machecek, Antonin; Wark, Justin

    1998-12-16

    Dramatic improvements in laser technology since 1984 have revolutionised high power laser technology. Application of chirped-pulse amplification techniques has resulted in laser intensities in excess of 10{sup 19} W/cm{sup 2}. In the mid to late eighties, C. K. Rhodes and K. Boyer discussed the possibility of shining laser light of this intensity onto solid surfaces and to cause nuclear transitions. In particular, irradiation of a uranium target could induce electro- and photofission in the focal region of the laser. In this paper it is shown that {mu}Ci of {sup 62}Cu can be generated via the ({gamma},n) reaction by a laser with an intensity of about 10{sup 19} Wcm{sup -2}.

  15. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

    PubMed

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A; García-Martín, Elena; Cornejo-García, José A; Perkins, James R; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  16. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

    PubMed Central

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  17. [4-aminopyridine induced rage reaction in mice].

    PubMed

    Xu, J H; Liu, H C; Zhang, Y P

    1991-03-01

    Rage reaction was induced in mice by sc 4-aminopyridine (4-AP) 6 mg . kg-1. Mice appeared hyperreactive after 8-12 min and then squeaked and fought each other. These manifestations were most distinct in 10-30 min and subsided after 40-60 min. The occurrence of rage reaction on this dose level was around 90%. At higher doses 4-AP caused convulsions and death after evocation of rage reaction. The ED50 of 4-AP for eliciting rage reaction was 4.7 +/- 0.7 mg . kg-1 sc. No significant difference in induction of rage reaction was seen between male and female mice of different body weights. Both neuroleptic drugs (chlorpromazine, haloperidol, tarden and clozapine) and anxiolytic drugs (diazepam, chlordiazepoxide, and meprobamate) inhibited 4-AP-induced rage reaction in mice. Barbiturates, Chloral hydrate, methaqualone, morphine hydrochloride, aspirin, phenytoin sodium, diphenhydramine hydrochloride, atropine sulfate, and procaine hydrochloride did not affect rage reaction. The 4-AP-induced aggressive behavior, similar to that induced by electric footshock or isolation, has the merits of convenience to deal with and time saving. Hence we recommended it as a screening method for drugs with neuroleptic and anxiolytic activities. PMID:1685615

  18. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  19. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  20. Cutaneous Adverse Drug Reactions in Dogs Treated with Antiepileptic Drugs

    PubMed Central

    Koch, Tina; Mueller, Ralf S.; Dobenecker, Britta; Fischer, Andrea

    2016-01-01

    Epilepsy is one of the most common neurologic disorders in dogs and life-long treatment with antiepileptic drugs (AED) is frequently required. Adverse events of AED targeting the skin are only rarely reported in veterinary medicine and the true incidence and spectrum of cutaneous reactions in epileptic dogs remains unknown. In this study, we hypothesized that cutaneous reactions commonly occur in epileptic dogs and are related to AED treatment. A retrospective case review of 185 dogs treated for epilepsy identified 20.0% with simultaneous appearance of dermatologic signs. In a subsequent prospective case investigation (n = 137), we identified newly appearing or distinct worsening of skin lesions following initiation of AED therapy in 10.9% of dogs treated for epilepsy (95% CI 6.8–17.7%). Cutaneous lesions were classified as probably drug-induced in 40.0% of these cases. Patch testing and intradermal testing were further investigated as potential diagnostic methods to confirm AED hypersensitivity. They were of high specificity but sensitivity and positive predictive value appeared inappropriate to recommend their routine use in clinical practice. PMID:27148543

  1. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

    There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

  2. Radiation-induced free radical reactions in polymer/drug systems for controlled release: an EPR investigation

    NASA Astrophysics Data System (ADS)

    Faucitano, A.; Buttafava, A.; Montanari, L.; Cilurzo, F.; Conti, B.; Genta, I.; Valvo, L.

    2003-05-01

    The primary and secondary free radical intermediates in the gamma radiolysis of poly(D,L-lactide-co-glycolide) (PLGA) and clonazepam loaded PLGA microspheres were investigated by matrix EPR spectroscopy in the temperature range 77-298 K. Drug-polymer interactions were found to be important leading to significant deviations of the G(radicals) from the additivity law. In particular, in the mixed system a stabilization of the polymer matrix with respect to the radiation damage was detected, witnessed by a decrease of the overall polymer radicals yield which is accompanied by an increase of the drug radicals yield. These effects have been attributed to the scavenging properties of the nitro group with respect to electrons and polymer radicals. It is conceivable that such conclusions be of general application for all pharmaceutical formulations containing drugs bearing nitro groups in their chemical structure.

  3. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  4. Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis

    PubMed Central

    Liu, Yue-Ping; Xu, Han-Qing; Li, Ming; Yang, Xiang; Yu, Shu; Fu, Wei-Ling; Huang, Qing

    2015-01-01

    Purpose Azathioprine (AZA) is widely used as an immunosuppressive drug in autoimmune diseases, but its use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating AZA therapy. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and AZA-induced ADRs using meta-analysis. Methods We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and AZA-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in patients with autoimmune diseases were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using Revman 5.3 software. Results Eleven published studies, with a total of 651 patients with autoimmune diseases, investigated associations between TPMT polymorphisms and AZA-induced ADRs, were included in this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with AZA-induced overall ADRs, bone marrow toxicity and gastric intolerance; pooled ORs were 3.12 (1.48–6.56), 3.76 (1.97–7.17) and 6.43 (2.04–20.25), respectively. TPMT polymorphisms were not associated with the development of hepatotoxicity; the corresponding pooled OR was 2.86 (95%CI: 0.32–25.86). However, the association in GI subset could be driven by one single study. After this study was excluded, the OR was 2.11 (95%CI: 0.36–12.42); namely, the association became negative. Conclusions Our meta-analysis demonstrated an association of TPMT polymorphisms with overall AZA-induced ADRs, bone marrow toxicity and gastric

  5. Adverse drug reactions: classification, susceptibility and reporting.

    PubMed

    Kaufman, Gerri

    2016-08-10

    Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme. PMID:27507394

  6. [Drug-induced laryngospasm].

    PubMed

    Nishikawa, T; Munakata, K

    1997-02-01

    We report a case of drug-induced laryngospasm due to Chlorpromazine. A drug-induced laryngospasm has not been previously reported in the literature. A 70-year-old male with the proximal end fracture of the femur was scheduled for the operative fixation. He had a past history of alcoholism and had underwent a long-term chlorpromazine therapy for 45 years until admission to our hospital. There have been a few reports on unexplained sudden deaths of patients receiving long-term treatment with chlorpromazine. Caution was therefore needed in general anesthesia, which was thought to be safer than epidural or spinal anesthesia in this case. Accordingly for the preparation of an emergency operation, the central venous catheterization via the internal jugular vein was performed under subcutaneous injection of lidocaine. Severe dyspnea and cyanosis occurred a few minutes after the administration of lidocaine. The specific diagnosis of laryngospasm was made by inspection of the vocal cords. Immediate oral intubation was performed and no complications ensued during and after the operation. This episode strongly suggests that one reason of the unexplained sudden deaths of patients receiving long term treatment with chlorpromazine could be laryngospasm. In conclusion, anesthesiologists should be aware of the possibility of laryngospasm under similar conditions. PMID:9071116

  7. Hepatic drug metabolism and adverse hepatic drug reactions.

    PubMed

    Schaffner, F

    1975-01-01

    Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin. PMID:171822

  8. Drug-induced renal disorders.

    PubMed

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  9. [Risk factors and subjective symptoms of drug-induced leucopenia].

    PubMed

    Hayashi, Kyoko; Ohtsu, Fumiko; Yano, Reiko; Sakakibara, Jinsaku; Goto, Nobuyuki

    2011-01-01

    The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting. PMID:21212623

  10. Drug-Induced Metabolic Acidosis.

    PubMed

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics. PMID:26918138

  11. Oxidative hemoglobin reactions: Applications to drug metabolism.

    PubMed

    Spolitak, Tatyana; Hollenberg, Paul F; Ballou, David P

    2016-06-15

    Hb is a protein with multiple functions, acting as an O2 transport protein, and having peroxidase and oxidase activities with xenobiotics that lead to substrate radicals. However, there is a lack of evidence for intermediates involved in these reactions of Hb with redox-active compounds, including those with xenobiotics such as drugs, chemical carcinogens, and sulfides. In particular, questions exist as to what intermediates participate in reactions of either metHb or oxyHb with sulfides. The studies presented here elaborate kinetics and intermediates involved in the reactions of Hb with oxidants (H2O2 and mCPBA), and they demonstrate the formation of high valent intermediates, providing insights into mechanistic issues of sulfur and drug oxidations. Overall, we propose generalized mechanisms that include peroxidatic reactions using H2O2 generated from the autooxidation of oxyHb, with involvement of substrate radicals in reactions of Hb with oxidizable drugs such as metyrapone or 2,4-dinitrophenylhydrazine and with sulfides. We identify ferryl intermediates (with a Soret band at 407 nm) in oxidative reactions with all of the above-mentioned reactions. These spectral properties are consistent with a protonated ferryl heme, such as Cpd II or Cpd ES-like species (Spolitak et al., JIB, 2006, 100, 2034-2044). Mechanism(s) of Hb oxidative reactions are discussed. PMID:27091316

  12. Pharmacogenetic markers of severe cutaneous adverse drug reactions.

    PubMed

    Borroni, R G

    2014-04-01

    Different responses, in terms both of efficacy and toxicity, are commonly observed for any drug administered to apparently homogeneous groups of patients. It is estimated that adverse drug reactions (ADRs) cause 3-6% of all hospitalizations, accounting for 5% to 9% of hospital admission costs. The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis. SCARs are associated with significant mortality and require prompt diagnosis and adequate treatment. Pharmacogenetics studies individual variants in the DNA sequence associated with drug efficacy and toxicity, allowing prescription of a drug to patients expected to benefit from it, and excluding from treatment those who are at risk of developing ADRs. Pharmacogenetics already achieved several important results in the prevention of SCARs, and pharmacogenetic testing is now recommended by regulatory agencies before administration of abacavir and carbamazepine, leading to reduced incidence of SCARs. In this review, the pharmacogenetic associations of SCARs that have been validated in independent, case-control association studies will be presented. By familiarizing with principles of pharmacogenetics, dermatologists should be able to correlate specific cutaneous ADR phenotypes to the underlying genotype, thus contributing to better drug safety and facilitating drug discovery, development and approval. PMID:24819643

  13. Adverse reactions to new anticonvulsant drugs.

    PubMed

    Wong, I C; Lhatoo, S D

    2000-07-01

    A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to

  14. Comparison of a New In-House and Three Published HLA-B*15:02 Screening Methods for Prevention of Carbamazepine-Induced Severe Drug Reactions

    PubMed Central

    Sripo, Thanya; Sukasem, Chonlaphat; Limprasert, Pornprot

    2016-01-01

    Currently, there are three published HLA-B*15:02 screening methods for prevention of carbamazepine-induced severe drug reactions in Asian populations. To analyze available HLA-B*15:02 screening methods, we compared four screening methods, including a multiplex PCR method, a nested PCR method, a LAMP method and our new in-house PCR-dot blot hybridization method. These methods were reviewed regarding their sensitivity, specificity, false positivity and technical considerations. Possible false positive (FP) alleles and genotypes were checked regarding the primers and probes designs, using the IMGT/HLA database. Expected FP rates in Asian populations were predicted using the Allele Frequencies Net Database. All methods had a sensitivity of more than 99.9%, although giving FP results to certain very rare alleles and genotypes. The multiplex PCR method was the only test that gave FP results to certain genotypes of HLA-B*15:13, the allele which is prevalent in Southeast Asian populations. In conclusion, the nested PCR, LAMP and our in-house methods could be applied in various Asian populations, but the multiplex PCR, or any test with FP to HLA-B*15:13, should be applied with caution in the Southeast Asian populations. PMID:27196420

  15. The pattern and risk factors associated with adverse drug reactions induced by Reteplase in patients with acute ST-elevation myocardial infarction: The first report from Iranian population

    PubMed Central

    Aslanabadi, Naser; Safaie, Naser; Shadfar, Faezeh; Taban-Sadeghi, Mohammad Reza; Feizpour, Hossein; Mashayekhi, Simin Ozar; Hamishehkar, Hadi; Aghdam, Naser Khezerlou; Dousti, Samaneh; Namdar, Hossein; Entezari-Maleki, Taher

    2015-01-01

    Objective: Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Reteplase is a fibrin-specific thrombolytic which is used in the treatment of AMI. There is a limited number of studies reporting the postmarketing adverse drug reactions (ADRs) induced by reteplase. This study was aimed to examine the reteplase pattern of ADR and its associated risk factors in patients with acute ST-elevation myocardial infarction. Methods: A cross-sectional, prospective study in an 8-month period was done at the University affiliated referral cardiovascular center. The Naranjo probability scale and World Health Organization criteria for severity of ADRs were used for assessing the ADRs. The linear regression and logistic regression tests were used to evaluate the correlation between ADRs and risk factors. Findings: The all 20 patients who received reteplase during the study period were entered. The majority of patients (n = 17) experienced at least one ADR. The results showed that the incidence of ADRs was mainly associated with gender and age, and the number of ADRs was associated with the history of diabetes and taking anti-diabetic agents. The gender was the main predictor in the occurrence of ADRs (odds ratio: 32, 95% confidence interval: 1.38–737.45; P = 0.030). Conclusion: The results showed that gender, age, diabetes mellitus, and using of anti-diabetes medications are the risk factors associated with the incidence of ADRs by reteplase. PMID:26645027

  16. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  17. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  18. A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin

    PubMed Central

    Mistry, Nisha; Shapero, Jonathan; Crawford, Richard I

    2009-01-01

    Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions. PMID:19826642

  19. Cutaneous drug reaction case reports: from the world literature.

    PubMed

    2003-01-01

    Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. Reactions Weekly is the complete drug safety alerting service and summarizes information selected from over 1600 biomedical journals. This newsletter is produced by Adis International and is available in a variety of formats. Please contact your nearest Adis office for subscription details. The use of tradenames, identified by ['~'] or the use of a registered ((R)) or trade mark ( trade mark ), is for product identification purposes only and does not imply endorsement. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reactions database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from National Centers of 65 affiliate countries. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage). PMID:12680808

  20. [Drug induced eosinophilic pleural effusion].

    PubMed

    Vasilescu, Raluca

    2014-01-01

    The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

  1. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  2. Drug-induced epistaxis?

    PubMed Central

    Watson, M G; Shenoi, P M

    1990-01-01

    To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of nonsteroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function. PMID:2325058

  3. Drug-induced pulmonary disease

    MedlinePlus

    ... improve. Some drug-induced lung diseases, such as pulmonary fibrosis, may never go away. ... Complications that may develop include: Diffuse interstitial pulmonary fibrosis Hypoxemia (low blood oxygen) Respiratory failure

  4. Drug-induced pancreatitis.

    PubMed

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs. PMID:22314811

  5. Drug-induced diarrhea

    MedlinePlus

    Diarrhea associated with medicines ... Nearly all medicines may cause diarrhea as a side effect. The drugs listed below, however, are more likely to cause diarrhea. Laxatives are meant to cause diarrhea. ...

  6. Drug-induced diarrhea

    MedlinePlus

    Diarrhea associated with medications ... Nearly all medicines may cause diarrhea as a side effect. The drugs listed below, however, are more likely to cause diarrhea. Laxatives are meant to cause diarrhea. ...

  7. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  8. Drug-induced pseudolupus.

    PubMed

    Grob, P J; Müller-Schoop, J W; Häcki, M A; Joller-Jemelka, H I

    1975-07-26

    Of fifteen patients with pseudolupus (a syndrome characterised by recurrent fever, myalgia, arthralgia, pleuritis, pulmonary infiltrates, pericarditis, myocarditis, and by mitochondrial antibodies in the absence of nuclear antibodies), all had been treated with "Venocuran", one of a great number of drugs used for venous diseases. This drug, available in twenty countries under various names, contains phenopyrazone, horse-chestnut extract, and cardiac glycosides extracted from various plants. Further studies revealed that up to 90% of long-term users of venocuran acquired mitochondrial antibodies. This was not true for patients with venous diseases being treated with other drugs. About 30% of long-term users of venocuran might experience prodronal symptoms, such as myalgia and arthralgia, while more than 10% could develop the full disease. PMID:49743

  9. Research challenges for drug-induced birth defects.

    PubMed

    Mitchell, A A

    2016-07-01

    Drug-induced birth defects (teratogenesis) represent unique adverse drug reactions (ADRs). Not only is the ADR manifest in a subject other than the one for whom treatment is intended, but most teratogens can be identified only after a drug is marketed. We know little about fetal safety for most marketed drugs, and identification of potential teratogens uniquely requires that study designs consider issues related to the effects of specific drugs, specific defects, and specific gestational timing. PMID:27037730

  10. Drug-induced nail disorders.

    PubMed

    2014-07-01

    Nail disorders are defined according to their appearance and the part of the nail affected: the nail plate, the tissues that support or hold the nail plate in place, or the lunula. The consequences of most nail disorders are purely cosmetic. Other disorders, such as ingrown nails, inflammation, erythema, abscesses or tumours, cause functional impairment or pain. The appearance of the lesions is rarely indicative of their cause. Possible causes include physiological changes, local disorders or trauma, systemic conditions, toxic substances and drugs. Most drug-induced nail disorders resolve after discontinuation of the drug, although complete resolution sometimes takes several years. Drugs appear to induce nail disorders through a variety of mechanisms. Some drugs affect the nail matrix epithelium, the nail bed or the nail folds. Some alter nail colour. Other drugs induce photosensitivity. Yet others affect the blood supply to the nail unit. Nail abnormalities are common during treatment with certain cytotoxic drugs: taxanes, anthracyclines, fluorouracil, EGFR, tyrosine kinase inhibitors, etc. Some drugs are associated with a risk of serious and painful lesions, such as abscesses. When these disorders affect quality of life, the benefits of withdrawing the drug must be weighed against the severity of the condition being treated and the drug's efficacy, taking into account the harm-benefit balance of other options. Various anti-infective drugs, including tetracyclines, quinolones, clofazimine and zidovudine, cause the nail plate to detach from the nail bed after exposure to light, or cause nail discoloration. Psoralens and retinoids can also have the same effects. PMID:25162091

  11. Drug-Induced Urinary Calculi

    PubMed Central

    Matlaga, Brian R; Shah, Ojas D; Assimos, Dean G

    2003-01-01

    Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary. PMID:16985842

  12. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  13. [Review on requirements of drug allergy or pseudoallergic reactions in pre-clinical evaluation].

    PubMed

    Han, Jia-yin; Yi, Yan; Liang, Ai-hua; Zhang, Yu-shi; Li, Chun-ying; Zhao, Yong; Wang, Lian-mei; Lu, Yu-ting; Li, Gui-qin

    2015-07-01

    Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug, drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years, FDA, SFDA OECD, ICH and WHO have published several guidelines on per-clinical immunotoxicity evaluation, however, no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation. PMID:26666009

  14. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  15. Drug-induced skin, nail and hair disorders.

    PubMed

    Valeyrie-Allanore, Laurence; Sassolas, Bruno; Roujeau, Jean-Claude

    2007-01-01

    Drug eruptions are among the most common adverse drug reactions, affecting approximately 3% of hospitalised patients. Although the rate of severe cutaneous adverse reactions to medications is low, these reactions can affect anyone who takes medication, and can result in death or disability. Two general patterns can be distinguished, depending on the type of onset of these cutaneous adverse drug reactions: acute or chronic. Acute-onset events are usually rather specific cutaneous 'syndromes' that constitute emergencies and should therefore be promptly recognised and treated, while chronic-onset events often present as dermatological diseases. The challenge is therefore to recognise the drug aetiology in front of a 'classical' dermatosis such as acne, lichen or pemphigus. Therefore, clinicians should carefully evaluate the signs or symptoms of all adverse reactions thought to be drug related, and discontinue the offending agent when feasible. Erythematous drug eruptions are the most frequent and less severe acute immune drug-induced rashes, and are sometimes difficult to differentiate from viral eruptions. On the other hand, acute urticaria and angioedema are sometimes life-threatening eruptions for which a drug aetiology must be investigated. Photosensitivity, vasculitis and skin necrosis belong to the acute onset reactions, which are not always drug-induced, in contrast to fixed drug eruptions. The early recognition of acute generalised exanthematous pustulosis, DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis are of high importance because of the specific mechanisms involved and the different prognosis of each of these diseases. Chronic onset drug-induced disorders include pigmentary changes, drug-induced autoimmune bullous diseases, lupus, pseudo lymphoma and acneiform eruptions; these are discussed, along with specific data on drug-induced hair and nail disorders. As the disorders are

  16. Psychotropic drug-induced neutropenia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-08-01

    Psychotropic medications have been known to cause blood dyscrasias, including neutropenia, and since the advent of clozapine, this side effect is now increasingly being recognized. Almost all the major classes of psychotropic medications have been associated with neutropenia. Operational definitions for blood dyscrasias have allowed us to create an epidemiological database on this rare side effect of psychotropic medications. With increased awareness of drug-induced neutropenia among physicians, methods of early detection and treatment of this side effect have also been the focus of recent literature. Another area of active research has been identifying the risk factors and mechanism of drug-induced neutropenia. This article attempts to synthesize our current understanding of psychotropic drug-induced neutropenia and also provide insights into future research in this realm. PMID:16234875

  17. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  18. Learning Lessons from Adverse Drug Reactions in Children

    PubMed Central

    Sammons, Helen M.; Choonara, Imti

    2016-01-01

    Drug toxicity is, unfortunately, a significant problem in children both in the hospital and in the community. Drug toxicity in children is different to that seen in adults. At least one in 500 children will experience an adverse drug reaction each year. For children in hospital, the risk is far greater (one in ten). Additionally, different and sometimes unique adverse drug reactions are seen in the paediatric age groups. Some of the major cases of drug toxicity historically have occurred in neonates. It is important that we understand the mechanism of action of adverse drug reactions. Greater understanding alongside rational prescribing should hopefully reduce drug toxicity in children in the future. PMID:27417239

  19. [Drug-induced Cognitive Impairment].

    PubMed

    Shinohara, Moeko; Yamada, Masahito

    2016-04-01

    Elderly people are more likely than young people to develop cognitive impairments associated with medication use. One of the reasons for this is that renal and liver functions are often impaired in elderly people. Dementia and delirium (an acute confused state) are known to be associated with drug toxicity. Anticholinergic medications are common causes of both acute and chronic cognitive impairment. Psychoactive drugs, antidepressants and anticonvulsants can cause dementia and delirium. In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, corticosteroids, NSAIDs (nonsteroidal anti-inflammatory agent), and cardiac medications, may cause acute or chronic cognitive impairment. Early diagnosis and withdrawal of the offending agent are essential for the prevention of drug-induced dementia and delirium. PMID:27056860

  20. Drug-induced visceral angioedema

    PubMed Central

    Thalanayar, Prashanth M.; Ghobrial, Ibrahim; Lubin, Fritz; Karnik, Reena; Bhasin, Robin

    2014-01-01

    Angioedema associated with angiotensin converting enzyme inhibitors (ACEIs) is due to the accumulation of bradykinin and its metabolites. Angiotensin receptor blockers (ARBs) produce anti-hypertensive effects by blocking the angiotensin II AT1 receptor action; hence bradykinin-related side effects are not expected. However, we notice the occurrence of ARB-induced angioedema as not a very rare side effect. Visceral drug-induced angioedema has been reported with ACEIs, not with ARBs. This underlying review will help educate readers on the pathophysiology and recent guidelines pertaining to ACEI- and ARB-induced visceral angioedema. PMID:25317271

  1. (Reaction mechanism studies of heavy ion induced nuclear reactions)

    SciTech Connect

    Mignerey, A.C.

    1991-01-01

    This report discusses the following research projects; decay of excited nuclei formed in La-induced reactions at E/A = 45 MeV; mass and charge distributions in Cl-induced heavy ion reactions; and mass and charge distributions in {sup 56}Fe + {sup 165}Ho at E/A = 12 MeV.

  2. Drug-Path: a database for drug-induced pathways.

    PubMed

    Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. PMID:26130661

  3. Drug-Path: a database for drug-induced pathways

    PubMed Central

    Zeng, Hui; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

  4. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  5. Bioactivation and bioinactivation of drugs and drug metabolites: Relevance to adverse drug reactions.

    PubMed

    Park, B K; Pirmohamed, M; Tingle, M D; Madden, S; Kitteringham, N R

    1994-08-01

    Adverse drug reactions that cannot be predicted from the pharmacological properties of the drug and which are not easily reproduced in laboratory animals are a major complication of drug therapy. It is necessary to investigate the mechanisms of such reactions in order to (1) define structural features within a given drug molecule which are responsible for causing toxicity and (2) to identify those individuals who are particularly sensitive to a given drug reaction. In theory, drug toxicity may arise by direct toxicity, genotoxicity or immune-mediated toxicity caused by either parent drug or chemical. In this respect chemically reactive metabolites are of particular importance and the balance between bioactivation and bioinactivation pathways of drug metabolism will be a critical factor in both the type and extent of toxicity. We have therefore developed in vitro techniques that incorporate human cells for the detection and characterization of stable, chemically reactive and cytotoxic metabolites. In such experiments bioactivation (by CYP1A, CYP2D6, CYP3A, etc.) can be investigated by use of a liver bank, while lymphocytes provide accessible human cells, which can be obtained from both patients and volunteers, genotyped and/or phenotyped for particular drug-metabolizing enzymes (eg. glutathione transferase mu). The relevance of in vitro experiments to drug toxicity observed in humans will be illustrated by reference to studies with anticonvulsants and antimalarials. PMID:20692973

  6. Drug-induced lupus erythematosus.

    PubMed

    Vedove, Camilla Dalle; Del Giglio, Micol; Schena, Donatella; Girolomoni, Giampiero

    2009-01-01

    Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Similarly to idiopathic lupus, DILE can be diveded into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE is characterized by typical lupus-like symptoms including skin signs, usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies, while anti-double strand (ds) DNA and anti-extractable nuclear antigens antibodies are rare. High risk drugs include hydralazine, procainamide and isoniazid. Drug-induced SCLE is very similar to idiopathic SCLE in terms of clinical and serologic characteristic, and it is more common than the systemic form of DILE. Drugs associated with SCLE include calcium channel blockers, angiotensin-converting enzyme inhibitors, interferons, thiazide diuretics and terbinafine. Drug-induced CCLE is very rarely reported in the literature and usually refers to fluorouracile agents or non steroidal anti-inflammatory drugs. Recently, cases of DILE have been reported with anti-TNFalpha agents. These cases present with disparate clinical features including arthritis/arthralgia, skin rash, serositis, cytopenia and variable laboratory abnormalities. DILE to anti-TNFalpha agents differs in several ways to classic DILE. The incidence of rashes is higher compared to classical systemic DILE. In most cases of classic DILE visceral involvement is rare, whereas several cases of anti-TNFalpha DILE with evidence of renal disease have been reported. Low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present in classic DILE, whereas they are reported in half the cases of anti-TNFalpha DILE; in contrast, anti

  7. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Pérez-Alzate, D; Pérez-Sánchez, N; Plaza-Serón, M C; Doña, I; Torres, M J; Canto, G; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID:26817135

  8. Drug-induced weight gain.

    PubMed

    Ness-Abramof, Rosane; Apovian, Caroline M

    2005-01-01

    Drug-induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and to exacerbation of comorbid conditions related to obesity. Improved glycemic control achieved by insulin, insulin secretagogues or thiazolidinedione therapy is generally accompanied by weight gain. It is a problematic side effect of therapy due to the known deleterious effect of weight gain on glucose control, increased blood pressure and worsening lipid profile. Weight gain may be lessened or prevented by adherence to diet and exercise or combination therapy with metformin. Weight gain is also common in psychotropic therapy. The atypical antipsychotic drugs (clozapine, olanzepine, risperidone and quetiapine) are known to cause marked weight gain. Antidepressants such as amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs) also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms. The same phenomenon is observed with mood stabilizers such as lithium, valproic acid and carbamazepine. Antiepileptic drugs (AEDs) that promote weight gain include valproate, carbamazepine and gabapentin. Lamotrigine is an AED that is weight-neutral, while topiramate and zonisamide may induce weight loss. PMID:16341287

  9. Drug-induced weight gain.

    PubMed

    Ness-Abramof, Rosane; Apovian, Caroline M

    2005-08-01

    Drug-induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and to exacerbation of comorbid conditions related to obesity. Improved glycemic control achieved by insulin, insulin secretagogues or thiazolidinedione therapy is generally accompanied by weight gain. It is a problematic side effect of therapy due to the known deleterious effect of weight gain on glucose control, increased blood pressure and worsening lipid profile. Weight gain may be lessened or prevented by adherence to diet and exercise or combination therapy with metformin. Weight gain is also common in psychotropic therapy. The atypical antipsychotic drugs (clozapine, olanzepine, risperidone and quetiapine) are known to cause marked weight gain. Antidepressants such as amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs) also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms. The same phenomenon is observed with mood stabilizers such as lithium, valproic acid and carbamazepine. Antiepileptic drugs (AEDs) that promote weight gain include valproate, carbamazepine and gabapentin. Lamotrigine is an AED that is weight-neutral, while topiramate and zonisamide may induce weight loss. PMID:16234878

  10. [Drug-induced ventricular tachycardia].

    PubMed

    Fauchier, J P; Fauchier, L; Babuty, D; Breuillac, J C; Cosnay, P; Rouesnel, P

    1993-05-01

    Certain drugs can induce ventricular tachycardia (VT) by creating reentry, ventricular after potentials or exaggerating the slope of phase 4. These may or may not be symptomatic, sustained or non-sustained and have variable ECG appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They risk degenerating into ventricular flutter of fibrillation and have been held responsible for the increased mortality observed unexpectedly in some long-term treatments. The drugs responsible are mainly those used in cardiology, probably due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe ventricular arrhythmias, therapeutic associations, metabolic abnormalities). These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil), digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications may be toxic or idiosyncratic, in patients with or without cardiac disease, and may also occur with other drugs: vasodilators and anti-anginal drugs (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and imipramine), antimitotics, antimalarials (chloroquine) or antibiotics (erythromycin, pentamidine). The prognosis is severe and the treatment is often difficult which makes prevention, helped by repeated surface ECG (or Holter monitoring), very important with careful assessment of patients at risk. PMID:8267504

  11. Blood dyscrasias induced by psychotropic drugs.

    PubMed

    Stübner, S; Grohmann, R; Engel, R; Bandelow, B; Ludwig, W-D; Wagner, G; Müller-Oerlinghausen, B; Möller, H-J; Hippius, H; Rüther, E

    2004-03-01

    Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions. PMID:15052517

  12. Drug-Induced Mitochondrial Toxicity.

    PubMed

    Hargreaves, Iain P; Al Shahrani, Mesfer; Wainwright, Luke; Heales, Simon J R

    2016-07-01

    The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy. PMID:26992920

  13. Acute and chronic drug-induced hepatitis.

    PubMed

    Pessayre, D; Larrey, D

    1988-04-01

    Adverse drug reactions may mimic almost any kind of liver disease. Acute hepatitis is often due to the formation of reactive metabolites in the liver. Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g. paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g. isoniazid). Both genetic factors (e.g. constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g. malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients. Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites. This may be the mechanism for acute hepatitis produced by many drugs (e.g. amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.). Genetic defects in several protective mechanisms (e.g. epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes. Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only. Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge. Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline). These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes. Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures. This

  14. Effective radii of deuteron-induced reactions

    SciTech Connect

    Hashimoto, Shintaro; Chiba, Satoshi; Yahiro, Masanobu; Ogata, Kazuyuki; Minomo, Kosho

    2011-05-15

    The continuum-discretized coupled-channels method (CDCC) for exclusive reactions and the eikonal reaction theory (ERT) as an extension of CDCC to inclusive reactions are applied to deuteron-induced reactions. The CDCC result reproduces experimental data on the reaction cross section for d+{sup 58}Ni scattering at 200 MeV/nucleon, and ERT provides data on the neutron-stripping cross section for inclusive {sup 7}Li(d,n) reaction at 40 MeV. For deuteron-induced reactions at 200 MeV/nucleon, target-dependence of the reaction, elastic-breakup, nucleon-stripping, nucleon-removal, and complete- and incomplete-fusion cross sections is clearly explained by simple formulas. Accuracy of the Glauber model is also investigated.

  15. A Survey of Adverse Drug Reactions in Family Practice

    PubMed Central

    Reynolds, J. L.

    1984-01-01

    In this study, 232 Canadian family physicians recorded suspected adverse drug reactions (SADRs) in their practices for five months. Patients' age and sex, the drug(s) implicated, type of reaction and any disability were recorded on a card and sent to a central coordinating office each week. The number of SADRs in clinical practice seems to be small. An estimated 300,000 patients were involved in the study, and a total of 314 suspected adverse drug reactions in 314 patients were reported. A proposal is made for a surveillance system for new drugs. Family physicians would monitor all patients taking a drug or group of drugs and matched controls. The status of patients and controls would be recorded regularly and any SADRs reported to a central coordinating centre. PMID:21283495

  16. Impact of New Genomic Technologies on Understanding Adverse Drug Reactions.

    PubMed

    Maggo, Simran D S; Savage, Ruth L; Kennedy, Martin A

    2016-04-01

    It is well established that variations in genes can alter the pharmacokinetic and pharmacodynamic profile of a drug and immunological responses to it. Early advances in pharmacogenetics were made with traditional genetic techniques such as functional cloning of genes using knowledge gained from purified proteins, and candidate gene analysis. Over the past decade, techniques for analysing the human genome have accelerated greatly as knowledge and technological capabilities have grown. These techniques were initially focussed on understanding genetic factors of disease, but increasingly they are helping to clarify the genetic basis of variable drug responses and adverse drug reactions (ADRs). We examine genetic methods that have been applied to the understanding of ADRs, review the current state of knowledge of genetic factors that influence ADR development, and discuss how the application of genome-wide association studies and next-generation sequencing approaches is supporting and extending existing knowledge of pharmacogenetic processes leading to ADRs. Such approaches have identified single genes that are major contributing genetic risk factors for an ADR, (such as flucloxacillin and drug-induced liver disease), making pre-treatment testing a possibility. They have contributed to the identification of multiple genetic determinants of a single ADR, some involving both pharmacologic and immunological processes (such as phenytoin and severe cutaneous adverse reactions). They have indicated that rare genetic variants, often not previously reported, are likely to have more influence on the phenotype than common variants that have been traditionally tested for. The problem of genotype/phenotype discordance affecting the interpretation of pharmacogenetic screening and the future of genome-based testing applied to ADRs are also discussed. PMID:26369774

  17. Drug-induced phospholipidosis caused by combinations of common drugs in vitro.

    PubMed

    Glock, Mareike; Muehlbacher, Markus; Hurtig, Henoch; Tripal, Philipp; Kornhuber, Johannes

    2016-09-01

    Drug-induced phospholipidosis (DIPLD), characterized by the accumulation of phospholipids within lysosomes, is suspected to impair lysosomal function and considered an adverse side effect of the administered medication. The increasing use of polypharmacy and the resultant elevated risks of adverse drug reactions raise the need to explore the effects of drug combinations with respect to their influence on side effects, such as DIPLD. In this study, we utilized an in vitro assay to investigate DIPLD that was caused by 24 commonly used drugs applied alone and in binary combinations with each other. Moreover, we attempted to predict the extent of DIPLD resulting from the combinations using a simple additive approach based on the increase in phospholipid levels caused by the single drugs. The results suggest that DIPLD, which was caused by combinations of drugs, occurs in an additive manner, depending on total drug concentration. Furthermore, we show that the extent of DIPLD can be predicted from the DIPLD caused by the single drugs. Thus, the simultaneous use of multiple drugs with PLD-inducing properties increases the event risk, as well as the severity of drug-induced phospholipidosis. The findings underline the importance of considering the DIPLD-inducing properties of drugs, especially in the context of polypharmacy. PMID:27221059

  18. Drug Induced Hearing Loss: What Is Ototoxicity?

    MedlinePlus

    ... page please turn JavaScript on. Feature: Drug-Induced Hearing Loss What Is Ototoxicity? Past Issues / Spring 2016 Table ... of patients taking these drugs." "Antibiotics Caused My Hearing Loss..." Gulab Lalwani Photo Courtesy of: Gulab Lalwani When ...

  19. [Adverse drug reaction - Definitions, risk factors and pharmacovigilance].

    PubMed

    Krähenbühl, Stephan

    2015-12-01

    Adverse drug reactions (ADR} are the downside of active pharmacotherapies and can only partially be avoided. Risk factors have been identified for certain ADR which should be taken into account for the choice and dosing of critical drugs. Medical staff have a legal obligation to report severe ADR and ADR caused by newly licensed drugs. Such reports are important for monitoring the safety of drugs that are on the market. PMID:26654809

  20. [Frequency of drug adverse reactions among hospitalized patients].

    PubMed

    González Martínez, L

    1995-01-01

    This article describes the frequency of adverse reactions to drugs in a sample of hospitalized patients in the internal medicine ward seen during a year's term. Of 61 medical charts, we found 8 patients with adverse reactions to drugs during their hospital stay and another 4 patients hospitalized due to adverse reactions to drugs. The majority of the adverse reactions were of moderate degree (75%) and were related to drugs of cardiovascular action (58%). The frequency of reactions in hospitalized patients (13%) is comparable with the results obtained from other hospitals. Yet, the real magnitude of the problem is probably greater since the source of information (hospital charts) the totality of the clinical manifestations are not registered. PMID:8581452

  1. The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions.

    PubMed

    Uetrecht, J P

    1992-01-01

    Evidence strongly suggests that many adverse drug reactions, including idiosyncratic drug reactions, involve reactive metabolites. Furthermore, certain functional groups, which are readily oxidized to reactive metabolites, are associated with a high incidence of adverse reactions. Most drugs can probably form reactive metabolites, but a simple comparison of covalent binding in vitro is unlikely to provide an accurate indication of the relative risk of a drug causing an idiosyncratic reaction because it does not provide an indication of how efficiently the metabolite is detoxified in vivo. In addition, the incidence and nature of adverse reactions associated with a given drug is probably determined in large measure by the location of reactive metabolite formation, as well as the chemical reactivity of the reactive metabolite. Such factors will determine which macromolecules the metabolites will bind to, and it is known that covalent binding to some proteins, such as those in the leukocyte membrane, is much more likely to lead to an immune-mediated reaction or other type of toxicity. Some reactive metabolites, such as acyl glucuronides, circulate freely and could lead to adverse reactions in almost any organ; however, most reactive metabolites have a short biological half-life, and although small amounts may escape the organ where they are formed, these metabolites are unlikely to reach sufficient concentrations to cause toxicity in other organs. Many idiosyncratic drug reactions involve leukocytes, especially agranulocytosis and drug-induced lupus. We and others have demonstrated that drugs can be metabolized by activated neutrophils and monocytes to reactive metabolites. The major reaction appears to be reaction with leukocyte-generated hypochlorous acid. Hypochlorous acid is quite reactive, and therefore it is likely that many other drugs will be found that are metabolized by activated leukocytes. Some neutrophil precursors contain myeloperoxidase and the NADPH

  2. Promoting adverse drug reaction reporting: comparison of different approaches

    PubMed Central

    Ribeiro-Vaz, Inês; Santos, Cristina Costa; Cruz-Correia, Ricardo

    2016-01-01

    ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report. PMID:27143614

  3. Immune-mediated drug-induced liver disease.

    PubMed

    Liu, Zhang-Xu; Kaplowitz, Neil

    2002-08-01

    Drug-induced immune-mediated hepatic injury is an adverse immune response against the liver that results in a disease with hepatitic, cholestatic, or mixed clinical features. Drugs such as halothane, tienilic acid, dihydralazine, and anticonvulsants trigger a hepatitic reaction, and drugs such as chlorpromazine, erythromycins, amoxicillin-calvulanic acid, sulfonamides and sulindac trigger a cholestatic or mixed reaction. Unstable metabolites derived from the metabolism of the drug may bind to cellular proteins or macromolecules, leading to a direct toxic effect on hepatocytes. Protein adducts formed in the metabolism of the drug may be recognized by the immune system as neoantigens. Immunocyte activation may then generate autoantibodies and cell-mediated immune responses, which in turn damage the hepatocytes. Cytochromes 450 are the major oxidative catalysts in drug metabolism, and they can form a neoantigen by covalently binding with the drug metabolite that they produce. Autoantibodies that develop are selectively directed against the particular cytochrome isoenzyme that metabolized the parent drug. The hapten hypothesis proposes that the drug metabolite can act as a hapten and can modify the self of the individual by covalently binding to proteins. The danger hypothesis proposes that the immune system only responds to a foreign antigen if the antigen is associated with a danger signal, such as cell stress or cell death. Most clinically overt adverse hepatic events associated with drugs are unpredictable, and they have intermediate (1 to 8 weeks) or long latency (up to 12 months) periods characteristic of hypersensitivity reactions. Immune-mediated drug-induced liver disease nearly always disappears or becomes quiescent when the drug is removed. Methyldopa, minocycline, and nitrofurantoin can produce a chronic hepatitis resembling AIH if the drug is continued. PMID:12362579

  4. Ofloxacin Induced Cutaneous Reactions in Children

    PubMed Central

    Mishra, Sailen Kumar; Rath, Bandana; Rath, Saroj Sekhar

    2015-01-01

    Cutaneous adverse effects to antimicrobials are a major health problem. Though majority of them are mild and self-limiting, severe variants like Steven Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) are not uncommon. Ofloxacin, a fluoroquinolone widely used for the treatment of urinary tract infections, acute bacterial diarrheas, enteric fever, STDs and other soft tissue infections either as a single drug or in combination with other drugs. Earlier a case of mucocutaneous maculopapular rash with oral ofloxacin and was reported in an adult. In the present hospital set up there were few reports of such reactions to adults. Here we report three different variants of reactions associated with oral ofloxacin in chlidren. Early detection of cutaneous lesions and immediate withdrawal of the offending drug can prevent progression of such reactions to their severe variants as well as morbidity and mortality. PMID:26266136

  5. Role of endoplasmic reticulum stress in drug-induced toxicity.

    PubMed

    Foufelle, Fabienne; Fromenty, Bernard

    2016-02-01

    Drug-induced toxicity is a key issue for public health because some side effects can be severe and life-threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug-induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug-induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug-induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models. PMID:26977301

  6. Drug-induced hair colour changes.

    PubMed

    Bublin, J G; Thompson, D F

    1992-10-01

    Drug-induced hair colour changes are not a common adverse effect from medications. A wide variety of drugs have been implicated in causing hair colour changes but very few have data to support a true relationship. Of the drugs reported, chloroquine and cancer chemotherapeutic agents have the best evidence to support an association. Other drugs, such as p-aminobenzoic acid, calcium pantothenate, anthralin, chinoform, mephenesin, minoxidil, propofol, valproic acid, and verapamil await confirmatory data. Drug-induced causes should be considered in any patient with unexplained hair colour changes. PMID:1464633

  7. Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.

    PubMed

    Conforti, Anita; Chiamulera, Christian; Moretti, Ugo; Colcera, Sonia; Fumagalli, Guido; Leone, Roberto

    2007-01-01

    The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed. PMID:18690950

  8. Tween-80 and impurity induce anaphylactoid reaction in zebrafish.

    PubMed

    Yang, Rui; Lao, Qiao-Cong; Yu, Hang-Ping; Zhang, Yong; Liu, Hong-Cui; Luan, Lin; Sun, Hui-Min; Li, Chun-Qi

    2015-03-01

    A number of recent reports suspected that Tween-80 in injectable medicines, including traditional Chinese medicine injections could cause life-threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug-induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate-based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N-benzoyl-dl-arginine p-nitroanilide as a substrate. We assessed 10 batches of Tween-80 solutions from various national and international suppliers and three Tween-80 impurities (ethylene glycol, 2-chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween-80 (nos 2, 20080709 and 20080616) and one Tween-80 impurity, hydrogen peroxide (H2 O2 ), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H2 O2 residue and peroxide value were much higher in Tween-80 samples 2, 20080709 and 20080616. These findings suggest that H2 O2 residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween-80 samples, but not Tween-80 itself, may induce anaphylactoid reaction. High-throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween-80-containing injectable medicines and potentially for screening novel mast cell-modulating drugs. PMID:25345596

  9. Drug-Induced Acute Pancreatitis: A Review

    PubMed Central

    Jones, Mark R.; Hall, Oliver Morgan; Kaye, Adam M.; Kaye, Alan David

    2015-01-01

    Background The majority of drug-induced pancreatitis cases are mild to moderate in severity, but severe and even fatal cases can occur. Management of drug-induced pancreatitis requires withdrawal of the offending agent and supportive care. Methods This review focuses on differential diagnosis, clinical presentation, drug-mediated effects, treatments, and mechanisms of pancreatitis, with an emphasis on drug-induced pancreatitis. Results Although only a minority of cases associated with acute pancreatitis are linked to drugs, clinical presentation and mechanisms of injury to the pancreas are not well understood by clinicians in terms of individual drug effects in the mediation or modulation of injury to the pancreas. In recent years, a large number of commonly prescribed medications has been linked to drug-induced pancreatitis pathogenesis. Although mechanisms are proposed, the exact cause of injury is either not well understood or controversial. Conclusion Future investigation into the mechanisms of pancreatitis and an appreciation by clinicians of the drugs commonly linked to the condition will help establish earlier diagnosis and quicker cessation of offending drugs in the treatment of drug-induced acute pancreatitis. PMID:25829880

  10. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs.

    PubMed

    Moore, Nicholas; Pollack, Charles; Butkerait, Paul

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug-drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. PMID:26203254

  11. [Successful drug desensitization after vemurafenib-induced rash].

    PubMed

    Klossowski, N; Kislat, A; Homey, B; Gerber, P A; Meller, S

    2015-04-01

    The BRAF inhibitor vemurafenib was approved in 2011 for the treatment of inoperable or metastatic melanoma. Vemurafenib therapy is associated with several side effects, such as arthralgia, secondary skin tumors or inflammatory rashes. In particular cutaneous toxicities represent a serious threat to patients' adherence. Here, we present the case of a successful drug desensitization in a patient that presented with a vemurafenib-induced rash. Lymphocyte activation tests failed to detect drug-specific T cells, suggesting that the development of the rash was based upon a nonallergic drug hypersensitivity reaction. A program of slow desensitization was initiated and subsequently, vemurafenib was tolerated at the full effective and recommended dosage. PMID:25698338

  12. [Toxic and drug-induced lesions of the pulmonary parenchyma].

    PubMed

    Russi, E

    1992-05-01

    Pulmonary tissue may be damaged by certain toxins or drugs in a dose-dependent way or by a hypersensitivity reaction. Pathological changes consist of a permeability pulmonary edema, an alveolar hemorrhage, an alveolitis and finally the formation of pulmonary fibrosis. Ingestion of the weed killer paraquat may induce a rapidly progressive and lethal form of fibrosing alveolitis, the inhalation of nitrous oxides may elicit lung edema. The most common drugs causing lung damage are cytotoxic agents, often used in combination, and the noncytotoxic drugs amiodarone and nitrofurantoin. PMID:1589677

  13. Employee drug use, demographic characteristics, work reactions, and absenteeism.

    PubMed

    Bass, A R; Bharucha-Reid, R; Delaplane-Harris, K; Schork, M A; Kaufmann, R; McCann, D; Foxman, B; Fraser, W; Cook, S

    1996-01-01

    Employees in a large work organization participated in an investigation of relationships between drug use and absenteeism and tardiness. Specifically, the study investigated the extent to which both self-reported and urine-screened drug use accounted for variance in several types of absenteeism, as well as tardiness, above and beyond that accounted for by demographic and work reaction variables. The results showed that employee drug use accounted for additional statistically significant variance in overall absenteeism and in absenteeism due to injuries and suspensions, as well as days tardy. Implications of these findings for organizational drug testing are discussed. PMID:9547039

  14. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  15. Treatment of drug-induced seizures.

    PubMed

    Chen, Hsien-Yi; Albertson, Timothy E; Olson, Kent R

    2016-03-01

    Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established. PMID:26174744

  16. Non-steroidal drug-induced glaucoma

    PubMed Central

    Razeghinejad, M R; Pro, M J; Katz, L J

    2011-01-01

    Numerous systemically used drugs are involved in drug-induced glaucoma. Most reported cases of non-steroidal drug-induced glaucoma are closed-angle glaucoma (CAG). Indeed, many routinely used drugs that have sympathomimetic or parasympatholytic properties can cause pupillary block CAG in individuals with narrow iridocorneal angle. The resulting acute glaucoma occurs much more commonly unilaterally and only rarely bilaterally. CAG secondary to sulfa drugs is a bilateral non-pupillary block type and is due to forward movement of iris–lens diaphragm, which occurs in individuals with narrow or open iridocorneal angle. A few agents, including antineoplastics, may induce open-angle glaucoma. In conclusion, the majority of cases with glaucoma secondary to non-steroidal medications are of the pupillary block closed-angle type and preventable if the at-risk patients are recognized and treated prophylactically. PMID:21637303

  17. A time-indexed reference standard of adverse drug reactions

    PubMed Central

    Harpaz, Rave; Odgers, David; Gaskin, Greg; DuMouchel, William; Winnenburg, Rainer; Bodenreider, Olivier; Ripple, Anna; Szarfman, Ana; Sorbello, Alfred; Horvitz, Eric; White, Ryen W.; Shah, Nigam H.

    2014-01-01

    Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance. PMID:25632348

  18. Republished: drug-induced valvular heart disease.

    PubMed

    Cosyns, Bernard; Droogmans, Steven; Rosenhek, Raphael; Lancellotti, Patrizio

    2013-03-01

    Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. PMID:23417686

  19. Drug-induced valvular heart disease.

    PubMed

    Cosyns, Bernard; Droogmans, Steven; Rosenhek, Raphael; Lancellotti, Patrizio

    2013-01-01

    Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. PMID:22875739

  20. Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

    PubMed Central

    Friedrich, Michaela-Elena; Akimova, Elena; Huf, Wolfgang; Konstantinidis, Anastasios; Papageorgiou, Konstantinos; Winkler, Dietmar; Toto, Sermin; Greil, Waldemar; Grohmann, Renate; Kasper, Siegfried

    2016-01-01

    Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction. PMID:26721950

  1. Azithromycin induced bullous fixed drug eruption

    PubMed Central

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID:26997729

  2. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges

    PubMed Central

    Wilke, Russell A.; Lin, Debbie W.; Roden, Dan M.; Watkins, Paul B.; Flockhart, David; Zineh, Issam; Giacomini, Kathleen M.; Krauss, Ronald M.

    2009-01-01

    Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered. PMID:17971785

  3. Cutaneous adverse drug reactions in Indian population: A systematic review

    PubMed Central

    Patel, Tejas K; Thakkar, Sejal H; Sharma, DC

    2014-01-01

    Background: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. Aims: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. Materials and Methods: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing “definite” and “probable” categories of causality analysis were labeled as “definite and probable causality (DPC) studies”. The other included studies were labeled as “non-DPC studies”. Results: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), β-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS

  4. Phenotype Standardization for Drug Induced Kidney Disease

    PubMed Central

    Mehta, Ravindra L; Awdishu, Linda; Davenport, Andrew; Murray, Patrick; Macedo, Etienne; Cerda, Jorge; Chakaravarthi, Raj; Holden, Arthur; Goldstein, Stuart L.

    2015-01-01

    Drug induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular and nephrolithiasis, along with primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease and chronic kidney disease. Establishing causality in drug induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is first step to recognizing drug induced kidney disease and developing strategies to prevent and manage this condition. PMID:25853333

  5. Antibiotic hypersensitivity in CF: drug-induced life-threatening hemolytic anemia in a pediatric patient.

    PubMed

    Chavez, Alma; Mian, Amir; Scurlock, Amy M; Blackall, Douglas; Com, Gulnur

    2010-12-01

    Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF. PMID:20833594

  6. Cellular basis of drug-induced torsades de pointes

    PubMed Central

    Roden, D M

    2008-01-01

    Striking QT prolongation and the morphologically distinctive ventricular tachycardia torsades de pointes can occur in up to 5% of patients treated with certain antiarrhythmic drugs. This adverse drug reaction also occurs, albeit far less frequently, during therapy with a range of drugs not used for cardiovascular indications; examples include certain antibiotics, antipsychotics and antihistamines. The common mechanism for drug-induced torsades de pointes is inhibition of a specific repolarizing potassium current, IKr. The key question facing clinicians, regulators and those who develop drugs is why torsades de pointes only occurs in some patients exposed to IKr block. This paper reviews the clinical, cellular, molecular and genetic features of the arrhythmia that may provide an answer to this question and proposes future studies in this area. PMID:18552874

  7. Severe Cutaneous Drug Reactions: Do Overlapping Forms Exist?

    PubMed

    Horcajada-Reales, C; Pulido-Pérez, A; Suárez-Fernández, R

    2016-01-01

    Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions. PMID:26520037

  8. The discovery of drug-induced illness.

    PubMed

    Jick, H

    1977-03-01

    The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users. PMID:834226

  9. [Drug-induced thyroid dysfunctions].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2014-01-01

    latrogenic disorders are an important cause of morbidity, mortality, and admission to hospital in developed countries. Similarly to many other organs, the thyroid gland may be affected by various drugs, often used for the treatment of non-thyroid disorders. Drugs may affect thyroid function via different mechanisms, including thyroid hormone production, storage, secretion and metabolism offering numerous targets for drug interventions. Usually, the effect of pharmacotherapy is observed more frequently and is stronger in case of the presence of the concomitant disorder of this gland. An understanding of the proposed mechanisms of these drug interactions and their evaluation and differential diagnosis is helpful in the interpretation of the findings associated thyroid disorders and in establishing the correct treatment. The purpose of this article is to review the present state of knowledge on the influence of various drugs on the hypothalamic-pituitary-adrenal axis. We discuss pros and cons of the use of these agents in patients with concomitant thyroid disease and provide the reader with recommendations concerning the diagnosis and treatment of iatrogenic thyroid disorders. PMID:26030960

  10. Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions-Potential and Limitations.

    PubMed

    Steiner, Markus; Harrer, Andrea; Himly, Martin

    2016-01-01

    Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions. PMID:27378928

  11. Permeability Changes in Reaction Induced Fracturing

    NASA Astrophysics Data System (ADS)

    Ulven, Ole Ivar; Malthe-Sørenssen, Anders; Kalia, Rajiv

    2013-04-01

    The process of fracture formation due to a volume increasing chemical reaction has been studied in a variety of different settings, e.g. weathering of dolerites by Røyne et al.[4], serpentinization and carbonation of peridotite by Rudge et al.[3] and replacement reactions in silica-poor igneous rocks by Jamtveit et al.[1]. It is generally assumed that fracture formation will increase the net permeability of the rock, and thus increase the reactant transport rate and subsequently the total reaction rate, as summarised by Kelemen et al.[2]. Røyne et al.[4] have shown that transport in fractures will have an effect on the fracture pattern formed. Understanding the feedback process between fracture formation and permeability changes is essential in assessing industrial scale CO2 sequestration in ultramafic rock, but little is seemingly known about how large the permeability change will be in reaction-induced fracturing under compression, and it remains an open question how sensitive a fracture pattern is to permeability changes. In this work, we study the permeability of fractures formed under compression, and we use a 2D discrete element model to study the fracture patterns and total reaction rates achieved with different permeabilities. We achieve an improved understanding of the feedback processes in reaction-driven fracturing, thus improving our ability to decide whether industrial scale CO2 sequestration in ultramafic rock is a viable option for long-term handling of CO2. References [1] Jamtveit, B, Putnis, C. V., and Malthe-Sørenssen, A., "Reaction induced fracturing during replacement processes," Contrib. Mineral Petrol. 157, 2009, pp. 127 - 133. [2] Kelemen, P., Matter, J., Streit, E. E., Rudge, J. F., Curry, W. B., and Blusztajn, J., "Rates and Mechanisms of Mineral Carbonation in Peridotite: Natural Processes and Recipes for Enhanced, in situ CO2 Capture and Storage," Annu. Rev. Earth Planet. Sci. 2011. 39:545-76. [3] Rudge, J. F., Kelemen, P. B., and

  12. Severe idiosyncratic drug reaction (Lyells syndrome) after ingesting dihydroartemisinin.

    PubMed

    Ugburo, A O; Ilombu, C A; Temiye, E O; Fadeyibi, I O; Akinolai, O I

    2009-06-01

    Lyells syndrome also called Toxic epidermal necrolysis is the extreme form of idiosyncratic drug reaction that is called Steven Johnsons Syndrome: The condition results in an extensive loss of the skin with mucous membrane involvement. Lyells syndrome has been induced by many agents. The commonest agent in the literature being sulphonamides. However, in our search of the medical literature there was no report of dihydroarthemisinin as a cause of Lyells syndrome. We report three patients seen at two tertiary health institutions with Lyells syndrome after treatment for malaria with dihydroarthemisinin. This resulted from administration of dihydroarthemisinin with chloroquine in two patients and dihydroarthemisinin with Amodiaquine in one patient. The first patient was a seven year old child who developed 90% cutaneous involvement and died from hemorrhagic shock. The second was a 28 old female that developed a 76% body surface involvement and died from septicemia. The third patient was a pregnant 37 year old woman that developed 52% body involvement and died from septic shock. In these patients the earliest symptoms were not recognized and there was considerable delay before referral. In view of the recent WHO recommendation ofArthemisinin Combination Treatment (ACT) for malaria, we expect more cases of Steven Johnson Syndrome and Lyells syndrome from ACT treatment. The aim of this report is to raise the awareness of clinicians to this potentially fatal complication. PMID:19764682

  13. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future. PMID:26310040

  14. Nuclear reactions induced by a pyroelectric accelerator.

    PubMed

    Geuther, Jeffrey; Danon, Yaron; Saglime, Frank

    2006-02-10

    This work demonstrates the use of pyroelectric crystals to induce nuclear reactions. A system based on a pair of pyroelectric crystals is used to ionize gas and accelerate the ions to energies of up to 200 keV. The system operates above room temperature by simply heating or cooling the pyroelectric crystals. A D-D fusion reaction was achieved with this technique, and 2.5 MeV neutrons were detected. The measured neutron yield is in good agreement with the calculated yield. This work also verifies the results published by Naranjo, Gimzewski, and Putterman [Nature (London) 434, 1115 (2005)]. PMID:16486940

  15. Drug reaction with eosinophilia and systemic symptoms syndrome associated with Nitrofurantoin

    PubMed Central

    Singh, Jitendra; Dinkar, Anju; Atam, Virendra; Gupta, Kamlesh K.; Sahani, Krishna Kumar

    2016-01-01

    Drug reaction with eosinophilia and systemic symptom (DRESS) is a severe adverse drug-induced reaction with a prolonged latency period which is characterized by a variety of clinical manifestations, usually fever, rash, lymphadenopathy, eosinophilia, and a wide range of mild-to-severe systemic presentations. Drugs are an important cause of DRESS in most of the cases. It is challenging to diagnose DRESS because of the diversity of cutaneous eruption and visceral organs involvement. We hereby report a 34-year-old female who developed DRESS syndrome following ingestion of nitrofurantoin for the treatment of urinary tract infection. She was managed conservatively and recovered after few weeks. Our aim of this study is to raise awareness to suspect DRESS syndrome in patients who present with unusual clinical features with skin involvement after initiating any drug. PMID:26985439

  16. Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital

    PubMed Central

    Palaniappan, Muthiah; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan

    2015-01-01

    Background Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. Aim To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Settings and Design Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. Materials and Methods All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. Statistical Analysis used The study used descriptive statistics and the values were expressed in numbers and percentages. Results During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo’s scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be

  17. Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.

    PubMed

    Yang, Fangping; Yang, Ying; Zhu, Qinyuan; Chen, Sheng-An; Fu, Xiaodan; Yan, Sijia; Meng, Chunjie; Ma, Li; Sun, Xinfen; Xu, Jinhua; Luo, Xiaoqun; Xing, Qinghe

    2015-07-01

    Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions. PMID:26067314

  18. CW CO2 Laser Induced Chemical Reactions

    NASA Astrophysics Data System (ADS)

    Pola, Joseph

    1989-05-01

    CW CO2 laser driven reactions between sulfur hexafluoride and carbon oxide, carbon suboxide, carbonyl sulfide and carbon disulfide proceed at subatmospheric pressures and yield fluorinated carbon compounds and sulfur tetrafluoride. CW CO2 laser driven reactions of organic compounds in the presence of energy-conveying sulfur hexafluoride show reaction course different from that normally observed due to elimination of reactor hot surface effects. The examples concern the decomposition of polychlorohydrocarbons, 2-nitropropane, tert.-butylamine, allyl chloride, spirohexane, isobornyl acetate and the oxidation of haloolefins. CW CO2 laser induced fragmentation of 1-methyl-l-silacyclobutanes and 4-silaspiro(3.4)octane in the presence of sulfur hexafluoride is an effective way for preparation and deposition of stable organosilicon polymers.

  19. Helium-induced reactions in astrophysics

    SciTech Connect

    Hale, G.M.

    1997-11-01

    Helium-induced reactions play a crucial role in stellar nucleosynthesis. Carbon and oxygen are produced mainly during the helium-burning phase by the chain of reactions {sup 8}Be({alpha}, {gamma} + e{sup +}e{sup {minus}}){sup 12}C({alpha}, {gamma}){sup 16}O. The first step, often called triple-{alpha} capture, was proposed by Hoyle to bypass the mass stability gap at {sup 8}Be. The second step gives rise to the largest uncertainty in most of the calculated stellar abundances. Later {alpha}-captures on {sup 13}C are believed to be a major source of s-process neutrons. The status of each of these important reactions is reviewed here.

  20. Systemic immunotoxicity reactions induced by adjuvanted vaccines.

    PubMed

    Batista-Duharte, Alexander; Portuondo, Deivys; Pérez, O; Carlos, Iracilda Zeppone

    2014-05-01

    Vaccine safety is a topic of concern for the treated individual, the family, the health care personnel, and the others involved in vaccination programs as recipients or providers. Adjuvants are necessary components to warrant the efficacy of vaccines, however the overstimulation of the immune system is also associated with adverse effects. Local reactions are the most frequent manifestation of toxicity induced by adjuvanted vaccines and, with the exception of the acute phase response (APR), much less is known about the systemic reactions that follow vaccination. Their low frequency or subclinical expression meant that this matter has been neglected. In this review, various systemic reactions associated with immune stimulation will be addressed, including: APR, hypersensitivity, induction or worsening of autoimmune diseases, modification of hepatic metabolism and vascular leak syndrome (VLS), with an emphasis on the mechanism involved. Finally, the authors analyze the current focus of discussion about vaccine safety and opportunities to improve the design of new adjuvanted vaccines in the future. PMID:24607449

  1. [Drug induced hemolytic anemia associated with agranulocytosis].

    PubMed

    Satoh, S; Takahashi, T; Hayashi, T; Okada, Y; Tokunoh, T; Adachi, M; Hinoda, Y; Endoh, T; Imai, K

    1996-10-01

    A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know. PMID:8952318

  2. Spin distribution in neutron induced preequilibrium reactions

    SciTech Connect

    Dashdorj, D; Kawano, T; Chadwick, M; Devlin, M; Fotiades, N; Nelson, R O; Mitchell, G E; Garrett, P E; Agvaanluvsan, U; Becker, J A; Bernstein, L A; Macri, R; Younes, W

    2005-10-04

    The preequilibrium reaction mechanism makes an important contribution to neutron-induced reactions above E{sub n} {approx} 10 MeV. The preequilibrium process has been studied exclusively via the characteristic high energy neutrons produced at bombarding energies greater than 10 MeV. They are expanding the study of the preequilibrium reaction mechanism through {gamma}-ray spectroscopy. Cross-section measurements were made of prompt {gamma}-ray production as a function of incident neutron energy (E{sub n} = 1 to 250 MeV) on a {sup 48}Ti sample. Energetic neutrons were delivered by the Los Alamos National Laboratory spallation neutron source located at the Los Alamos Neutron Science Center facility. The prompt-reaction {gamma} rays were detected with the large-scale Compton-suppressed Germanium Array for Neutron Induced Excitations (GEANIE). Neutron energies were determined by the time-of-flight technique. The {gamma}-ray excitation functions were converted to partial {gamma}-ray cross sections taking into account the dead-time correction, target thickness, detector efficiency and neutron flux (monitored with an in-line fission chamber). Residual state population was predicted using the GNASH reaction code, enhanced for preequilibrium. The preequilibrium reaction spin distribution was calculated using the quantum mechanical theory of Feshback, Kerman, and Koonin (FKK). The multistep direct part of the FKK theory was calculated for a one-step process. The FKK preequilibrium spin distribution was incorporated into the GNASH calculations and the {gamma}-ray production cross sections were calculated and compared with experimental data. The difference in the partial {gamma}-ray cross sections using spin distributions with and without preequilibrium effects is significant.

  3. Drug-Induced Oxidative Stress and Toxicity

    PubMed Central

    Deavall, Damian G.; Martin, Elizabeth A.; Horner, Judith M.; Roberts, Ruth

    2012-01-01

    Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. PMID:22919381

  4. Fluid transport in reaction induced fractures

    NASA Astrophysics Data System (ADS)

    Ulven, Ole Ivar; Sun, WaiChing; Malthe-Sørenssen, Anders

    2015-04-01

    The process of fracture formation due to a volume increasing chemical reaction has been studied in a variety of different settings, e.g. weathering of dolerites by Røyne et al. te{royne}, serpentinization and carbonation of peridotite by Rudge et al. te{rudge} and replacement reactions in silica-poor igneous rocks by Jamtveit et al. te{jamtveit}. It is generally assumed that fracture formation will increase the net permeability of the rock, and thus increase the reactant transport rate and subsequently the total rate of material conversion, as summarised by Kelemen et al. te{kelemen}. Ulven et al. te{ulven_1} have shown that for fluid-mediated processes the ratio between chemical reaction rate and fluid transport rate in bulk rock controls the fracture pattern formed, and Ulven et al. te{ulven_2} have shown that instantaneous fluid transport in fractures lead to a significant increase in the total rate of the volume expanding process. However, instantaneous fluid transport in fractures is clearly an overestimate, and achievable fluid transport rates in fractures have apparently not been studied in any detail. Fractures cutting through an entire domain might experience relatively fast advective reactant transport, whereas dead-end fractures will be limited to diffusion of reactants in the fluid, internal fluid mixing in the fracture or capillary flow into newly formed fractures. Understanding the feedback process between fracture formation and permeability changes is essential in assessing industrial scale CO2 sequestration in ultramafic rock, but little is seemingly known about how large the permeability change will be in reaction-induced fracturing. In this work, we study the feedback between fracture formation during volume expansion and fluid transport in different fracture settings. We combine a discrete element model (DEM) describing a volume expanding process and the related fracture formation with different models that describe the fluid transport in the

  5. Ibuprofen-induced aseptic meningoencephalitis confirmed by drug challenge.

    PubMed

    Moreno-Ancillo, A; Gil-Adrados, A C; Jurado-Palomo, J

    2011-01-01

    Drug-induced aseptic meningitis (DIAM) is a diagnostic challenge. The major causative agents are nonsteroidal anti-inflammatory drugs (particularly ibuprofen), antibiotics, intravenous immunoglobulin, and OKT3 monoclonal antibodies. DIAM is more frequently observed in patients with autoimmune diseases. A 36-year-old woman was attended in our department 3 months after being diagnosed with aseptic meningoencephalitis. She had had 2 episodes in 9 months. Neurological symptoms were associated with ibuprofen. A challenge with acetylsalicylic acid was negative, whereas a drug challenge with ibuprofen was positive. Thirty minutes after ingesting 50 mg of ibuprofen, she experienced general malaise and progressively developed chills, fever (39.5 degrees C), headache, and nuchal rigidity. Lumbar puncture showed normal glucose and high protein levels. Neutrophilic pleocytosis was observed at the first admission; lymphocytosis was predominant in the second and third episodes. DIAM is a rare and severe hypersensitivity reaction. Drug challenge enabled us to make an accurate diagnosis. PMID:21995183

  6. Drug-induced arrhythmia: pharmacogenomic prescribing?

    PubMed Central

    Behr, Elijah R.; Roden, Dan

    2013-01-01

    Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has become a major issue in novel drug development and for the regulatory authorities. This review describes the problem, predisposing factors, and the underlying genetic predisposition as it is understood currently. The future potential for pharmacogenomic-guided and personalized prescription to prevent drug-induced Torsades de Pointes is discussed. Database searches utilized reports from www.qtdrugs.org up to January 2012, case reports and articles from www.pubmed.com up to January 2012, and the British National Formulary edition at www.bnf.org. PMID:23091201

  7. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions.

    PubMed

    McNeil, Benjamin D; Pundir, Priyanka; Meeker, Sonya; Han, Liang; Undem, Bradley J; Kulka, Marianna; Dong, Xinzhong

    2015-03-12

    Mast cells are primary effectors in allergic reactions, and may have important roles in disease by secreting histamine and various inflammatory and immunomodulatory substances. Although they are classically activated by immunoglobulin (Ig)E antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions. The pathogenic roles of these substances have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, Mrgprb2, the orthologue of the human G-protein-coupled receptor MRGPRX2. Secretagogue-induced histamine release, inflammation and airway contraction are abolished in Mrgprb2-null mutant mice. Furthermore, we show that most classes of US Food and Drug Administration (FDA)-approved peptidergic drugs associated with allergic-type injection-site reactions also activate Mrgprb2 and MRGPRX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that Mrgprb2 and MRGPRX2 are targets of many small-molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice; and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MRGPRX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects. PMID:25517090

  8. Drug-induced immune neutropenia/agranulocytosis.

    PubMed

    Curtis, Brian R

    2014-01-01

    Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/pL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole- trimethoprim, [3-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs-DIIN PMID:25247619

  9. Drug-induced valvulopathy: an update.

    PubMed

    Elangbam, Chandikumar S

    2010-10-01

    Drug-induced valvulopathy is a serious liability for certain compound classes in development and for some marketed drugs intended for human use. Reports of valvulopathy led to the withdrawal of fenfluramines (anorexigens) and pergolide (antiparkinson drug) from the United States market in 1997 and 2007, respectively. The mechanism responsible for the pathogenesis of valvulopathy by these drugs is likely a result of an "off-target" effect via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets. Microscopically, the affected valve leaflets showed plaques of proliferative myofibroblasts in an abundant extracellular matrix, composed primarily of glycosaminoglycans. However, the valvular effects caused by fenfluramines and pergolide were not initially predicted from routine preclinical toxicity studies, and to date there are no specific validated animal models or preclinical/toxicologic screens to accurately predict drug-induced valvulopathy. This review covers the structure and function of heart valves and highlights major advances toward understanding the 5-HT2BR-mediated pathogenesis of the lesion and subsequently, development of appropriate animal models using novel techniques/experiments, use of functional screens against 5-HT2BR, and more consistent sampling and pathologic evaluation of valves in preclinical studies that will aid in avoidance of future drug-induced valvulopathy in humans. PMID:20716786

  10. Drug-Induced Nephrotoxicity and Its Biomarkers

    PubMed Central

    Kim, Sun Young; Moon, Aree

    2012-01-01

    Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identifi ed for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity. PMID:24130922

  11. Drug-Induced Long QT Syndrome

    PubMed Central

    Kannankeril, Prince; Darbar, Dawood

    2010-01-01

    The drug-induced long QT syndrome is a distinct clinical entity that has evolved from an electrophysiologic curiosity to a centerpiece in drug regulation and development. This evolution reflects an increasing recognition that a rare adverse drug effect can profoundly upset the balance between benefit and risk that goes into the prescription of a drug by an individual practitioner as well as the approval of a new drug entity by a regulatory agency. This review will outline how defining the central mechanism, block of the cardiac delayed-rectifier potassium current IKr, has contributed to defining risk in patients and in populations. Models for studying risk, and understanding the way in which clinical risk factors modulate cardiac repolarization at the molecular level are discussed. Finally, the role of genetic variants in modulating risk is described. PMID:21079043

  12. Pharmacodynamics of drug-induced weight gain.

    PubMed

    Kulkarni, S. K.; Kaur, Gurpreet

    2001-08-01

    Body weight gain during treatment with drugs for any kind of disease may represent improvement of the disease itself. However, sometimes these drug-induced alterations of the body's appetite-regulating mechanisms result in excessive weight gain, thus jeopardizing compliance with prescribed medication. A number of drugs are capable of changing body weight as an adverse consequence of their therapeutic effect. Included in this category are the psychotropic drugs such as antipsychotics, antidepressants and mood stabilizers. Antipsychotics are well-known culprits of weight gain. The low-potency (e.g., chlorpromazine and thioridazine) and atypical agents (e.g., clozapine, olanzapine, quetiapine and risperidone) are most often associated with weight gain. Antidepressants such as tricyclic antidepressants and monoamine oxidase (MAO) inhibitors are most often associated with significant weight gain. The tertiary tricyclic antidepressant amitriptyline is thought to induce the most weight gain. Mood stabilizers such as lithium carbonate, valproic acid and carbamazepine also induce weight gain in a considerable number of patients. Treatment with corticosteroids is associated with dose-dependent body weight gain in many patients and corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases body weight. Finally, sulfonylurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause body weight gain as well. (c) 2001 Prous Science. All rights reserved. PMID:12743638

  13. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  14. Drug reaction with eosinophilia and systemic symptoms without skin rash

    PubMed Central

    Sasidharanpillai, Sarita; Binitha, Manikoth P.; Manikath, Neeraj; Janardhanan, Anisha K.

    2015-01-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal. PMID:26729967

  15. Association between SLCO1B1 -521T>C and -388A>G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis.

    PubMed

    Jiang, Jiajia; Tang, Qing; Feng, Jing; Dai, Rong; Wang, Yang; Yang, Yuan; Tang, Xiaojun; Deng, Changkai; Zeng, Huan; Zhao, Yong; Zhang, Fan

    2016-01-01

    An increasing number of studies have investigated the association between SLCO1B1 -521T>C and -388A>G polymorphisms and the risk of statin-induced adverse drug reactions (ADRs), but the results have been inconsistent. This meta-analysis was performed to gain more insight into the relationship. PubMed, Embase, Cochrane Library and Web of Science were searched for relevant articles published before March 5th, 2015. The quality of included studies was evaluated by the Newcastle-Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios [HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess the association in overall and subgroup analyses for various genetic models. Begg's rank correlation test and Egger's linear regression test were used to examine the publication bias. A total of nine cohort and four case-control studies involving 11, 246 statin users, of whom 2, 355 developing ADRs were included in the analysis. Combined analysis revealed a significant association between the SLCO1B1-521T>C polymorphism and increased risk for ADRs caused by various statins, but the synthesis heterogeneity was generally large (dominant model: pooled effect estimate = 1.85, 95 % CI 1.20-2.85, P = 0.005; I (2) = 80.70 %, Pheterogeneity < 0.001). Subgroup analysis by statin type showed that the ADRs risk was significantly elevated among simvastatin users (dominant model: pooled effect estimate = 3.43, 95 % CI 1.80-6.52, P = 0.001; I (2) = 59.60 %, Pheterogeneity = 0.060), but not among atorvastatin users. No significant relationship was found between the -388A>G polymorphism and ADRs caused by various statins (dominant model: pooled effect estimate = 0.94, 95 % CI 0.79-1.13, P = 0.526; I (2) = 40.10 %, Pheterogeneity = 0.196). The meta-analysis suggests that SLCO1B1 -521T>C polymorphism may be a risk factor for statin-induced ADRs, especially in simvastatin therapy. Conversely, there may be no significant

  16. Pustular psoriasis and drug-induced pustulosis.

    PubMed

    Serra, D; Gonçalo, M; Mariano, A; Figueiredo, A

    2011-04-01

    We report the case of a 65-year-old female patient that has suffered several flares of exanthematous pustulosis, some of them attributable to pustular psoriasis and others that were drug-induced, resembling acute generalized exanthematous pustulosis. In particular, we describe two severe flares that were induced by ciprofloxacin. Patch tests yielded positive results to ciprofloxacin and to other quinolones and reproduced the original lesional pattern both clinically and histologically. We discuss the diagnostic challenge that exanthematous pustulosis represents and the value of patch testing in this setting, as a helpful tool to assess drug participation in these eruptions. PMID:21505400

  17. Ursodeoxycholic acid induced generalized fixed drug eruption.

    PubMed

    Ozkol, Hatice Uce; Calka, Omer; Dulger, Ahmet Cumhur; Bulut, Gulay

    2014-09-01

    Fixed drug eruption (FDE) is a rare form of drug allergies that recur at the same cutaneous or mucosal site in every usage of drug. Single or multiple round, sharply demarcated and dusky red plaques appear soon after drug exposure. Ursodeoxycholic acid (UDCA: 3α,7β-dihydroxy-5β-cholanic acid) is used for the treatment of cholestatic liver diseases. Some side effects may be observed, such as diarrhea, dyspepsia, pruritus and headaches. We encountered only three cases of lichenoid reaction regarding the use of UDCA among previous studies. In this article, we reported a generalized FDE case related to UDCA intake in a 59-year-old male patient with cholestasis for the first time in the literature. PMID:24147950

  18. The radiology of adverse drug reactions and toxic hazards

    SciTech Connect

    Ansell, G.

    1985-01-01

    Dr. Ansell has produced a scholarly review of the radiology of drug reactions and toxic hazards in his latest book, which is based on over 1,200 articles in the world literature. About 800 of these articles are taken from outside the radiology literature, which indicates the need for this subject to be brought to the attention of the radiologist, particularly as concern about drug reactions and toxic hazards is always increasing. The book includes sections covering the chest, gastrointestinal tract, renal tract, skeletal system and soft tissues, and skull and central nervous system. Each section treats specific substances, such as steroids and heavy metals; specific radiologic signs, such as ureteric dilation; specific symptoms, such as dysphagia; industrial toxins; radiographic abnormalities are discussed; and numerous high-quality radiographs.

  19. Pityriasis rosea-like drug reaction to asenapine.

    PubMed

    Makdisi, Joy; Amin, Bijal; Friedman, Adam

    2013-09-01

    Pityriasis rosea (PR) is a relatively common, benign skin disease of unknown etiology. In rare cases, medications can induce a morphologically similar eruption. We present a case of a PR-like drug eruption caused by the atypical antipsychotic asenapine. The clinical presentation consisted of a rapidly progressive, disseminated, and severely pruritic dermatitis comprised of ovoid, scaly, pink-violaceous plaques. The initial histopathologic specimen was consistent with PR, but upon re-sampling a week later, the findings favored a drug eruption. PR-like drug eruptions, though rare, can occur in response to a wide variety of medications. Because the findings may be only subtly different than those of typical PR, careful clinical and histopathological correlation must be sought. To our knowledge, this is the first reported case of a PR-like drug eruption to asenapine. PMID:24002155

  20. Alternate Alpha Induced Reactions for NIF Radiochemistry

    SciTech Connect

    Shaughnessy, D A; Moody, K J; Bernstein, L A

    2010-02-26

    Radiochemical analysis of NIF capsule residues has been identified as a potential diagnostic of NIF capsule performance. In particular, alpha-induced nuclear reactions that occur on tracer elements added to the NIF capsule have been shown through simulation to be a very sensitive diagnostic for mix. The short range of the alpha particles makes them representative of the hot spot where they are created through the fusion of deuterium and tritium. Reactions on elements doped into the innermost part of the capsule ablator would therefore be sensitive to material that had mixed into the hot spot. Radiochemical determinations of activated detector elements may perhaps be the only true measure of mix that occurs in a NIF capsule, particularly in cases when the capsule fails.

  1. Competing reaction channels in IR-laser-induced unimolecular reactions

    SciTech Connect

    Berman, M.R.

    1981-01-01

    The competing reaction channels in the unimolecular decomposition of two molecules, formaldehyde and tetralin were studied. A TEA CO/sub 2/ laser was used as the excitation source in all experiments. The dissociation of D/sub 2/CO was studied by infrared multiphoton dissociation (MPD) and the small-molecule nature of formaldehyde with regard to MPD was explored. The effect of collisions in MPD were probed by the pressure dependence of the MPD yield and ir fluorescence from multiphoton excited D/sub 2/CO. MPD yield shows a near cubic dependence in pure D/sub 2/CO which is reduced to a 1.7 power dependence when 15 torr of NO is added. The peak amplitude of 5 ..mu..m ir fluorescence from D/sub 2/CO is proportional to the square of the D/sub 2/CO pressure in pure D/sub 2/CO or in the presence of 50 torr of Ar. Results are explained in terms of bottlenecks to excitation at the v = 1 level which are overcome by a combination of vibrational energy transfer and rotational relaxation. The radical/molecule branching ratio in D/sub 2/CO MPD was 0.10 +- 0.02 at a fluence of 125 J/cm/sup 2/ at 946.0 cm/sup -1/. The barrier height to molecular dissociation was calculated to be 3.6 +- 2.0 kcal/mole below the radical threshold or 85.0 +- 3.0 kcal/mole above the ground state of D/sub 2/CO. In H/sub 2/CO, this corresponds to 2.5 +- 2.0 kcal/mole below the radical threshold or 83.8 +- 3.0 kcal/mole above the ground state. Comparison with uv data indicate that RRKM theory is an acceptable description of formaldehyde dissociation in the 5 to 10 torr pressure range. The unimolecular decomposition of tetralin was studied by MPD and SiF/sub 4/ - sensitized pyrolysis. Both techniques induce decomposition without the interference of catalytic surfaces. Ethylene loss is identified as the lowest energy reaction channel. Dehydrogenation is found to result from step-wise H atom loss. Isomerization via disproportionation is also identified as a primary reaction channel.

  2. [Adverse drug reactions in multidrug-resistant tuberculosis].

    PubMed

    Palmero, Domingo; Cruz, Víctor; Museli, Tomás; Pavlovsky, Hernán; Fernández, Juan; Waisman, Jaime

    2010-01-01

    Multidrug-resistant tuberculosis (MDRTB) poses difficulties in diagnosis and treatment, including increased frequency of adverse reactions to antituberculosis drugs (ADRAs), which compromise the effectiveness of treatment. This is specially complicated in the treatment of patients co-infected with HIV which includes the antiretroviral therapy plus the treatment of eventual comorbidities. A total of 121 MDRTB patients, 87 HIV-negative and 34 HIV positive, assisted in the Hospital F. J. Muñiz, Buenos Aires, during the period 2003-2007 were retrospectively studied. The incidence of ADRAs among the two groups of patients was compared. All the patients with adherence to treatment (no more than one abandon, recovered) were included in the study. Antituberculosis drugs used were: ethambutol, pyrazinamide, ofloxacin, moxifloxacin, cycloserine, ethionamide, PAS, streptomycin, kanamycin, amikacin and linezolid. The emergence of ADRAs and the proportion of severe reactions attributed to antituberculosis drugs were similar in both groups: 44.8% in HIV negative and 44.1% in HIV positive, but it was observed an additional 23.5% of adverse reactions to antiretroviral therapy in the second group. There were differences in the type of reactions and time of occurrence between the two groups. One HIV positive patient died of epidermolysis. The proportion of adverse reactions in HIV/AIDS patients increased 50% when those attributed to antiretroviral treatment were included. We conclude that the studied population showed a frequency of ADRAs higher than it would be expected in the treatment of susceptible TB, but there was no difference in its frequency among HIV-negative and positive patients. PMID:20920959

  3. Identification of a mast cell specific receptor crucial for pseudo-allergic drug reactions

    PubMed Central

    McNeil, Benjamin D.; Pundir, Priyanka; Meeker, Sonya; Han, Liang; Undem, Bradley J.; Kulka, Marianna; Dong, Xinzhong

    2014-01-01

    Mast cells are primary effectors in allergic reactions, and may have significant roles in diseases by secreting histamine and various inflammatory and immunomodulatory substances1,2. While classically they are activated by IgE antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions1,3. Roles for these substances in pathology have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, MrgprB2, the orthologue of the human G-protein coupled receptor (GPCR) MrgprX2. Secretagogue-induced histamine release, inflammation, and airway contraction are abolished in MrgprB2 null mutant mice. Further, we show that most classes of FDA-approved peptidergic drugs associated with allergic-type injection-site reactions also activate MrgprB2 and MrgprX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that MrgprB2 and MrgprX2 are targets of many small molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice, and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MrgprX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects. PMID:25517090

  4. [Drug-induced dystonia misinterpreted as hysteria].

    PubMed

    Magnusson, A; Opjordsmoen, S; Dietrichs, E

    1996-03-10

    Psychic distress is often expressed in the form of physical pain or disease, but the converse also occurs. Illnesses with an organic aetiology are sometimes misdiagnosed as psychogenic. We describe three patients who developed rare forms of acute drug-induced dystonia when treated with antipsychotic drugs. All three cases were initially misdiagnosed as "hysteria" because the patients had psychiatric illnesses and because the symptoms were bizarre and became worse when the patients became very anxious. Furthermore, if the patients were helped to relax the symptoms disappeared for a moment. One of the patients developed dystonia 24 hours after ingestion of 750 mg tetrabenazine in an attempt at suicide. Another patient who had HIV/AIDS developed severe dystonia after receiving only 2 mg haloperidol by mouth. The clinical presentation, treatment, and possible mechanisms of the pathophysiology of acute drug-induced dystonia are briefly reviewed. PMID:8644096

  5. Anticancer Drug Induced Palmar Plantar Erythrodysesthesia

    PubMed Central

    Srinivasamurthy, Sureshkumar; Dubashi, Biswajit; Chandrasekaran, Adithan

    2014-01-01

    Background: Palmar plantar erythrodysesthesia (PPE) is a dose limiting toxicity of anticancer agents. In some cases it may mandate for discontinuation of anticancer agents. Evaluation of data of PPE among reported adverse drug reactions (ADRs) from the Department of Medical Oncology could quantify the burden. Aim: To evaluate and analyse the PPE among reported ADRs from medical Oncology. Materials and Methods: The data of all cases of reported PPE were collected during January 2012 to September 2013 and were analysed with WHO causality assessment scale. The severity was clinically graded. The follow-up data regarding outcome of ADRs were also noted. Results: During the study period of 21 months a total of 1418 ADRs have been reported from 1076 patients. Among them PPE was reported from 31 cases (2.9%). Majority (32.2%) of these patients were on chemotherapy for breast cancer. Patient’s age ranged from 17 to 68 y and the median age was 50 y. There were 18 female (58%) and 13 male patients (42%). Capecitabine was the leading drug involved in PPE, reported with 20 cases (64.5%), and followed by docetaxel with 5 cases (16.1%). Majority (67.7%) of the reactions was categorized as certain and 64.5% was grade II severity clinically. Conclusion: Our findings show that PPE accounts for 2.9% of total reported ADRs from Medical Oncology during 21 months. Majority of the reactions were classified as certain. Capecitabine is commonly implicated drug. PMID:25478366

  6. Adverse drug reactions and organ damage: The liver.

    PubMed

    Licata, Anna

    2016-03-01

    Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in western countries have reported other drugs associated with DILI, including nonsteroidal anti-inflammatory drugs, statins, and herbal and dietary supplements. An important safety issue, DILI is one of the most frequently cited reasons for cessation of drug development during or after preclinical studies and for withdrawal of a drug from the market. This review summarizes the epidemiology, risk factors, commonly implicated drugs, clinical features, and diagnosis of DILI, with the aim of aiding physicians in the management of this debated problem. Old and new biomarkers for DILI and pharmacogenetic studies are also described. PMID:26827101

  7. Physician access to drug profiles to reduce adverse reactions

    NASA Astrophysics Data System (ADS)

    Yasnoff, William A.; Tomkins, Edward L.; Dunn, Louise M.

    1995-10-01

    Adverse drug reactions (ADRs) are a major source of preventable morbidity and mortality, especially among the elderly, who use more drugs and are more sensitive to them. The insurance industry has recently addressed this problem through the implementation of drug interaction alerts to pharmacists in conjunction with immediate online claims adjudication for almost 60% of prescriptions (expected to reach 90% within 5 years). These alerts are based on stored patient drug profiles maintained by pharmacy benefit managers (PBMs) which are updated whenever prescriptions are filled. While these alerts are very helpful, the pharmacist does not prescribe, resulting in time-consuming and costly delays to contact the physician and remedy potential interactions. We have developed and demonstrated the feasibility of the PINPOINT (Pharmaceutical Information Network for prevention of interactions) system for making the drug profile and interaction information easily available to the physician before the prescription is written. We plan to test the cost-effectiveness of the system in a prospective controlled clinical trial.

  8. Attitudinal survey of voluntary reporting of adverse drug reactions

    PubMed Central

    Eland, I A; Belton, K J; van Grootheest, A C; Meiners, A P; Rawlins, M D; Stricker, B H Ch

    1999-01-01

    Aims Voluntary adverse drug reaction (ADR) reporting schemes have operated since the early sixties in many Western countries. It is generally recognized, however, that only a small proportion of ADRs is actually reported. The current survey was conducted to assess attitudes towards reporting of ADRs, and to study which types of ADRs are reported. Methods A questionnaire seeking reasons for nonreporting was sent to a random sample of 10% of medical practitioners in The Netherlands in October 1997. After 6 weeks, a reminder was sent to those who had not responded. Results One thousand four hundred and forty-two (73%) questionnaires were returned, of which 94% were complete. The percentage of GPs (51%) which had ever reported an ADR to the national reporting centre was significantly higher than the percentage of specialists (35%), who reported more often to the pharmaceutical industry (34%vs 48%). 86% of GPs, 72% of surgical specialists and 81% of medical specialists had ever diagnosed an ADR, which they had not reported. Uncertainty as to whether the reaction was caused by a drug (72%), the ADR being trivial (75%) or too well known (93%) were the most important reasons for not reporting. 18% were not aware of the need to report ADRs, 22% did not know how to report ADRs, 38% did not have enough time, 36% thought that reporting was too bureaucratic and only 26% of Dutch physicians knew which ADRs to report. A serious ADR, an unlabelled ADR, an ADR to a new drug, history of reporting of one or more ADRs, and specialty were all independently associated with reporting of 16 hypothetical ADRs. Surgical and medical specialists tended to report less often than GPs. Conclusions There is a considerable degree of underreporting, which might partly be explained by lack of knowledge and misconceptions about spontaneous reporting of adverse drug reactions. PMID:10583035

  9. Drug induced acute pancreatitis: does it exist?

    PubMed

    Tenner, Scott

    2014-11-28

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis. PMID:25469020

  10. Drug induced acute pancreatitis: Does it exist?

    PubMed Central

    Tenner, Scott

    2014-01-01

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis. PMID:25469020

  11. Drug-Induced Hyperglycaemia and Diabetes.

    PubMed

    Fathallah, Neila; Slim, Raoudha; Larif, Sofien; Hmouda, Houssem; Ben Salem, Chaker

    2015-12-01

    Drug-induced hyperglycaemia and diabetes is a global issue. It may be a serious problem, as it increases the risk of microvascular and macrovascular complications, infections, metabolic coma and even death. Drugs may induce hyperglycaemia through a variety of mechanisms, including alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Antihypertensive drugs are not equally implicated in increasing serum glucose levels. Glycaemic adverse events occur more frequently with thiazide diuretics and with certain beta-blocking agents than with calcium-channel blockers and inhibitors of the renin-angiotensin system. Lipid-modifying agents may also induce hyperglycaemia, and the diabetogenic effect seems to differ between the different types and daily doses of statins. Nicotinic acid may also alter glycaemic control. Among the anti-infectives, severe life-threatening events have been reported with fluoroquinolones, especially when high doses are used. Protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors have been reported to induce alterations in glucose metabolism. Pentamidine-induced hyperglycaemia seems to be related to direct dysfunction in pancreatic cells. Phenytoin and valproic acid may also induce hyperglycaemia. The mechanisms of second-generation antipsychotic-associated hyperglycaemia, diabetes mellitus and ketoacidosis are complex and are mainly due to insulin resistance. Antidepressant agents with high daily doses seem to be more frequently associated with an increased risk of diabetes. Ketoacidosis may occur in patients receiving beta-adrenergic stimulants, and theophylline may also induce hyperglycaemia. Steroid diabetes is more frequently associated with high doses of glucocorticoids. Some chemotherapeutic agents carry a higher risk of hyperglycaemia, and calcineurin inhibitor-induced hyperglycaemia is mainly due to a decrease in insulin secretion

  12. Pharmacogenetic determinants of immediate and delayed reactions of drug hypersensitivity.

    PubMed

    Guéant, J L; Guéant-Rodriguez, R M; Gastin, I Aimone; Cornejo-García, J A; Viola, M; Barbaud, A; Mertes, P M; Blanca, M; Romano, A

    2008-01-01

    Drug allergy refers to a hypersensitivity reaction for which either an IgE or T-cell-mediated mechanism is demonstrated. The recognition of the drug by B and T cells is influenced by variants of HLA genes. The genetic factors involved in IgE-mediated mechanisms have been studied mainly in beta-lactam reactions, and they appear to be related to human leukocyte antigen presentation (HLA A2 and DRw52), TNFA -308G>A, class switching to IgE by B cells (variants of IL-13 and of IL-4RA), and expression of IgE receptors on target cells (variant of the FcepsilonRIbeta gene). Delayed T-cell-mediated reactions are also associated with HLA alleles. Studies have reported an association of HLA-B*1502 and HLA-B*5801 in patients with the Stevens-Johnson syndrome or toxic epidermal necrolysis provoked by carbamazepine, as well as of HLA-B*5701 with abacavir hypersensitivity. HLA-B*5701 seems to be a strong predictor in whites, but not in Hispanics or Africans. Carbamazepine hypersensitivity is also influenced by gene variants of cytochrome P450 enzymes on the generation of reactive metabolites, while CYP2C9*2 and CYP2C9*3 polymorphisms influence the bioactivation of sulfamethoxazole in prohapten. Pharmacogenetic studies on aspirin hypersensitivity have identified distinct types of predictors, such as HLA genotypes, a polymorphism in the promoter of the FcepsilonRIalpha gene, and variants in genes of enzymes from the arachidonic acid pathway. In the future, identification of genetic predictors will benefit from genomewide association studies that also take ethnic differences into account. Ideally, predictors will help to prevent adverse reactions, as suggested by a recent study on the effectiveness of prospective HLA-B*5701 screening to prevent hypersensitivity reactions to abacavir in HIV patients. PMID:18991696

  13. Non-chemotherapy drug-induced agranulocytosis.

    PubMed

    Garbe, Edeltraut

    2007-05-01

    Acute agranulocytosis is a rare, potentially life-threatening condition, which is attributable to drugs in > 70% of cases. Agranulocytosis is characterised by a peripheral neutrophil count < 0.5 x 10(9)/l. It often manifests with a severe sore throat, but isolated fever, pneumonia or septicaemia are not uncommon. Agranulocytosis may be caused by many drugs. High-risk drugs include antithyroid drugs, clozapine, ticlopidine, sulfasalazine, dipyrone, trimethoprim/sulfamethoxazole, carbamazepine and probably rituximab. Suspect drugs should be stopped immediately. In febrile patients, blood cultures and, where indicated, site-specific cultures should be obtained and treatment with empirical broad spectrum antibiotics started. Haematopoietic growth factors should be considered in patients with poor prognostic factors (e.g., a neutrophil count < 0.1 x 10(9)/l), severe clinical infection or severe underlying disease or comorbidity. Case fatality has decreased to ~ 5% in recent years, probably owing to improved intensive care treatment and increased alertness of physicians to this severe adverse reaction. PMID:17480181

  14. Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

    PubMed

    Bano, Nusrat; Najam, Rahila; Qazi, Faaiza; Mateen, Ahmed

    2016-01-01

    Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan. PMID:27221832

  15. Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

    PubMed Central

    Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

    2013-01-01

    Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

  16. Meprobamate-induced fixed drug eruption.

    PubMed

    Zaïem, Ahmed; Kaabi, Widd; Badri, Talel; Lakhoua, Ghozlane; Sahnoun, Rym; Kastalli, Sarrah; Daghfous, Riadh; Lakhal, Mohamed; El Aidli, Sihem

    2014-01-01

    Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report a case of FDE induced by meprobamate with positive patch test. A 22-year-old woman was prescribed for depression meprobamate, aceprometazine, valpromide and lorazepam. On the second day of treatment, the patient presented red erythematous and pruriginous plaques in the limbs and the face. After stopping the previous treatment, the patient's lesions resolved completely within 3 weeks with residual pigmentation. One month later, patch tests were performed and were positive to meprobamate. Exceptional cases of FDE were reported in literature with meprobamate. None has reported the use of patch test to confirm the diagnosis. PMID:24446836

  17. Predicting risk of adverse drug reactions in older adults.

    PubMed

    Lavan, Amanda Hanora; Gallagher, Paul

    2016-02-01

    Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID:26834959

  18. Predicting risk of adverse drug reactions in older adults

    PubMed Central

    Lavan, Amanda Hanora; Gallagher, Paul

    2016-01-01

    Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID:26834959

  19. Drug-induced mitochondrial dysfunction and cardiotoxicity.

    PubMed

    Varga, Zoltán V; Ferdinandy, Peter; Liaudet, Lucas; Pacher, Pál

    2015-11-01

    Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Györgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities. PMID:26386112

  20. [Drug-induced impairment of renal function].

    PubMed

    Krüger, B; Benck, U; Singer, T; Krämer, B K

    2012-09-01

    Acute kidney injury (AKI) of any origin is a common complication/disease in hospitalized patients, going along with significantly increased mortality and morbidity, as well as hospitalization duration and expenses. Drug-induced AKI is usually seen in patients with concurrent risk factors such as existing kidney disease, dehydration with or without hypotension, older age or diabetes mellitus. In cases with multiple risk factors or therapies the triggering drug is often impossible to define. Hemodynamic alterations, intrinsic tubulointerstitial damages and intrarenal (i. e. tubular) obstructions as a result of drug precipitations are the pathophysiological basis of this disease entity. Clinically the AKI is perceived as the most important problem, due to the development of hyperhydration (including pulmonary edema) and reduced/lacking clearance of toxic metabolites. The prognosis of drug-induced AKI is usually good, especially if the agents are stopped early in the process, but nevertheless some patients experience severe acute AKI requiring dialysis with/without subsequent restoration. Considering and recognizing potential risk factors may help to identify patients at risk and lead to introduction of prophylactic actions. Identification of risk factors and the introduction of prevention strategies should be an integral part of everybody's daily clinical work, especially in intensive care medicine due to the high susceptibility to AKI. PMID:22971974

  1. Severe cutaneous reactions to drugs in the setting of a general hospital*

    PubMed Central

    Grando, Luciana Rosa; Schmitt, Tatiana Aline Berger; Bakos, Renato Marchiori

    2014-01-01

    BACKGROUND Cutaneous drug reactions are frequently found. Assessing the clinical and epidemiological profile of severe forms is extremely relevant for their better recognition and management. Few studies have assessed the severe forms of cutaneous drug reactions in patients hospitalized in our setting. OBJECTIVES To assess the clinical and epidemiological aspects of severe cutaneous adverse reactions to drugs in a tertiary hospital in Porto Alegre, Brazil. METHODS All cases of severe cutaneous adverse reactions to drugs in patients hospitalized from January/2005 to December/2010 were retrospectively analyzed for clinical and epidemiological variables. Cases of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, drug hypersensitivity syndrome or Drug Reaction with Eosinophilia and Systemic Symptoms and acute generalized exanthematous pustulosis were included. RESULTS An occurrence rate of 1 serious reaction for every 3,048 inpatients was found (total of 173,767 inpatients admitted in the period). Drug Reaction with Eosinophilia and Systemic Symptoms was the most frequent presentation. The drugs most frequently involved were anticonvulsants (40.4%), antibiotics (26.3%), and analgesics/anti-inflammatory drugs (10.5%). Thirty seven patients (64.9%) were admitted to hospital because of the cutaneous drug reaction. Ten patients (17.5%) died and in most of those (60%), the drug causing the reaction could not be determined. CONCLUSIONS The frequency of severe cutaneous adverse reactions to drugs in our setting is significant. Drug Reaction with Eosinophilia and Systemic Symptoms seems to be the most frequent presentation of severe cutaneous drug reactions. Most patients developed cutaneous drug reactions outside the hospital. Mortality rates were higher for Toxic Epidermal Necrolysis and this presentation significantly affected older people. Not knowing the drug causing the reaction was related to mortality. PMID:25184915

  2. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

    Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

    1999-01-01

    Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

  3. [Future direction of pharmacogenomics: identification of genes associated with risk of adverse drug reactions using genome-wide association study].

    PubMed

    Mushiroda, Taisei

    2014-01-01

    Drug-induced skin rash characterized by an acute inflammatory reaction of skin and mucous membranes is dose-independent, unpredictable, and sometimes life-threatening. In recent years, the U.S. Food and Drug Administration (FDA) has recommended genotyping of polymorphisms in the human leukocyte antigen (HLA) prior to drug administration for the avoidance of severe skin rash induced by drugs, such as abacavir and carbamazepine. A genome-wide association study (GWAS) is useful for the identification of genomic biomarkers that can predict the efficacy or risk of toxicity of various drugs. We identified novel susceptibility loci associated with the risk of a skin rash induced by nevirapine and carbamazepine in Thai and Japanese populations, respectively, through case-control GWAS with high-throughput single-nucleotide polymorphism (SNP) genotyping technology. In order to apply the genomic biomarkers to clinical therapeutics, prospective clinical trials will be necessary for the evaluation of an intervention based on genetic tests. PMID:24724431

  4. Salicylate intolerance: a masquerader of multiple adverse drug reactions

    PubMed Central

    Fernando, Suran Loshana; Clarke, Lesley R

    2009-01-01

    A female in her early 50s presented with a long-standing history of episodic urticaria and angioedema. She also reported urticarial reactions after ingestion of aspirin, prednisone and multiple antibiotics. These medications were all taken during upper respiratory tract infections. An elimination diet followed by a series of open challenges to food chemicals demonstrated an urticarial eruption following the ingestion of mints, which contain high levels of salicylates. A double-blinded placebo-controlled challenge to salicylate confirmed her sensitivity and explained her reaction to aspirin. The patient informed her treating physician of her copious ingestion of mints during upper respiratory tract infections. Drug hypersensitivity to antibiotics and prednisone was excluded on the basis of negative radioallergosorbent tests (RASTs) and/or absent skin-test responses and/or tolerance to oral challenges. This patient had a salicylate intolerance that caused her episodic urticaria and angioedema, and also masqueraded as a drug allergy due to the concurrent ingestion of mints. PMID:21918670

  5. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

    PubMed

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. PMID:25576362

  6. An overview on adverse drug reactions to traditional Chinese medicines.

    PubMed

    Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu

    2015-10-01

    The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. PMID:25619530

  7. Drug-induced acute pancreatitis: a rare manifestation of an incomplete "dapsone syndrome".

    PubMed

    Das, Anup K; Jawed, Qaiser

    2014-01-01

    Drug-induced acute pancreatitis (AP) is under-reported, and a large number of drugs are listed as offenders, but are often overlooked. Knowledge about the possible association of medications in causing AP is important, and needs a high index of suspicion, especially with drugs that have been reported to be the etiology only rarely. Dapsone, a commonly used drug, can cause various hypersensitivity reactions including AP collectively called "dapsone syndrome." Here, we report dapsone-induced AP in a young man. Our case shows certain dissimilarities like associated acute renal failure and acute hemolysis not previously described. PMID:25097293

  8. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    SciTech Connect

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

  9. Drug-Induced Rosacea-like Dermatitis.

    PubMed

    Rezaković, Saida; Bukvić Mokos, Zrinka; Paštar, Zrinjka

    2016-04-01

    Rosacea is a common, chronic cutaneous disorder with a prevalence of 0.5-10%, predominantly affecting women. The disease presents with a heterogeneous clinical picture characterized by transient flushing, persistent facial redness, telangiectasias, and, in more severe clinical forms, the presence of inflammatory papules and pustules in the central third of the face. Although its pathophysiology is complex and still remains unknown, factors that exacerbate the disease are well defined. They include genetic predisposition as well as external factors such as exposure to UV light, high temperature, and diet. Besides these well-known factors, recent studies suggest that drugs and vitamins could also be possible factors inducing rosacea-like dermatitis or aggravating pre-existing rosacea. Although these are less common possible triggering factors, the aim of this article is to present the current knowledge on the association between use of certain drugs or vitamins and rosacea. PMID:27149131

  10. Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study

    PubMed Central

    Mirošević Skvrce, Nikica; Macolić Šarinić, Viola; Mucalo, Iva; Krnić, Darko; Božina, Nada; Tomić, Siniša

    2011-01-01

    Aim To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence. Methods In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them. Results HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter. Conclusion The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education. PMID:21990078

  11. Drug-induced lymphocyte stimulation test is not useful for the diagnosis of drug-induced pneumonia.

    PubMed

    Matsuno, Osamu; Okubo, Toshiyuki; Hiroshige, Shigeo; Takenaka, Rhyuichi; Ono, Emiko; Ueno, Takuya; Nureki, Shinichi; Ando, Masaru; Miyazaki, Eishi; Kumamoto, Toshihide

    2007-05-01

    Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method. PMID:17464103

  12. Adverse Drug Reactions Causing Admission to Medical Wards

    PubMed Central

    Mouton, Johannes P.; Njuguna, Christine; Kramer, Nicole; Stewart, Annemie; Mehta, Ushma; Blockman, Marc; Fortuin-De Smidt, Melony; De Waal, Reneé; Parrish, Andy G.; Wilson, Douglas P.K.; Igumbor, Ehimario U.; Aynalem, Getahun; Dheda, Mukesh; Maartens, Gary; Cohen, Karen

    2016-01-01

    Abstract Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions. We prospectively followed patients admitted to 4 hospitals’ medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission. There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34–65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06–2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09–1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07–1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17–3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable. In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect

  13. Pharmacovigilance on Twitter? Mining Tweets for Adverse Drug Reactions

    PubMed Central

    O’Connor, Karen; Pimpalkhute, Pranoti; Nikfarjam, Azadeh; Ginn, Rachel; Smith, Karen L; Gonzalez, Graciela

    2014-01-01

    Recent research has shown that Twitter data analytics can have broad implications on public health research. However, its value for pharmacovigilance has been scantly studied – with health related forums and community support groups preferred for the task. We present a systematic study of tweets collected for 74 drugs to assess their value as sources of potential signals for adverse drug reactions (ADRs). We created an annotated corpus of 10,822 tweets. Each tweet was annotated for the presence or absence of ADR mentions, with the span and Unified Medical Language System (UMLS) concept ID noted for each ADR present. Using Cohen’s kappa1, we calculated the inter-annotator agreement (IAA) for the binary annotations to be 0.69. To demonstrate the utility of the corpus, we attempted a lexicon-based approach for concept extraction, with promising success (54.1% precision, 62.1% recall, and 57.8% F-measure). A subset of the corpus is freely available at: http://diego.asu.edu/downloads. PMID:25954400

  14. Uveitis attack and drug reaction due to cefuroxime axetil.

    PubMed

    Akman, Canan; Duran, Arif; Kalafat, Utku Murat; Ocak, Tarık

    2016-09-01

    Antibiotics are natural or synthetic substances that are used to control bacterial infections because antibiotics are by definition only effective against bacteria. A 30-year-old female came to our emergency clinic complaining rubor in both eyes, especially in the left eye, with swelling, rubor and pain in ears, and eruption in lips extremities. In her anamnesis, it has been determined that she did not have any medical disease that requires regular utilization of drugs. After the patient received cefuroxime axetil for acute tonsillitis, she observed eruptions in lip extremities on the 3rd day, but she did not care about it. On the 5th day, rubor in both eyes and, especially in the left eye, have been developed, and complaints such as unable to look toward light and pain have started together with swelling, rubor, and pain in both ears. She came to our clinic because she was very much worried about the situation. In this study, we aimed to discuss a drug reaction characterized by face and ear skin observations, due to uveitis after the use of antibiotics including cefuroxime axetil for acute tonsillitis. PMID:26203731

  15. Adverse drug reactions in special populations - the elderly.

    PubMed

    Davies, E A; O'Mahony, M S

    2015-10-01

    The International Conference on Harmonization considers older people a 'special population', as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  16. Drug-induced erythrocyte membrane internalization

    PubMed Central

    Ben-Bassat, Isaac; Bensch, Klaus G.; Schrier, Stanley L.

    1972-01-01

    In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of 37Co-labeled vitamin B12 and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events. Images PMID:4555785

  17. Retrospective Analysis of Pattern of Cutaneous Adverse Drug Reactions in Tertiary Hospital of Pauri Garhwal

    PubMed Central

    Dimri, Deepak; Thapliyal, Swati; Thawani, Vijay

    2016-01-01

    Introduction Cutaneous Adverse Drug Reactions (CADR) are the common drug induced adverse reactions which usually have wide range of manifestations and severity. Aim To describe the prevalence and clinical spectrum of CADR’s in a tertiary hospital of the Garhwal region in Uttarakhand, India. Materials and Methods All patients suspected of having CADRs reported in the various out-patient departments, and in-patients of HNB Base & Teaching Hospital, from 1st January 2012 to 31st December 2014 were retrospectively analysed. Drug history was recorded in a format specified in Indian National Pharmacovigilance Programme. Results Total 111 cases of CADRs were reported from Jan 2012 to Dec 2014. Mean age of patients was 33.34±18.7 years and maximum ADRs were reported in the age group of 20-39 years (36.9%). Female were affected more than male (W:M :: 66:45). Most of the ADRs were exanthematous eruptions (EE) type (33.3%). Medicine department reported maximum cases of CADRs (47.7%), followed by Dermatology. Most of the CADRs were reported with antimicrobial agents (69.4%). Significant associations of different types of various cutaneous reactions were observed in relation to the duration (in days) of ADRs (p = 0.038), types of outcome (p= 0.006), different departments (p= 0.014) and between different groups of medicines (p = 0.008). Conclusion CADRs have proved a significant problem in healthcare for decades. Major bulk of CADR result from physician prescribed drugs. Hence, awareness on part of the physician can help in timely detection of cutaneous reactions, thereby restricting damage from them. PMID:27437240

  18. Drug-induced spatial dispersion of repolarization

    PubMed Central

    Antzelevitch, Charles

    2008-01-01

    Spatial dispersion of repolarization in the form of transmural, trans-septal and apico-basal dispersion of repolarization creates voltage gradients that inscribe the J wave and T wave of the ECG. Amplification of this spatial dispersion of repolarization (SDR) underlies the development of life-threatening ventricular arrhythmias associated with inherited or acquired ion channelopathies giving rise to the long QT, short QT and Brugada syndromes (BrS). This review focuses on the role of spatial dispersion of repolarization in drug-induced arrhythmogenesis associated with the long QT and BrS. In the long QT syndrome, drug-induced amplification of SDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the BrS, it is thought to be due to selective abbreviation of the APD of right ventricular epicardium. Among the challenges ahead is the identification of a means to quantitate SDR non-invasively. This review also discusses the value of the interval between the peak and end of the T wave (Tpeak–Tend, Tp–Te) as an index of SDR and transmural dispersion of repolarization, in particular. PMID:18651395

  19. Anticancer drug-induced kidney disorders.

    PubMed

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  20. Patient with Terbinafine-Induced Subacute Cutaneous Lupus Erythematosus Followed by Thalidomide-Induced Orofacial Neuropathy; Beta Blocker Use, Hypertension, and the Risk of Psoriasis; Eczematous Reaction to Intravenous Immunoglobulin; Nicolau Syndrome After Intra-Articular Glucocorticoid Injection; Troponin Leak Associated with Drug-Induced Methemoglobinemia

    PubMed Central

    Mancano, Michael A.

    2015-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:25684795

  1. Analysis of Adverse Drug Reactions of Atypical Antipsychotic Drugs in Psychiatry OPD

    PubMed Central

    Piparva, Kiran G.; Buch, J. G.; Chandrani, Kalpesh V.

    2011-01-01

    Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized. PMID:22345840

  2. Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

    PubMed

    Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

    2016-05-01

    Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes. PMID:26951484

  3. Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

    PubMed Central

    Moore, Nicholas; Pollack, Charles; Butkerait, Paul

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. PMID:26203254

  4. [Application analysis of adverse drug reaction terminology WHOART and MedDRA].

    PubMed

    Liu, Jing; Xie, Yan-ming; Gai, Guo-zhong; Liao, Xing

    2015-12-01

    Drug safety has always been a global focus. Discovery and accurate information acquisition of adverse drug reaction have been the most crucial concern. Terminology of adverse drug reaction makes adverse reaction medical report meaningful, standardized and accurate. This paper discussed the domestic use of the terminology WHOART and MedDRA in terms of content, structure, and application situation. It also analysed the differences between the two terminologies and discusses the future trend of application in our country PMID:27245013

  5. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital

    PubMed Central

    Saini, V. K.; Sewal, R. K.; Ahmad, Yusra; Medhi, B.

    2015-01-01

    Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy. PMID:26997696

  6. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital.

    PubMed

    Saini, V K; Sewal, R K; Ahmad, Yusra; Medhi, B

    2015-01-01

    Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy. PMID:26997696

  7. Drug-induced immune hemolytic anemia

    MedlinePlus

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... In some cases, a drug can cause the immune system to mistake your own red blood cells for foreign substances. The body responds by making ...

  8. Drug-induced immune hemolytic anemia

    MedlinePlus

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  9. Nefazadone-induced acute dystonic reaction.

    PubMed

    Burda, A; Webster, K; Leikin, J B; Chan, S B; Stokes, K A

    1999-10-01

    A 53-y-o patient presented approximately 2 h after taking her first dose of nefazadone. Chief complaint was lip smacking with hand and arm gesturing. The patient also took 25 mg meclizine which she had used before with no adverse effects. Diphenhydramine followed by benztropine led to resolution of symptoms within 1 h. Patient subsequently used meclizine with no untoward reactions. Nefazadone should be added to the list of agents that cause acute dystonic reactions. PMID:10509438

  10. Incidence of adverse cutaneous drug reactions in 22,866 Chinese inpatients: a prospective study.

    PubMed

    Tian, Xiao-Yin; Liu, Bing; Shi, Hao; Zhao, Zi-Ran; Zhou, Xi-Ping; Zhang, Tao; Sun, Qiu-Ning; Zuo, Ya-Gang

    2015-11-01

    Cutaneous adverse drug reactions (ADRs) are common. However, no prospective study assessing cutaneous ADRs is available for Chinese populations. This study aimed to assess the incidence, manifestations, causative drugs, and other factors related to cutaneous ADRs. A total of 22,866 inpatients were surveyed prospectively from January to April 2012 at the Peking Union Medical College Hospital. Only cutaneous ADRs induced by systemic drugs were considered. Fifty cases were confirmed as cutaneous ADRs, for an estimated incidence of 2.2 per 1000 during this period (95 % confidence interval 1.6-2.8). Cases of cutaneous ADRs comprised 69 % females, while 63 % of all inpatients were female (χ (2) = 0.641, P = 0.427). The department of infectious diseases was the most frequently involved department. Morbilliform exanthema (40 %) was the most frequent cutaneous ADR, followed by urticaria (23.1 %). Anti-infection drugs (36.9 %) caused most cases of cutaneous ADRs, followed by iodinated contrast media (ICM, 18.5 %) and non-steroidal anti-inflammatory drugs (NSAIDs, 18.5 %). The most frequently associated disorders were cancer (24 %), infection (22 %), cardiovascular and cerebrovascular diseases (20 %), and autoimmune diseases (18 %). In this first prospective study assessing the incidence of cutaneous ADRs in China, anti-infection drugs were the most commonly involved drugs, followed by ICM and NSAIDs. No evidence of increased cutaneous ADR incidence in AIDS or SLE patients was observed. Our findings indicate that cancer and its treatments were often related to cutaneous ADRs in China. PMID:26246330

  11. Neutron-induced reaction studies using stored ions

    NASA Astrophysics Data System (ADS)

    Glorius, Jan; Litvinov, Yuri A.; Reifarth, René

    2015-11-01

    Storage rings provide unique possibilities for investigations of nuclear reactions. Radioactive ions can be stored if the ring is connected to an appropriate facility and reaction studies are feasible at low beam intensities because of the recycling of beam particles. Using gas jet or droplet targets, charged particle-induced reactions on short-lived isotopes can be studied in inverse kinematics. In such a system a high-flux reactor could serve as a neutron target extending the experimental spectrum to neutron-induced reactions. Those could be studied over a wide energy range covering the research fields of nuclear astrophysics and reactor safety, transmutation of nuclear waste and fusion.

  12. Non-steroidal anti-inflammatory drugs with adverse psychiatric reactions: five case reports.

    PubMed

    Jiang, H K; Chang, D M

    1999-01-01

    Adverse drug reactions of non-steroidal anti-inflammatory drugs (NSAIDs) are quite prevalent, but there are few reports about possible adverse psychiatric reactions, which may be ignored or underestimated. We describe here five psychiatric outpatients, two with major depressive disorders, one bipolar disorder, one schizophrenic disorder and one anxiety disorder, who were treated with NSAIDs for pain due to rheumatoid arthritis, osteoarthritis or other painful neuromuscular conditions. All five patients developed a moderate to severe depressive state, three patients became obviously paranoid, and four had either thoughts of suicide or an attempt while undergoing co-administration of NSAIDs. The psychiatric symptoms remitted when the NSAIDs were stopped. The depressive and paranoid symptoms returned on seven occasions of re-use or re-challenge with the same or a different type of NSAID in all five patients. When the NSAIDs were stopped again, the patients had another remission of the adverse psychiatric reactions, and eventually recovered to their baseline mental states in clear temporal relationships. The cases presented suggest that NSAIDs can induce or exacerbate idiosyncratic reproducible adverse psychiatric symptoms in certain vulnerable patients, including those with a variety of psychotic or neurotic disorders, and also in elderly persons, but these undesirable side-effects were generally transient and disappeared on withdrawal of the NSAIDs. PMID:10468178

  13. Perception of Nigerian medical students on adverse drug reaction reporting.

    PubMed

    Abubakar, Abdullahi Rabiu; Chedi, Bashir A Z; Mohammed, Khalid Garba; Haque, Mainul

    2015-01-01

    Spontaneous reporting (SPR) and intensive monitoring are the conventional systems used for detecting, recording, and reporting adverse drug reactions (ADRs). Using spontaneous reporting a lot of successes has been made as existing ADRs were identified and new ones prevented through this methods. The aim of this appraisal was to evaluate the knowledge, attitude, and the practice of medical students with regards to ADRs reporting and to see if differences exist between the level of study and genders. The questionnaire was adopted, modified, and validated from previous studies. It comprised of 25 questions. It was administered year-IV and V medical students of Bayero University Kano, Nigeria. The data collected were coded and analyzed using the Statistical Package for the Social Sciences (SPSS) version 20, currently known as IBM SPSS Statistics. The response rate was 74%. Among the 108 participants, 80% got the definition of ADRs correct; 63% of them knew the precise functions of pharmacovigilance (PV). In addition, 82% strongly agreed that ADR reporting is health care workers responsibility; 82% also said PV should be taught in detail. Meanwhile, 99% have noticed patient experiencing ADRs; 67% said even mild ADRs should be reported. The outcome of this study showed good knowledge and attitude with respect to ADRs and PV among the medical students surveyed. Unfortunately, the practice of medical students was found to be unsatisfactory. There is a need to upgrade the students teaching the curriculum with respect to ADRs monitoring. PMID:26605155

  14. An update on risk factors for drug-induced arrhythmias.

    PubMed

    Vlachos, Konstantinos; Georgopoulos, Stamatis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ''effect amplifiers'' which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, Tpeak-Tend/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias. PMID:26460585

  15. Quality check of spontaneous adverse drug reaction reporting forms of different countries.

    PubMed

    Bandekar, M S; Anwikar, S R; Kshirsagar, N A

    2010-11-01

    Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge-rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. PMID:20845409

  16. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  17. Drug-induced lupus erythematosus: incidence, management and prevention.

    PubMed

    Chang, Christopher; Gershwin, M Eric

    2011-05-01

    The generation of autoantibodies and autoimmune diseases such as systemic lupus erythematosus has been associated with the use of certain drugs in humans. Early reports suggested that procainamide and hydralazine were associated with the highest risk of developing lupus, quinidine with a moderate risk and all other drugs were considered low or very low risk. More recently, drug-induced lupus has been associated with the use of the newer biological modulators such as tumour necrosis factor (TNF)-α inhibitors and interferons. The clinical features and laboratory findings of TNFα inhibitor-induced lupus are different from that of traditional drug-induced lupus or idiopathic lupus, and standardized criteria for the diagnosis of drug-induced lupus have not been established. The mechanism(s) responsible for the development of drug-induced lupus may vary depending on the drug or even on the patient. Besides lupus, other autoimmune diseases have been associated with drugs or toxins. Diagnosis of drug-induced lupus requires identification of a temporal relationship between drug administration and symptom development, and in traditional drug-induced lupus there must be no pre-existing lupus. Resolution of symptoms generally occurs after cessation of the drug. In this review, we will discuss those drugs that are more commonly associated with drug-induced lupus, with an emphasis on the new biologicals and the difficulty of making the diagnosis of drug-induced lupus against a backdrop of the autoimmune diseases that these drugs are used to treat. Stimulation of the immune system by these drugs to cause autoimmunity may in fact be associated with an increased effectiveness in treating the pathology for which they are prescribed, leading to the dilemma of deciding which is worse, the original disease or the adverse effect of the drug. Optimistically, one must hope that ongoing research in drug development and in pharmacogenetics will help to treat patients with the maximum

  18. Myalgias and Myopathies: Drug-Induced Myalgias and Myopathies.

    PubMed

    Holder, Kathryn

    2016-01-01

    Drugs can cause myalgias and myopathies through a variety of mechanisms. Most drug-induced myopathies are potentially reversible if recognized early. Prescribers should be familiar with common drug-induced myopathies and drug-drug interactions. Clinical presentations can be subacute or acute, ranging from benign muscle pain with mild elevations of serum creatine kinase to fulminant rhabdomyolysis with high creatine kinase levels and potentially life-threatening acute kidney injury. Myalgias and proximal muscle weakness are typical symptoms; onset can be weeks to months after drug exposure. Endocrine disorders and inflammatory etiologies should be excluded because their management may differ from that of drug-induced myopathies. Statin drugs are prescribed widely, and statin-induced myopathy is one of the most commonly recognized and studied myopathies. Risk factors include dose and type of statin prescribed, older age, female sex, genetic predisposition, and concomitant use of other drugs metabolized by the cytochrome P450 system. Glucocorticoids, immunologic drugs, and antimicrobials, as well as other drugs and alcohol, can cause myopathies. Management typically involves discontinuing the drug and switching to an alternative drug or considering an alternative dosing schedule. Referral to a neuromuscular subspecialist is warranted if symptoms persist. PMID:26734833

  19. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report

    PubMed Central

    2014-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. Case presentation A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6×109/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. Conclusions We report the first adult case of

  20. Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

    PubMed

    Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

    2016-06-01

    In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26948519

  1. Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection.

    PubMed

    Xu, Yubin; Dou, Deqiang; Ran, Xiaoku; Liu, Chunyan; Chen, Jing

    2015-10-16

    Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction. PMID:26372445

  2. Cross sections of neutron-induced reactions

    SciTech Connect

    Mukhopadhyay, Tapan; Lahiri, Joydev; Basu, D. N.

    2010-10-15

    We study the properties of the neutron-nucleus total and reaction cross sections for several nuclei. We have applied an analytical model, the nuclear Ramsauer model, justified it from the nuclear reaction theory approach, and extracted the values of 12 parameters used in the model. The given parametrization has an advantage as phenomenological optical model potentials are limited up to 150-200 MeV. The present model provides good estimates of the total cross sections for several nuclei particularly at high energies.

  3. Drug-induced thrombocytopenia secondary to natalizumab treatment

    PubMed Central

    Cachia, David; Izzy, Saef; Berriosmorales, Idanis; Ionete, Carolina

    2014-01-01

    Summary A 52-year-old woman with a 10-year history of relapsing-remitting multiple sclerosis (RRMS) was started on natalizumab after she developed side effects for interferon β-1a and glatiramer acetate. The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura. Laboratory testing revealed progressive worsening thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet antibodies to platelet-specific antigen as well as antibodies against natalizumab were positive. Bone marrow biopsy was negative. The patient was diagnosed with drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side effect which was treated with intravenous methylprednisolone followed by rituximab with successful resolution of thrombocytopenia. The patient had a stable course of RRMS with no relapses and no brain MRI changes at 2 years after initiation of rituximab. PMID:24879724

  4. Bullous Fixed Drug Eruption Probably Induced by Paracetamol

    PubMed Central

    Agarwala, Manoj Kumar; Mukhopadhyay, Sramana; Sekhar, M Raja; Peter, CV Dincy

    2016-01-01

    We report a case of a 42-year-old male who presented with second episode of bullous eruptions after ingestion of paracetamol. There were no systemic complaints. The temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous fixed drug due to paracetamol. Applying Naranjo's algorithm, a causality score of 8 was obtained and was categorized as probable reaction to paracetamol. Clinicians should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Drug alert cards could play an important role in preventing recurrences. PMID:26951737

  5. Clinical and endoscopic characteristics of drug-induced esophagitis

    PubMed Central

    Kim, Su Hwan; Jeong, Ji Bong; Kim, Ji Won; Koh, Seong-Joon; Kim, Byeong Gwan; Lee, Kook Lae; Chang, Mee Soo; Im, Jong Pil; Kang, Hyoun Woo; Shin, Cheol Min

    2014-01-01

    AIM: To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. METHODS: Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed. RESULTS: Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers. CONCLUSION: Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%. PMID:25152603

  6. Nuclear Astrophysics and Neutron Induced Reactions: Quasi-Free Reactions and RIBs

    SciTech Connect

    Cherubini, S.; Spitaleri, C.; Crucilla, V.; Gulino, M.; La Cognata, M.; Lamia, L.; Pizzone, R. G.; Puglia, S.; Rapisarda, G. G.; Romano, S.; Sergi, M. L.; Coc, A.; Kubono, S.; Binh, D. N.; Hayakawa, S.; Wakabayashi, Y.; Yamaguchi, H.; Burjan, V.; Kroha, V.; De Sereville, N.

    2010-08-12

    The use of quasi-free reactions in studying nuclear reactions between charged particles of astrophysical interest has received much attention over the last two decades. The Trojan Horse Method is based on this approach and it has been used to study a number of reactions relevant for Nuclear Astrophysics. Recently we applied this method to the study of nuclear reactions that involve radioactive species, namely to the study of the {sup 18}F+p{yields}{sup 15}O+{alpha} process at temperatures corresponding to the energies available in the classical novae scenario. Quasi-free reactions can also be exploited to study processes induced by neutrons. This technique is particularly interesting when applied to reaction induced by neutrons on unstable short-lived nuclei. Such processes are very important in the nucleosynthesis of elements in the sand r-processes scenarios and this technique can give hints for solving key questions in nuclear astrophysics where direct measurements are practically impossible.

  7. Drug-Induced Glomerular Disease: Immune-Mediated Injury

    PubMed Central

    Markowitz, Glen S.; Radhakrishnan, Jai

    2015-01-01

    Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed. PMID:26092827

  8. Mechanisms of drug-induced proarrhythmia in clinical practice

    PubMed Central

    Konstantopoulou, Arkadia; Tsikrikas, Spyros; Asvestas, Dimitrios; Korantzopoulos, Panagiotis; Letsas, Konstantinos P

    2013-01-01

    Drug-induced proarrhythmia represents a great challenge for those involved in the development of novel pharmaceuticals and in the regulatory bodies for drug approval as well as for the prescribing clinicians. Our understanding of the mechanisms that underlie drug-induced proarrhythmia has grown dramatically over the last two decades. A growing number of cardiac and non-cardiac agents have been shown to alter cardiac repolarization predisposing to fatal cardiac arrhythmias such as ventricular tachycardia or ventricular fibrillation and sudden cardiac death. These agents may induce the phenotype of long QT syndrome and less commonly of short QT syndrome and Brugada syndrome (BS). Although, genetic susceptibility underlie drug-induced proarrhythmia in certain cases, current data are limited regarding this topic. The present review surveys the current published literature on the mechanisms and the offending medical agents that predispose to drug-induced long QT syndrome, short QT syndrome and BS. Drug-induced proarrhythmia should be considered as a predictor of sudden cardiac death and should prompt critical re-evaluation of the risks and benefits of the suspicious medication. Survivors of drug-induced proarrhythmia and family members require careful examination and possibly genetic testing for the presence of a channelopathy. Treating physicians are advised to follow the lists of agents implicated in drug-induced proarrhythmia in order to minimize the risk of arrhythmia and sudden cardiac death. PMID:23847724

  9. A continuous GRASP to determine the relationship between drugs and adverse reactions

    SciTech Connect

    Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle; Resende, Mauricio G. C.

    2007-11-05

    Adverse drag reactions (ADRs) are estimated to be one of the leading causes of death. Many national and international agencies have set up databases of ADR reports for the express purpose of determining the relationship between drugs and adverse reactions that they cause. We formulate the drug-reaction relationship problem as a continuous optimization problem and utilize C-GRASP, a new continuous global optimization heuristic, to approximately determine the relationship between drugs and adverse reactions. Our approach is compared against others in the literature and is shown to find better solutions.

  10. Determining molecular predictors of adverse drug reactions with causality analysis based on structure learning

    PubMed Central

    Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua

    2014-01-01

    Objective Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. Methods We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. Results CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. Conclusions The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs. PMID:24334612

  11. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  12. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  13. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

    PubMed Central

    Stewart, J

    2000-01-01

    Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain. PMID:10740986

  14. Alpha-induced reactions in iridium

    SciTech Connect

    Bhardwaj, M.K.; Rizvi, I.A.; Chaubey, A.K. )

    1992-05-01

    The excitation function of ({alpha},{ital xn}) reactions on {sup 191}Ir (abundance 37.3%) and on {sup 193}Ir (abundance 62.7%) has been measured for the 17--55 MeV alpha-particle bombarding energy range. The stacked foil activation technique and {gamma}-ray spectroscopy were used to determine the cross sections. The experimental data were compared with calculated values obtained by means of a geometry-dependent hybrid model. The initial exciton number {ital n}{sub 0}=4 with {ital n}=2, {ital p}=2, and {ital h}=0 gives the best agreements with the presently measured results. To calculate the excitation function theoretically a computer code was used. This set of excitation functions provides a data basis for probing the validity of combined equilibrium and preequilibrium reaction models in a considerable energy range.

  15. Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

    PubMed Central

    Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

    2013-01-01

    OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

  16. Laser-induced reactions in energetic materials

    NASA Astrophysics Data System (ADS)

    Ling, Ping

    1999-07-01

    Several energetic materials have been investigated under shock wave loading, heating, and photodissociation. This dissertation highlights some efforts to understand energetic material from an angle of basic physical processes and elementary chemical reactions. The first series of experiments was performed to study laser-generated shock waves in energetic materials. Shock waves are generated by pulsed laser vaporization of thin aluminum films. The rapidly expanding aluminum plasma launches a shock wave into the adjacent layer of energetic material, initiating chemical reactions. The shock velocity has been measured by a velocity interferometer. Shock pressures as high as 8 GPa have been generated in this manner. A simple model is proposed to predict laser-generated shock pressure. Several energetic materials have been studied under laser- generated shock wave. The second series of experiments was conducted to study thermal decomposition and photodissociation of energetic materials. Glycidyl azide polymer (GAP) and poly(glycidyl nitrate) (PGN) have been investigated by pulsed infrared laser pyrolysis and ultraviolet laser photolysis of thin films at 17-77 K. Reactions are monitored by transmission infrared spectroscopy. Photolysis of GAP at 266 nm shows that the initial reaction steps are elimination of molecular nitrogen with subsequent formation of imines. Thermal decomposition of GAP by infrared laser pyrolysis reveals products similar to the UV experiments after warming. Laser pyrolysis of PGN indicated that the main steps of decomposition are elimination of NO2 and CH2O from the nitrate ester functional group. It seems that the initial thermal decomposition mechanism of GAP and PGN are the same from heating rate of several degrees per second to 107 oC/s. The third series of experiments is about detailed study of photodissociation mechanism of methyl nitrate. Photodissociation of methyl nitrate isolated in an argon matrix at 17 K has been investigated by 266 nm

  17. [THREE CASES OF DRUG-INDUCED PNEUMONIA CAUSED BY MESALAZINE].

    PubMed

    Akiyama, Norimichi; Yokomura, Koshi; Nozue, Tsuyoshi; Abe, Takefumi; Matsui, Takashi; Suda, Takafumi

    2015-12-01

    We report three cases of drug-induced pneumonia caused by mesalazine. They were all diagnosed as ulcerative colitis and treated with mesalazine orally. Our three cases and literature review revealed that mesalazine-induced pneumonia resemble like eosinophilic pneumonia or organizing pneumonia and that have good prognosis with drug cessation or administration of corticosteroid. The patient of ulcerative colitis is increasing every year and it is anticipated that the patient with mesalazine-induced pneumonia may also increase. In the treatment of ulcerative colitis with mesalazine, we should pay attention with patient's cough or fever for early detection of drug-induced pneumonia. PMID:26727138

  18. Patients' Induced Pluripotent Stem Cells to Model Drug Induced Adverse Events: A Role in Predicting Thiopurine Induced Pancreatitis?

    PubMed

    Stocco, Gabriele; Lanzi, Gaetana; Yue, Fengming; Giliani, Silvia; Sasaki, Katsunori; Tommasini, Alberto; Pelin, Marco; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2015-01-01

    Induced pluripotent stem cells (iPSC) can be produced from adult cells by transfecting them with a definite set of pluripotency-associated genes. Under adequate growth conditions and stimulation iPSC can differentiate to almost every somatic lineage in the body. Patients' derived iPSC are an innovative model to study mechanisms of adverse drug reactions in individual patients and in cell types that cannot be easily obtained from human subjects. Proof-of concept studies with known toxicants have been performed for liver, cardiovascular and central nervous system cells: neurons obtained from iPSC have been used to elucidate the mechanism of chemotherapy-induced peripheral neuropathy by evaluating the effects of neurotoxic drugs such as vincristine. However, no study has been performed yet on pancreatic tissue and drug induced pancreatitis. Thiopurines (azathioprine and mercaptopurine) are immunosuppressive antimetabolite drugs, commonly used to treat Crohn's disease. About 5% of Crohn's disease patients treated with thiopurines develop pancreatitis, a severe idiosyncratic adverse event; these patients have to stop thiopurine administration and may require medical treatment, with significant personal and social costs. Molecular mechanism of thiopurine induced pancreatitis (TIP) is currently unknown and no fully validated biomarker is available to assist clinicians in preventing this adverse event. Hence, in this review we have reflected upon the probable research applications of exocrine pancreatic cells generated from patient specific iPS cells. Such pancreatic cells can provide excellent insights into the molecular mechanism of TIP. In particular three hypotheses on the mechanism of TIP could be explored: drug biotransformation, innate immunity and adaptative immunity. PMID:26526832

  19. Drug-induced valvular heart disease: an update.

    PubMed

    Andrejak, Michel; Tribouilloy, Christophe

    2013-05-01

    Numerous reports have shown an unquestionable association between fibrotic valve disease and the following drugs: ergot alkaloids (such as methysergide and ergotamine), ergot-derived dopaminergic agonists (such as pergolide and cabergoline) and drugs metabolized into norfenfluramine (such as fenfluramine, dexfenfluramine and benfluorex). This review focuses on different aspects of drug-induced valvular heart disease: historical background; echocardiographic features; different drugs recognized as being responsible for valvular heart disease; and pathophysiology. PMID:23769407

  20. Computational Catalysis Using the Artificial Force Induced Reaction Method.

    PubMed

    Sameera, W M C; Maeda, Satoshi; Morokuma, Keiji

    2016-04-19

    The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local minima (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent organic reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equilibrium structures are possible, leading to a number of reaction pathways. The AFIR method in the GRRM strategy determines all of the important equilibrium structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be determined. The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aqueous media. Some AFIR applications have targeted the selectivity-determining step of transition-metal-catalyzed asymmetric reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is critical. In this direction, AFIR is very useful for performing a systematic and automatic determination of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calculated more accurately

  1. Shock-induced reaction synthesis (SRS) of nickel aluminides

    SciTech Connect

    Thadhani, N.N.; Work, S. , New Mexico Tech, Socorro, New Mexico 87801 ); Graham, R.A.; Hammetter, W.F. )

    1992-05-01

    Shock-induced chemical reactions between nickel and aluminum powders (mixed in Ni{sub 3}Al stoichiometry) are used for the synthesis of nickel aluminides. It is shown that the extent of shock-induced chemical reactions and the nature of the shock-synthesized products are influenced by the morphology of the starting powders. Irregular (flaky type) and fine morphologies of the powders undergo complete reactions in contrast to partial reactions occurring in coarse and uniform morphology powders under identical shock loading conditions. Furthermore, irregular morphology powders result in the formation of the equiatomic (B2 phase) NiAl compound while the Ni{sub 3}Al (L1{sub 2} phase) compound is the reaction product with coarse and regular morphology powders. Shock-induced reaction synthesis can be characterized as a bulk reaction process involving an intense mechanochemical'' mechanism. It is a process in which shock compression induces fluid-like plastic flow and mixing, and enhances the reactivity due to the introduction of defects and cleansing of particle surfaces, which strongly influence the synthesis process.

  2. Adverse drug reactions and safety considerations of NSAIDs: clinical analysis.

    PubMed

    Bahadur, Shiv; Keshri, Lav; Pathak, Kamla

    2011-11-01

    NSAIDs are the most frequently used drugs for treatment, in Europe and the United States, accounting for approximately 5% of all prescriptions. Moreover, the use of NSAIDs is increasing because these constitute the first-line drug therapy for a wide range of rheumatic conditions. This increase is in part the result of the increasing population of elderly patients, who constitute the group of patients with greatest demand for these agents. There are many types of NSAIDs that vary in potency, action and potential side effects. Thus various efforts have been made to determine the safety considerations including adverse drug effects, duration of drug therapy, drug interactions, precautions and other drugs applied to reduce side effects. Researchers have introduced some novel techniques to diagnose NSAIDs related adverse effects on the gastrointestinal mucosa. The researchers dealing with the development of drug delivery system for these drugs should aim at designing a therapeutically efficacious dosage form with reduced side/adverse effects. Thus an effort has been made in this review to deal with the safety parameters of various NSAIDs with a special emphasis on preclinical and clinical safety analysis and various attempts to minimize the side effects by structural modification or by drug delivery system. PMID:22424538

  3. Nivolumab-Induced Sarcoid-Like Granulomatous Reaction in a Patient With Advanced Melanoma.

    PubMed

    Danlos, François-Xavier; Pagès, Cécile; Baroudjian, Barouyr; Vercellino, Laetitia; Battistella, Maxime; Mimoun, Maurice; Jebali, Majdi; Bagot, Martine; Tazi, Abdellatif; Lebbé, Céleste

    2016-05-01

    To our knowledge, we report the first case of sarcoid-like granulomatous reaction induced by nivolumab, a fully human IgG4 anti-programmed death 1 (PD-1) immune checkpoint inhibitor antibody. A 57-year-old man was treated with nivolumab 3 mg/kg for 2 weeks for a desmoplastic melanoma stage III American Joint Commission on Cancer, with no BRAF, NRAS, and cKit mutations. At 10 months, although melanoma complete response was achieved, he developed sarcoid-like granulomatous reaction in the mediastinal lymph node and skin, which resumed after nivolumab arrest. Melanoma did not relapse after 12 months of follow-up. Considering the recently demonstrated role of activated PD-1/PDL-1 axis in sarcoidosis, granulomatous reaction in the patient seems to be a paradoxical reaction, but similar observations have been reported with ipilimumab, another immune checkpoint inhibitor. Sarcoid-like granulomatous reaction during immunotherapy treatment could be a manifestation of cell-mediated immunity induced by these drugs. Impact of granulomatous reaction induced by immune checkpoint inhibitor on melanoma progression is not known and requires further study. Melanoma patients treated by immunotherapy (anti-cytotoxic T-lymphocyte-associated protein-4/anti-PD-1) should be considered for developing sarcoid-like granulomatous reaction that must not be confused with tumor progression. PMID:27157227

  4. Drug-induced QT interval prolongation: mechanisms and clinical management

    PubMed Central

    Nachimuthu, Senthil; Assar, Manish D.

    2012-01-01

    The prolonged QT interval is both widely seen and associated with the potentially deadly rhythm, Torsades de Pointes (TdP). While it can occur spontaneously in the congenital form, there is a wide array of drugs that have been implicated in the prolongation of the QT interval. Some of these drugs have either been restricted or withdrawn from the market due to the increased incidence of fatal polymorphic ventricular tachycardia. The list of drugs that cause QT prolongation continues to grow, and an updated list of specific drugs that prolong the QT interval can be found at www.qtdrugs.org. This review focuses on the mechanism of drug-induced QT prolongation, risk factors for TdP, culprit drugs, prevention and monitoring of prolonged drug-induced QT prolongation and treatment strategies. PMID:25083239

  5. Cinnamon-induced Oral Mucosal Contact Reaction

    PubMed Central

    Vivas, Ana P. M; Migliari, Dante A

    2015-01-01

    Contact stomatitis associated with consumption of cinnamon flavoring agents is a relatively uncommon disorder. Of relevance, both clinical features and the histopathologic findings of this condition are nonspecific, and, more importantly, may resemble some other inflammatory oral mucosa disorders, eventually making diagnosis difficult. Usually a patient exhibits a combination of white and erythematous patches of abrupt onset, accompanied by a burning sensation. To shed some light on this subject, a case of a 64-year-old woman with hypersensitivity contact reaction on the oral mucosa due to cinnamon mints is presented, with emphasis on differential diagnosis and the process for confirmation of the diagnosis. The treatment consists of discontinuing the use of cinnamon products. Clinicians will be able to recognize this disorder following a careful clinical examination and detailed history. This recognition is important in order to avoid invasive and expensive diagnostic procedures. PMID:26312097

  6. Drug induced `softening' in phospholipid monolayers

    NASA Astrophysics Data System (ADS)

    Basak, Uttam Kumar; Datta, Alokmay; Bhattacharya, Dhananjay

    2015-06-01

    Compressibility measurements on Langmuir monolayers of the phospholipid Dimystoryl Phospatidylcholine (DMPC) in pristine form and in the presence of the Non-steroidal Anti-inflammatory Drug (NSAID) Piroxicam at 0.025 drug/lipid (D/L) molecular ratio at different temperatures, show that the monolayer exhibits large increase (and subsequent decrease) in compressibility due to the drug in the vicinity of the Liquid Expanded - Liquid Condensed (LE-LC) phase transition. Molecular dynamics simulations of the lipid monolayer in presence of drug molecules show a disordering of the tail tilt, which is consistent with the above result.

  7. Hypothesis for synergistic toxicity of organophosphorus poisoning-induced cholinergic crisis and anaphylactoid reactions

    SciTech Connect

    Cowan, F.M.; Shih, T.M.; Lenz, D.E.; Madsen, J.M.; Broomfield, C.A.

    1996-08-01

    The neurotoxicity of organophosphorus (OP) compounds Involves the Inhibition of acetylchollnesterase (AChE), causing accumulation of acetyicholine (ACh) at synapses. However, cholinergic crisis may not be the sole mechanism of OP toxicity. Adverse drug reactions caused by synergistic toxicity between drugs with distinct pharmacological mechanisms are a common problem. Likewise, the multiple pharmacological activities of a single molecule might also contribute to either toxicity or efficacy. For example, certain OP compounds (e.g. soman) exhibit anti-AChE activity and also act as secretagogues by inducing mast cell degranulation with associated autacoid release and anaphylactoid reactions. Anaphylactoid shock can produce a lethal syndrome with symptoms of respiratory failure and circulatory collapse similar to the physiological sequelae observed for OP poisoning. Moreover, the major classes of drugs used as antidotes for OP intoxication can affect anaphylaxis. Acetylcholine can act as an agonist of autacoid release, and autacoids such as histamine can augment soman-Induced bronchial spasm. In concert with the demonstrably critical role of cholinergic crisis In OP toxicity, the precepts of neuroimmunology indicate that secondary adverse reactions encompassing anaphylactold reactions may complicate OP toxicity.

  8. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia

    PubMed Central

    ARNOLD, D. M.; KUKASWADIA, S.; NAZI, I.; ESMAIL, A.; DEWAR, L.; SMITH, J. W.; WARKENTIN, T. E.; KELTON, J. G.

    2016-01-01

    Summary Background Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. Objective To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. Patients/Methods We developed a grading system to evaluate the quality of DITP laboratory testing. The ‘DITP criteria’ were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. Results Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. Conclusions We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient. PMID:23121994

  9. US data show sharply rising drug-induced death rates.

    PubMed

    Paulozzi, Leonard J; Annest, Joseph L

    2007-04-01

    Substantial numbers of deaths are related to disease and injury resulting from the use of drugs, alcohol and firearms worldwide. Death rates associated with these exposures were compared with those from motor vehicle crashes in the US from 1979 to 2003 by race. Among Caucasians, drug-induced death rates rose sharply after 1990 and surpassed deaths involving alcohol and firearms in 2001 and 2002, respectively. Among African-Americans, drug-induced deaths surpassed alcohol-induced deaths for the first time in 1999. PMID:17446255

  10. Low-energy electron-induced reactions in condensed matter

    NASA Astrophysics Data System (ADS)

    Arumainayagam, Christopher R.; Lee, Hsiao-Lu; Nelson, Rachel B.; Haines, David R.; Gunawardane, Richard P.

    2010-01-01

    The goal of this review is to discuss post-irradiation analysis of low-energy (≤50 eV) electron-induced processes in nanoscale thin films. Because electron-induced surface reactions in monolayer adsorbates have been extensively reviewed, we will instead focus on low-energy electron-induced reactions in multilayer adsorbates. The latter studies, involving nanoscale thin films, serve to elucidate the pivotal role that the low-energy electron-induced reactions play in high-energy radiation-induced chemical reactions in condensed matter. Although electron-stimulated desorption (ESD) experiments conducted during irradiation have yielded vital information relevant to primary or initial electron-induced processes, we wish to demonstrate in this review that analyzing the products following low-energy electron irradiation can provide new insights into radiation chemistry. This review presents studies of electron-induced reactions in nanoscale films of molecular species such as oxygen, nitrogen trifluoride, water, alkanes, alcohols, aldehydes, ketones, carboxylic acids, nitriles, halocarbons, alkane and phenyl thiols, thiophenes, ferrocene, amino acids, nucleotides, and DNA using post-irradiation techniques such as temperature-programmed desorption (TPD), reflection-absorption infrared spectroscopy (RAIRS), X-ray photoelectron spectroscopy (XPS), high-resolution electron energy loss spectroscopy (HREELS), gel electrophoresis, and microarray fluorescence. Post-irradiation temperature-programmed desorption, in particular, has been shown to be useful in identifying labile radiolysis products as demonstrated by the first identification of methoxymethanol as a reaction product of methanol radiolysis. Results of post-irradiation studies have been used not only to identify radiolysis products, but also to determine the dynamics of electron-induced reactions. For example, studies of the radiolysis yield as a function of incident electron energy have shown that dissociative

  11. Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview

    PubMed Central

    Singh, Divya; Cho, William C.; Upadhyay, Ghanshyam

    2016-01-01

    The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for drug-induced liver damage. Endorsed medications represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and natural products in the treatment of various disorders led the investigators to look into their potential in countering drug-induced liver toxicity. Several natural products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less adverse reactions of the natural products provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication. PMID:26858648

  12. Basic Cardiac Electrophysiology and Common Drug-induced Arrhythmias.

    PubMed

    Lee, Aimee; Pickham, David

    2016-09-01

    Drugs can be a double-edged sword, providing the benefit of symptom alleviation and disease modification but potentially causing harm from adverse cardiac arrhythmic events. Proarrhythmia is the ability of a drug to cause an arrhythmia, the number one reason for drugs to be withdrawn from the patient. Drug-induced arrhythmias are defined as the production of de novo arrhythmias or aggravation of existing arrhythmias, as a result of previous or concomitant pharmacologic treatment. This review summarizes normal cardiac cell and tissue functioning and provides an overview of drugs that effect cardiac repolarization and the adverse effects of commonly administered antiarrhythmics. PMID:27484663

  13. Factors affecting drug-induced liver injury: antithyroid drugs as instances.

    PubMed

    Heidari, Reza; Niknahad, Hossein; Jamshidzadeh, Akram; Abdoli, Narges

    2014-09-01

    Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed. PMID:25320726

  14. Female gender as a susceptibility factor for drug-induced liver injury.

    PubMed

    Amacher, David E

    2014-09-01

    Adverse drug reactions (ADRs) can involve all tissues and organs, but liver injuries are considered among the most serious. A number of prospective, multicenter studies have confirmed a higher risk of ADRs in general among female subjects compared to a male cohort. Although drug-induced liver injury (DILI) is infrequently encountered, the preponderance of evidence suggests that women appear to be more susceptible than men to fulminate hepatic/acute liver failure especially in response to some anti-infective drugs and to autoimmune-like hepatitis following exposure to certain other therapeutic drugs. A number of hypotheses have been proposed to explain this sex difference in susceptibility to DILI. Collectively, these hypotheses suggest three basic sex-dependent mechanisms that include differences in various aspects of drug pharmacokinetics (PK) or pharmacodynamics following the administration of certain drugs; specific hormonal effects or interactions with immunomodulating agents or signaling molecules; and differences in the adverse response of the immune system to some drugs, reactive drug metabolites, or drug-protein adducts. At the preclinical drug safety stage, there is a need for more research on hormonal effects on drug PK and for additional research on gender differences in aberrant immune responses that may lead to idiosyncratic DILI in some female patients. Because the detection of rare but serious hepatic ADRs requires the exposure of very large patient populations, pharmacovigilance networks will continue to play a key role in the postmarketing surveillance for their detection and reporting. PMID:24299907

  15. Deuterium separation by infrared-induced addition reaction

    DOEpatents

    Marling, John B.

    1977-01-01

    A method for deuterium enrichment by the infrared-induced addition reaction of a deuterium halide with an unsaturated aliphatic compound. A gaseous mixture of a hydrogen halide feedstock and an unsaturated aliphatic compound, particularly an olefin, is irradiated to selectively vibrationally excite the deuterium halide contained therein. The excited deuterium halide preferentially reacts with the unsaturated aliphatic compound to produce a deuterated addition product which is removed from the reaction mixture.

  16. Nuclear reactions induced by high-energy alpha particles

    NASA Technical Reports Server (NTRS)

    Shen, B. S. P.

    1974-01-01

    Experimental and theoretical studies of nuclear reactions induced by high energy protons and heavier ions are included. Fundamental data needed in the shielding, dosimetry, and radiobiology of high energy particles produced by accelerators were generated, along with data on cosmic ray interaction with matter. The mechanism of high energy nucleon-nucleus reactions is also examined, especially for light target nuclei of mass number comparable to that of biological tissue.

  17. Drug-induced glomerular disease: direct cellular injury.

    PubMed

    Markowitz, Glen S; Bomback, Andrew S; Perazella, Mark A

    2015-07-01

    The potential of medications to cause kidney injury is well known. Although nephrotoxicity is most commonly associated with injury in the tubulointerstitial compartment as either acute tubular necrosis or acute interstitial nephritis, a growing body of literature has also highlighted the potential for drug-induced glomerular lesions. This review surveys the three primary patterns of drug-induced glomerular diseases stratified by the cell type at which the glomerular lesion is focused: visceral epithelial cell (or podoctye) injury, endothelial cell injury, and mesangial cell injury. A number of commonly prescribed medications, including IFNs, bisphosphonates, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and antiangiogenesis drugs, that are both prescribed and available over the counter, have been implicated in these iatrogenic forms of glomerular disease. Recognition of these drug-induced etiologies of glomerular disease and rapid discontinuation of the offending agent are critical to maximizing the likelihood of renal function recovery. PMID:25862776

  18. In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells

    PubMed Central

    Galbiati, Valentina; Papale, Angela; Kummer, Elena; Corsini, Emanuela

    2016-01-01

    Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated (“allergic”) and non-immune-mediated (“pseudo allergic”) reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon. We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells. PMID:27462271

  19. In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells.

    PubMed

    Galbiati, Valentina; Papale, Angela; Kummer, Elena; Corsini, Emanuela

    2016-01-01

    Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ("allergic") and non-immune-mediated ("pseudo allergic") reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon. We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells. PMID:27462271

  20. Innovative Drug Injection via Laser Induced Plasma

    NASA Astrophysics Data System (ADS)

    Han, Tae-hee; Yoh, Jack J.

    2010-10-01

    A laser based needle-free liquid drug injection device has been developed. A laser beam is focused inside the liquid contained in the rubber chamber of micro scale. The focused laser beam causes explosive bubble growth and the sudden volume increase in a sealed chamber drives a microjet of liquid drug through the micronozzle. The exit diameter of the nozzle is 125 um and the injected microjet reaches an average velocity of 264 m/s. This device adds the time-varying feature of microjet to the current state of liquid injection for drug delivery.

  1. [Lichenoid drug eruption induced by olanzapine].

    PubMed

    Fernández-Torres, R; Almagro, M; del Pozo, J; Robles, O; Martínez-González, C; Mazaira, M; Fonseca, E

    2008-04-01

    Lichenoid drug eruptions can mimic idiopathic lichen planus and other dermatoses. The list of drugs that can cause them is long and growing steadily. Although cutaneous side effects of antipsychotics are rare, various cutaneous manifestations have been reported in association with olanzapine. We present the case of a patient who developed an atypical lichenoid eruption due to olanzapine. A review of the literature in Medline from 1951 to 2007 and in the Indice Médico Español (Spanish Medical Index) revealed no previous cases of lichenoid eruptions associated with the use of this drug. PMID:18358199

  2. Management of Psychotropic Drug-Induced DRESS Syndrome: A Systematic Review.

    PubMed

    Bommersbach, Tanner J; Lapid, Maria I; Leung, Jonathan G; Cunningham, Julie L; Rummans, Teresa A; Kung, Simon

    2016-06-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous eruption that has been linked to several common drugs and drug categories, including antiepileptics, allopurinol, sulfonamides, and various antibiotics; however, because of a number of recent case reports linking psychotropic medications to this condition, DRESS is increasingly recognized among psychiatrists. We systematically reviewed all psychotropic drugs linked to DRESS syndrome, and this article summarizes the clinical management relevant to psychiatric professionals. A comprehensive search was performed using Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Litt's Drug Eruption and Reaction Database for articles published in English during the past 20 years (1996-2015) using the search terms (1) psychotropic drugs OR serotonin uptake inhibitors AND DRESS or (2) psychotropic drugs AND drug reaction (or rash) eosinophilia systemic syndrome, and all article abstracts were screened for inclusion and exclusion criteria by 3 reviewers. Two independent reviewers examined the full text of 163 articles, of which 96 (25 original articles, 12 review articles, 55 case reports, and 4 letters to the editor) were included in the systematic review. We identified 1072 cases of psychotropic drug-induced DRESS, with carbamazepine, lamotrigine, phenytoin, valproate, and phenobarbital being the most implicated drugs. Based on our review of the literature, we outline management principles that include prompt withdrawal of the causative drug, hospitalization, corticosteroid therapy, and novel treatments, including intravenous immunoglobulin, cyclophosphamide, and cyclosporine, for corticosteroid-resistant DRESS. Finally, we outline strategies for treating comorbid psychiatric illness after a DRESS reaction to the psychotropic medication. PMID:27126302

  3. Drug-induced pancreatitis: A Potentially Serious and Underreported Problem.

    PubMed

    Kaufman, Michele B

    2013-06-01

    There have been many published reports of possible cases of drug-induced pancreatitis. In addition, some disease states and patient characteristics predispose particular populations to the development of this condition. Three case histories are presented. PMID:23946630

  4. Photo- and neutrino-induced reactions for SNe nucleosynthesis

    NASA Astrophysics Data System (ADS)

    Shima, Tatsushi

    2014-09-01

    Neutrino-induced nuclear reactions are considered to play important roles in the dynamics of supernova explosions and in supernova nucleosynthesis. For example, neutrino-inelastic scattering off light nuclei are supposed to assist the explosion by supplying the kinetic energy to the outgoing matters. The neutrino-nucleus reactions via the neutral and charged current of the weak interaction are the key reactions in the r-process nucleosynthesis in neutrino-driven wind. To quantitatively understand those phenomena, precise data of the neutrino-nucleus reaction rates are indispensable. Recently developed secondary particle beams provide good experimental opportunities for determining the neutrino-nucleus reaction rates. A quasi-monochromatic laser Compton-scattered (LCS) photon beam is useful for studying the photonuclear reactions which are the direct analogue of the neutrino inelastic scatterings caused by the weak neutral current. On the other hand, real neutrino beams are ideal tools to directly measure the absolute neutrino-nucleus reaction rates. Another interesting probe will be the nuclear muon-capture reaction, because it can be applied for measurement of the targets with very small quantities thanks to its large capture probability. In this talk recent progress in ongoing experiments with LCS gamma-rays and muon beams will be presented. A new plan for direct measurement of the neutrino-nucleus reactions with an accelerator-driven neutrino beam will be also discussed.

  5. Targeted drug induces responses in aggressive lymphomas

    Cancer.gov

    Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.

  6. Dynamics of synchrotron VUV-induced intracluster reactions

    SciTech Connect

    Grover, J.R.

    1993-12-01

    Photoionization mass spectrometry (PIMS) using the tunable vacuum ultraviolet radiation available at the National Synchrotron Light Source is being exploited to study photoionization-induced reactions in small van der Waals mixed complexes. The information gained includes the observation and classification of reaction paths, the measurement of onsets, and the determination of relative yields of competing reactions. Additional information is obtained by comparison of the properties of different reacting systems. Special attention is given to finding unexpected features, and most of the reactions investigated to date display such features. However, understanding these reactions demands dynamical information, in addition to what is provided by PIMS. Therefore the program has been expanded to include the measurement of kinetic energy release distributions.

  7. Identifying genomic and developmental causes of adverse drug reactions in children

    PubMed Central

    Becker, Mara L; Leeder, J Steven

    2011-01-01

    Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed. PMID:21121777

  8. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias.

    PubMed

    Cubeddu, Luigi X

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended. PMID:26926294

  9. Thermally Induced And Base Catalyzed Reactions Of Naphthoquinone Diazides

    NASA Astrophysics Data System (ADS)

    Koshiba, Mitsunobu; Murata, Makoto; Matsui, Mariko; Harita, Yoshiyuki

    1988-01-01

    Thermally induced and base catalyzed reactions of a phenol ester of 1,2-naphthoquinone-diazide-5-sulfonic acid (DAM) with p-cresol were investigated. In total seven reaction products were obtained for the thermally induced reaction. The three major products, TR--F4, TR-F6 and TR-F7, were isolated and their structures were determined by means of several advanced spectroscopic techniques like Fourier transform nuclear magnetic resonance (FTNMR) and field desorption mass spectroscopy (FD-MS). Besides a cresol ester of indenecarboxylic acid (TR-F6) and an azo compound which contains two DAM originated moieties and cresol (TR-F7), the formation of a novel compound was found; a phenol ester of 2-cresyl-l-naphthol-5-sulfonic acid. On the other hand, four reaction products were found in the base (a 2.38wt% tetramethylammonium hydroxide aq. solution) catalyzed reaction products of DAM with p-cresol, and two major products, BC-Fl and BC-F3, which appeared at the initial stage of the reaction were isolated. The structure determination of the two major products was carried out in the same manner as described above. It was discovered that BC-Fl was a cresol ester of 1-naphthol while BC-F3 was an azoxy compound. Brief discussions will be made on those reactions of naphthoquinone diazides with a matrix novolak resin with reference to the results obtained by the present study.

  10. Drug-Induced Ocular Hypertension and Angle-Closure Glaucoma.

    PubMed

    Badhu, Badri P; Bhattarai, Balkrishna; Sangraula, Himal P

    2013-01-01

    The objective of this study was to review the available literature on the drugs causing ocular hypertension and glaucoma. Electronic literature search was carried out using the Web sites www.pubmed.gov and www.google.com published through the year 2011. The search words were "drug induced ocular hypertension" and "drug induced glaucoma" used in combination. The articles published or translated into English were studied. Quite a significant number of drugs commonly prescribed by various physicians of different specialties can induce ocular hypertension or glaucoma. A brief account of various drugs that can induce ocular hypertension has been given in this article. Those drugs are parasympatholytics; steroids; anticholinergics, adrenergics, and antidepressants; cholinomimetics; antineoplastic agents; antipsychotic and antiparkinsonism agents; H1 and H2 receptor blockers; botulinum toxin, cardiac agents, and anticoagulants; silicone oil; sulfa drugs; and anesthetic agents. Rational use of these drugs and knowledge of their potential adverse effects can help prevent the devastating complications resulting in loss of vision and compromised quality of life. PMID:26108110

  11. On reaction mechanisms involved in the deuteron–induced surrogate reactions

    SciTech Connect

    Avrigeanu, M.; Avrigeanu, V.; Mănăilescu, C.

    2015-02-24

    An extended analysis of the nuclear reaction mechanisms involved within deuteron interaction with nuclei, namely the breakup, stripping, pick-up, pre-equilibrium emission, and evaporation from fully equilibrated compound nucleus, is presented in order to highlight the importance of the direct mechanisms still neglected in the analysis of deuteron-induced surrogate reactions. Particularly, the dominance of the breakup mechanism at low energies around the Coulomb barrier should be considered in the case of (d,x) surrogate reactions on actinide target nuclei.

  12. [Reaction mechanism studies of heavy ion induced nuclear reactions]. Annual progress report, [January 1992--February 1993

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  13. On reaction mechanisms involved in the deuteron-induced surrogate reactions

    NASA Astrophysics Data System (ADS)

    Avrigeanu, M.; Avrigeanu, V.; Mǎnǎilescu, C.

    2015-02-01

    An extended analysis of the nuclear reaction mechanisms involved within deuteron interaction with nuclei, namely the breakup, stripping, pick-up, pre-equilibrium emission, and evaporation from fully equilibrated compound nucleus, is presented in order to highlight the importance of the direct mechanisms still neglected in the analysis of deuteron-induced surrogate reactions. Particularly, the dominance of the breakup mechanism at low energies around the Coulomb barrier should be considered in the case of (d,x) surrogate reactions on actinide target nuclei.

  14. Phenotype standardization for drug-induced kidney disease.

    PubMed

    Mehta, Ravindra L; Awdishu, Linda; Davenport, Andrew; Murray, Patrick T; Macedo, Etienne; Cerda, Jorge; Chakaravarthi, Raj; Holden, Arthur L; Goldstein, Stuart L

    2015-08-01

    Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition. PMID:25853333

  15. [Understanding and reducing the risk of adverse drug reactions in pediatric patients].

    PubMed

    Gotta, Verena; van den Anker, Johannes; Pfister, Marc

    2015-12-01

    Developmental pharmacology influences the safety profile of drugs in pediatrics. Altered pharmacokinetics and/ or pharmacodynamics of drugs make pediatric patients susceptible to adverse drug reactions (ADRs), especially infants and newborns. Since the efficacy/ safety balance of most available drugs has not been formally evaluated in pediatric clinical trials, optimal dosing is rarely known in pediatrics. Suboptimal pediatric drug formulations make dose optimization even more difficult exposing pediatric patients to medication errors like overdosing and associated ADRs. We provide an overview of pediatric ADRs and discuss recent regulatory and pharmacological measures to understand and reduce risk of ADRs in pediatric patients. PMID:26654811

  16. Non-chemotherapy drug-induced agranulocytosis in a tertiary hospital.

    PubMed

    Navarro-Martínez, R; Chover-Sierra, E; Cauli, O

    2016-03-01

    Drug-induced agranulocytosis is a rare haematological disorder considered as severe adverse drug reaction. Due to its low incidence, the number of studies are low and the variability of clinical features and presentation in hospitalized patients is rarely described. Awe performed an observational, transversal and retrospective study in the haematology and toxicology unit in a tertiary hospital located in Spain (Valencia) (1996-2010) in order to assess its incidence, the drugs involved, the management and outcomes of drug-induced agranulocytosis. Twenty-one cases of agranulocytosis were retrieved. All of them presented severe and symptomatic agranulocytosis (fever and infection). The most common drug associated with drug-induced agranulocytosis was metamizole administration but other drugs belonging to different pharmacological classes as well (carbimazol, sulfasalazine, bisoprolol, itraconazole, amitryptiline, ketorolac and claritomicine+cefuroxime). No differences between sex and age were found in relationship with the manifestations or course of agranulocytosis. In contrast, a significantly negative association was found between age of patients and the percentage of increase in neutrophil count. Administration of human granulocyte colony-stimulating factor did not significantly enhance the recovery of the process or the restoration of leucocytes count, suggesting a limited utility in this type of agranulocytosis. PMID:25845587

  17. Adverse Drug Reactions of Spontaneous Reports in Shanghai Pediatric Population

    PubMed Central

    Du, Wen-Min; Xu, Jin-Fang; Zhang, Xin-Ji; He, Jia

    2014-01-01

    Background Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009. Methodology and Principal Findings Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter. Results A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (χ2 = 15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors. Conclusions In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China. PMID:24587066

  18. Drug-induced QT interval prolongation and torsades de pointes

    PubMed Central

    Tisdale, James E.

    2016-01-01

    Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval–prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration. Pharmacokinetic drug interactions associated with the highest risk of TdP include antifungal agents, macrolide antibiotics (except azithromycin) and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide. Other important pharmacokinetic interactions include antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting with flecainide, quinidine or thioridazine. Pharmacists play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through knowledge of drugs that are associated with a known or possible risk of TdP, individualized assessment of risk of drug-induced QTc interval prolongation, awareness of drug interactions most likely to result in TdP and attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease. Treatment of hemodynamically stable TdP consists of discontinuation of the offending drug(s), correction of electrolyte abnormalities and administration of intravenous magnesium sulfate 1 to 2 g. PMID:27212965

  19. Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice.

    PubMed

    Caroff, Stanley N; Campbell, E Cabrina

    2016-09-01

    The development of drugs to treat psychosis is a fascinating nexus for understanding mechanisms underlying disorders of mind and movement. Although the risk of drug-induced extrapyramidal syndromes has been mitigated by the acceptance of less potent dopamine antagonists, expansive marketing and off-label use has increased the number of susceptible people who may be at risk for these neurologic effects. Clinicians need to be familiar with advances in diagnosis and management, which are reviewed herein. A better understanding of drug-induced effects on the motor circuit may improve patient safety, enhance antipsychotic effectiveness, and provide insights into mechanisms underlying antipsychotic activity in parallel brain circuits. PMID:27514296

  20. DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome.

    PubMed

    Luo, Heng; Chen, Jian; Shi, Leming; Mikailov, Mike; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun

    2011-07-01

    Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical-protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical-protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user's molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug-drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. PMID:21558322

  1. Metabolic activation and drug-induced liver injury: in vitro approaches for the safety risk assessment of new drugs.

    PubMed

    Gómez-Lechón, M José; Tolosa, Laia; Donato, M Teresa

    2016-06-01

    Drug-induced liver injury (DILI) is a significant leading cause of hepatic dysfunction, drug failure during clinical trials and post-market withdrawal of approved drugs. Many cases of DILI are unexpected reactions of an idiosyncratic nature that occur in a small group of susceptible individuals. Intensive research efforts have been made to understand better the idiosyncratic DILI and to identify potential risk factors. Metabolic bioactivation of drugs to form reactive metabolites is considered an initiation mechanism for idiosyncratic DILI. Reactive species may interact irreversibly with cell macromolecules (covalent binding, oxidative damage), and alter their structure and activity. This review focuses on proposed in vitro screening strategies to predict and reduce idiosyncratic hepatotoxicity associated with drug bioactivation. Compound incubation with metabolically competent biological systems (liver-derived cells, subcellular fractions), in combination with methods to reveal the formation of reactive intermediates (e.g., formation of adducts with liver proteins, metabolite trapping or enzyme inhibition assays), are approaches commonly used to screen the reactivity of new molecules in early drug development. Several cell-based assays have also been proposed for the safety risk assessment of bioactivable compounds. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26691983

  2. Flare-up reactions in severe drug hypersensitivity: infection or ongoing T-cell hyperresponsiveness

    PubMed Central

    Jörg-Walther, Lukas; Schnyder, Benno; Helbling, Arthur; Helsing, Karin; Schüller, Alexandra; Wochner, Annette; Pichler, Werner

    2015-01-01

    Key Clinical Message “Flare-up” reactions are late manifestations of severe T-cell-mediated drug hypersensitivity reactions. Management is anti-inflammatory treatment and avoiding unnecessary medicines. Symptoms like fever, lymph node swelling, and blood count abnormalities may lead to confusion with bacterial infections. For prompt recognition it is important to keep the differential diagnosis in mind. PMID:26509009

  3. A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.

    PubMed

    Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R

    2016-01-01

    Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/. PMID:27189608

  4. Levetiracetam induced psoriasiform drug eruption: a rare case report.

    PubMed

    Gencler, Onur Serdar; Gencler, Bilgen; Altunel, Cemile Tugba; Arslan, Nur

    2015-11-01

    Levetiracetam (LEV) is an established second generation anti-epileptic drug and LEV associated severe cutaneous reactions are rare. Here we report the case of psoriasiform drug eruption in a patient with newly diagnosed epilepsy who had been treated with levetiracetam. To our knowledge this is the first report of a patient with a psoriasiform eruption that appeared after the administration of LEV. PMID:26702269

  5. Drug-induced discoloration of teeth: an updated review.

    PubMed

    Kumar, Arun; Kumar, Vijay; Singh, Janardhan; Hooda, Anita; Dutta, Samir

    2012-02-01

    The problem of tooth discoloration is emerging in our society because of the poor oral hygiene, physical agents, environmental chemicals, mouth rinses, some dental procedures, general systemic conditions, and drugs. Other common causes of tooth discoloration include excessive use of tea, coffee, tobacco smoking and chewing, chewing of betel morsel (piper betel, paan), and so on. Drug-induced tooth discoloration can be prevented by avoiding prescriptions of well-known offender drugs known to cause tooth discoloration during pregnancy and in young children. This review describes some important groups of drugs that cause tooth discoloration. PMID:21917545

  6. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    PubMed Central

    Rabinowich, Liane; Shibolet, Oren

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis. PMID:26273591

  7. A prospective study on Adverse Drug Reactions of antibiotics in a tertiary care hospital

    PubMed Central

    Shamna, M.; Dilip, C.; Ajmal, M.; Linu Mohan, P.; Shinu, C.; Jafer, C.P.; Mohammed, Yahiya

    2013-01-01

    Adverse reactions are the recognized hazards of drug therapy and they can occur with any class of drugs and many studies revealed that the incidence is more in case of antibiotics. The main aim of this study was to detect and analyze Adverse Drug Reactions of antibiotics in inpatients of a tertiary care hospital. A prospective spontaneous reporting study by active and passive methods was carried out for a period of six months. A total of 49 ADRs were reported during the study period with male predominance (53.06%) and geriatric age group. More number of ADRs was from General Medicine and Pediatric departments in which the most affected organ systems were the GIT (38.77%) and the skin (30.61%). The antibiotic classes mostly accounted were cephalosporins (34.69%) followed by fluoroquinolones and others in which type A reactions were more compared to type B and 59.18% of them were predictable. The severity assessment revealed that most of them were moderate (63.26%) followed by mild and severe reactions. Of the reported reactions, 55.10% were definitely preventable and causality assessment was done which showed that 71.42% of the reactions were probable, possible (18.36%), definite (10.20%) and no reactions were unlikely. The study concluded that Adverse Drug Reactions to antibiotics are common and some of them resulted in increased healthcare cost due to the need of some interventions and increased length of hospital stay. The health system should promote the spontaneous reporting of Adverse Drug Reactions to antibiotics, proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety. PMID:25161373

  8. Contemporary review of drug-induced pancreatitis: A different perspective.

    PubMed

    Hung, Whitney Y; Abreu Lanfranco, Odaliz

    2014-11-15

    Although gallstone and alcohol use have been considered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are associated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pancreatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal relationship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classification systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continuously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifactorial nature of acute pancreatitis call for a different approach. In this article, we review the potential mechanisms of drug induced acute pancreatitis and provide the perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pancreatitis with limited data. PMID:25400984

  9. Contemporary review of drug-induced pancreatitis: A different perspective

    PubMed Central

    Hung, Whitney Y; Abreu Lanfranco, Odaliz

    2014-01-01

    Although gallstone and alcohol use have been considered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are associated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pancreatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal relationship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classification systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continuously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifactorial nature of acute pancreatitis call for a different approach. In this article, we review the potential mechanisms of drug induced acute pancreatitis and provide the perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pancreatitis with limited data. PMID:25400984

  10. Pulmonary and generalized lysosomal storage induced by amphiphilic drugs.

    PubMed Central

    Hruban, Z

    1984-01-01

    Administration of amphiphilic drugs to experimental animals causes formation of myelinoid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myelinoid bodies. The administration of amphiphilic compounds thus causes pulmonary intra-alveolar histiocytosis which is a part of a drug-induced lysosomal storage or generalized lipidosis. The accumulation of drug-lipid complexes in myelinoid bodies and in pulmonary foam cells may lead to alteration of cellular functioning and to clinical disease. Currently over 50 amphiphilic drugs are known. Unique pharmacological properties necessitate clinical use of some of these drugs. The occurrence and severity of potential clinical side effects depend on the nature of each drug, dosage and duration of treatment, simultaneous administration of other drugs and foods, individual metabolic pattern of the patient and other factors. Further studies on factors preventing and potentiating adverse effects of amphiphilic drugs are indicated. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. PMID:6376111

  11. Adverse drug reactions in elderly patients: alternative approaches to postmarket surveillance.

    PubMed

    Noah, B A; Brushwood, D B

    2000-01-01

    In the last three years, the Food and Drug Administration has withdrawn seven prescription drugs from the market, and it has required intensified warnings for a number of others, all due to the discovery of previously unforeseen side effects associated with their use. Adverse drug reactions are a leading cause of death in the United States. For a variety of physiological and socio-medical reasons, the elderly are particularly susceptible to adverse drug reactions. Because the pre-approval process cannot expose all potential risks associated with a drug, the authors assert that policymakers should consider implementing a more extensive, and more integrated, post-approval surveillance and testing system. They conclude that the recent cluster of drug withdrawals due to safety problems raises legitimate questions about the rigor and effectiveness of the post-approval monitoring system for new drugs, and these questions extend beyond the obvious difficulties associated with the collection and analysis of risk data. Traditionally viewed as a regulatory problem for the FDA, the problem of adverse drug reactions implicates patient welfare and the provision of medical care more broadly, and a purely regulatory mind set unnecessarily constrains thinking about possible approaches to improving drug safety. Possible solutions to the problem ought to contemplate more formalized involvement of the medical community, pharmacists, and patients. This Article introduces a proposed systems approach to detecting and preventing adverse drug reactions, and discusses several other incremental reforms to existing systems that may help the medical community to improve the overall safety of prescription drug therapy for the elderly, and ultimately for all patients. PMID:11184355

  12. Unity from diversity: the evidential use of anecdotal reports of adverse drug reactions and interactions.

    PubMed

    Aronson, Jeffrey K

    2005-04-01

    Anecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes. Useful paradigms are the dramatic unities (of time, place, and action), comprehensive catalogues, and pattern formations. Here I give examples of each of these types of paradigm and show how they can be used to interpret anecdotes about adverse drug reactions and interactions. The dramatic unities show how a proper classification of adverse drug reactions can be achieved, according to dose-relation, time-course, and susceptibility factors; use of this classification should improve the evidential use of anecdotal reports. A high background incidence of the effect (the medical equivalent of subplots, which violate the unity of action) makes it more difficult to detect adverse drug effects using anecdotal reports. To make best evidential use of the corpus of anecdotal reports of adverse drug reactions, comprehensiveness is important: each suspected adverse reaction should be reported in detail and reactions should be reported in sufficient numbers for proper classification and for patterns to be recognized. One form of pattern recognition, teleoanalysis of data, should, when possible, include not only randomized controlled trials and observational studies, but also case series and anecdotal reports. PMID:15813716

  13. Photo-induced chemical reaction of trans-resveratrol.

    PubMed

    Zhao, Yue; Shi, Meng; Ye, Jian-Hui; Zheng, Xin-Qiang; Lu, Jian-Liang; Liang, Yue-Rong

    2015-03-15

    Photo-induced chemical reaction of trans-resveratrol has been studied. UV B, liquid state and sufficient exposure time are essential conditions to the photochemical change of trans-resveratrol. Three principal compounds, cis-resveratrol, 2,4,6-phenanthrenetriol and 2-(4-hydroxyphenyl)-5,6-benzofurandione, were successively generated in the reaction solution of trans-resveratrol (0.25 mM, 100% ethanol) under 100 μW cm(-2) UV B radiation for 4h. cis-Resveratrol, originated from isomerization of trans-resveratrol, resulted in 2,4,6-phenanthrenetriol through photocyclisation reaction meanwhile loss of 2 H. 2,4,6-Phenanthrenetriol played a role of photosensitizer producing singlet oxygen in the reaction pathway. The singlet oxygen triggered [4+2] cycloaddition reaction of trans-resveratrol, and then resulted in the generation of 2-(4-hydroxyphenyl)-5,6-benzofurandione through photorearrangement and oxidation reaction. The singlet oxygen reaction was closely related to the substrate concentration of trans-resveratrol in solution. PMID:25308653

  14. Drug-Induced Torsade de Pointes and Implications for Drug Development

    PubMed Central

    Fenichel, Robert R.; Malik, Marek; Antzelevitch, Charles; Sanguinetti, Michael; Roden, Dan M.; Priori, Silvia G.; Ruskin, Jeremy N.; Lipicky, Raymond J.; Cantilena, Lou

    2006-01-01

    Torsade de pointes is a potentially lethal arrhythmia that occasionally appears as an adverse effect of pharmacotherapy. Recently-developed understanding of the underlying electrophysiology allows better estimation of the drug-induced risks, and explains the failures of older approaches through the surface electrocardiogram. The article expresses a consensus reached by an independent academic task force on the physiologic understanding of drug-induced repolarisation changes, on their preclinical and clinical evaluation, and on the risk-benefit interpretation of drug-induced torsade de pointes. The consensus of the task force includes suggestions on how to evaluate the risk of torsade within drug development program. Individual sections of the text discuss the techniques and limitations of methods directed at drug-related ion-channel phenomena, investigations aimed at action potentials changes, preclinical studies of phenomena seen only in the whole (or nearly whole) heart, and at interpretation of human electrocardiograms obtained in clinical studies. Final section of the text discusses drug-induced torsade within the larger evaluation of drug-related risks and benefits. PMID:15090000

  15. Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens.

    PubMed

    Wickramasinghe, S N

    1987-01-01

    After interaction with human macrophages derived from blood, bone marrow or spleen, solutions of sodium phenobarbitone, phenytoin sodium and chlorpromazine hydrochloride showed reduced cytotoxicity towards K562 cells. The reduction in cytotoxicity was partially suppressed in the presence of tetrahydrofurane, an inhibitor of cytochrome P450. These data suggest that macrophages are capable of metabolizing certain drugs, probably via a cytochrome P450-dependent mechanism. The present findings raise the possibility that some drug-induced blood dyscrasias are caused by metabolism of the drug by bone marrow macrophages and the consequent release of relatively short-lived molecules which are toxic to adjacent haemopoietic cells. The generation of cytotoxic molecules during drug metabolism by macrophages may also be responsible for drug-induced damage to other macrophage-rich tissues. In addition, since cytochrome P450-dependent reactions seem to occur within macrophages, these cells may activate environmental procarcinogens and thus plays a role in carcinogenesis and leukaemogenesis. PMID:3652639

  16. Intrinsic versus Idiosyncratic Drug-Induced Hepatotoxicity—Two Villains or One?

    PubMed Central

    Ganey, Patricia E.

    2010-01-01

    “Intrinsic” and “idiosyncratic” drug-induced liver injury reactions are commonly thought to arise by different modes of action. Intrinsic toxicity is reproducible in animals and occurs dose-dependently at sublethal doses. Environmental and genetic sensitivity factors can influence the toxicity of intrinsic hepatotoxicants. Among these is inflammatory stress. For example, exposure of mice to inflammatory bacterial lipopolysaccharide (LPS) causes a leftward shift in the dose-response relationship for acetaminophen hepatotoxicity; that is, acetaminophen toxicity is enhanced by LPS-induced inflammatory stress. Idiosyncratic reactions present themselves very differently than intrinsic ones; they happen in a minority of patients, with variable time of onset and no obvious relationship to drug dose, and they are not reproducible in usual animal tests. Although these characteristics seem to distinguish them from intrinsic reactions, consideration of fundamental principles of dose response can explain the differences. For a drug that causes idiosyncratic hepatotoxicity, the liver may not be a typical target for toxicity because the dose-response curve for hepatotoxicity lies to the right of the lethal dose. However, a sporadically occurring sensitivity factor, such as an inflammatory episode, could shift the dose-response curve for hepatotoxicity to the left, thereby bringing hepatotoxic doses into the therapeutic range. This hypothesis can account for the bizarre characteristics of idiosyncratic reactions and is supported by recent results showing that several drugs associated with human idiosyncratic reactions can be rendered hepatotoxic to rodents upon interaction with an inflammatory stimulus. In light of this view, intrinsic and idiosyncratic reactions may not be that different after all. PMID:20019161

  17. Alpha Induced Reaction Cross Section Calculations of Tantalum Nucleus

    NASA Astrophysics Data System (ADS)

    Tel, E.; Ugur, F. A.; Gokce, A. A.

    2013-04-01

    The fusion energy is attractive as an energy source because the fusion will not produce CO2 or SO2 and so fusion will not contribute to environmental problems, such as particulate pollution and excessive CO2 in the atmosphere. The fusion reaction does not produce radioactive nuclides and it is not self-sustaining, as is a fission reaction when a critical mass of fissionable material is assembled. Since the fusion reaction is easily and quickly quenched the primary sources of heat to drive such an accident are heat from radioactive decay and heat from chemical reactions. Both the magnitude and time dependence of the generation of heat from radioactive decay can be controlled by proper selection and design of materials. Tantalum is one of the candidate materials for the first wall of fusion reactors and for component parts of irradiation chambers. Accurate experimental cross-section data of alpha induced reactions on Tantalum are also of great importance for thermonuclear reaction rate determinations since the models used in the study of stellar nucleosynthesis are strongly dependent on these rates (Santos et al. in J Phys G 26:301, 2000). In this study, neutron-production cross sections for target nuclei 181Ta have been investigated up to 100 MeV alpha energy. The excitation functions for (α, xn) reactions (x = 1, 2, 3) have been calculated by pre-equilibrium reaction mechanism. And also neutron emission spectra for 181Ta (α, xn) reactions at 26.8 and 45.2 MeV have been calculated. The mean free path multiplier parameters has been investigated. The pre-equilibrium results have been calculated by using the hybrid model, the geometry dependent hybrid (GDH) model. Calculation results have been also compared with the available measurements in literature.

  18. Fatal anaphylactoid reaction associated with heparin-induced thrombocytopenia.

    PubMed

    Singla, Atul; Amini, Mohammad R; Alpert, Martin A; Gornik, Heather L

    2013-06-01

    Acute systemic (anaphylaxis and anaphylactoid) reactions have been well described in patients with heparin-induced thrombocytopenia (HIT). Both necrotizing and non-necrotizing skin lesions at heparin injection sites have been reported and may occur in 10-20% of patients with HIT. We report herein a patient treated with subcutaneous enoxaparin sodium who developed non-necrotizing erythematous skin lesions at enoxaparin sodium injection sites. A subsequent intravenous bolus of unfractionated heparin produced a fatal anaphylactoid reaction. This suggests that caution should be exercised in the administration of intravenous heparin to patients with non-necrotizing erythematous skin lesions at prior heparin injection sites. PMID:23579400

  19. Mitochondrial involvement in drug-induced liver injury.

    PubMed

    Pessayre, Dominique; Mansouri, Abdellah; Berson, Alain; Fromenty, Bernard

    2010-01-01

    Mitochondrial dysfunction is a major mechanism of liver injury. A parent drug or its reactive metabolite can trigger outer mitochondrial membrane permeabilization or rupture due to mitochondrial permeability transition. The latter can severely deplete ATP and cause liver cell necrosis, or it can instead lead to apoptosis by releasing cytochrome c, which activates caspases in the cytosol. Necrosis and apoptosis can trigger cytolytic hepatitis resulting in lethal fulminant hepatitis in some patients. Other drugs severely inhibit mitochondrial function and trigger extensive microvesicular steatosis, hypoglycaemia, coma, and death. Milder and more prolonged forms of drug-induced mitochondrial dysfunction can also cause macrovacuolar steatosis. Although this is a benign liver lesion in the short-term, it can progress to steatohepatitis and then to cirrhosis. Patient susceptibility to drug-induced mitochondrial dysfunction and liver injury can sometimes be explained by genetic or acquired variations in drug metabolism and/or elimination that increase the concentration of the toxic species (parent drug or metabolite). Susceptibility may also be increased by the presence of another condition, which also impairs mitochondrial function, such as an inborn mitochondrial cytopathy, beta-oxidation defect, certain viral infections, pregnancy, or the obesity-associated metabolic syndrome. Liver injury due to mitochondrial dysfunction can have important consequences for pharmaceutical companies. It has led to the interruption of clinical trials, the recall of several drugs after marketing, or the introduction of severe black box warnings by drug agencies. Pharmaceutical companies should systematically investigate mitochondrial effects during lead selection or preclinical safety studies. PMID:20020267

  20. Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options

    PubMed Central

    Khoury, Tawfik; Rmeileh, Ayman Abu; Yosha, Liron; Benson, Ariel A.; Daher, Saleh; Mizrahi, Meir

    2015-01-01

    Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments. PMID:26356634

  1. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury.

    PubMed

    Chalasani, Naga P; Hayashi, Paul H; Bonkovsky, Herbert L; Navarro, Victor J; Lee, William M; Fontana, Robert J

    2014-07-01

    Idiosyncratic drug-induced liver injury (DILI) is a rare adverse drug reaction and it can lead to jaundice, liver failure, or even death. Antimicrobials and herbal and dietary supplements are among the most common therapeutic classes to cause DILI in the Western world. DILI is a diagnosis of exclusion and thus careful history taking and thorough work-up for competing etiologies are essential for its timely diagnosis. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis and management of DILI with special emphasis on DILI due to herbal and dietary supplements and DILI occurring in individuals with underlying liver disease. PMID:24935270

  2. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs.

    PubMed

    Lopez, Soledad; Gomez, Enrique; Torres, Maria J; Pozo, David; Fernandez, Tahia D; Ariza, Adriana; Sanz, Maria L; Blanca, Miguel; Mayorga, Cristobalina

    2015-11-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKs and activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. PMID:26254762

  3. Heparin-induced anaphylactoid reaction associated with heparin-induced thrombocytopenia in the ED.

    PubMed

    Foreman, Juron S; Daniels, Lauren M; Stettner, Edward A

    2014-12-01

    Although rare, heparin-induced anaphylactic and anaphylactoid reactions have been previously described in the literature. We present a case of a patient who presented to the emergency department with dyspnea and was subsequently diagnosed with an acute pulmonary venous thromboembolism. Shortly after being started on intravenous unfractionated heparin, she developed sudden cardiovascular collapse leading to a cardiopulmonary arrest. She was successfully resuscitated and, after further diagnostic evaluation, was found to have developed a heparin-induced anaphylactoid reaction. PMID:25097093

  4. Imaging of Drug-induced Complications in the Gastrointestinal System.

    PubMed

    McGettigan, Melissa J; Menias, Christine O; Gao, Zhenqiang J; Mellnick, Vincent M; Hara, Amy K

    2016-01-01

    Drug-induced injury commonly affects the gastrointestinal and hepatobiliary systems because of the mechanisms of absorption and metabolism. In pill esophagitis, injury is frequently related to direct contact with the esophageal mucosa, resulting in small superficial ulcers in the mid esophagus. Nonsteroidal anti-inflammatory drugs can lead to gastrointestinal tract ulcers and small bowel mucosal diaphragms (thin weblike strictures). Injury to the pancreatic and hepatobiliary systems can manifest as pancreatitis, acute or chronic hepatitis, cholestasis, or steatosis and steatohepatitis (which may progress to cirrhosis). Various drugs may also insult the hepatic vasculature, resulting in Budd-Chiari and sinusoidal obstructive syndromes. Focal lesions such as hepatic adenomas may develop after use of oral contraceptives or anabolic steroids. Ultrasonography, computed tomography, and magnetic resonance imaging can aid in diagnosis of drug-induced injuries and often are necessary to exclude other causes. PMID:26761532

  5. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back.

    PubMed

    Schrijvers, Rik; Gilissen, Liesbeth; Chiriac, Anca Mirela; Demoly, Pascal

    2015-01-01

    Drug hypersensitivity reactions (DHR) have been present since the advent of drugs. In particular T-cell mediated delayed-type hypersensitivity reactions represent a heterogeneous clinical entity with a diverse pathogenesis and result in a considerable burden of morbidity and mortality not only driven by the reactions themselves but also by the use of alternatives which are sometimes less effective or even more dangerous. Diagnostic procedures rely on clinical history, skin testing and potential provocation testing, whereas validated in vitro diagnostic procedures are still lacking for most of them. Recent work in the field of pharmacogenomics combined with basic scientific research has provided insights in the pathogenesis of abacavir and carbamazepine hypersensitivities linked with certain human leucocyte antigen risk alleles. Nevertheless, important scientific questions on how other DHR arise and how host-drug interactions occur, remain unanswered. Recent work indicates an intricate relation between host, drug and pathogens in severe cutaneous and systemic reactions and provides more insights in the role of regulatory T-cells and viral reactivation in these reactions. In this review we focus on type IV delayed-type DHR, and address recent advances in the pathogenesis, pharmacogenomics, and diagnosis of these reactions with an emphasis on the understandings arising from basic research. PMID:26339470

  6. Drug induced osteonecrosis of the jaw.

    PubMed

    Hamadeh, Issam S; Ngwa, Bridget A; Gong, Yan

    2015-05-01

    Despite the widespread use of bisphosphonates and their unequivocal efficacy for the treatment of various disease states, osteonecrosis of the jaw remains one of the most feared complications associated with their use. Current evidence, however, suggests that there is also a relationship between occurrence of osteonecrosis of the jaw and use of other classes of pharmacotherapies namely RANKL inhibitors as well as angiogenesis inhibitors. Although these drugs have different mechanisms of action than bisphosphonates, they all seem to interfere with the bone remodeling process i.e. alter the balance between bone resorption and bone formation which may be the most plausible explanation for pathogenesis of osteonecrosis of the jaw. The main objective of this review is to introduce the readership to a number of relatively new medications that may cause osteonecrosis of the jaw. Accordingly, we will summarize latest findings from clinical studies, meta analyses and case reports published in medical literature on this topic. For some of these medications, the evidence may not appear as robust as that for bisphosphonates; yet, the possibility of this adverse event occurring with these non bisphosphonate drugs should never be precluded unless proven otherwise. Thus, it is imperative that health care providers implement preventive measures so as to circumvent the incidence of osteonecrosis of the jaw. In this day of age where medical care is becoming personalized, we will highlight some of significant findings from studies seeking to identify genetic markers that may potentially play a role in development of osteonecrosis of the jaw. PMID:25913713

  7. Granulomatous Drug Eruptions.

    PubMed

    Dodiuk-Gad, Roni P; Shear, Neil H

    2015-07-01

    Granuloma formation is usually regarded as a means of defending the host from persistent irritants of either exogenous or endogenous origin. Noninfectious granulomatous disorders of the skin encompass a challenging group of diseases owing to their clinical and histologic overlap. Drug reactions characterized by a granulomatous reaction pattern are rare, and defined by a predominance of histiocytes in the inflammatory infiltrate. This review summarizes current knowledge on the various types of granulomatous drug eruptions, focusing on the 4 major types: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, and drug-induced sarcoidosis. PMID:26143430

  8. In silico modeling to predict drug-induced phospholipidosis

    SciTech Connect

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G. Sadrieh, Nakissa

    2013-06-01

    Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure–activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80–81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ≥ 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. - Highlights: • New in silico models for predicting drug-induced phospholipidosis (DIPL) are described. • The training set data in the models is derived from the FDA's phospholipidosis database. • We find excellent predictivity values of the models based on external validation. • The models can support drug screening and regulatory decision-making on DIPL.

  9. Biomarkers to monitor drug-induced phospholipidosis

    SciTech Connect

    Baronas, Elizabeth Tengstrand; Lee, Ju-Whei; Alden, Carl; Hsieh, Frank Y. . E-mail: frank.hsieh@nextcea.com

    2007-01-01

    Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) was identified as a promising phospholipidosis (PL) biomarker in rats treated with either amiodarone, gentamicin, or azithromycin. Sprague-Dawley rats received either amiodarone (150 mg/kg), gentamicin (100 mg/kg) or azithromycin (30 mg/kg) once daily for ten consecutive days. Histopathological examination of tissues by transmission electron microscopy (TEM) indicated different degrees of accumulation of phospholipidosis in liver, lung, mesenteric lymph node, and kidney of drug-treated rats but not controls. Liquid chromatography coupled to mass spectrometry (LC/MS) was used to identify levels of endogenous biochemical profiles in rat urine. Urinary levels of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) correlated with induction of phospholipidosis for amiodarone, gentamicin and azithromycin. Rats treated with gentamicin also had increased urinary levels of several phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) species.

  10. Gamma hydroxybutyrate--a coma inducing recreational drug.

    PubMed Central

    Ryan, J M; Stell, I

    1997-01-01

    The effects of gamma hydroxybutyrate, a coma inducing recreational drug, are described and illustrated by case reports of five patients presenting to accident and emergency (A&E). All had depressed levels of consciousness. There was strong circumstantial evidence of gamma hydroxybutyrate ingestion in all cases, and laboratory evidence in two. All recovered and supportive treatment. gamma Hydroxybutyrate has become a fashionable recreational drug. The majority of people who have ingested it will recover spontaneously without long term sequelae but its toxic effects may be dramatic while they last, particularly when it is taken with other drugs or alcohol. Images Figure 3 Figure 1 PMID:9248920

  11. [Imaging features of drug-induced lung diseases].

    PubMed

    Mellot, F; Scherrer, A

    2005-05-01

    Drug-induced lung diseases are an increasingly frequent cause of morbidity. Over 350 drugs are now recognized as being implicated in drug-induced lung diseases. Early diagnosis is critical. Discontinuing the drug may result in regression of the adverse effect. Diagnosis is based on a history of drug exposure with a temporal relationship between the introduction of the drug and the onset of symptoms, histologic evidence of lung damage and exclusion of other causes of lung injury. Unfortunately there is no specific test available. Histologic and radiologic findings are often non specific and diagnosis can be difficult. Drugs can cause a constellation of distinct patterns of respiratory involvement and all anatomic compartments of the lungs may be involved. The most common patterns are: non specific interstitial pneumonia and fibrosis, pulmonary eosinophilia, hypersensitivity pneumonitis, pulmonary edema with or without diffuse alveolar damage, bronchiolitis obliterans organizing pneumonia, pulmonary hemorrhage and vasculitis. It is important to be familiar with their common radiologic appearances. PMID:16106793

  12. DAT imaging in drug-induced and psychogenic parkinsonism.

    PubMed

    Tolosa, Eduardo; Coelho, Miguel; Gallardo, Marisol

    2003-10-01

    Parkinson's syndrome (PS) is frequently encountered in disorders associated with prominent degeneration of the nigrostriatal pathway as in Parkinson's disease, multisystem atrophy, and progressive supranuclear palsy (presynaptic PS). Drug-induced parkinsonism, a common, underdiagnosed health problem and psychogenic parkinsonism are causes of Parkinson's syndrome which, evidence suggests, occurs without degeneration of nigrostriatal structures. We review clinical features and results of DAT imaging in drug-induced parkinsonism and psychogenic parkinsonism. These two conditions normally give normal striatal DAT imaging results; an abnormal result in either case could exclude both conditions, corroborating a diagnosis of organic parkinsonism in uncertain cases. PMID:14531043

  13. Inferior phrenic artery pseudoaneurysm complicating drug-induced acute pancreatitis.

    PubMed

    Salem, Jean F; Haydar, Ali; Hallal, Ali

    2014-01-01

    Inferior phrenic artery (IPA) pseudoaneurysm is an extremely rare complication of chronic pancreatitis with only three cases reported in the literature so far. It is a serious condition that can be life-threatening if not diagnosed promptly. Recent advances in endovascular interventions made angiography with embolisation the modality of choice for diagnosis and treatment. We presented the first report of a case of ruptured IPA pseudoaneurysm complicating a drug-induced acute pancreatitis that was successfully treated by transcatheter arterial embolisation. Despite its rarity, rupture of pseudoaneurysm due to drug-induced pancreatitis should be suspected and included in the differential diagnosis when associated with haemodynamic instability. PMID:24385392

  14. An Update on Drug-induced Liver Injury.

    PubMed

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  15. An Update on Drug-induced Liver Injury

    PubMed Central

    Devarbhavi, Harshad

    2012-01-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  16. Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

    PubMed Central

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-01-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity. PMID:22194678

  17. Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

    PubMed Central

    Arnold, Donald M.; Nazi, Ishac; Warkentin, Theodore E.; Smith, James W.; Toltl, Lisa J.; George, James N.; Kelton, John G.

    2013-01-01

    Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is under-recognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fiban-dependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 109/L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and ideally should be reproducible across laboratories. Improved standardization and accessibility of laboratory testing should be a focus of future research. PMID:23845922

  18. Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

    PubMed

    Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

    2009-08-01

    Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model. PMID:19482095

  19. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    PubMed

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected. PMID:26941185

  20. Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources.

    PubMed

    Bicalho, Millena Drumond; Soares, Danielly Botelho; Botoni, Fernando Antonio; Reis, Adriano Max Moreira; Martins, Maria Auxiliadora Parreiras

    2015-09-01

    : Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX(®), UpToDate(®), Medscape(®) and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss' kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211-0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292-0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality. PMID:26371029

  1. Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources

    PubMed Central

    Bicalho, Millena Drumond; Soares, Danielly Botelho; Botoni, Fernando Antonio; Reis, Adriano Max Moreira; Martins, Maria Auxiliadora Parreiras

    2015-01-01

    Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX®, UpToDate®, Medscape® and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss’ kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211–0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292–0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality. PMID:26371029

  2. Updating the French method for the causality assessment of adverse drug reactions.

    PubMed

    Arimone, Yannick; Bidault, Irène; Dutertre, Jean-Paul; Gérardin, Marie; Guy, Claire; Haramburu, Françoise; Hillaire-Buys, Dominique; Meglio, Carmine; Penfornis, Catherine; Théophile, Hélène; Valnet-Rabier, Marie-Blanche

    2013-01-01

    The Imputability Working Group (CRI) updated the French drug reaction causality assessment method. This tripartite group is made up of staff from the French network of regional pharmacovigilance centres, pharmaceutical companies, and the French National Agency for the Safety of Medicines and Health Products (ANSM). After reviewing the strengths and weaknesses of the previous method, several ideas for improvement were proposed: a better-worded and more discriminating scale for certain chronological and semiological criteria, a larger scale for the intrinsic score (increased from 5 to 7 levels), a new bibliographical scale to differentiate between expected and unexpected adverse drug reactions, and a new informativeness scale. PMID:23773347

  3. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity.

    PubMed

    Magro, C M; Crowson, A N; Schapiro, B L

    1998-02-01

    We present 20 patients in whom drug therapy was associated with interstitial histiocytic infiltrates with variable degeneration of collagen and elastic fibers mimicking early lesions of granuloma annulare (GA). Most patients had a reproducible clinical presentation comprising erythematous-to-violaceous, nonpruritic plaques, often with an annular pattern, predominantly involving inner aspects of the arms, medial thighs and intertriginous areas. The most frequent clinical differential diagnoses included cutaneous T cell lymphoma, erythema annulare centrifigum (EAC), GA, and lupus erythematosus. A drug reaction was suspected in only 3 cases. The implicated drug classes included calcium channel blockers, angiotensin converting enzyme inhibitors, beta-blockers, lipid-lowering agents, antihistamines, anticonvulsants and antidepressants. Patients were often on two or more of these drugs; all have been associated with pseudolymphomatous infiltrates of the skin, the presumptive basis of which is iatrogenic pertubation of immune function. The defining histomorphology was diffuse infiltration of the interstitium by lymphocytes and histiocytes with piecemeal fragmentation of collagen and elastic fibers in concert with a vacuolar interface dermatitis. Ten cases showed intermediate and transformed lymphocytes with hyperchromatic convoluted nuclei disposed interstitially within the dermis or along the dermoepiderma junction with variable epidermotropism. In the 15 patients who discontinued the implicated drug, lesional resolution occurred. We propose the designations interstitial granulomatous drug reaction for this novel cutaneous reaction pattern. PMID:9521495

  4. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria.

    PubMed

    Han, Derick; Dara, Lily; Win, Sanda; Than, Tin Aung; Yuan, Liyun; Abbasi, Sadeea Q; Liu, Zhang-Xu; Kaplowitz, Neil

    2013-04-01

    Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythroid 2-related factor 2 (Nrf-2), a transcription factor that upregulates antioxidant defenses. Owing to adaptation, drugs alone rarely cause liver injury, with acetaminophen (APAP) being the notable exception. Drug-induced liver injury (DILI) usually involves other extrinsic factors, such as the adaptive immune system, that cause 'stressed' hepatocytes to become injured, leading to idiosyncratic DILI, the rare and unpredictable adverse drug reaction in the liver. Hepatocyte injury, due to drug and extrinsic insult, causes a second wave of signaling changes associated with adaptation, cell death, and repair. If the stress and injury reach a critical threshold, then death signaling pathways such as c-Jun N-terminal kinase (JNK) become dominant and hepatocytes enter a failsafe mode to undergo self-destruction. DILI can be seen as an active process involving recruitment of death signaling pathways that mediate cell death rather than a passive process due to overwhelming biochemical injury. In this review, we highlight the role of signal transduction pathways, which frequently involve mitochondria, in the development of DILI. PMID:23453390

  5. Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures.

    PubMed

    Lee, Haeseung; Kang, Seungmin; Kim, Wankyu

    2016-01-01

    An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019

  6. Discreteness-induced transitions in multibody reaction systems.

    PubMed

    Saito, Yohei; Sughiyama, Yuki; Kaneko, Kunihiko; Kobayashi, Tetsuya J

    2016-08-01

    A decrease in system size can induce qualitatively different behavior compared to the macroscopic behavior of the corresponding large-size system. The mechanisms of this transition, which is known as the small-size transition, can be attributed to either a relative increase in the noise intensity or to the discreteness of the state space due to the small system size. The former mechanism has been intensively investigated using several toy and realistic models. However, the latter has rarely been analyzed and is sometimes confused with the former, because a toy model that extracts the essence of the discreteness-induced transition mechanism is lacking. In this work, we propose a one- and three-body reaction system as a minimal model of the discreteness-induced transition and derive the conditions under which this transition occurs in more complex systems. This work enriches our understanding of the influence of small system size on system behavior. PMID:27627279

  7. Recovering drug-induced apoptosis subnetwork from Connectivity Map data.

    PubMed

    Yu, Jiyang; Putcha, Preeti; Silva, Jose M

    2015-01-01

    The Connectivity Map (CMAP) project profiled human cancer cell lines exposed to a library of anticancer compounds with the goal of connecting cancer with underlying genes and potential treatments. Since the therapeutic goal of most anticancer drugs is to induce tumor-selective apoptosis, it is critical to understand the specific cell death pathways triggered by drugs. This can help to better understand the mechanism of how cancer cells respond to chemical stimulations and improve the treatment of human tumors. In this study, using CMAP microarray data from breast cancer cell line MCF7, we applied a Gaussian Bayesian network modeling approach and identified apoptosis as a major drug-induced cellular-pathway. We then focused on 13 apoptotic genes that showed significant differential expression across all drug-perturbed samples to reconstruct the apoptosis network. In our predicted subnetwork, 9 out of 15 high-confidence interactions were validated in the literature, and our inferred network captured two major cell death pathways by identifying BCL2L11 and PMAIP1 as key interacting players for the intrinsic apoptosis pathway and TAXBP1 and TNFAIP3 for the extrinsic apoptosis pathway. Our inferred apoptosis network also suggested the role of BCL2L11 and TNFAIP3 as "gateway" genes in the drug-induced intrinsic and extrinsic apoptosis pathways. PMID:25883971

  8. The role of the clinical pharmacologist in the management of adverse drug reactions.

    PubMed

    Moore, N

    2001-01-01

    The classical definition of clinical pharmacology is the study or the knowledge of the effects of drugs in humans. The activities of a clinical pharmacologist can vary from country to country, usually ranging from involvement in clinical trials, especially fundamental pharmacodynamic studies, to studies of pharmacokinetics and drug metabolism, to pharmacogenetics. Most clinical pharmacologists outside industry are in hospitals or university hospitals and research centres. In addition to research, this implies teaching of clinical pharmacology, and interacting with other medical staff: in the field of research, giving advice on clinical trials methodology and often managing a therapeutic drug monitoring centre. Some clinical pharmacologists have clinical departments with beds or consulting offices. Can there be another role for the clinical pharmacologist that would increase his or her usefulness for the medical community? Adverse drug reactions (ADRs) are remarkably complex events, related to drug effects, patient characteristics (background diseases, genetics), and drug/disease interactions. Evaluation of ADRs requires understanding of drug mechanisms and interactions, and of disease diagnostics, especially in the discussion of alternative diagnoses. This implies expertise as a pharmacologist and a clinician. In addition, because not all adverse reactions or interactions are in the Summary of Product Characteristics, and because problems arise long before they report in the literature, it is necessary for the clinical pharmacologist to have knowledge of ongoing regulatory processes, in addition to having access to the published literature. Helping clinicians cope with individual patient problems will also improve the clinical pharmacologist's integration into the healthcare process. PMID:11219484

  9. Drug-induced liver injury: Is it somehow foreseeable?

    PubMed Central

    Tarantino, Giovanni; Di Minno, Matteo Nicola Dario; Capone, Domenico

    2009-01-01

    The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neo-substances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients’ health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider. PMID:19533803

  10. Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model

    PubMed Central

    Cao, D-S; Xiao, N; Li, Y-J; Zeng, W-B; Liang, Y-Z; Lu, A-P; Xu, Q-S; Chen, AF

    2015-01-01

    Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug–ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug–ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug–ADR interactions. PMID:26451329

  11. Laser-induced reaction alumina coating on ceramic composite

    NASA Astrophysics Data System (ADS)

    Xiao, Chenghe

    Silicon carbide ceramics are susceptible to corrosion by certain industrial furnace environments. It is also true for a new class of silicon carbide-particulate reinforced alumina-matrix composite (SiCsb(P)Alsb2Osb3) since it contains more than 55% of SiC particulate within the composite. This behavior would limit the use of SiCsb(P)Alsb2Osb3 composites in ceramic heat exchangers. Because oxide ceramics corrode substantially less in the same environments, a laser-induced reaction alumina coating technique has been developed for improving corrosion resistance of the SiCsb(P)Alsb2Osb3 composite. Specimens with and without the laser-induced reaction alumina coating were subjected to corrosion testing at 1200sp°C in an air atmosphere containing Nasb2COsb3 for 50 ˜ 200 hours. Corroded specimens were characterized via x-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS). The uncoated SiCsbP/Alsb2Osb3 composite samples experienced an initial increase in weight during the exposure to Nasb2COsb3 at 1200sp°C due to the oxidation of residual aluminum metal in the composite. There was no significant weight change difference experienced during exposure times between 50 and 200 hours. The oxidation layer formed on the as-received composite surface consisted of Si and Alsb2Osb3 (after washing with a HF solution). The oxidation layer grew outward and inward from the original surface of the composite. The growth rate in the outward direction was faster than in the inward direction. The formation of the Si/Alsb2Osb3 oxidation layer on the as-received composite was nonuniform, and localized corrosion was observed. The coated samples experienced very little mass increase. The laser-induced reaction alumina coating effectively provided protection for the SiCsbP/Alsb2Osb3 composite by keeping the corrodents from contacting the composite and by the formation of some refractory compounds such as Nasb2OAlsb2Osb3SiOsb2 and Nasb2Alsb{22}Osb

  12. An Experimental Analysis of Reaction to Filmed Drug Abuse Information. Drug Abuse Information Research Project.

    ERIC Educational Resources Information Center

    Hanneman, Gerhard J.; McEwen, William J.

    Message strategies relating to information about social problems such as drug abuse have been based on the assumption that exposure to relevant information via mass media will result in behavior modification. There is need, however, for scientific inquiry into methods of information acquisition and perceptual response to information. A two-part…

  13. Drug-induced liver injury: the role of drug metabolism and transport.

    PubMed

    Corsini, Alberto; Bortolini, Michele

    2013-05-01

    Many studies have pinpointed the significant contribution of liver-mediated drug metabolism and transport to the complexity of drug-induced liver injury (DILI). Phase I cytochrome P450 (CYP450) enzymes can lead to altered drug metabolism and formation of toxic metabolites, whilst Phase II enzymes are also associated with DILI. The emerging role of hepatic transporters in regulating the movement of endogenous and exogenous chemicals (e.g., bile acids and drugs) across cellular and tissue membranes is critical in determining the pathophysiology of liver disease as well as drug toxicity and efficacy. Genetic and environmental factors can have a significant impact on drug metabolism and transporter proteins, consequently increasing the risk of DILI in susceptible individuals. The assessment of these factors therefore represents an important approach for predicting and preventing DILI, by better understanding the pharmacological profile of a specific drug. This review focuses on the mechanisms of DILI associated with drug metabolism and hepatic transport, and how they can be influenced by underlying factors. PMID:23436293

  14. Probable ceftiofur-induced cutaneous drug reaction in a cow.

    PubMed Central

    Tyler, J W; Ruffin, D C; Yu, A

    1998-01-01

    A cow with pyelonephritis was treated with ceftiofur (3 mg/kg body weight, IV, q12 h). Hair loss and pruritis were observed after 8 and 12 d of treatment, respectively. Ancillary laboratory tests supported a diagnosis of allergic disease. Clinical signs and laboratory test results normalized after ceftiofur administration was stopped. PMID:9592617

  15. Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

    PubMed

    Wu, Yi Wei; Leow, Kheng Song; Zhu, Yujin; Tan, Cher Heng

    2016-04-01

    Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM. PMID:27292007

  16. Serious drug-induced liver disease secondary to ezetimibe

    PubMed Central

    Castellote, José; Ariza, Javier; Rota, Rosa; Girbau, Anna; Xiol, Xavier

    2008-01-01

    Ezetimibe is the first member of a new family of lipid-lowering drugs that inhibits uptake of dietary and biliary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce serious toxic hepatitis and prompt withdrawal is mandatory in case of a significant abnormality in liver testing after beginning or during treatment with ezetimibe. PMID:18763297

  17. Deep Learning for Drug-Induced Liver Injury.

    PubMed

    Xu, Youjun; Dai, Ziwei; Chen, Fangjin; Gao, Shuaishi; Pei, Jianfeng; Lai, Luhua

    2015-10-26

    Drug-induced liver injury (DILI) has been the single most frequent cause of safety-related drug marketing withdrawals for the past 50 years. Recently, deep learning (DL) has been successfully applied in many fields due to its exceptional and automatic learning ability. In this study, DILI prediction models were developed using DL architectures, and the best model trained on 475 drugs predicted an external validation set of 198 drugs with an accuracy of 86.9%, sensitivity of 82.5%, specificity of 92.9%, and area under the curve of 0.955, which is better than the performance of previously described DILI prediction models. Furthermore, with deep analysis, we also identified important molecular features that are related to DILI. Such DL models could improve the prediction of DILI risk in humans. The DL DILI prediction models are freely available at http://www.repharma.cn/DILIserver/DILI_home.php. PMID:26437739

  18. Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

    PubMed

    Federico, Alessandro; Aitella, Ernesto; Sgambato, Dolores; Savoia, Alfonso; De Bartolomeis, Fabio; Dallio, Marcello; Ruocco, Eleonora; Pezone, Luciano; Abbondanza, Ciro; Loguercio, Carmela; Astarita, Corrado

    2015-01-01

    The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism. PMID:25864225

  19. (Studies of heavy-ion induced reactions): Annual progress report

    SciTech Connect

    Mignerey, A.C.

    1986-10-01

    An experiment was performed at the Lawrence Berkeley Laboratory Bevalac, extending previous studies using inverse reactions to 50 MeV/u /sup 139/La incident on targets of C and Al. Studies of excitation energy division in lower energy division in lower energy heavy-ion reactions were furthered using kinematic coincidences to measure the excitation energies of primary products in the Fe + Ho reaction at 12 MeV/u. These results will provide important systematics for comparisons with previous measurements at 9 MeV/u on the same system and at 15 MeV/u on the Fe + Fe and Fe + U systems. Also studied were different aspects of 15 MeV/u Fe-induced reactions, with experiments performed at the Oak Ridge HHIRF. The first three contributions of this report constitute a major portion of the results from this research. Finally, at the Lawrence Berkeley Laboratory Bevalac a large detector array for coincident detection of fragmentation products in heavy-ion collisions below 100 MeV/u is being built. A list of publications, personnel, and activities is provided.

  20. The impact of herbal drug use on adverse drug reaction profiles of patients on antiretroviral therapy in zimbabwe.

    PubMed

    Mudzviti, Tinashe; Maponga, Charles C; Khoza, Star; Ma, Qing; Morse, Gene D

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076-0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292-0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

  1. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    PubMed Central

    Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

  2. Drug-induced sleep endoscopy: a two drug comparison and simultaneous polysomnography.

    PubMed

    Carrasco Llatas, Marina; Agostini Porras, Gabriela; Cuesta González, Maria Teresa; Rodrigo Sanbartolomé, Adelaida; Giner Bayarri, Pau; Gómez-Pajares, Fernando; Dalmau Galofre, José

    2014-01-01

    The purpose of the present study was to compare pharyngeal and polysomnographical findings during drug-induced sleep endoscopy (DISE) performed with either propofol or midazolam as a single sedative agent. It is prospective, non-randomized, double-blinded case series study. Sixteen patients with sleep disordered breathing were sedated first with propofol and after full wake up with midazolam. Simultaneous polysomnography (PSG) was performed. We compared the zones of obstruction and vibration found with both drugs using the VOTE classification. Simultaneous PSG findings are also compared. There were 15 men and one woman; the mean age was 42.7 years old, mean body mass index 26.9 kg/m(2). Average DISE duration was 20 min with Propofol and 14.3 min with Midazolam. The induced sleep stage obtained was N2 with both drugs. Outpatient physical exam did not correlate with drug-induced sleep findings. There was a good correlation between DISE results with both drugs in all the areas of collapse except the velum (p < 0.005). Using a continuous perfusion, there is a good agreement in the findings observed in DISE performed with propofol and midazolam and PSG. PMID:23665745

  3. Multiple Targets for Drug-Induced Mitochondrial Toxicity.

    PubMed

    Wallace, Kendall B

    2015-01-01

    Mitochondrial toxicity is rapidly gaining the interest of researchers and practitioners as a prominent liability in drug discovery and development, accounting for a growing proportion of preclinical drug attrition and post-market withdrawals or black box warnings by the U.S. FDA. To date, the focus of registries of drugs that elicit mitochondrial toxicity has been largely restricted to those that either inhibit the mitochondrial electron transport chain (ETC) or uncouple mitochondrial oxidative phosphorylation. Less appreciated are the toxicities that are secondary to the drug affecting either the molecular regulation, assembly or incorporation of the ETC into the inner mitochondrial membrane or those that limit substrate availability. The current article describes the complexities of molecular events and biochemical pathways required to sustain mitochondrial fidelity and substrate homeostasis with examples of drugs that interfere which the various pathways. The principal objective of this review is to shed light on the broader scope of drug-induced mitochondrial toxicities and how these secondary targets may account for a large portion of drug failures. PMID:25973981

  4. Synthesis of the antimalarial drug FR900098 utilizing the nitroso-ene reaction.

    PubMed

    Fokin, Andrey A; Yurchenko, Alexander G; Rodionov, Vladimir N; Gunchenko, Pavel A; Yurchenko, Raisa I; Reichenberg, Armin; Wiesner, Jochen; Hintz, Martin; Jomaa, Hassan; Schreiner, Peter R

    2007-10-11

    The antimalarial drug FR900098 was prepared from diethyl allylphosphonate involving the nitroso-ene reaction with nitrosocarbonyl methane as the key step followed by hydrogenation and dealkylation. The utilization of dibenzyl allylphosphonate as the starting compound allows one-step hydrogenation with dealkylation, which simplifies the preparative scheme further. PMID:17887769

  5. Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures

    PubMed Central

    Lee, Haeseung; Kang, Seungmin; Kim, Wankyu

    2016-01-01

    An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug’s mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019

  6. Granulomatous tattoo reaction induced by intense pulse light treatment.

    PubMed

    Tourlaki, Athanasia; Boneschi, Vinicio; Tosi, Diego; Pigatto, Paolo; Brambilla, Lucia

    2010-10-01

    Cosmetic tattooing involves implantation of pigments into the dermis in order to create a permanent makeup. Here, we report a case of sarcoidal granulomatous reaction to old cosmetic tattoos after an intense pulsed light (IPL) treatment for facial skin rejuvenation. We consider this case as a peculiar example of photo-induced reaction to tattoo. In addition, we hypothesize that an underlying immune dysfunction was present, and acted as a predisposing factor for this unusual response, as the patient had suffered from an episode of acute pulmonary sarcoidosis 15 years before. Overall, our observation suggests that IPL treatment should be used cautiously in patients with tattoos, especially when a history of autoimmune disease is present. PMID:21175859

  7. Two-photon-induced cycloreversion reaction of chalcone photodimers

    NASA Astrophysics Data System (ADS)

    Träger, J.; Härtner, S.; Heinzer, J.; Kim, H.-C.; Hampp, N.

    2008-04-01

    The photocleavage reaction of chalcone photodimers has been studied using a two-photon process. For this purpose, a novel chalcone dimer has been synthesized as a low molecular weight model substance for polymer bound chalcones and its photochemistry triggered by two-photon-absorption (2PA) has been investigated using a pulsed frequency-doubled Nd:YAG-laser. The 2PA-induced cycloreversion reaction selectively leads to the cleavage of the chalcone photodimers resulting in the formation of monomeric chalcone molecules. Hence, as an application chalcones can be used as a photosensitive linker which can be cleaved beyond an UV-absorbing barrier. The 2PA cross section of the chalcone photodimer was determined to be of 1.1 × 10 -49 cm 4 s photon -1 (11 GM).

  8. Pharmacogenetic testing in idiosyncratic drug-induced liver injury: current role in clinical practice.

    PubMed

    Aithal, Guruprasad P

    2015-07-01

    In contrast to the studies that have explored association of genetic variants with other complex traits, those investigating hepatotoxicity have identified risk alleles with substantially higher risk ratios for the susceptibility to drug-induced liver injury (DILI). In addition, a relatively small number of human leukocyte antigen (HLA) alleles have overlapping associations with a variety of adverse reactions including DILI, cutaneous hypersensitivity and drug-induced pancreatitis. However, if used as a test prior to prescription to prevent potential adverse reaction, genotyping would have a very high negative predictive value, yet a low positive predictive value based on the low incidence of DILI. One potential consideration is to treat all relevant HLA genotypes as one panel covering different forms of adverse drug reactions, thereby improving the positive predictive value of the panel and widen its application. The majority of HLA alleles associated with DILI have a very high negative predictive value; therefore, they can be used to rule out hepatotoxicity caused by particular drugs. A high negative predictive value of a genetic test can be used to identify the correct agent underlying DILI when the patient had been exposed to two concomitant medications with a potential to cause DILI. Inclusion of genetic tests in the causality assessment of an event, where DILI is suspected, may improve consistency and precision of causality assessment tools. A recent clinical trial used N-acetyltransferase 2 genotyping to determine the appropriate dose of isoniazid in an anti-tuberculosis therapeutic regimen and demonstrated that pharmacogenetic-based clinical algorithms have the potential to improve efficacy of a drug and to reduce DILI. PMID:25809692

  9. A Prospective, Observational Study of Adverse Reactions to Drug Regimen for Multi-Drug Resistant Pulmonary Tuberculosis in Central India

    PubMed Central

    Hire, Rohan; Kale, A. S.; Dakhale, G. N.; Gaikwad, Nilesh

    2014-01-01

    Objective 1) To assess the adverse drug reactions (ADRs) of second-line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR-TB) in central India on the basis of causality, severity and avoidability scales. 2) To investigate the relationship of MDR-TB (primary or secondary) and the presence of diabetes mellitus (DM) with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug-resistant tuberculosis patients enrolled for DOTS-Plus regimen at TB and Chest Disease Department from January 2012 to December 2012 with a follow-up of nine months. Encountered ADRs were noted along with the time of sputum conversion. Results Total 64 ADRs were reported in 55 patients out of total 110 patients (n=110). As per the Naranjo causality assessment of ADRs, seven patients had definite, 45 had probable, and 3 had possible causal relation with drugs of DOTS-Plus regimen. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being definitely avoidable, 26 possibly avoidable, 23 not avoidable and three not evaluable. Mean sputum smear conversion time was significantly higher in patients with a secondary type than that of primary type of MDR TB and in patients with DM than those without DM. Conclusion ADRs were common in patients of MDR-TB on DOTs-Plus drug regimen. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regimen compared to DOTS regimen in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and clinical parameters and instituting appropriate measures. PMID:25237474

  10. Establishing a theory for deuteron induced surrogate reactions

    DOE PAGESBeta

    Potel, G; Nunes, F M; Thompson, I J

    2015-09-18

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the priormore » formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the Nb93(d,p)X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We then look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states.Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. We finally make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.« less

  11. Establishing a theory for deuteron induced surrogate reactions

    SciTech Connect

    Potel, G; Nunes, F M; Thompson, I J

    2015-09-18

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the Nb93(d,p)X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We then look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states.Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. We finally make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

  12. Establishing a theory for deuteron-induced surrogate reactions

    NASA Astrophysics Data System (ADS)

    Potel, G.; Nunes, F. M.; Thompson, I. J.

    2015-09-01

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the 93Nb(d ,p )X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states. Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. Finally, we make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

  13. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

    PubMed

    Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

    2016-08-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. PMID:26991315

  14. Reaction mechanism studies of heavy ion induced nuclear reactions. Annual progress report

    SciTech Connect

    Mignerey, A.C.

    1981-07-01

    The research summarized in this report was performed during the period August 1, 1980 to June 30, 1981. The experimental emphasis in the heavy-ion-induced reaction studies continues to be discrete charge and mass resolution of all projectile-like fragments measured. In an experiment performed at the Argonne National Laboratory Superconducting LINAC, the /sup 37/Cl beam was used to bombard targets of /sup 40/Ca and /sup 209/Bi. This experiment is compared to results of our previous /sup 56/Fe-induced experiments. Attempts were made to extend the /sup 56/Fe reactions to lower energies at the Lawrence Berkeley Laboratory SuperHILAC. In a desire to improve the mass and charge resolution of previous experiments we tried a time-of-flight telescope employing both a channel-plate start and stop signal. This was backed by an ion chamber ..delta..E and silicon E detector. The operational difficulties encountered are being corrected and we hope to have a reliable system ready this fall. Studies of target fragmentation in /sup 4/He-induced reactions are continuing via experiments and model calculations. The program which began at the University of Maryland Cyclotron has been continued at the Indiana University Cyclotron with 120 and 200 MeV /sup 4/He incident on /sup 12/C and /sup 27/Al targets. While the Indiana data are currently being analyzed and no results are yet available, a summary of the Maryland work is given. Also presented in this section are the model calculations used to describe the data. 28 refs.

  15. Nuclear reactions induced by. pi. /sup -/ at rest

    SciTech Connect

    Gadioli, E.; Gadioli Erba, E.

    1987-08-01

    The experimental information on reactions induced by stopped ..pi../sup -/ absorbed in nuclei is critically reviewed. Evidence for the presence of ..cap alpha..-cluster absorptions is presented and arguments are given to show that approx. =25% of ..pi../sup -/ absorptions are of this kind. In the case of two-nucleon absorption, the existing experimental information concerning the ratio of n-p to p-p absorbing pairs is discussed. Calculations of particle spectra and residue spallation yield distributions that, in addition to two-nucleon absorption, include ..cap alpha..-cluster absorption are presented, and it is shown that a satisfactory reproduction of the data is achieved.

  16. Spin Modes, Neutrino-Induced Reactions and Nucleosynthesis in Stars

    SciTech Connect

    Suzuki, Toshio; Otsuka, Takaharu; Honma, Michio; Higashiyama, Koji

    2008-11-11

    Recent advances in shell model calculations of spin modes in nuclei with the use of new shell model Hamiltonians are discussed. Important roles of tensor interaction in shell evolutions toward drip-lines are pointed out. Electromagnetic transitions in exotic carbon isotopes are investigated. Anomalous supressions of transition strengths in the isotopes are found to be rather well explained. Neutrino-induced reactions on {sup 56}Fe and {sup 56}Ni are studied, and implications on production yields of heavy elements in stars are discussed.

  17. Adverse drug reactions to fluoroquinolones at a tertiary care hospital in northern India.

    PubMed

    Uppal, R; Jhaj, R; Malhotra, S

    1998-11-01

    Use of fluoroquinolones has increased considerably in the last 5-6 years in our hospitals. With a view to ascertain their safety and the type of adverse drug reactions (ADRs) in our population, spontaneous reports were collected and analysed to ciprofloxacin (the most prescribed fluoroquinolone in our hospital) over a period of three and a half years. The pattern of reactions were rash in 18, severe reactions like Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in 4, gastritis and diarrhoea in 3, shivering and rigors in 2, hemorrhagic purpuric spots in 2 and oedema of eye and lids with topical application in 1 patient. Most cases recovered on stoppage of the drug and symptomatic treatment. However, one case of SJS and one of TEN proved fatal. Care needs to be exercised in their use and they do not appear to be innocuous to severe and disturbing ADRs. PMID:11229222

  18. Computerized Detection of Adverse Drug Reactions in the Medical Intensive Care Unit

    PubMed Central

    Kane-Gill, Sandra L.; Visweswaran, Shyam; Saul, Melissa I.; Wong, An-Kwok Ian; Penrod, Louis E.; Handler, Steven M.

    2011-01-01

    Objective Clinical event monitors are a type of active medication monitoring system that can use signals to alert clinicians to possible adverse drug reactions. The primary goal was to evaluate the positive predictive values of select signals used to automate the detection of ADRs in the medical intensive care unit. Method This is a prospective, case series of adult patients in the medical intensive care unit during a six-week period who had one of five signals presents: an elevated blood urea nitrogen, vancomycin, or quinidine concentration, or a low sodium or glucose concentration. Alerts were assessed using 3 objective published adverse drug reaction determination instruments. An event was considered an adverse drug reaction when 2 out of 3 instruments had agreement of possible, probable or definite. Positive predictive values were calculated as the proportion of alerts that occurred, divided by the number of times that alerts occurred and adverse drug reactions were confirmed. Results 145 patients were eligible for evaluation. For the 48 patients (50% male) having an alert, the mean ± SD age was 62 ± 19 years. A total of 253 alerts were generated. Positive predictive values were 1.0, 0.55, 0.38 and 0.33 for vancomycin, glucose, sodium, and blood urea nitrogen, respectively. A quinidine alert was not generated during the evaluation. Conclusions Computerized clinical event monitoring systems should be considered when developing methods to detect adverse drug reactions as part of intensive care unit patient safety surveillance systems, since they can automate the detection of these events using signals that have good performance characteristics by processing commonly available laboratory and medication information. PMID:21621453

  19. Drug-induced pulmonary arterial hypertension: a recent outbreak.

    PubMed

    Montani, David; Seferian, Andrei; Savale, Laurent; Simonneau, Gérald; Humbert, Marc

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. PMID:23997051

  20. [Hypomania/mania induced by cessation of antidepressant drugs].

    PubMed

    Kora, Kaan; Kaplan, Pelin

    2008-01-01

    Although rarely reported, the induction of hypomanic/manic episodes due to sudden or gradual cessation of antidepressant drugs is a phenomenon observed in clinical settings. Herein we present 2 patients that had manic episodes induced by gradual cessation of antidepressant drugs. Common features of both cases were as follows: patients were female; a major depressive episode was the reason for starting treatment; familial loading for unipolar depressive disorder; venlafaxine was administered for treatment of the episode; mood elevation symptoms while gradually decreasing the medication dose; absence of physical symptoms related to withdrawal; antipsychotic and mood stabilizing drugs were required for the treatment of the episode. In both cases 1) a hypomanic/manic episode induced by the use of antidepressants, 2) agitated depression, 3) physical withdrawal syndrome, and 4) spontaneous episodes in the natural course of the illness were the 4 different states that were taken into consideration for differential diagnosis. Hypomanic/manic episodes induced by cessation of antidepressant drugs are thought to shed light on the etiology of bipolar disorder, which this report discusses with reference to the case reports. PMID:18791886

  1. Shock induced chemical reactions in energetic structural materials

    NASA Astrophysics Data System (ADS)

    Reding, Derek J.

    Energetic structural materials (ESMs) constitute a new class of materials that provide dual functions of strength and energetic characteristics. ESMs are typically composed of micron-scale or nano-scale intermetallic mixtures or mixtures of metals and metal oxides, polymer binders, and structural reinforcements. Voids are included to produce a composite with favorable chemical reaction characteristics. In this thesis, a continuum approach is used to simulate gas-gun or explosive loading experiments where a strong shock is induced in the ESM by an impacting plate. Algorithms are developed to obtain equations of state of mixtures. It is usually assumed that the shock loading increases the energy of the ESM and causes the ESM to reach the transition state. It is also assumed that the activation energy needed to reach the transition state is a function of the temperature of the mixture. In this thesis, it is proposed that the activation energy is a function of temperature and the stress state of the mixture. The incorporation of such an activation energy is selected in this thesis. Then, a multi-scale chemical reaction model for a heterogeneous mixture is introduced. This model incorporates reaction initiation, propagation, and extent of completed reaction in spatially heterogeneous distributions of reactants. A new model is proposed for the pore collapse of mixtures. This model is formulated by modifying the Carol, Holt, and Nesterenko spherically symmetric model to include mixtures and compressibility effects. Uncertainties in the model result from assumptions in formulating the models for continuum relationships and chemical reactions in mixtures that are distributed heterogeneously in space and in numerical integration of the resulting equations. It is important to quantify these uncertainties. In this thesis, such an uncertainty quantification is investigated by systematically identifying the physical processes that occur during shock compression of ESMs which are

  2. Risk factors for drug-induced long-QT syndrome

    PubMed Central

    Paulussen, A.D.C.; Aerssens, J.

    2005-01-01

    Congenital long-QT syndrome (cLQTS) is a ventricular arrhythmia that is characterised by a prolonged QT interval on the surface electro-cardiogram (ECG). Clinical symptoms include sudden loss of consciousness (syncopes), seizures, cardiac arrest and sudden death. The prevalence of this inherited disease is approximately one in 10,000 in Caucasians. Over the last decade, more than 200 different diseases causing mutations have been identified in five genes that encode ion channels involved in the delicate balance of inward and outward K/Ca currents during the cardiac action potential. A prolonged QT interval accompanied by very similar clinical symptoms as in cLQTS can also occur in otherwise healthy individuals after the intake of specific drug(s). This phenomenon is known as 'acquired' or 'drug-induced' long-QT syndrome. Because the clinical symptoms of the two forms are very similar, the question arises whether a common underlying genetic basis also exists. Several studies indicate that only a minority (approximately 10%) of the drug-induced LQTS cases can be explained by a mutation or polymorphism in one of the known LQTS genes. Even though the disease can often at least partially be explained by environmental factors, mutations or polymorphisms in other genes are also expected to be involved, including genes encoding drug-metabolising enzymes, adrenergic receptors, hormone-related genes and mitochondrial genes. This article reviews the current knowledge on risk factors for drug-induced LQTS, with a special emphasis on the role of genetic determinants. ImagesFigure 1AFigure 2Figure 3 PMID:25696450

  3. Severe idiosyncratic drug reactions with epidermal necrolysis: A 5-year study

    PubMed Central

    Fadeyibi, I. O.; Ademiluyi, S. A.; Ajose, F. O.; Jewo, P. I.; Akinola, O. I.

    2011-01-01

    Introduction: Idiosyncratic drug reactions (IDRs) are unexpected responses to a drug. The spectrums of severe cutaneous reactions include Stevens–Johnson Syndrome (SJS), SJS/Lyell Syndrome and Toxic Epidermal Necrolysis (TEN). The conditions are associated with high mortality. This study was designed to determine the causal agents, patterns of presentations, review the management and make recommendations to reduce the incidence and mortality of this class of drug reactions. Materials and Methods: A retrospective study was made of patients seen with IDR in the Lagos State University Teaching Hospital, LASUTH, between January, 2004 and December, 2008. They were cases admitted with bullous skin eruptions with associated systemic symptoms. Results: Sixty-seven patients were seen, with 45 (67.2%) satisfying the inclusion criteria. Fifteen males and 30 females were involved, giving a male to female (M:F) ratio of 1:2. Their ages ranged from 7 to 79 years (mean, 40.02 ± 17.89 years). Peak incidences occurred among the 20–24 and 30–34 year age groups. The causal agents were antibiotics (48.89%), sulphonamides (24.44%), herbal preparations (17.78%) and artemisinin drugs (8.89%). Conclusions: The age groups with the peak incidence are the most likely to indulge more in drug abuse in environments with poor drug control. Diagnosis of SJS, SJS/TEN and TEN were missed in many patients at first contact due to the progressive nature of the conditions. Patients needed reviews at regular intervals when IDR was suspected. Health education to prevent drug abuse is important and herbal preparations should be scientifically studied to determine the efficacy and side-effects. PMID:22279281

  4. Adverse Drug Reactions: A Retrospective Review of Hospitalized Patients at a State Psychiatric Hospital

    PubMed Central

    Iuppa, Courtney A.; Nelson, Leigh Anne; Elliott, Ellie; Sommi, Roger W.

    2013-01-01

    Background: There is a paucity of information regarding adverse drug reactions (ADRs) in psychiatric patients. Information on common and preventable ADRs (pADRs) in psychiatric patients will allow for targeted improvement projects. Objective: To characterize reported ADRs and pharmacist interventions to prevent ADRs in an extended-care state psychiatric hospital. Methods: Four years of ADR reports were assessed for probability, reaction severity, pharmacological class of medication involved, preventability, change in therapy, and transfers to a medical facility. The pharmacist intervention database was queried for interventions classified as “prevention of ADR.” The interventions were assessed for type of medication and recommendation acceptance. Results: Medication classes responsible for ADRs included mood stabilizers (30%), typical antipsychotics (25%), atypical antipsychotics (25%), and antidepressants (8%). Nine percent resulted in transfer to a medical facility. Of all ADRs, 34.4% were pADRs; mood stabilizers (41%) and atypical antipsychotics (27%) were the most common pADRs. The most common causes of pADRs were supratherapeutic serum concentrations, drug-drug interactions, and history of reaction. There were 87 pharmacist interventions that were classified as “prevention of ADR,” and the acceptance rate of pharmacists’ recommendations was 96.5%. Mood stabilizers (20%), atypical antipsychotics (17%), and typical antipsychotics (11%) were commonly associated with prevented ADRs. Lithium accounted for 13.8% of prevented ADRs; these ADRs were most often due to a drug–drug interaction with a nonsteroidal anti-inflammatory drug. Conclusions: ADRs were most commonly associated with mood stabilizers and antipsychotics, and pADRs were common. There is an opportunity to provide education to medical staff on therapeutic drug monitoring and drug–drug interactions for these classes, particularly lithium. PMID:24474834

  5. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... Adverse reactions to drugs are common. (adverse means unwanted or unexpected.) Almost any drug can cause an adverse reaction. Reactions range from irritating ...

  6. Nucleation and reaction rates controlled by local reaction volume and reaction-induced stress - spinel layer growth as an example

    NASA Astrophysics Data System (ADS)

    Götze, Lutz C.; Milke, Ralf; Dohmen, Ralf; Wirth, Richard

    2014-05-01

    %) and a positive volume change at the Sp-Cor interface (by +17 %). We observed in TEM images formation of porosity at the Sp-Per substrate interface and lattice strain in the polycrystalline corundum substrate at the Sp-Cor substrate interface, both observations being fully in line with the respective local volume changes. We infer that the local stress field between the growing reaction layer and the rigid single crystal substrate is responsible for the dramatic effect on both the nucleation and reaction rates. With respect to minerals growing at dry conditions in the Earth's crust (granulite facies) we infer that rates of reactions might strongly depend on local volume changes at interfaces, that reactions are impeded by compressive reaction-induced stress applied to rigid neighboring grains, and that nucleation of thermodynamically stable phases on grain boundaries might be suppressed by a positive reaction volume.

  7. Mass and charge distributions in Fe-induced reactions

    SciTech Connect

    Madani, H.; Mignerey, A.C.; Marchetti, A.A.; Weston-Dawkes, A.P.; Kehoe, W.L.; Obenshain, F.

    1995-02-21

    The charge and mass of the projectile-like fragments produced in the 12-MeV/nucleon {sup 56}Fe + {sup 165}Ho reaction were measured at a laboratory scattering angle of 16 degrees. The mass and charge distributions of the projectile-like fragments were generated as a function of total kinetic energy loss (TKEL), and characterized by their neutron and proton centroids and variances, and correlation factors. A weak drift of the system towards mass asymmetry, opposite to the direction which minimizes the potential energy of the composite system, was observed. The increase in the variances with energy loss is consistent with a nucleon exchange mechanism as a means for energy dissipation. Predictions of two nucleon exchange models, Randrup`s and, Tassan-Got`s models, are compared to the experimental results of the 672-MeV {sup 56}Fe + {sup 165}Ho reaction and to other Fe-induced reactions. The proton and neutron centroids were found to be generally better reproduced by Tassan-Got`s model than by Randrup`s model. The variances and correlation factor are well reproduced for asymmetric systems by both models.

  8. Reactions of model proteins with aurothiomalate, a clinically established gold(I) drug: The comparison with auranofin.

    PubMed

    Darabi, Farivash; Marzo, Tiziano; Massai, Lara; Scaletti, Federica; Michelucci, Elena; Messori, Luigi

    2015-08-01

    Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug that is currently being reconsidered as a candidate drug for cancer treatment and for other therapeutic indications within a more general drug repositioning program. As the biological effects of gold drugs seem to be mediated, mainly, by their interactions with protein targets we have analyzed here, in detail, the metalation patterns produced by aurothiomalate in a few model proteins. In particular, the reactions of aurothiomalate with the small proteins ribonuclease A, cytochrome c and lysozyme were explored through ESI MS (electrospray ionization mass spectrometry) analysis. Notably, characteristic and rather constant features emerged in the protein metalation patterns induced by AuTm that are markedly distinct from those caused by auranofin; a non-covalent interaction mode is invoked for AuTm binding to the mentioned proteins. The affinity constants of AuTm toward the three mentioned proteins were also initially assessed. The implications of the present findings are discussed. PMID:25865000

  9. Dominant roles of Fenton reaction in sodium nitroprusside-induced chondrocyte apoptosis.

    PubMed

    Quan, Ying-Yao; Qin, Gui-Qi; Huang, Hao; Liu, Yu-Hong; Wang, Xiao-Ping; Chen, Tong-Sheng

    2016-05-01

    Sodium nitroprusside (SNP) has been widely used as an exogenous nitric oxide (NO) donor to explore the molecular mechanism of NO-mediated chondrocyte apoptosis during the latest two decades. We have recently found that NO-independent ROS play a key role in SNP-induced apoptosis in rabbit chondrocytes. This study aims to investigate what kind of ROS and how the reliable ROS mediators mediate the SNP-induced apoptosis. Data shows that SNP and NO-exhausted SNP (SNPex) induced ROS production or cytotoxicity to identically degree. SNP induced a marked increase in iron ions, superoxide anion (O2(•-)), hydrogen peroxide (H2O2) and hydroxyl radical ((•)OH) level. H2O2 scavenger (CAT) and (•)OH scavenger (DMSO) significantly inhibited SNP-induced chondrocyte apoptosis. Iron ions chelator (DFO) entirely prevented SNP-induced chondrocyte apoptosis. In contrast, O2(•-) scavenger (SOD) and glutathione depletion agent (BSO) promoted SNP-induced cytotoxicity. K3[Fe(CN)6] exhibited no cytotoxicity, and H2O2 alone up to 250µM or iron ions alone up to 90µM is non-cytotoxic to chondrocytes. Combination of 25µM FeSO4 and 100µM H2O2 in the presence of BSO induced chondrocyte death similar to SNP treatment. Fetal bovine serum (FBS) enhanced iron ions release from SNP and the cytotoxicity of SNP. Our data shows that the extracellular Fenton reaction between iron ions released from SNP and H2O2 induced by SNP plays a key role in SNP-induced chondrocyte apoptosis. Overall, our results indicate that the potential of SNP to increase iron ions and ROS should be especially considered for some biological functions and, possibly, also for clinical applications of this drug. PMID:26923801

  10. Patterns of Adverse Drug Reactions in Different Age Groups: Analysis of Spontaneous Reports by Community Pharmacists

    PubMed Central

    Yu, Yun Mi; Shin, Wan Gyoon; Lee, Ju-Yeun; Choi, Soo An; Jo, Yun Hee; Youn, So Jung; Lee, Mo Se; Choi, Kwang Hoon

    2015-01-01

    Purpose To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age. Methods ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female. Results Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively. Conclusions According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups. PMID:26172050

  11. A case of hydrocortisone desensitization in a patient with radiocontrast-induced anaphylactoid reaction and corticosteroid allergy.

    PubMed

    Lee-Wong, Mary; McClelland, Suzanne; Chong, Kaman; Fernandez-Perez, Evans R; Fernandez, Evans

    2006-01-01

    Allergic reactions and systemic desensitization to corticosteroids have been documented rarely in English language literature. These reactions appear more often when the agent is applied topically and may lead to dangerous complications in patients if administered i.v. Therefore, the safety and efficacy of using an i.v. corticosteroid for desensitization in a patient who has a history of allergy to corticosteroid must be weighed carefully, especially when the aim of its use is to prevent an allergic reaction from a second drug. We report a case of successful systemic hydrocortisone desensitization in a patient with radiocontrast-induced anaphylactoid reaction and corticosteroid allergy. Sensitization to corticosteroids was determined through skin testing. The patient was desensitized to hydrocortisone and premedicated with hydrocortisone and diphenhydramine and subsequently underwent cardiac catheterization with radiocontrast without adverse reaction. PMID:16913271

  12. Multistep Reaction Based De Novo Drug Design: Generating Synthetically Feasible Design Ideas.

    PubMed

    Masek, Brian B; Baker, David S; Dorfman, Roman J; DuBrucq, Karen; Francis, Victoria C; Nagy, Stephan; Richey, Bree L; Soltanshahi, Farhad

    2016-04-25

    We describe a "multistep reaction driven" evolutionary algorithm approach to de novo molecular design. Structures generated by the approach include a proposed synthesis path intended to aid the chemist in assessing the synthetic feasibility of the ideas that are generated. The methodology is independent of how the design ideas are scored, allowing multicriteria drug design to address multiple issues including activity at one or more pharmacological targets, selectivity, physical and ADME properties, and off target liabilities; the methods are compatible with common computer-aided drug discovery "scoring" methodologies such as 2D- and 3D-ligand similarity, docking, desirability functions based on physiochemical properties, and/or predictions from 2D/3D QSAR or machine learning models and combinations thereof to be used to guide design. We have performed experiments to assess the extent to which known drug space can be covered by our approach. Using a library of 88 generic reactions and a database of ∼20 000 reactants, we find that our methods can identify "close" analogs for ∼50% of the known small molecule drugs with molecular weight less than 300. To assess the quality of the in silico generated synthetic pathways, synthesis chemists were asked to rate the viability of synthesis pathways: both "real" and in silico generated. In silico reaction schemes generated by our methods were rated as very plausible with scores similar to known literature synthesis schemes. PMID:27031173

  13. Role of Biotransformation in Drug-Induced Toxicity: Influence of Intra- and Inter-Species Differences in Drug Metabolism

    PubMed Central

    Baillie, Thomas A.; Rettie, Allan E.

    2015-01-01

    It is now widely appreciated that drug metabolites, in addition to the parent drugs themselves, can mediate the serious adverse effects of new therapeutic agents, as a result of which there has been heightened interest in the field of drug metabolism from researchers in academia, the pharmaceutical industry, and regulatory agencies. Much progress has been made in recent years in understanding mechanisms of toxicities caused by drug metabolites, and the numerous factors that influence individual exposure to products of drug biotransformation. This review addresses some of these factors, including the role of drug-drug interactions, reactive metabolite formation, individual susceptibility, and species differences in drug disposition caused by genetic polymorphisms in drug metabolizing enzymes. Examples are provided of adverse reactions that are linked to drug metabolism, and the mechanisms underlying variability in toxic response are discussed. Finally, some future directions for research in this field are highlighted in the context of the discovery and development of new therapeutic agents. PMID:20978360

  14. A case of severe psychosis induced by novel recreational drugs

    PubMed Central

    Dragogna, Filippo; Oldani, Lucio; Buoli, Massimiliano; Altamura, A. Carlo

    2014-01-01

    Introduction:  The use of novel recreational drugs is becoming of public interest, especially after recent international alerts about their cardiovascular and neurological toxicity. Additionally, little is known about the psychiatric consequences of the long-term use of these compounds. Case presentation: We describe a case of severe psychotic episode likely induced by chronic use of a combination of new recreational drugs (methylenedioxypyrovalerone, mephedrone, butylone and alpha-pyrrolidinopentiophenone). The patient had no psychiatric history and showed poor response to conventional antipsychotic treatment (haloperidol). Conclusions: This case illustrates the potential negative effects of recreational drugs that cannot be limited to an acute psychotic episode but might determine a condition of prolonged paranoid psychosis. Although the use of these compounds is currently increasing, such molecules might often pass undetected in patients accessing the emergency room, leading to misdiagnosis (e.g. schizophrenic episode) and lack of appropriate treatment. PMID:25352977

  15. Antituberculous drug-induced liver injury: current perspective.

    PubMed

    Devarbhavi, Harshad

    2011-01-01

    Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. Single center registries of DILI continue to highlight the high incidence of DILI and DIALF, much of it due to diagnostic errors and inappropriate prescriptions. The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. TB DILI can occur across all age groups including children with significant morbidity and mortality. Although TB DILI develops more commonly in males, ALF is noted to be commoner in females with a worse prognosis. Contrasting reports on the role of genetic and environmental factors continue to be published. Since DILI is a diagnosis of exclusion, acute viral hepatitis particularly hepatitis E needs to be excluded in such cases. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy and high prothrombin time are poor prognostic markers. Recent reports of the beneficial role of N-acetylcysteine in DIALF and in preventing TB DILI in elderly individuals needs further investigation. Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. Although monitoring and rechallenge practices vary greatly, the importance of early clinical symptoms cannot be underestimated. Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. The combined affliction of HIV or chronic hepatitis B or C and tuberculosis poses multiple challenges including the greatly increased risks of DILI. PMID:22332331

  16. [Novel oral anticancer drugs: a review of adverse drug reactions, interactions and patient adherence].

    PubMed

    Bartal, Alexandra; Mátrai, Zoltán; Szucs, Attila; Belinszkaja, Galina; Langmár, Zoltán; Rosta, András

    2012-01-15

    Each aspect of oncological care is widely affected by the spread of oral anticancer agents, which raises several questions in terms of safe medication use and patient adherence. Over the past decade targeted therapies have appeared in clinical practice and revolutionized the pharmacological treatment of malignancies. Regular patient - doctor visits and proper patient education is crucial in order to comply with the therapy previously agreed upon with the oncologist, to increase patient adherence, to detect and to treat adverse effects in early stages. Since the information on the new medicines in Hungarian language is sparse it is the intention of the authors to give an overview of the basic knowledge, patient safety issues, adverse effects and interactions. Official drug information summaries and data on pharmacokinetics, interactions and adverse effects from the literature are reviewed as the basis for this overview. PMID:22217686

  17. Troponin leak associated with drug-induced methemoglobinemia.

    PubMed

    Cannon, Robert D; Wagner, Michael; Jacoby, Jeanne L

    2014-10-01

    Drug-induced methemoglobinemia is a well-described entity but has not been previously associated with elevated troponins in the absence of cardiac symptoms. We report a case of a patient presenting to the emergency department (ED) with complaints related to an exacerbation of her long-standing cystitis. A low pulse oximetry reading prompted an evaluation, revealing a troponin leak, which peaked at 10 hours. Her methemoglobin level was found to be elevated at 11.4%, but a preexisting anemia apparently prevented the clinical recognition of cyanosis. The methemoglobinemia was determined to be secondary to her ingestion of phenazopyridine and trimethoprim-sulfa methoxizole. Although phenazopyridine and sulfa agents have long been known to cause methemoglobinemia, our patient exhibited an asymptomatic troponin leak that has not been previously reported as a complication of drug-induced methemoglobinemia. Clinicians should be aware of this potential association. PMID:24686024

  18. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia.

    PubMed

    Miyazaki, Masayuki; Tanaka, Masatake; Ueda, Akihiro; Yoshimoto, Tsuyoshi; Kato, Masaki; Nakamuta, Makoto; Kotoh, Kazuhiro; Takayanagi, Ryoichi

    2011-11-28

    Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS. PMID:22171136

  19. Drug-Induced Pancreatitis: A Rare Manifestation of Doxycycline Administration

    PubMed Central

    Inayat, Faisal; Virk, Hafeez Ul Hassan; Yoon, Daniel J.; Riaz, Iqra

    2016-01-01

    Context: Drug-induced pancreatitis (DIP) is rare, but as there are no systematic data on it, the true incidence is not known. Although numerous and varied drugs have been associated with DIP, the clinical evidence on doxycycline-induced pancreatitis is sparse. Case Report: We present the case of a 58-year-old female who presented with complaints of nausea and severe epigastric pain. Her medications included doxycycline which she had been on for only 2 days. Computed tomography of her abdomen showed mild enlargement of body of the pancreas with peripancreatic fatty infiltration, along with lipase level suggestive of acute pancreatitis. In the absence of classical risk factors for acute pancreatitis, a diagnosis of DIP secondary to doxycycline therapy was made. Immediate withdrawal of the drug was accompanied by relief of symptoms and resolution of pancreatitis. Conclusion: This report implicates doxycycline as an etiological factor for acute pancreatitis. Knowledge regarding doxycycline related pancreatitis is of paramount importance in order to diagnose cases early and institute effective treatment in patients who are undergoing therapy with this drug. PMID:27042611

  20. Antiplatelet drugs induce apoptosis in cultured cancer cells.

    PubMed

    Chen, W H; Yin, H L; Chang, Y Y; Lan, M Y; Hsu, H Y; Liu, J S

    1997-10-01

    In order to understand if antiplatelet drugs possess direct antineoplastic property, we tested the apoptotic effect of 5 popularly marketed antiplatelet drugs in Taiwan in 6 cultured cancer cell lines (Hep 3B hepatocarcinoma, U87-MG malignant glioma, PC-3 prostate adenocarcinoma, HeLa cervical adenocarcinoma, HL-60 preleukemia and K-562 chronic myelogenous leukemia). While acetylsalicylate and flunarizine exerted no effect on these cancer cells, pentoxifyline (PTX), dipyridamole (DYA) and ticlopidine hydrochloride (T. HCl) displayed a time and dose-dependent apoptotic effect on them except for HL-60 and K-562 cells. PTX induced apoptosis in U87-MG, Hep 3B and HeLa cells, DYA in HeLa cells, while T. HCl in U87-MG, Hep 3B, PC-3 and HeLa cells. Adriamycin also provoked apoptotic effect in all 6 cell lines but neither PTX, DYA nor T. HCl acted synergy with adriamycin to HeLa cells, implicating that they may share a similar pathway for inducing apoptosis. Therefore, our results show that the antiplatelet drugs do possess antineoplastic property in vitro. A co-administration of antiplatelet drugs is noteworthy for an alternative adjunctive therapy in cancer patients. PMID:9385774

  1. Metformin-Induced Fixed-Drug Eruption Confirmed by Multiple Exposures

    PubMed Central

    Steber, Carolyn J.; Perkins, Scott L.; Harris, Kira B.

    2016-01-01

    Patient: Female, 56 Final Diagnosis: Fixed-drug eruption Symptoms: — Medication: Metformin Clinical Procedure: Discontinued metformin Specialty: Family Medicine Objective: Unusual or unexpected effect of treatment Background: A fixed-drug eruption (FDE) is a reaction characterized by cutaneous lesions that appear due to exposure to a particular drug. Barbiturates, carbamazepine, sulfamethoxazole, and tetracyclines have all been associated with causation of FDEs. Although these drugs are more commonly associated with FDEs, any introduction of a medication has the potential to result in a FDE. Metformin, a commonly used medication to improve glycemic control, has been reported to cause dermatologic reactions in some case reports, but only a single previously documented case report discusses the potential of metformin-associated FDE. Case Report: We describe a 56-year-old woman who developed a FDE with multiple exposures to metformin. Upon each exposure, small, round, erythematic lesions developed on the palms of the hands and soles of the feet; these lesions resolved each time after discontinuation of metformin. According to the Naranjo scale, there is a definite association between metformin and FDE in this case (score of 8). Conclusions: This report contributes to the limited documented literature on metformin-induced FDE. Clinicians should be made aware of possible FDEs associated with this commonly used medication. PMID:27056044

  2. Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

    PubMed Central

    Kantarci, A.

    2015-01-01

    Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine- and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies. PMID:25680368

  3. Pregnane X receptor and drug-induced liver injury

    PubMed Central

    Wang, Yue-Ming; Chai, Sergio C.; Brewer, Christopher T; Chen, Taosheng

    2014-01-01

    Introduction The liver plays a central role in transforming and clearing foreign substances. The continuous exposure of the liver to xenobiotics sometimes leads to impaired liver function, referred to as drug-induced liver injury (DILI). The pregnane X receptor (PXR) tightly regulates the expression of genes in the hepatic drug-clearance system and its undesired activation plays a role in DILI. Areas covered This review focuses on the recent progress in understanding PXR-mediated DILI and highlights the efforts made to assess and manage PXR-mediated DILI during drug development. Expert opinion Future efforts are needed to further elucidate the mechanisms of PXR-mediated liver injury, including the epigenetic regulation and polymorphisms of PXR. Novel in vitro models containing functional PXR could improve our ability to predict and assess DILI during drug development. PXR inhibitors may provide chemical tools to validate the potential of PXR as a therapetic target and to develop drugs to be used in the clinic to manage PXR-mediated DILI. PMID:25252616

  4. Confirming false adverse reactions to drugs by performing individualized, randomized trials.

    PubMed

    Knowles, Sandra R; Uetrecht, Jack P; Shear, Neil H

    2002-01-01

    One-patient, randomized, double-blind, controlled trials (N-of-1 RCTs) have traditionally been used to assess the efficacy of treatment. At the Drug Safety Clinic, Toronto, this methodology is used to evaluate adverse effects related to medication use, specifically when the symptoms are vague and are in response to more than one medication. Two patients are described with histories of drug allergies to multiple medications; as well, guidelines for conducting N-of-1 trials are summarized. The first patient had a history of prolonged periorbital and generalized weakness lasting up to one week after exposure to a variety of drugs. Because of the ambiguous results of local anesthetic skin testing, an N-of-1 trial was performed using lidocaine without preservative. Two short-lived episodes of blepharospasm and lethargy were observed with placebo; no subjective or objective reaction occurred with active drug. The second patient had a history of prolonged weakness and drowsiness after exposure to many medications; she had been told that she was allergic to all drugs with a benzene ring. During the first N-of-1 trial, generalized weakness was observed with 10 mg of dimenhydrinate and all four placebo doses. During the second N-of-1 challenge using codeine, no unwarranted reactions occurred with either active or placebo drug. Traditional testing of these patients to disprove the clinical symptoms is often difficult because of the anxiety level associated with the patients' past experiences. N-of-1 trials provide a useful alternative for the management of patients with nonspecific symptomatology attributed to drug ingestion. PMID:12422252

  5. Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients.

    PubMed

    Mizokami, Fumihiro; Takahashi, Yoshiko; Hasegawa, Keiko; Hattori, Hideyuki; Nishihara, Keiji; Endo, Hidetoshi; Furuta, Katsunori; Isogai, Zenzo

    2016-04-01

    Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. PMID:26364579

  6. Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption.

    PubMed Central

    Teraki, Y.; Moriya, N.; Shiohara, T.

    1994-01-01

    The mechanism(s) and the factor(s) that contribute to preferential localization of fixed drug eruption (FDE) lesions to certain skin sites remain speculative. Previous studies suggested that populations of T cells residing in the lesional epidermis may be involved in selective destruction of the epidermis in FDE. In this study, to define the earliest cellular and molecular events with potential relevance to activation of the epidermal T cells, expression of adhesion molecules on keratinocytes (KC) and vascular endothelium was examined sequentially in the lesional skin of FDE patients after challenge with the causative drug. Rapid and intense intercellular adhesion molecule-1 (ICAM-1) expression was induced on the vascular endothelium and KC as early as 1.5 hours after challenge, at which time E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were not up-regulated. In vitro studies using skin organ culture showed that the lesional KC and endothelium responded more rapidly and intensely to express ICAM-1 to tumor necrosis factor-alpha or interferon-gamma compared with those in the nonlesional skin. Surprisingly, such selective induction of KC ICAM-1 restricted to the lesional skin was also observed after exposure to the causative drug alone in skin organ culture. Pretreatment of the lesional skin with anti-tumor necrosis factor completely abrogated in vitro induction of KC ICAM-1 expression by the drug. Drug-induced, TNF-alpha-dependent KC ICAM-1 expression in the lesional skin suggests that induction of ICAM-1 expression by the lesional KC after ingestion of the drug would probably provide a localized initiating stimulus for activation of the disease-associated epidermal T cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7915886

  7. Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in an Adolescent Treated With Lamotrigine.

    PubMed

    Ginory, Almari; Chaney-Catchpole, Michelle; Demetree, Julie M; Mayol Sabatier, Laura M; Nguyen, Mathew

    2013-07-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome most commonly associated with antiepileptic agents, allopurinol, and sulfonamides. It is a severe adverse reaction associated with fever, rash, eosinophilia, lymphadenopathy, and internal organ involvement. We present the case of a 17-year-old Caucasian female with bipolar disorder type II and posttraumatic stress disorder treated with lamotrigine for a non-Food and Drug Administration-approved indication that developed DRESS syndrome at an initial dose higher than that recommended. Her symptoms were atypical in that she developed a rash with influenza-like symptoms that resolved after discontinuation of lamotrigine and returned 8 days later. She was hospitalized because of elevated liver enzymes and treated with corticosteroids. In patients presenting with rash and systemic symptoms, DRESS syndrome should be considered and treated appropriately to reduce mortality, which can be as high as 10%. Treatment includes withdrawal of the offending agent and corticosteroids. PMID:24052787

  8. Ontological representation of adverse drug reactions using the Foundational Model of Anatomy.

    PubMed

    Bousquet, Cédric; Gasperina, Philippe; Trombert, Béatrice; Clavel, Lucienne; Kumar, Anand; Rodrigues, Jean Marie

    2009-01-01

    In a previous work we proposed a categorial structure for the representation of adverse drug reactions consisting of 16 semantic categories and 20 relations. We present an implementation of this categorial structure in Protégé based on four WHO-ART system organ classes: Gastro-intestinal system disorders, Liver and biliary system disorders, Central & peripheric nervous system disorders, and Psychiatric disorders. We compared classification according to anatomy using SNOMED CT within the PharmARTS tool and the FMA with the Pellet reasoner. This ontology contains 210 concepts for Gastroenterology, 66 concepts for Psychiatry and 85 concepts for Neurology. Classification of disorders located in the upper gastro intestinal tract was similar using both SNOMED CT and the FMA. This work is a first step towards the comparison of two models of anatomy within a common ontology of adverse drug reactions. PMID:19745363

  9. Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury.

    PubMed

    Hadi, Mackenzie; Westra, Inge M; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Marjolijn T; Groothuis, Geny M M

    2013-05-20

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict IDILI in humans. According to the inflammatory stress hypothesis, the effects of inflammation interact with the effects of a drug or its reactive metabolite, precipitating toxic reactions in the liver. As a follow-up to our recently published mouse precision-cut liver slices model, an ex vivo model involving human precision-cut liver slices (hPCLS), co-incubated for 24 h with IDILI-related drugs and lipopolysaccharide (LPS), was developed to study IDILI mechanisms related to inflammatory stress in humans and to detect potential biomarkers. LPS exacerbated the effects of ketoconazole and clozapine toxicity but not those of their non-IDILI-related comparators, voriconazole and olanzapine. However, the IDILI-related drugs diclofenac, carbamazepine, and troglitazone did not show synergistic toxicity with LPS after incubation for 24 h. Co-incubation of ketoconazole and clozapine with LPS decreased the levels of glutathione in hPCLS, but this was not seen for the other drugs. All drugs affected LPS-induced cytokine release, but interestingly, only ketoconazole and clozapine increased the level of LPS-induced TNF release. Decreased levels of glutathione and cysteine conjugates of clozapine were detected in IDILI-responding livers following cotreatment with LPS. In conclusion, we identified ketoconazole and clozapine as drugs that exhibited synergistic toxicity with LPS, while glutathione and TNF were found to be potential biomarkers for IDILI-inducing drugs mediated by inflammatory stress. hPCLS appear to be suitable for further unraveling the mechanisms of inflammatory stress-associated IDILI. PMID:23565644

  10. Structure effects on reaction mechanisms in collisions induced by radioactive ion beams

    SciTech Connect

    Pietro, A. Di Figuera, P.; Scuderi, V.; Amorini, F.; Angulo, C.; Cardella, G.; Casarejos, E.; Cherubini, S.; Lu, J.; Marchetta, C.; Musumarra, A.; Papa, M.; Pellegriti, M.; Pizzone, R. G.; Raabe, R.; Rizzo, F.; Sida, J. L.; Tian, W.

    2006-08-15

    The present paper concerns the study of reactions induced by radioactive beams of halo and weakly bound nuclei at energies around and above the Coulomb barrier. The results obtained for the reaction induced by the halo nucleus {sup 6}He on {sup 64}Zn have been compared with the results for the reaction induced by {sup 4}He on the same target. The results of the reaction induced by the weakly bound unstable {sup 13}N on the weakly bound {sup 9}Be have been compared with those for the reaction {sup 10}B + {sup 12}C.

  11. Adverse drug reaction monitoring: support for pharmacovigilance at a tertiary care hospital in Northern Brazil

    PubMed Central

    2013-01-01

    Background Adverse drug reactions (ADRs) are recognised as a common cause of hospital admissions, and they constitute a significant economic burden for hospitals. Hospital-based ADR monitoring and reporting programmes aim to identify and quantify the risks associated with the use of drugs provided in a hospital setting. This information may be useful for identifying and minimising preventable ADRs and may enhance the ability of prescribers to manage ADRs more effectively. The main objectives of this study were to evaluate ADRs that occurred during inpatient stays at the Hospital Geral de Palmas (HGP) in Tocantins, Brazil, and to facilitate the development of a pharmacovigilance service. Methods A prospective study was conducted at HGP over a period of 8 months, from January 2009 to August 2009. This observational, cross-sectional, descriptive study was based on an analysis of medical records. Several parameters were utilised in the data evaluation, including patient demographics, drug and reaction characteristics, and reaction outcomes. The reaction severity and predisposing factors were also assessed. Results The overall incidence of ADRs in the patient population was 3.1%, and gender was not found to be a risk factor. The highest ADR rate (75.8%) was found in the adult age group 15 to 50 years, and the lowest ADR rate was found in children aged 3 to 13 years (7.4%). Because of the high frequency of ADRs in orthopaedic (25%), general medicine (22%), and oncology (16%) patients, improved control of the drugs used in these specialties is required. Additionally, the nurse team (52.7%) registered the most ADRs in medical records, most likely due to the job responsibilities of nurses. As expected, the most noticeable ADRs occurred in skin tissues, with such ADRs are more obvious to medical staff, with rashes being the most common reactions. Metamizole, tramadol, and vancomycin were responsible for 21, 11.6, and 8.4% of ADRs, respectively. The majority of ADRs had

  12. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

    PubMed

    Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

    2014-12-01

    This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients. PMID:25711751

  13. In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for pathophysiology.

    PubMed

    Elzagallaai, Abdelbaset A; Rieder, Michael J

    2015-10-01

    Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post-marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug's known pharmacology and have no clear dose-effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible, without the aid of a reliable diagnostic test. The drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential harm to patients. However, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here. PMID:25199801

  14. Laser induced sonofusion: A new road toward thermonuclear reactions

    NASA Astrophysics Data System (ADS)

    Sadighi-Bonabi, Rasoul; Gheshlaghi, Maryam

    2016-03-01

    The Possibility of the laser assisted sonofusion is studied via single bubble sonoluminescence (SBSL) in Deuterated acetone (C3D6O) using quasi-adiabatic and hydro-chemical simulations at the ambient temperatures of 0 and -28.5 °C. The interior temperature of the produced bubbles in Deuterated acetone is 1.6 × 106 K in hydro-chemical model and it is reached up to 1.9 × 106 K in the laser induced SBSL bubbles. Under these circumstances, temperature up to 107 K can be produced in the center of the bubble in which the thermonuclear D-D fusion reactions are promising under the controlled conditions.

  15. A Transport Model for Nuclear Reactions Induced by Radioactive Beams

    SciTech Connect

    Li Baoan; Chen Liewen; Das, Champak B.; Das Gupta, Subal; Gale, Charles; Ko, C.M.; Yong, G.-C.; Zuo Wei

    2005-10-14

    Major ingredients of an isospin and momentum dependent transport model for nuclear reactions induced by radioactive beams are outlined. Within the IBUU04 version of this model we study several experimental probes of the equation of state of neutron-rich matter, especially the density dependence of the nuclear symmetry energy. Comparing with the recent experimental data from NSCL/MSU on isospin diffusion, we found a nuclear symmetry energy of Esym({rho}) {approx_equal} 31.6({rho}/{rho}0)1.05 at subnormal densities. Predictions on several observables sensitive to the density dependence of the symmetry energy at supranormal densities accessible at GSI and the planned Rare Isotope Accelerator (RIA) are also made.

  16. Inflammation-Enhanced Drug-Induced Liver Injury.

    PubMed

    Maruf, Abdullah Al; O'Brien, Peter

    2014-10-01

    Drug-induced liver injury is a major concern in clinical studies as well as in post-marketing surveillance. Previous evidence suggests that drug exposure during periods of inflammation can increase an individual's susceptibility to toxicity. Inflammation caused by infections or endotoxin markedly activates NADPH oxidase that generates superoxide radicals by transferring electrons from NADPH. In the phagosome, superoxide radicals spontaneously form hydrogen peroxide (H2O2) and other reactive oxygen species. Neutrophils or Kupffer cells also release myeloperoxidase on activation. The aim of this study was to develop and validate an in vitro oxidative stress inflammation model to identify compounds that may increase hepatotoxicity during inflammation. When a non-toxic H2O2 generating system (glucose/glucose oxidase) with peroxidase or Fe(II) (to simulate in vivo inflammation) were added to the freshly isolated rat hepatocytes prior to the addition of the investigated drug which increased drug-induced cytotoxicity and ROS formation. This was reversed by 6-N-propyl-2-thiouracil (a peroxidase inhibitor) or desferoxamine (an Fe(II) chelator), respectively. Flutamide, nilutamide, nimesulide, methotrexate, and 6-mercaptopurine were found to form pro-oxidant radicals leading to oxidative stress and mitochondrial injury whereas azathioprine did not form any radicals with this inflammation system. Electron spin resonance spectrometry spin trapping studies of 6-mercaptopurine metabolism by HRP (horseradish peroxidase)/H2O2 was also investigated. A mixture of two radicals were trapped using DMPO (5,5-dimethyl-1-pyrroline-N-oxide) which were previously reported as purine-6-thiyl and superoxide radicals. This system may provide a more robust in vitro pre-clinical tool for screening of drugs for potential hepatotoxicity associated with inflammation. PMID:26461367

  17. Reaction-induced strain localization: Torsion experiments on dolomite

    NASA Astrophysics Data System (ADS)

    Delle Piane, Claudio; Burlini, Luigi; Grobety, Bernard

    2007-04-01

    We investigated the mechanical behaviour and microstructural evolution of a dolomite marble from Mt. Frerone (Adamello, N-Italy) during decarbonation to calcite and periclase in torsion experiments. Tests were performed in a Paterson gas-medium apparatus on cylindrical samples of 10 mm diameter and 10 mm length. Experiments were conducted at 800 °C, 300 MPa confining pressure under both vented and non-vented conditions, up to a maximum bulk shear strain of about γ = 1.8, at different strain rates (3 × 10 - 5 s - 1 up to 3 × 10 - 4 s - 1 ). Under hydrostatic conditions the nominal equilibrium P(CO 2) should be around 100 MPa, but in the vented experiments the CO 2 was free to escape, causing the breakdown of dolomite. During the decomposition, deformation was systematically localized at the ends of the specimens, near the porous spacers into a fine-grained mixture of calcite and periclase. Due to the low permeability of the marble, pore fluid could not escape from the central part of the sample building up CO 2 pressure which suppressed the decarbonation reaction. The fluid pressure embrittled the material and caused the development of en-echelon tension fractures, inclined opposite to the sense of shear. We conclude that decarbonation produced a weak polyphase matrix composed of submicron sized reaction products. Such a small grain size induced strain localization which was probably promoted by a switch from grain-size insensitive to grain-size sensitive deformation mechanism.

  18. Electro-induced manipulations of liquid marbles for chemical reactions

    NASA Astrophysics Data System (ADS)

    Liu, Zhou; Fu, Xiangyu; Binks, Bernard P.; Shum, Ho Cheung; Microfluidics; Soft Matter Group in University of Hong Kong Team; Surfactant; Colloid Group at Hull Team

    2015-11-01

    Liquid marbles, liquid droplets coated by non-wetting particles, have been well demonstrated as a promising template for various droplet-based applications, in particular for chemical reactions. In these applications, controlled manipulations on liquid marbles, including coalescence and mixing, are highly demanded but yet rarely investigated. In this work, we study the coalescence and mixing of liquid marbles controlled by an electric field. We found that a sufficiently large applied voltage can cause the coalescence of two or multiple marbles arranged in a chain. This critical voltage, leading to the consequent coalescence, increases with the number of the liquid marbles. In addition, the imposed electric stress can induce convective liquid flow within the different liquid marbles, resulting in rapid and efficient mixing. The mixing efficiency can be conveniently tuned through varying the applied voltage. Our approach based on electro-assisted manipulations of liquids marbles represents a robust and feasible template for chemical or biomedical reactions involving multiple reagents and steps. We have demonstrated its potential by performing a chemiluminescence to detect the hydrogen peroxide encapsulated in liquid marbles.

  19. Modeling chemical reactions in laser-induced plasmas

    NASA Astrophysics Data System (ADS)

    Shabanov, S. V.; Gornushkin, I. B.

    2015-11-01

    Under the assumption of local thermal equilibrium, a numerical algorithm is proposed to find the equation of state for laser-induced plasmas (LIPs) in which chemical reactions are permitted in addition to ionization processes. The Coulomb interaction in plasma is accounted for by the Debye-Hückel method. The algorithm is used to calculate the equation of state for LIPs containing carbon, silicon, nitrogen, and argon. The equilibrium reaction constants are calculated using the latest experimental and ab initio data of spectroscopic constants for the molecules {N}_2, {C}_2, {Si}_2, {CN}, {SiN}, {SiC} and their ions. The algorithm is incorporated into a fluid dynamic numerical model based on the Navier-Stokes equations describing an expansion of LIP plumes into an ambient gas. The dynamics of LIP plumes obtained by the ablation of SiC, solid silicon, or solid carbon in an ambient gas containing {N}_2 and Ar is simulated to study formation of molecules and molecular ions.

  20. Photon- and meson-induced reactions on the nucleon

    NASA Astrophysics Data System (ADS)

    Feuster, T.; Mosel, U.

    1999-01-01

    Starting from a unitary effective Lagrangian model for the meson-nucleon scattering developed in T. Feuster and U. Mosel, Phys. Rev. 58, 457 (1998), we come to a unified description of both meson scattering and photon-induced reactions on the nucleon. To this end the photon is added perturbatively, yielding both Compton scattering and meson photoproduction amplitudes. In a simultaneous fit to all available data the parameters of the nucleon resonances are extracted. We find that a global fit to the data of the various channels involving the final states γN, πN, ππN, ηN, and KΛ is possible. Especially in eta photoproduction a readjustment of the masses and widths found in the fits to hadronic reactions alone is necessary to describe the data. Only for the D13(1520) do we find a possible disagreement for the helicity couplings extracted using the combined data set and pion photoproduction multipoles alone. The model dependence introduced by the restoration of gauge invariance is discussed and found to be significant mainly for resonances with small helicity couplings.

  1. Investigation of GEV Proton-Induced Spallation Reactions

    NASA Astrophysics Data System (ADS)

    Hilscher, D.; Herbach, C.-M.; Jahnke, U.; Tishchenko, V. G.; Galin, J.; Lott, B.; Letourneau, A.; Peghaire, A.; Filges, D.; Goldenbaum, F.; Nünighoff, K.; Schaal, H.; Sterzenbach, G.; Wohlmuther, M.; Pienkowski, L.; Schröder, W. U.; Toke, J.

    2004-09-01

    A reliable modeling of GeV proton-induced spallation reactions is indispensable for the design of the spallation module and the target station of future accelerator driven hybrid reactors (ADS) or spallation neutron sources (ESS), in particular, to provide precise predictions for the neutron production, the radiation damage of materials (window), and the production of radioactivity (3H, 7Be etc.) in the target medium. Detailed experimental nuclear data are needed for sensitive validations and improvements of the models, whose predictive power is strongly dependent on the correct physical description of the three main stages of a spallation reaction: (i) the Intra-Nuclear-Cascade (INC) with the fast heating of the target nucleus, (ii) the de-excitation due to pre-equilibrium emission including the possibility of multi-fragmentation, and (iii) the statistical decay of thermally excited nuclei by evaporation of light particles and fission in the case of heavy nuclei. Key experimental data for this endeavor are absolute production cross sections and energy spectra for neutrons and light charged-particles (LCPs), emission of composite particles prior and post to the attainment of an equilibrated system, distribution of excitation energies deposited in the nuclei after the INC, and fission probabilities. Systematic measurements of such data are furthermore needed over large ranges of target nuclei and incident proton energies. Such data has been measured with the NESSI detector. An overview of new and previous results will be given.

  2. Histopathologic spectrum of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): a diagnosis that needs clinico-pathological correlation.

    PubMed

    Borroni, G; Torti, S; Pezzini, C; Vassallo, C; Rosso, R; D'Ospina, R M; Tomasini, C; Brazzelli, V

    2014-06-01

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by an heterogeneous group of severe dermatologic manifestations and systemic involvement, due to several groups of medicaments. A series of 9 consecutive cases, observed from 2008 to 2013 in the Department of Dermatology, University of Pavia, is reported, all satisfying the clinical, hematological and systemic diagnostic criteria of DRESS. Clinically, 4 out of 9 patients had an urticarial and papular eruption, 2 an erythema-multiforme-like (EM-like) pattern, 2 erythroderma and 1 had an erythematous and macular reaction. Aim of the study was to describe the histopathologic features of DRESS and to trace a possible correlation between the four clinical recognized types of the syndrome and the histopathological patterns. Predominantly, a superficial perivascular lymphocytic infiltrate, extravasation of erythrocytes, and focal interface changes characterized DRESS cases. Less frequently, histopathology revealed the presence of necrotic keratinocytes; surprisingly, only in 2 cases the presence of rare dermal eosinophils was detected, even if all the patients had significant peripheral eosinophilia. A histopathological diagnosis of DRESS seems per se, according to our data, not feasible, since the main histopathological changes (interface changes, superficial perivascular dermatitis, focal spongiosis, lichenoid infiltrate, rare presence of necrotic keratinocytes) can be interpreted generically as a drug induced dermatitis. The above mentioned histopathological changes, however, when associated with clinical information on cutaneous and systemic involvement of the patient, allow the pathologist or the dermatopathologist to make a diagnosis of DRESS with a reliable margin of certainty. PMID:24819756

  3. Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain.

    PubMed

    d'Errico, Michele; Sammarco, Paolo; Vairo, Giuseppe

    2015-09-01

    Pharmacokinetics induced by drug eluting stents (DES) in coronary walls is modeled by means of a one-dimensional multi-layered model, accounting for vessel curvature and non-homogeneous properties of the arterial tissues. The model includes diffusion mechanisms, advection effects related to plasma filtration through the walls, and bio-chemical drug reactions. A non-classical Sturm-Liouville problem with discontinuous coefficients is derived, whose closed-form analytical solution is obtained via an eigenfunction expansion. Soundness and consistency of the proposed approach are shown by numerical computations based on possible clinical treatments involving both hydrophilic and hydrophobic drugs. The influence of the main model parameters on drug delivery mechanisms is analyzed, highlighting the effects induced by vessel curvature and yielding comparative indications and useful insights into the concurring mechanisms governing the pharmacokinetics. PMID:26162517

  4. A Rare Complication of Trimethoprim-Sulfamethoxazole: Drug Induced Aseptic Meningitis

    PubMed Central

    Stromich, Jeremiah; Cohen, Mallory; Wainaina, Jane Njeri

    2016-01-01

    Drug induced aseptic meningitis is a rare but challenging diagnosis, most commonly reported with nonsteroidal anti-inflammatory drugs and antibiotics. Trimethoprim/sulfamethoxazole is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. Drug induced aseptic meningitis, when seen with trimethoprim/sulfamethoxazole, occurs predominantly in patients with some degree of immune compromise and is less commonly seen in immune competent individuals. The patient often exhibits the classic symptoms of meningitis. Early diagnosis is important, since the cessation of the antibiotic leads to rapid clinical improvement. Trimethoprim/sulfamethoxazole induced aseptic meningitis has been underreported to FDA/MED-WATCH program. Here we report two cases of trimethoprim/sulfamethoxazole: an immune competent individual and immune compromised individual, both of which presented with signs of meningitis and a negative infectious workup. Trimethoprim/sulfamethoxazole is an uncommon and mysterious adverse reaction to a commonly used antibiotic. It should be considered in the differential diagnosis of patients presenting with acute signs and symptoms of meningitis especially after infectious causes have been ruled out. PMID:27579194

  5. A Rare Complication of Trimethoprim-Sulfamethoxazole: Drug Induced Aseptic Meningitis.

    PubMed

    Jha, Pinky; Stromich, Jeremiah; Cohen, Mallory; Wainaina, Jane Njeri

    2016-01-01

    Drug induced aseptic meningitis is a rare but challenging diagnosis, most commonly reported with nonsteroidal anti-inflammatory drugs and antibiotics. Trimethoprim/sulfamethoxazole is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. Drug induced aseptic meningitis, when seen with trimethoprim/sulfamethoxazole, occurs predominantly in patients with some degree of immune compromise and is less commonly seen in immune competent individuals. The patient often exhibits the classic symptoms of meningitis. Early diagnosis is important, since the cessation of the antibiotic leads to rapid clinical improvement. Trimethoprim/sulfamethoxazole induced aseptic meningitis has been underreported to FDA/MED-WATCH program. Here we report two cases of trimethoprim/sulfamethoxazole: an immune competent individual and immune compromised individual, both of which presented with signs of meningitis and a negative infectious workup. Trimethoprim/sulfamethoxazole is an uncommon and mysterious adverse reaction to a commonly used antibiotic. It should be considered in the differential diagnosis of patients presenting with acute signs and symptoms of meningitis especially after infectious causes have been ruled out. PMID:27579194

  6. Automated Summarization of Publications Associated with Adverse Drug Reactions from PubMed

    PubMed Central

    Finkelstein, Joseph; Chen, Qinlang; Adams, Hayden; Friedman, Carol

    2016-01-01

    Academic literature provides rich and up-to-date information concerning adverse drug reactions (ADR), but it is time consuming and labor intensive for physicians to obtain information of ADRs from academic literature because they would have to generate queries, review retrieved articles and summarize the results. In this study, a method is developed to automatically detect and summarize ADRs from journal articles, rank them and present them to physicians in a user-friendly interface. The method studied ADRs for 6 drugs and returned on average 4.8 ADRs that were correct. The results demonstrated this method was feasible and effective. This method can be applied in clinical practice for assisting physicians to efficiently obtain information about ADRs associated with specific drugs. Automated summarization of ADR information from recent publications may facilitate translation of academic research into actionable information at point of care. PMID:27570654

  7. Automated Determination of Publications Related to Adverse Drug Reactions in PubMed

    PubMed Central

    Adams, Hayden; Friedman, Carol; Finkelstein, Joseph

    2015-01-01

    Timely dissemination of up-to-date information concerning adverse drug reactions (ADRs) at the point of care can significantly improve medication safety and prevent ADRs. Automated methods for finding relevant articles in MEDLINE which discuss ADRs for specific medications can facilitate decision making at the point of care. Previous work has focused on other types of clinical queries and on retrieval for specific ADRs or drug-ADR pairs, but little work has been published on finding ADR articles for a specific medication. We have developed a method to generate a PubMED query based on MESH, supplementary concepts, and textual terms for a particular medication. Evaluation was performed on a limited sample, resulting in a sensitivity of 90% and precision of 93%. Results demonstrated that this method is highly effective. Future work will integrate this method within an interface aimed at facilitating access to ADR information for specified drugs at the point of care. PMID:26306227

  8. Calreticulin binds to gentamicin and reduces drug-induced ototoxicity.

    PubMed

    Karasawa, Takatoshi; Wang, Qi; David, Larry L; Steyger, Peter S

    2011-12-01

    Aminoglycosides like gentamicin are among the most commonly used antibiotics in clinical practice and are essential for treating life-threatening tuberculosis and Gram-negative bacterial infections. However, aminoglycosides are also nephrotoxic and ototoxic. Although a number of mechanisms have been proposed, it is still unclear how aminoglycosides induce cell death in auditory sensory epithelia and subsequent deafness. Aminoglycosides bind to various intracellular molecules, such as RNA and phosphoinositides. We hypothesized that aminoglycosides, based on their tissue-specific susceptibility, also bind to intracellular proteins that play a role in drug-induced ototoxicity. By conjugating an aminoglycoside, gentamicin, to agarose beads and conducting a gentamicin-agarose pull-down assay, we have isolated gentamicin-binding proteins (GBPs) from immortalized cells of mouse organ of Corti, HEI-OC1. Mass spectrometry identified calreticulin (CRT) as a GBP. Immunofluorescence revealed that CRT expression is concentrated in strial marginal cells and hair cell stereocilia, primary locations of drug uptake and cytotoxicity in the cochlea. In HEI-OC1 cells treated with gentamicin, reduction of CRT expression using small interfering RNA (siRNA) reduced intracellular drug levels. CRT-deficient mouse embryonic fibroblast (MEF) cells as well as CRT siRNA-transfected wild-type MEFs also had reduced cell viability after gentamicin treatment. A pull-down assay using deletion mutants of CRT determined that the carboxyl C-domain of CRT binds to gentamicin. HeLa cells transfected with CRT C-domain deletion mutant construct were more susceptible to gentamicin-induced cytotoxicity compared with cells transfected with full-length CRT or other deletion mutants. Therefore, we conclude that CRT binding to gentamicin is protective against gentamicin-induced cytotoxicity. PMID:21785162

  9. Identifying plausible adverse drug reactions using knowledge extracted from the literature.

    PubMed

    Shang, Ning; Xu, Hua; Rindflesch, Thomas C; Cohen, Trevor

    2014-12-01

    Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to "rediscover" these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831

  10. Identifying plausible adverse drug reactions using knowledge extracted from the literature

    PubMed Central

    Shang, Ning; Xu, Hua; Rindflesch, Thomas C.; Cohen, Trevor

    2014-01-01

    Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to “rediscover” these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831

  11. Increasing the Number of Adverse Drug Reactions Reporting: the Role of Clinical Pharmacy Residents

    PubMed Central

    Baniasadi, Shadi; Habibi, Maryam; Haghgoo, Roodabeh; Karimi Gamishan, Masoumeh; Dabaghzadeh, Fatemeh; Farasatinasab, Maryam; Farsaei, Shadi; Gharekhani, Afshin; Kafi, Hamidreza; Karimzadeh, Iman; Kharazmkia, Ali; Najmeddin, Farhad; Nikvarz, Naemeh; Oghazian, Mohammad Bagher; Rezaee, Haleh; Sadeghi, Kourosh; Tafazzoli, Ali; Shahsavari, Nahid; Fahimi, Fanak

    2014-01-01

    Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents' involvement in the ADR reporting program could improve the ADR reporting system. PMID:24734083

  12. Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

    PubMed

    Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

    2015-03-01

    We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes. PMID:25680092

  13. Detection of metabolic activation leading to drug-induced phospholipidosis in rat hepatocyte spheroids.

    PubMed

    Takagi, Masashi; Sanoh, Seigo; Santoh, Masataka; Ejiri, Yoko; Kotake, Yaichiro; Ohta, Shigeru

    2016-02-01

    Drug-induced phospholipidosis (PLD) is one of the adverse reactions to treatment with cationic amphiphilic drugs. Recently, simple and reliable evaluation methods for PLD have been reported. However, the predictive power of these methods for in vivo PLD induction is insufficient in some cases. To accurately predict PLD, we focused on drug metabolism and used three-dimensional cultures of hepatocytes known as spheroids. Here we used the fluorescent phospholipid dye N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE) to detect PLD induction. After 48 hr exposure to 20 µM amiodarone and amitriptyline, PLD inducers, NBD-PE fluorescence in the spheroids was significantly higher than that in the control. In contrast, 1 mM acetaminophen, as a negative control, did not increase fluorescence. Furthermore, the combination of NBD-PE fluorescence and LysoTracker Red fluorescence and the accumulation of intrinsic phospholipids reflected PLD induction in spheroids. To evaluate metabolic activation, we assessed PLD induction by loratadine. NBD-PE fluorescence intensity was significantly increased by 50 µM loratadine treatment. However, the fluorescence was markedly decreased by co-treatment with 500 µM 1-aminobenzotriazole, a broad cytochrome P450 inhibitor. The formation of desloratadine, a metabolite of loratadine, was observed in spheroids after treatment with loratadine alone. These results showed that metabolic activation is the key factor in PLD induction by treatment with loratadine. We demonstrated that rat primary hepatocyte spheroid culture is a useful model for evaluating drug-induced PLD induction mediated by metabolic activation of the drug using the fluorescence probe technique. PMID:26763403

  14. Ocular changes induced by drugs commonly used in dermatology.

    PubMed

    Turno-Kręcicka, Anna; Grzybowski, Andrzej; Misiuk-Hojło, Marta; Patryn, Eliza; Czajor, Karolina; Nita, Małgorzata

    2016-01-01

    The use of many drugs in dermatologic diseases may cause ocular side effects. Some may regress after discontinuation of the therapy, but others persist or progress even after the cessation of treatment. This review presents four groups of commonly prescribed drugs-antimalarial medicines, glucocorticoids, retinoids, and psoralens + ultraviolet A (UVA) therapy-and discusses their possible ocular side effects. The most significant complication of antimalarial drugs is retinopathy with the risk of permanent visual impairment. There are different recommendations for screening for this drug-related retinopathy. The most important ocular manifestations of steroid management are irreversible optic nerve damage in "steroid responders" (steroid glaucoma) and cataract. Some other side effects may disappear after discontinuation of the therapy. Retinoid-induced ocular side effects include ocular surface disease as well as retinal dysfunction. It is recommended to modify the therapy when night blindness occurs or after the decrease of color vision. Protective eyewear is sufficient to avoid ocular surface problems during psoralen + UVA therapy. The knowledge of screening schemes and closer cooperation between physicians may decrease the risk of serious or irreversible ocular side effects. PMID:26903180

  15. [Role of Human Orphan Esterases in Drug-induced Toxicity].

    PubMed

    Fukami, Tatsuki

    2015-01-01

    Esterases hydrolyze compounds containing ester, amide, and thioester bonds, causing prodrug activation or detoxification. Among esterases, carboxylesterases have been studied in depth due to their ability to hydrolyze a variety of drugs. However, there are several drugs for which the involved esterase(s) is unknown. We found that flutamide, phenacetin, rifamycins (rifampicin, rifabutin, and rifapentine), and indiplon are hydrolyzed by arylacetamide deacetylase (AADAC), which is highly expressed in human liver and gastrointestinal tissues. Flutamide hydrolysis is considered associated with hepatotoxicity. Phenacetin, a prodrug of acetaminophen, was withdrawn due to side effects such as methemoglobinemia and renal failure. It was demonstrated in vitro and in vivo using mice that AADAC is responsible for phenacetin hydrolysis, which leads to methemoglobinemia. In addition, it was shown that AADAC-mediated hydrolysis attenuates the cytotoxicity of rifamycins. Thus AADAC plays critical roles in drug-induced toxicity. Another orphan esterase, α/β hydrolase domain containing 10 (ABHD10), was found responsible for deglucuronidation of acyl-glucuronides including mycophenolic acid acyl-glucuronide and probenecid acyl-glucuronide. Because acyl-glucuronides appear associated with toxicity, ABHD10 would function as a detoxification enzyme. The roles of orphan esterases are becoming increasingly understood. Further studies will facilitate our knowledge of the pharmacologic and toxicological significance of orphan esterases in drug therapy. PMID:26521872

  16. Virus reactivation and intravenous immunoglobulin (IVIG) therapy of drug-induced hypersensitivity syndrome.

    PubMed

    Kano, Yoko; Inaoka, Miyuki; Sakuma, Keiichi; Shiohara, Tetsuo

    2005-04-15

    Drug-induced hypersensitivity syndrome (DIHS) is a severe multi-organ system reaction caused by specific drugs. Many reports have revealed that human herpesvirus 6 (HHV-6) reactivation contributes to the development of DIHS. In addition, recent articles have shown that reactivation of other herpesviruses such as human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), cytomegalovirus (CMV) might be also implicated in the development of DIHS. These observations suggest that not only HHV-6 but also other herpesvirses might reactivate from the latency and play an important role in the appearance of clinical manifestations of DIHS. Several patients with DIHS were treated with intravenous immunoglobulin (IVIG) in addition to systemic corticosteroids. The results have been encouraging although virus reactivation could not be suppressed. Although the pathomechanism of IVIG treatment in patients with DIHS remains unknown, the therapeutic effects of IVIG could be dependent, in part, on functional capabilities of anti-virus IgG contained in IVIG. PMID:15767030

  17. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  18. Gastric erosions induced by analgesic drug mixtures in the rat.

    PubMed

    Seegers, A J; Jager, L P; Van Noordwijk, J

    1978-02-01

    Gastric erosions after oral administration of analgesics separately and in admixture have been examined in adult rats. After administration of acetylsalicylic acid (aspirin), phenacetin, paracetamol and caffeine as single drugs, gastric erosions were only observed with aspirin. The combination of aspirin with phenacetin did not change, that of aspirin with caffeine significantly increased, and aspirin with paracetamol significantly decreased the incidence of gastric lesions compared with aspirin alone. The results for aspirin with paracetamol did not differ from those for the vehicle. Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred. The mechanisms underlying the effects of these drugs on aspirin-induced erosions are discussed. PMID:24109

  19. Drug-Induced Liver Injury: Pattern Recognition and Future Directions

    PubMed Central

    Haque, Tanvir; Sasatomi, Eizaburo; Hayashi, Paul H.

    2016-01-01

    Drug-induced liver injury (DILI) remains a significant clinical challenge and is the leading cause of acute liver failure in most countries. An aging population that uses more medications, a constant influx of newly developed drugs and a growing risk from unfamiliar herbal and dietary supplements will make DILI an increasing part of clinical practice. Currently, the most effective strategy for disease management is rapid identification, withholding the inciting agents, supportive care and having a firm understanding of the expected natural history. There are resources available to aid the clinician, including a new online “textbook” as well as causality assessment tools, but a heightened awareness of risk and the disease’s varying phenotypes and good history-taking remain cornerstones to diagnosis. Looking ahead, growing registries of cases, pharmacoepidemiology studies and translational research into the mechanisms of injury may produce better diagnostic tools, markers for risk and disease, and prevention and therapeutics. PMID:26696029

  20. Drug-induced liver injury with autoimmune features.

    PubMed

    deLemos, Andrew S; Foureau, David M; Jacobs, Carl; Ahrens, Will; Russo, Mark W; Bonkovsky, Herbert L

    2014-05-01

    Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an important category of hepatotoxicity due to medication exposure. Drugs repeatedly associated with AI-DILI include diclofenac, α-methyl DOPA, hydralazine, nitrofurantoin, minocycline, and more recently statins and anti-TNF-α agents. Usually, symptoms of acute liver injury occur within a few months after initiation of a culprit medication, but a longer latency period is possible. Like idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are frequently present in sera from patients with AI-DILI. If performed, a liver biopsy should demonstrate interface hepatitis with a prominent plasma cell infiltrate. The severity of AI-DILI is variable, but a complete resolution after withdrawal of the offending medication is the expectation. A response to corticosteroid therapy supports the diagnosis, whereas a lack of recurrence of symptoms or signs following corticosteroid cessation distinguishes AI-DILI from idiopathic autoimmune hepatitis. PMID:24879983

  1. Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development

    PubMed Central

    Wehbe, Mohamed; Anantha, Malathi; Backstrom, Ian; Leung, Ada; Chen, Kent; Malhotra, Armaan; Edwards, Katarina; Bally, Marcel B.

    2016-01-01

    The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2 inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients. PMID:27055237

  2. Completeness of adverse drug reactions reports of the Saudi adverse event reporting system

    PubMed Central

    Alshammari, Thamir M.; Al-Kathiri, Wa’ad H.; Louet, Hervé Le; Aljadhey, Hisham S.

    2015-01-01

    Objectives: To assess completeness of reports in the Saudi Adverse Event Reporting System (SAERS), which is a part of the Saudi Food and Drug Authority pharmacovigilance system for monitoring the safety of medications. Methods: A cross-sectional study was conducted in Riyadh, Saudi Arabia using the reports that were received between December 2009 and June 2012 in the SAERS. The completeness was assessed by reviewing the components of the adverse drug reactions (ADRs) form, and how many fields were completed. Descriptive statistics are reported. Result: There were 14,783 reports during the study period. Eighty percent of these reports were spontaneous reports. Information related to the drug (99%) and adverse events (98%) of the reports were completed. While the patient’s demographic data were completed only in 38% of all reports, the least completed item in the ADRs form was the reporter information (15%). The most reported drug class was tumor necrosis factor inhibitors (7%), whereas events involving the respiratory organ system were the most frequently reported (4.5%). Conclusion: Although the SAERS is considered new, it has a high number of reports. More efforts are needed to improve the completeness of the SAERS to be a good source to assess the signals between events and suspected drugs, especially when there is a high number of reports. PMID:26108586

  3. Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

    PubMed

    Mangoni, Arduino A

    2012-05-01

    Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings. PMID:22512705

  4. Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development.

    PubMed

    Wehbe, Mohamed; Anantha, Malathi; Backstrom, Ian; Leung, Ada; Chen, Kent; Malhotra, Armaan; Edwards, Katarina; Bally, Marcel B

    2016-01-01

    The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2 inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients. PMID:27055237

  5. Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program

    PubMed Central

    Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

    2012-01-01

    Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

  6. Doxorubicin induces drug efflux pumps in Candida albicans.

    PubMed

    Kofla, Grzegorz; Turner, Vincent; Schulz, Bettina; Storch, Ulrike; Froelich, Daniela; Rognon, Bénédicte; Coste, Alix T; Sanglard, Dominique; Ruhnke, Markus

    2011-02-01

    Candida albicans is one of the most important opportunistic fungal pathogens. It can cause serious fungal diseases in immunocompromised patients, including those with cancer. Treatment failures due to the emergence of drug-resistant C. albicans strains have become a serious clinical problem. Resistance incidents were often mediated by fungal efflux pumps which are closely related to the human ABC transporter P-glycoprotein (P-gp). P-gp is often overexpressed in cancer cells and confers resistance to many cytotoxic drugs. We examined whether cytotoxic drugs commonly used for cancer treatment (doxorubicin and cyclophosphamide) could alter the expression of genes responsible for the development of fluconazole resistance in Candida cells in the way they can influence homologous genes in cancer cell lines. ABC transporters (CDR1 and CDR2) and other resistance genes (MDR1 and ERG11) were tested by real-time PCR for their expression in C. albicans cells at the mRNA level after induction by antineoplastic drugs. The results were confirmed by a lacZ gene reporter system and verified at the protein level using GFP and immunoblotting. We showed that doxorubicin is a potent inducer of CDR1/CDR2 expression in C. albicans at both the mRNA and protein level and thus causes an increase in fluconazole MIC values. However, cyclophosphamide, which is not a substrate of human P-gp, did not induce ABC transporter expression in C. albicans. Neither doxorubicin nor cyclophosphamide could influence the expression of the other resistance genes (MDR1 and ERG11). The induction of CDR1/CDR2 by doxorubicin in C. albicans and the resulting alteration of antifungal susceptibility might be of clinical relevance for the antifungal treatment of Candida infections occurring after anticancer chemotherapy with doxorubicin. PMID:20818920

  7. The validation of an invitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions

    SciTech Connect

    Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David

    2010-06-15

    Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.

  8. Spontaneous Reporting of Adverse Drug Reactions through Electronic Submission from Regional Society Healthcare Professionals in Korea

    PubMed Central

    Lee, Jae-Hyun; Park, Kyung Hee; Moon, Hyun Joo; Lee, Yong Won; Park, Jung-Won

    2012-01-01

    Purpose Pharmacovigilance Research Network built a spontaneous reporting system and collected adverse drug reactions (ADRs) by electronic submission (e-sub) in Korea. We analyzed ADRs spontaneously reported through e-sub from regional health professionals. Materials and Methods Nine hundred and thirty three ADR cases were collected and analyzed from January to December in 2008. "A matter" was defined as one symptom matched to one culprit drug included in an ADR case. We collected and analyzed e-sub ADR cases and matters to determine common culprits and organ specified ADR matters. Results There were 3,049 matters in 933 ADR cases for 1 year, and 3.3 matters per case were reported. In organ specific ADR classification, skin reactions which took the first place in 866 matters (28%) included urticaria and rash. The next cases were neurologic symptom (624 matters, 21%) and gastrointestinal symptom (581 matters, 19%). Doctor (53%) and pharmacist (31%) were the most important participants in e-sub spontaneous reporting system, and 3% of ADR cases were reported by patients or their guardians. WHO-Uppsala Monitoring Center causality assessment results showed certain 10.6%, probable 37.7%, possible 41.7% and below unlikely 10.0%. Culprit drugs were antibiotics (23.4%), neurologic agents (14.7%) and non-steroidal anti-inflammatory drugs (9.4%). Conclusion In our study, antibiotic was most common culprit drug, and skin manifestation was most common symptom in e-sub ADRs collected from regional healthcare practitioners in Korea. PMID:22869488

  9. Role of mitochondria in drug-induced cholestatic injury.

    PubMed

    Kass, George E N; Price, Shirley C

    2008-02-01

    Mitochondria have multiple functions in eukaryotic cells and are organized into dynamic tubular networks that continuously undergo changes through coordinated fusion and fission and migration through the cytosol. Mitochondria integrate cell-signaling networks, especially those involving the intracellular messenger Ca(2+), into the regulation of metabolic pathways. Recently, it has become clear that mitochondria are central to the three main cell death pathways, namely necrosis, apoptosis, and autophagic cell death. This article discusses the role of mitochondria in drug-induced cholestatic injury to the liver. The role of mitochondria in the cellular adaptation against the toxic effects of bile acids is discussed also. PMID:18242496

  10. An Update on Treatment of Drug-Induced Liver Injury

    PubMed Central

    Rivas, John; Zervos, Xaralambos

    2014-01-01

    Drug-induced liver injury (DILI) has been linked to more than 1,000 medications and remains the most common cause of acute liver failure in the United States. Here, we review the most current literature regarding treatment and make recommendations for the management of this relatively common disease. Since treatment of DILI remains largely elusive, recent studies have attempted to define new management strategies for these difficult patients. Early diagnosis and withdrawal of the suspected medication is the mainstay of treatment of DILI. For acetaminophen and Amanita mushroom poisoning, there are specific therapies in use. Finally, there are other possible management modalities for DILI, including corticosteroids and ursodeoxycholic acid. PMID:26356645

  11. Early monitoring for detection of antituberculous drug-induced hepatotoxicity

    PubMed Central

    Lee, Chang Min; Lee, Sang Soo; Lee, Jeong Mi; Cho, Hyun Chin; Kim, Wan Soo; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok Jae

    2016-01-01

    Background/Aims: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. Methods: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. Results: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 ± 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The ≤ 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the ≤ 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. Conclusions: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen. PMID:26767859

  12. Siderite breakdown and pressure induced Fe-C redox reactions

    NASA Astrophysics Data System (ADS)

    Lavina, Barbara; Dera, Przemyslaw; Kim, Eunja; Downs, Robert T.

    2010-05-01

    Siderite, FeCO3, was investigated at high pressure (up to ~ 40 GPa) and high temperature (up to about 2400K) using a laser heated diamond anvil cell. The structure of the sample was probed with a synchrotron monochromatic beam; powder, multigrain and single crystaldiffraction techniques were used according to changing size of the crystallites in the course of the experiment. At about 35 GPa we observed the breakdown of the carbonate into h-Fe3O4 (the orthorhombic high pressure phase of Fe3O4[1]) and undetected carbon phases. We suggest the breakdown was achieved through a redox reaction where the iron formal valence is increased at the expense of the carbon reduction. This observation is in agreement with results of shock experiments on siderite [2-4] in which however the presence of hematite in the starting material prevented to discriminate among possible reactions determining the synthesis of Fe3O4. Oxygen fugacity and the crystal chemistry of deep Earth mineral assemblages exert a major control on ionic speciation, therefore experimental confirmation are necessary to determine the actual redox equilibrium between iron and carbon in the mantle. Remarkably, perovskite strongly favor the partitioning of Fe3+ [5] and so it might favor the C reduction. If the pressure effect on Fe-C redox equilibrium found in this experiment is active in the deep Earth, the speciation of carbon would be strongly affected, in particular, the stability of carbonates and CO2 might be controlled by pressure induced reductions rather than by the stability of the pure phases. Carbon reduction at pressure might account for the greater subduction of carbon with respect to hydrogen [6]. On the other hand uplifting of reduced carbon assembly might release C-O fluids through reduction of Fe3+. Our results suggest that Fe-C redox reactions might have a crucial role on the carbon speciation which has a major importance on deep Earth processes. References [1] Haavik, et al. (2000) American

  13. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    PubMed

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. PMID:26141794

  14. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy.

    PubMed

    Biju, Vasudevanpillai

    2014-02-01

    As prepared nanomaterials of metals, semiconductors, polymers and carbon often need surface modifications such as ligand exchange, and chemical and bioconjugate reactions for various biosensor, bioanalytical, bioimaging, drug delivery and therapeutic applications. Such surface modifications help us to control the physico-chemical, toxicological and pharmacological properties of nanomaterials. Furthermore, introduction of various reactive functional groups on the surface of nanomaterials allows us to conjugate a spectrum of contrast agents, antibodies, peptides, ligands, drugs and genes, and construct multifunctional and hybrid nanomaterials for the targeted imaging and treatment of cancers. This tutorial review is intended to provide an introduction to newcomers about how chemical and bioconjugate reactions transform the surface of nanomaterials such as silica nanoparticles, gold nanoparticles, gold quantum clusters, semiconductor quantum dots, carbon nanotubes, fullerene and graphene, and accordingly formulate them for applications such as biosensing, bioimaging, drug and gene delivery, chemotherapy, photodynamic therapy and photothermal therapy. Nonetheless, controversial reports and our growing concerns about toxicity and pharmacokinetics of nanomaterials suggest the need for not only rigorous in vivo experiments in animal models but also novel nanomaterials for practical applications in the clinical settings. Further reading of original and review articles cited herein is necessary to buildup in-depth knowledge about the chemistry, bioconjugate chemistry and biological applications of individual nanomaterials. PMID:24220322

  15. Normal lipase drug-induced pancreatitis: a novel finding.

    PubMed

    Shafqet, Muhammad A; Brown, Teresa V; Sharma, Ranita

    2015-03-01

    Acute pancreatitis (AP) in the setting of a normal serum amylase has been previously reported in the literature. Serum lipase on the other hand has a negative predictive value approaching 100% and therefore is an excellent test to rule out AP in the emergency department. The occurrence of AP with a normal lipase is extremely rare and has never been reported in the setting of drug-induced pancreatitis. Thiazide diuretics have been implicated as a cause of pancreatic injury via a number of proposed mechanisms. However, all such cases have been in the setting of elevated serum amylase or lipase. We report the first case of radiographically proven hydrochlorothiazide-induced pancreatitis with a normal lipase. PMID:25227976

  16. A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction.

    PubMed

    Li, Hui; Li, Junjie; Ke, Wendong; Ge, Zhishen

    2015-10-01

    Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX)-loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels-Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b-POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR-triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation. PMID:26274805

  17. Misuse of the Naranjo Adverse Drug Reaction Probability Scale in toxicology

    PubMed Central

    Seger, Donna; BARKER, Kimberly; McNAUGHTON, Candace D.

    2014-01-01

    Context When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo and colleagues developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients. Objective The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application. Methods A Medline search via PubMed without language limits, through September 2012, using the search terms “Naranjo” and “overdose” or “poisoning” yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients. Results From the 146 publications, we identified 17 case reports or series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Conclusion Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case

  18. Over-Pressure Suppresses Ultrasonic-Induced Drug Uptake

    PubMed Central

    Stringham, S. Briant; Viskovska, Maria A.; Richardson, Eric S.; Ohmine, Seiga; Husseini, Ghaleb A.; Murray, Byron K.; Pitt, William G.

    2012-01-01

    Ultrasound (US) is used to enhance and target delivery of drugs and genes to cancer tissues. The present study further examines the role of acoustic cavitation in US-induced permeabilization of cell membranes and subsequent drug or gene uptake by the cell. Rat colon cancer cells were exposed to ultrasound at various static pressures to examine the hypothesis that oscillating bubbles, also known as cavitating bubbles, permeabilize cells. Increasing pressure suppresses bubble cavitation activity; thus if applied pressure were to reduce drug uptake, cell permeabilization would be strongly linked to bubble cavitation activity. Cells were exposed to 476 kHz pulsed ultrasound at average intensities of 2.75 W/cm2 and 5.5 W/cm2 at various pressures and times in an isothermal chamber. Cell fractions with reversible membrane damage (calcein uptake) and irreversible damage (propidium iodide uptake) were analyzed by flow cytometry. Pressurization to 3 atm nearly eliminated the biological effect of US in promoting calcein uptake. Data also showed a linear increase in membrane permeability based upon increased time and intensity. This research shows that US-mediated cell membrane permeability is likely linked to cavitation bubble activity. PMID:19056161

  19. Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

    PubMed Central

    Tangiisuran, Balamurugan; Scutt, Greg; Stevenson, Jennifer; Wright, Juliet; Onder, G.; Petrovic, M.; van der Cammen, T. J.; Rajkumar, Chakravarthi; Davies, Graham

    2014-01-01

    Background Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. Methods We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). Results Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. Conclusions We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported. PMID:25356898

  20. MONITORING POTENTIAL DRUG INTERACTIONS AND REACTIONS VIA NETWORK ANALYSIS OF INSTAGRAM USER TIMELINES

    PubMed Central

    CORREIA, RION BRATTIG; LI, LANG; ROCHA, LUIS M.

    2015-01-01

    Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this “Bibliome”, the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products—including cannabis—which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015. We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that

  1. MONITORING POTENTIAL DRUG INTERACTIONS AND REACTIONS VIA NETWORK ANALYSIS OF INSTAGRAM USER TIMELINES.

    PubMed

    Correia, Rion Brattig; Li, Lang; Rocha, Luis M

    2016-01-01

    Much recent research aims to identify evidence for Drug-Drug Interactions (DDI) and Adverse Drug reactions (ADR) from the biomedical scientific literature. In addition to this "Bibliome", the universe of social media provides a very promising source of large-scale data that can help identify DDI and ADR in ways that have not been hitherto possible. Given the large number of users, analysis of social media data may be useful to identify under-reported, population-level pathology associated with DDI, thus further contributing to improvements in population health. Moreover, tapping into this data allows us to infer drug interactions with natural products-including cannabis-which constitute an array of DDI very poorly explored by biomedical research thus far. Our goal is to determine the potential of Instagram for public health monitoring and surveillance for DDI, ADR, and behavioral pathology at large. Most social media analysis focuses on Twitter and Facebook, but Instagram is an increasingly important platform, especially among teens, with unrestricted access of public posts, high availability of posts with geolocation coordinates, and images to supplement textual analysis. Using drug, symptom, and natural product dictionaries for identification of the various types of DDI and ADR evidence, we have collected close to 7000 user timelines spanning from October 2010 to June 2015.We report on 1) the development of a monitoring tool to easily observe user-level timelines associated with drug and symptom terms of interest, and 2) population-level behavior via the analysis of co-occurrence networks computed from user timelines at three different scales: monthly, weekly, and daily occurrences. Analysis of these networks further reveals 3) drug and symptom direct and indirect associations with greater support in user timelines, as well as 4) clusters of symptoms and drugs revealed by the collective behavior of the observed population. This demonstrates that Instagram

  2. Adherence to Drug Label Recommendations for Avoiding Drug Interactions Causing Statin-Induced Myopathy–A Nationwide Register Study

    PubMed Central

    Settergren, Jennifer; Eiermann, Birgit; Mannheimer, Buster

    2013-01-01

    found no evidence for avoiding co-prescriptions of statins and antibiotics with an increased risk of statin-induced adverse drug reactions. Co-prescription of statins and gemfibrozil is paradoxically associated with a marked increased statin dose, further aggravating the risk for severe myopathy. PMID:23940522

  3. Zebrafish as model organisms for studying drug-induced liver injury

    PubMed Central

    Vliegenthart, A D Bastiaan; Tucker, Carl S; Del Pozo, Jorge; Dear, James W

    2014-01-01

    Drug-induced liver injury (DILI) is a major challenge in clinical medicine and drug development. New models are needed for predicting which potential therapeutic compounds will cause DILI in humans, and new markers and mediators of DILI still need to be identified. This review highlights the strengths and weaknesses of using zebrafish as a high-throughput in vivo model for studying DILI. Although the zebrafish liver architecture is different from that of the mammalian liver, the main physiological processes remain similar. Zebrafish metabolize drugs using similar pathways to those in humans; they possess a wide range of cytochrome P450 enzymes that enable metabolic reactions including hydroxylation, conjugation, oxidation, demethylation and de-ethylation. Following exposure to a range of hepatotoxic drugs, the zebrafish liver develops histological patterns of injury comparable to those of mammalian liver, and biomarkers for liver injury can be quantified in the zebrafish circulation. The zebrafish immune system is similar to that of mammals, but the zebrafish inflammatory response to DILI is not yet defined. In order to quantify DILI in zebrafish, a wide variety of methods can be used, including visual assessment, quantification of serum enzymes and experimental serum biomarkers and scoring of histopathology. With further development, the zebrafish may be a model that complements rodents and may have value for the discovery of new disease pathways and translational biomarkers. PMID:24773296

  4. Will water act as a photocatalyst for cluster phase chemical reactions? Vibrational overtone-induced dehydration reaction of methanediol

    SciTech Connect

    Kramer, Zeb C.; Takahashi, Kaito; Skodje, Rex T.; Vaida, Veronica

    2012-04-28

    The possibility of water catalysis in the vibrational overtone-induced dehydration reaction of methanediol is investigated using ab initio dynamical simulations of small methanediol-water clusters. Quantum chemistry calculations employing clusters with one or two water molecules reveal that the barrier to dehydration is lowered by over 20 kcal/mol because of hydrogen-bonding at the transition state. Nevertheless, the simulations of the reaction dynamics following OH-stretch excitation show little catalytic effect of water and, in some cases, even show an anticatalytic effect. The quantum yield for the dehydration reaction exhibits a delayed threshold effect where reaction does not occur until the photon energy is far above the barrier energy. Unlike thermally induced reactions, it is argued that competition between reaction and the irreversible dissipation of photon energy may be expected to raise the dynamical threshold for the reaction above the transition state energy. It is concluded that quantum chemistry calculations showing barrier lowering are not sufficient to infer water catalysis in photochemical reactions, which instead require dynamical modeling.

  5. Systematic Analysis of the Associations between Adverse Drug Reactions and Pathways

    PubMed Central

    Chen, Xiaowen; Wang, Yanqiu; Wang, Pingping; Lian, Baofeng; Li, Chunquan; Wang, Jing; Li, Xia; Jiang, Wei

    2015-01-01

    Adverse drug reactions (ADRs) are responsible for drug candidate failure during clinical trials. It is crucial to investigate biological pathways contributing to ADRs. Here, we applied a large-scale analysis to identify overrepresented ADR-pathway combinations through merging clinical phenotypic data, biological pathway data, and drug-target relations. Evaluation was performed by scientific literature review and defining a pathway-based ADR-ADR similarity measure. The results showed that our method is efficient for finding the associations between ADRs and pathways. To more systematically understand the mechanisms of ADRs, we constructed an ADR-pathway network and an ADR-ADR network. Through network analysis on biology and pharmacology, it was found that frequent ADRs were associated with more pathways than infrequent and rare ADRs. Moreover, environmental information processing pathways contributed most to the observed ADRs. Integrating the system organ class of ADRs, we found that most classes tended to interact with other classes instead of themselves. ADR classes were distributed promiscuously in all the ADR cliques. These results reflected that drug perturbation to a certain pathway can cause changes in multiple organs, rather than in one specific organ. Our work not only provides a global view of the associations between ADRs and pathways, but also is helpful to understand the mechanisms of ADRs. PMID:26495310

  6. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  7. Fabrication of biodendrimeric β-cyclodextrin via click reaction with potency of anticancer drug delivery agent.

    PubMed

    Toomari, Yousef; Namazi, Hassan; Entezami, Ali Akbar

    2015-08-01

    The aim of this work was the synthesis of biodendrimeric β-cyclodextrin (β-CD) on the secondary face with encapsulation efficacy, with β-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 β-CD residues attached to the core β-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with (1)H NMR, (13)C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment. PMID:26056989

  8. Measuring the preventability of adverse drug reactions in France: A 2015 overview.

    PubMed

    Olivier-Abbal, Pascale

    2016-01-01

    In recent years, the preventability of adverse drug reactions (ADRs) has gradually gained ground as an additional criterion for assessing drug-related risk, alongside seriousness, causality mechanism of action or frequency. However, the definition of preventability itself remains a concept that needs to be defined clearly so as to compare study results. After an overview of the current methods of measuring preventability, which include a French instrument, this work proposes a synthesis of the French studies assessing the preventability of ADRs over the last 30 years. Measuring preventability is important to classify ADRs as preventable/not preventable, but the ultimate aim remains to characterize these preventable ADRs, highlighting the clinical situations and drug classes related to the risk. It is then possible to provide targeted clinical actions to correct these situations and improve the clinical use of these drugs. Thus, assessing medical preventability should address the causes of ADRs and not the responsibility of healthcare professionals. Finally, certain ideas are proposed to improve the French scale and pursue its validation. PMID:27080838

  9. A Systematic Investigation of Computation Models for Predicting Adverse Drug Reactions (ADRs)

    PubMed Central

    Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

    2014-01-01

    Background Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. Principal Findings In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Conclusion Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms. PMID:25180585

  10. RUCAM in Drug and Herb Induced Liver Injury: The Update.

    PubMed

    Danan, Gaby; Teschke, Rolf

    2016-01-01

    RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common

  11. MicroRNAs and drug-induced kidney injury.

    PubMed

    Pavkovic, Mira; Vaidya, Vishal S

    2016-07-01

    Drug-induced kidney injury (DIKI) is a severe complication in hospitalized patients associated with higher probabilities of developing progressive chronic kidney disease or end-stage renal diseases. Furthermore, DIKI is a problem during preclinical and clinical phases of drug development leading to high rates of project terminations. Understanding the molecular perturbations caused by DIKI would pave the way for a new class of therapeutics to mitigate the damage. Yet, another approach to ameliorate DIKI is identifying sensitive and specific translational biomarkers that outperform the current diagnostic analytes like serum creatinine and facilitate early diagnosis. MicroRNAs (miRNAs), a class of non-coding RNAs, are increasingly being recognized to have a two-pronged approach toward DIKI management: 1) miRNAs have a regulatory role in gene expression and signaling pathways thereby making them novel interventional targets and 2) miRNAs enable diagnosis and prognosis of DIKI because of their stable presence in biofluids. In this review, apart from summarizing the literature on miRNAs in DIKI, we report small RNA sequencing results showing miRNA expression profiles at baseline in normal kidney samples from mice and humans. Additionally, we also compared the miRNA expression in biopsies of normal human kidneys to patients with acute tubular necrosis, and found 76 miRNAs significantly downregulated and 47 miRNAs upregulated (FDR adjusted p<0.05, +/-2-fold change). In summary, we highlight the transformative potential of miRNAs in therapeutics and translational medicine with a focus on drug-induced kidney damage. PMID:27126472

  12. RUCAM in Drug and Herb Induced Liver Injury: The Update

    PubMed Central

    Danan, Gaby; Teschke, Rolf

    2015-01-01

    RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common

  13. Adverse drug reactions in a psychiatric department of tertiary care teaching hospital in India: Analysis of spontaneously reported cases.

    PubMed

    Patel, Tejas K; Bhabhor, Prakash H; Desai, Nimisha; Shah, Saurabh; Patel, Parvati B; Vatsala, Ela; Panigrahi, Sanjibani

    2015-10-01

    The epidemiological data are limited for the spontaneous adverse drug reaction (ADR) reporting system in psychiatry and its comparison with intensive monitoring studies in terms of causative drugs, seriousness, preventability and drug interactions. This spontaneous ADR reporting study was carried out over a period of three years in the psychiatry department. We adopted WHO definition for an ADR, Naranjo's algorithm for causality, WHO-ADR terminology for the labeling of involved organ-system, International conference on harmonisation (ICH) E2A guidelines for seriousness, modified Schumock and Thornton's criteria for preventability and Medscape drug interaction checker for drug interactions. Two subgroup analyses were performed to find out the risk factors for the serious and preventable reactions. A total of 97 ADRs from 67 patients were included for analysis. The incidence of 'overall' and 'serious ADRs were 0.69% (95% CI: 0.54%, 0.88%) and 0.18% (95% CI: 0.12-0.29%), respectively. The females experienced more ADRs than males. The most commonly reported ADR, incriminated pharmacology group and drug, were extrapyramidal movement disorders (22.68%), atypical antipsychotics (35.62%) and escitalopram (13.91%), respectively. One out of five and one out three reactions were considered as 'serious' and 'preventable', respectively. The drug interactions contributed in 34.02% reactions. The factors significantly associated with 'serious' reactions were typical antipsychotics [OR: 5.47 (1.68, 17.87)], central and peripheral nervous system disorders [OR: 24.00 (5.12, 112.5)] and extrapyramidal reactions [OR: 14.03 (4.43, 44.43)]. The polypharmacy [OR: 5.85 (1.90, 18.03)] was significantly associated with 'preventable' reactions. The spontaneous reporting system is efficient to detect serious reactions and preventable reactions. PMID:26216702

  14. Mechanism of coupling drug transport reactions located in two different membranes.

    PubMed

    Zgurskaya, Helen I; Weeks, Jon W; Ntreh, Abigail T; Nickels, Logan M; Wolloscheck, David

    2015-01-01

    Gram- negative bacteria utilize a diverse array of multidrug transporters to pump toxic compounds out of the cell. Some transporters, together with periplasmic membrane fusion proteins (MFPs) and outer membrane channels, assemble trans-envelope complexes that expel multiple antibiotics across outer membranes of Gram-negative bacteria and into the external medium. Others further potentiate this efflux by pumping drugs across the inner membrane into the periplasm. Together these transporters create a powerful network of efflux that protects bacteria against a broad range of antimicrobial agents. This review is focused on the mechanism of coupling transport reactions located in two different membranes of Gram-negative bacteria. Using a combination of biochemical, genetic and biophysical approaches we have reconstructed the sequence of events leading to the assembly of trans-envelope drug efflux complexes and characterized the roles of periplasmic and outer membrane proteins in this process. Our recent data suggest a critical step in the activation of intermembrane efflux pumps, which is controlled by MFPs. We propose that the reaction cycles of transporters are tightly coupled to the assembly of the trans-envelope complexes. Transporters and MFPs exist in the inner membrane as dormant complexes. The activation of complexes is triggered by MFP binding to the outer membrane channel, which leads to a conformational change in the membrane proximal domain of MFP needed for stimulation of transporters. The activated MFP-transporter complex engages the outer membrane channel to expel substrates across the outer membrane. The recruitment of the channel is likely triggered by binding of effectors (substrates) to MFP or MFP-transporter complexes. This model together with recent structural and functional advances in the field of drug efflux provides a fairly detailed understanding of the mechanism of drug efflux across the two membranes. PMID:25759685

  15. Mechanism of coupling drug transport reactions located in two different membranes

    PubMed Central

    Zgurskaya, Helen I.; Weeks, Jon W.; Ntreh, Abigail T.; Nickels, Logan M.; Wolloscheck, David

    2015-01-01

    Gram- negative bacteria utilize a diverse array of multidrug transporters to pump toxic compounds out of the cell. Some transporters, together with periplasmic membrane fusion proteins (MFPs) and outer membrane channels, assemble trans-envelope complexes that expel multiple antibiotics across outer membranes of Gram-negative bacteria and into the external medium. Others further potentiate this efflux by pumping drugs across the inner membrane into the periplasm. Together these transporters create a powerful network of efflux that protects bacteria against a broad range of antimicrobial agents. This review is focused on the mechanism of coupling transport reactions located in two different membranes of Gram-negative bacteria. Using a combination of biochemical, genetic and biophysical approaches we have reconstructed the sequence of events leading to the assembly of trans-envelope drug efflux complexes and characterized the roles of periplasmic and outer membrane proteins in this process. Our recent data suggest a critical step in the activation of intermembrane efflux pumps, which is controlled by MFPs. We propose that the reaction cycles of transporters are tightly coupled to the assembly of the trans-envelope complexes. Transporters and MFPs exist in the inner membrane as dormant complexes. The activation of complexes is triggered by MFP binding to the outer membrane channel, which leads to a conformational change in the membrane proximal domain of MFP needed for stimulation of transporters. The activated MFP-transporter complex engages the outer membrane channel to expel substrates across the outer membrane. The recruitment of the channel is likely triggered by binding of effectors (substrates) to MFP or MFP-transporter complexes. This model together with recent structural and functional advances in the field of drug efflux provides a fairly detailed understanding of the mechanism of drug efflux across the two membranes. PMID:25759685

  16. Knowledge discovery of drug data on the example of adverse reaction prediction

    PubMed Central

    2014-01-01

    Background Antibiotics are the widely prescribed drugs for children and most likely to be related with adverse reactions. Record on adverse reactions and allergies from antibiotics considerably affect the prescription choices. We consider this a biomedical decision-making problem and explore hidden knowledge in survey results on data extracted from a big data pool of health records of children, from the Health Center of Osijek, Eastern Croatia. Results We applied and evaluated a k-means algorithm to the dataset to generate some clusters which have similar features. Our results highlight that some type of antibiotics form different clusters, which insight is most helpful for the clinician to support better decision-making. Conclusions Medical professionals can investigate the clusters which our study revealed, thus gaining useful knowledge and insight into this data for their clinical studies. PMID:25079450

  17. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  18. Effects of temperature on biochemical reactions and drug resistance of virulent and avirulent Aeromonas salmonicida

    USGS Publications Warehouse

    Hahnel, G.B.; Gould, R.W.

    1982-01-01

    Incubation temperatures of 11°, 18° and 28° did not substantially affect biochemical reactions of either virulent or avirulent forms of Aeromonas salmonicida subspecies salmonicida. The only change observed, amygdalin fermentation, was positive at 11° and 18° but negative at 28°C. Several isolates utilized sucrose, a characteristic not normally recognized for A. salmonicida subspecies salmonicida.Antimicrobial susceptibility screening indicated resistance to novobiocin increased at the higher incubation temperatures. Standardized drug sensitivity testing procedures and precise zone diameter interpretive standards for bacterial fish pathogens are needed.

  19. Adverse Drug Reactions Associated with Antipsychotics, Antidepressants, Mood Stabilizers, and Stimulants.

    PubMed

    Givens, Courtney J

    2016-06-01

    The advent of psychotropic medications in the 1950s greatly impacted the practice of psychiatry. Since then, efforts have been made to produce effective medications with few side effects (SEs) or adverse drug reactions (ADRs). Newer psychotropics have been developed but are not without risk. ADRs and SEs can lead to medication noncompliance, morbidity, and mortality. In many cases, ADRs can be prevented and common SEs relieved through proper interventions. Nursing interventions are vital to improving patient safety and outcomes in mental health populations. This article discusses ADRs and SEs of antipsychotics, antidepressants, mood stabilizers, and stimulants. PMID:27229284

  20. What if skin eruption is not caused by allergic reaction to drugs?

    PubMed

    Bobik, O; Bobik, O; Arganova, H

    2010-01-01

    In this case report authors have described a case of a 39 years old Caucasian single man who was unsuccessfully treated for an allergic reaction to drugs by multiple dermatologists, due to two etiologically different diseases. It was a classical second stage syphilitic infection and positive serologic tests for HIV infection, proved by screening and confirmatory tests. Syphilitic infection was treated and followed up by dermatologist and for the treatment of HIV infection, the patient was referred to the Centre for treatment HIV/AIDS in Kosice (Fig. 4, Ref. 3). PMID:20586153

  1. Building an ontology of adverse drug reactions for automated signal generation in pharmacovigilance.

    PubMed

    Henegar, Corneliu; Bousquet, Cédric; Lillo-Le Louët, Agnès; Degoulet, Patrice; Jaulent, Marie-Christine

    2006-01-01

    Automated signal generation in pharmacovigilance implements unsupervised statistical machine learning techniques in order to discover unknown adverse drug reactions (ADR) in spontaneous reporting systems. The impact of the terminology used for coding ADRs has not been addressed previously. The Medical Dictionary for Regulatory Activities (MedDRA) used worldwide in pharmacovigilance cases does not provide formal definitions of terms. We have built an ontology of ADRs to describe semantics of MedDRA terms. Ontological subsumption and approximate matching inferences allow a better grouping of medically related conditions. Signal generation performances are significantly improved but time consumption related to modelization remains very important. PMID:16185681

  2. Current challenges and controversies in drug-induced liver injury.

    PubMed

    Corsini, Alberto; Ganey, Patricia; Ju, Cynthia; Kaplowitz, Neil; Pessayre, Dominique; Roth, Robert; Watkins, Paul B; Albassam, Mudher; Liu, Baolian; Stancic, Saray; Suter, Laura; Bortolini, Michele

    2012-12-01

    Current key challenges and controversies encountered in the identification of potentially hepatotoxic drugs and the assessment of drug-induced liver injury (DILI) are covered in this article. There is substantial debate over the classification of DILI itself, including the definition and validity of terms such as 'intrinsic' and 'idiosyncratic'. So-called idiosyncratic DILI is typically rare and requires one or more susceptibility factors in individuals. Consequently, it has been difficult to reproduce in animal models, which has limited the understanding of its underlying mechanisms despite numerous hypotheses. Advances in predictive models would also help to enable preclinical elimination of drug candidates and development of novel biomarkers. A small number of liver laboratory tests have been routinely used to help identify DILI, but their interpretation can be limited and confounded by multiple factors. Improved preclinical and clinical biomarkers are therefore needed to accurately detect early signals of liver injury, distinguish drug hepatotoxicity from other forms of liver injury, and differentiate mild from clinically important liver injury. A range of potentially useful biomarkers are emerging, although so far most have only been used preclinically, with only a few validated and used in the clinic for specific circumstances. Advances in the development of genomic biomarkers will improve the prediction and detection of hepatic injury in future. Establishing a definitive clinical diagnosis of DILI can be difficult, since it is based on circumstantial evidence by excluding other aetiologies and, when possible, identifying a drug-specific signature. DILI signals based on standard liver test abnormalities may be affected by underlying diseases such as hepatitis B and C, HIV and cancer, as well as the concomitant use of hepatotoxic drugs to treat some of these conditions. Therefore, a modified approach to DILI assessment is justified in these special populations

  3. An effective and more convenient drug regimen for prophylaxis against paclitaxel-associated hypersensitivity reactions.

    PubMed

    Markman, M; Kennedy, A; Webster, K; Peterson, G; Kulp, B; Belinson, J

    1999-07-01

    "Standard" prophylaxis for paclitaxel-associated hypersensitivity reactions has included the systemic administration of H1 and H2 histamine antagonists, along with oral dexamethasone taken both the night prior to, and the morning of, each paclitaxel treatment. To improve patient convenience and compliance with steroid delivery, the Gynecologic Cancer Program of the Cleveland Clinic Foundation has treated patients with an all-intravenous prophylaxis regimen (diphenhydramine 50 mg, famotidine 20 mg, dexamethasone 20 mg) given 30 min prior to paclitaxel (without any earlier oral steroid dosing). To date, we have treated more than 200 patients who received all courses of paclitaxel with this simplified prophylactic regimen, of whom approximately 9% developed hypersensitivity reactions (major or minor). This incidence is comparable to our previously reported experience with hypersensitivity reactions in a similar number of patients receiving the standard prophylaxis (including oral dexamethasone) with their initial course of paclitaxel, and subsequent cycles employing this all-intravenous program. We conclude that this "modified" regimen for paclitaxel-associated hypersensitivity reactions (with all drugs administered approximately 30 min prior to the delivery of paclitaxel) is as effective as, and more convenient than, the standard regimen, and avoids delaying chemotherapy as a result of a patient failing to remember to take one or both oral steroid doses. PMID:10394964

  4. Neutral and acidic hydrolysis reactions of the third generation anticancer drug oxaliplatin.

    PubMed

    Lucas, Maria Fatima A; Pavelka, Mateij; Alberto, Marta E; Russo, Nino

    2009-01-22

    The hydrolysis of oxaliplatin, a third generation anticancer drug, is expected to play an important role in the activation of this compound before it reaches DNA. The first and second hydrolysis corresponding to the addition of the first water molecule concomitant with the ring-opening, followed by addition of a second water and loss of the monodentate oxalato ligand, respectively, were studied combining density functional theory (DFT) with the conductor-like dielectric continuum model (CPCM) approach. The reaction was studied in neutral and acidic conditions, and all stationary points have been identified. The computed potential energy surfaces show that, for the neutral hydrolysis, the ring-opening reaction is the rate-limiting process, with an activation barrier of about 28 kcal/mol. For the acid degradation in water, according to experimental data, the reaction is expected to proceed in a faster biphasic process, and the rate-limiting process is the ligand detachment that occurs with a barriers of about 22 kcal/mol. According to the calculated results, we expect that the reaction is favored in acidic conditions and that the monoaquated complex should be the species reacting with DNA. PMID:19143575

  5. Epinephrine Treatment is Infrequent and Biphasic Reactions Are Rare in Food-Induced Reactions During Oral Food Challenges in Children

    PubMed Central

    Järvinen, Kirsi M.; Amalanayagam, Sujitha; Shreffler, Wayne G.; Noone, Sally; Sicherer, Scott H.; Sampson, Hugh A.; Nowak-Węgrzyn, Anna

    2009-01-01

    Background Data about epinephrine utilization and biphasic reactions in childhood food-induced anaphylaxis during oral food challenges are scarce. Objective To determine the prevalence and risk factors of reactions requiring epinephrine and the rate of biphasic reactions during oral food challenges (OFCs) in children. Methods Reaction details of positive OFCs in children between 1999 and 2007 were collected using a computerized database. Selection of patients for OFCs was generally predicated on ≤50% likelihood of a positive challenge and a low likelihood of a severe reaction based on the clinical history, specific IgE levels, and skin prick tests (SPTs). Results A total of 436 of 1273 OFCs resulted in a reaction (34%). Epinephrine was administered in 50 challenges (11% of positive challenges, 3.9% overall); for egg (n=15, 16% of positive OFCs to egg), milk (n=14, 12%), peanut (n=10, 26%), tree nuts (n=4, 33%), soy (n=3, 7%), wheat (n=3, 9%), and fish (n=1, 9%). Reactions requiring epinephrine occurred in older children (median 7.9 vs. 5.8 years, P<0.001), and were more often caused by peanuts (P=0.006) when compared to reactions not treated with epinephrine. There was no difference in the gender, prevalence of asthma, history of anaphylaxis, specific IgE level, SPTs, or amount of food administered. Two doses of epinephrine were required in 3/50 patients (6%) reacting to wheat, cow’s milk, and pistachio. There was one (2%) biphasic reaction. No reaction resulted in life-threatening respiratory or cardiovascular compromise. Conclusion Older age and reactions to peanuts were risk factors for anaphylaxis during oral food challenges. Reactions requiring multiple doses of epinephrine and biphasic reactions were infrequent. PMID:20004784

  6. Anticancer Agent Shikonin Is an Incompetent Inducer of Cancer Drug Resistance

    PubMed Central

    Wu, Hao; Xie, Jiansheng; Pan, Qiangrong; Wang, Beibei; Hu, Danqing; Hu, Xun

    2013-01-01

    Purpose Cancer drug resistance is a major obstacle for the success of chemotherapy. Since most clinical anticancer drugs could induce drug resistance, it is desired to develop candidate drugs that are highly efficacious but incompetent to induce drug resistance. Numerous previous studies have proven that shikonin and its analogs not only are highly tumoricidal but also can bypass drug-transporter and apoptotic defect mediated drug resistance. The purpose of this study is to investigate if or not shikonin is a weak inducer of cancer drug resistance. Experimental Design Different cell lines (K562, MCF-7, and a MDR cell line K562/Adr), after repeatedly treated with shikonin for 18 months, were assayed for drug resistance and gene expression profiling. Results After 18-month treatment, cells only developed a mere 2-fold resistance to shikonin and a marginal resistance to cisplatin and paclitaxel, without cross resistance to shikonin analogs and other anticancer agents. Gene expression profiles demonstrated that cancer cells did strongly respond to shikonin treatment but failed to effectively mobilize drug resistant machineries. Shikonin-induced weak resistance was associated with the up-regulation of βII-tubulin, which physically interacted with shikonin. Conclusion Taken together, apart from potent anticancer activity, shikonin and its analogs are weak inducers of cancer drug resistance and can circumvent cancer drug resistance. These merits make shikonin and its analogs potential candidates for cancer therapy with advantages of avoiding induction of drug resistance and bypassing existing drug resistance. PMID:23300986

  7. [Reaction mechanism studies of heavy ion induced nuclear reactions]. [Dept. of Chemistry and Biochemistry, Univ. of Maryland, College Park, Maryland

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  8. [Analyze causes of adverse reactions induced by traditional Chinese medicine injections from its quality standards].

    PubMed

    Cui, Hong-Yu; Liang, Ai-Hu

    2014-03-01

    Reviewing the literatures about adverse reactions induced by traditional Chinese medicine injections (TCMI) reported on CNKI from 1983 to 2013. Analyzing the causes of adverse reactions induced by TCMI from its quality standards. Provide ideas for improving security of TCMI and completing its quality standards. This review indicates that TCMI-induced adverse reactions have little relationship with the number of compositions, but have tight connection with chemical ingredients and solvents. Adverse reactions can be decreased by perfecting the quality standards of TCMI. PMID:25204194

  9. An Adverse Drug Reaction to Trimethoprim-Sulfamethoxazole Revealing Primary HIV: A Case Report and Literature Review

    PubMed Central

    Meyer, Charles; Behm, Nicole; Brown, Emily; Copeland, Nathanial K.; Sklar, Marvin J.

    2015-01-01

    Adverse drug reactions (ADRs) to antibiotics complicate the management of any infection, particularly opportunistic infections in advanced HIV as some ADRs are potentiated by HIV. Trimethoprim-sulfamethoxazole (TMP-SMX) causes ADRs in 40–80% of HIV infected individuals, compared to 3–5% in the general population. The incidence and severity of ADRs among HIV infected individuals appear to increase as they progress from latent infection to AIDS. We present a single case report of a 55-year-old African American male found to have an otherwise asymptomatic acute HIV infection who developed an ADR to TMP-SMX, despite having previously tolerating the medication. The proposed mechanisms for the increased incidence of sulfa hypersensitivity reactions among HIV infected individuals focus on either (1) HIV-induced changes in the immune function driven by falling levels of CD4 cells or (2) other HIV-specific factors correlated with rising viral load. To our knowledge this is the first reported case of new sulfa hypersensitivity in primary HIV and may provide clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count, though further research is necessary. This case also demonstrates a rare and easily overlooked presentation of HIV that may aid in early diagnosis. PMID:26798528

  10. An Adverse Drug Reaction to Trimethoprim-Sulfamethoxazole Revealing Primary HIV: A Case Report and Literature Review.

    PubMed

    Meyer, Charles; Behm, Nicole; Brown, Emily; Copeland, Nathanial K; Sklar, Marvin J

    2015-01-01

    Adverse drug reactions (ADRs) to antibiotics complicate the management of any infection, particularly opportunistic infections in advanced HIV as some ADRs are potentiated by HIV. Trimethoprim-sulfamethoxazole (TMP-SMX) causes ADRs in 40-80% of HIV infected individuals, compared to 3-5% in the general population. The incidence and severity of ADRs among HIV infected individuals appear to increase as they progress from latent infection to AIDS. We present a single case report of a 55-year-old African American male found to have an otherwise asymptomatic acute HIV infection who developed an ADR to TMP-SMX, despite having previously tolerating the medication. The proposed mechanisms for the increased incidence of sulfa hypersensitivity reactions among HIV infected individuals focus on either (1) HIV-induced changes in the immune function driven by falling levels of CD4 cells or (2) other HIV-specific factors correlated with rising viral load. To our knowledge this is the first reported case of new sulfa hypersensitivity in primary HIV and may provide clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count, though further research is necessary. This case also demonstrates a rare and easily overlooked presentation of HIV that may aid in early diagnosis. PMID:26798528

  11. Polyethylene Glycol (PEG)-Induced Anaphylactic Reaction During Bowel Preparation

    PubMed Central

    2015-01-01

    Barium enema is used to screen patients with gastrointestinal bleeding who do not want to undergo colonoscopy. Polyethylene glycol (PEG) is usually the bowel preparation of choice. Few allergic reactions from this product have been reported; these include urticaria, angioedema, and anaphylaxis. Reactions are thought to result from a small amount of PEG crossing the intestinal mucosa, which, in some patients, is sufficient to provoke an anaphylactic reaction. PMID:26203443

  12. Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils.

    PubMed

    Jiang, X; Khursigara, G; Rubin, R L

    1994-11-01

    Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo. PMID:7973636

  13. Possibly drug-induced palpable migratory arciform erythema*

    PubMed Central

    Dantas, Fernando Luiz Teixeira; Valente, Neusa Yuriko Sakai; Veronez, Isis Suga; Kakizaki, Priscila; Leitão, Juliana Ribeiro; Fraga, Rafael Cavanellas

    2015-01-01

    Palpable migratory arciform erythema is an entity of unknown etiology, with few published cases in the literature. The clinical and histopathological features of this disease are difficult to be distinguished from those of Jessner’s lymphocytic infiltration of the skin, lupus erythematous tumidus and the deep erythema annulare centrifugum. We describe here the first two Brazilian cases of palpable migratory arciform erythema. The patients presented with infiltrated annular plaques and erythematous arcs without scales. These showed centrifugal growth before disappearing without scarring or residual lesions after a few days. They had a chronic course with repeated episodes for years. In addition, these cases provide evidence of a drug-induced etiology. PMID:26312680

  14. Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.

    PubMed

    Perrin, C; Lacour, J P; Castanet, J; Michiels, J F

    2001-08-01

    The interstitial granulomatous drug reaction (IGDR) is a novel drug-associated entity, characterized by violaceous plaques with a predilection for skin fold areas. Light microscopically, it resembles the incipient diffuse interstitial phase of granuloma annulare. Differentiating light microscopic features include the absence of complete collagen necrobiosis, the presence of interface dermatitis, and variable lymphoid atypia. The lack of vasculitis rules out the extravascular necrotizing granuloma (Winkelmann granuloma) associated with systemic disease. The differential diagnosis with interstitial granulomatous dermatitis with arthritis as defined by Ackerman et al. has not been studied until now. Our aim was to determine the histologic criteria allowing us to differentiate IGDR without interface dermatitis and lymphoid atypia from interstitial granulomatous dermatitis. W