Science.gov

Sample records for drug reactions induced

  1. Adverse drug reactions induced by valproic acid.

    PubMed

    Nanau, Radu M; Neuman, Manuela G

    2013-10-01

    Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. Epidemiology of cutaneous drug-induced reactions.

    PubMed

    Naldi, L; Crotti, S

    2014-04-01

    Cutaneous reactions represent in many surveillance systems, the most frequent adverse events attributable to drugs. The spectrum of clinical manifestations is wide and virtually encompasses any known dermatological disease. The introduction of biological agents and so-called targeted therapies has further enlarged the number of reaction patterns especially linked with cytokine release or in balance. The frequency and clinical patterns of cutaneous reactions are influenced by drug use, prevalence of specific conditions (e.g., HIV infection) and pharmacogenetic traits of a population, and they may vary greatly among the different populations around the world. Studies of reaction rates in cohorts of hospitalized patients revealed incidence rates ranging from, 1 out 1000 to 2 out 100 of all hospitalized patients. For drugs such as aminopenicillines and sulfamides the incidence of skin reactions is in the order of 3-5 cases out of 100 exposed people. Although the majority of cutaneous reactions are mild and self-limiting, there are reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) which are associated with significant morbidity and mortality. Surveillance systems routed on sound epidemiologic methodology, are needed to raise signals and to assess risks associated with specific reactions and drug exposures. Identification of risk factors for adverse reactions and appropriate genetic screening of groups at higher risk may improve the outcomes of skin reactions.

  3. 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

  4. [DRUG INDUCED EXANTHEMA AND SEVERE CUTANEOUS DRUG REACTIONS].

    PubMed

    Bensaïd, Benoît; Valeyrie-Allanore, Laurence; Lebrun-Vignes, Bénédicte; Nicolas, Jean-François

    2015-09-01

    Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation and severity are very diverse ranging from the frequent and benign exanthemas to the rare but severe CADR involving deep organs in the case of drug reaction with eosinophilia and systemic symptoms (DRESS) or leading to skin bulla and epidermal detachment in toxic epidermal necrolysis. The main differential diagnoses are infections, especially viral ones, which could give clinical symptoms identical to those occurring in CADR.

  5. 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

  6. Ofloxacin Induced Angioedema: A Rare Adverse Drug Reaction

    PubMed Central

    Yadav, Sankalp; Kumar, Raj; Wani, Umar Rasool

    2016-01-01

    The Adverse Drug Reaction (ADR) to a commonly prescribed anti-microbial can pose a major public health problem. The authors report a rare case of 24-year-old young lady who presented with angioedema of lips after ingestion of Ofloxacin, prescribed to her for treatment of loose motions. Fluoroquinolones are widely prescribed antibiotics for various disease conditions. The history, clinical examination and normal laboratory parameters led to the diagnosis of ofloxacin induced hypersensitivity reaction and the patient was successfully treated with corticosteroids and antihistamines. The hypersensitivity reactions to fluoroquinolones are rare with an incidence of 0.4% to 2%. The pharmacovigilance program and self-reporting of all the ADR’s by the health care workers can help in ensuring the judicious use of the drug, drug safety and thus decrease the associated morbidity and mortality. PMID:28050397

  7. 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

  8. Drug Reactions

    MedlinePlus

    ... or diabetes. But medicines can also cause unwanted reactions. One problem is interactions, which may occur between ... more serious. Drug allergies are another type of reaction. They can be mild or life-threatening. Skin ...

  9. Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys.

    PubMed

    Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C; Houle, Christopher; Adkins, Karissa K

    2017-01-01

    Drug-induced hypersensitivity reactions can significantly impact drug development and use. Studies to understand risk factors for drug-induced hypersensitivity reactions have identified genetic association with specific human leukocyte antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can occur in nonhuman primates; however, association between drug-induced hypersensitivity reactions and major histocompatibility complex (MHC) alleles has not been described. In this study, tissue samples were collected from 62 cynomolgus monkeys from preclinical studies in which 9 animals had evidence of drug-induced hypersensitivity reactions. Microsatellite analysis was used to determine MHC haplotypes for each animal. A total of 7 haplotypes and recombinant MHC haplotypes were observed, with distribution frequency comparable to known MHC I allele frequency in cynomolgus monkeys. Genetic association analysis identified alleles from the M3 haplotype of the MHC I B region (B*011:01, B*075:01, B*079:01, B*070:02, B*098:05, and B*165:01) to be significantly associated (χ(2) test for trend, p < 0.05) with occurrence of drug-induced hypersensitivity reactions. Sequence similarity from alignment of alleles in the M3 haplotype B region and HLA alleles associated with drug-induced hypersensitivity reactions in humans was 86% to 93%. These data demonstrate that MHC alleles in cynomolgus monkeys are associated with drug-induced hypersensitivity reactions, similar to HLA alleles in humans.

  10. Acute generalized exanthematous pustulosis: an enigmatic drug-induced reaction.

    PubMed

    Momin, Saira B; Del Rosso, James Q; Michaels, Brent; Mobini, Narciss

    2009-06-01

    Acute generalized exanthematous pustulosis (AGEP) is a diffuse pustular disorder that is primarily drug induced and characterized by acute, extensive, small, nonfollicular, sterile pustules that usually begin in intertriginous folds with widespread edema and erythema. This article reports a case in which thalidomide, dexamethasone, or meloxicam may have been the etiologic agent to induce AGEP and the skin condition may have worsened with administration of additional medications during hospital admission. A good thorough medical history, including a drug history, along with clinicopathologic correlation is extremely important in a patient presenting with acute diffuse pustular lesions.

  11. Recurrence of drug-induced reactions in DRESS patients.

    PubMed

    Picard, D; Vellar, M; Janela, B; Roussel, A; Joly, P; Musette, P

    2015-04-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) may relapse following introduction of drugs structurally unrelated to the initial culprit drug. To assess the frequency and characteristics of recurrent drug eruptions in patients with history of DRESS. Patients who had developed adverse cutaneous reaction after DRESS occurrence were recruited from the regional database of Upper Normandy in France. Rate of recurrences were compared with patients with Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson syndrome (SJS) patients during the same time frame. Of the 60 cases of DRESS collected, 15 (25%) with recurrences were retained for analysis. Seven patients had a single recurrence, whereas eight patients had several relapses. In the patients with pre-existing DRESS, recurrences were incomplete, corresponding to cutaneous rash in 13 cases and associated with eosinophilia in seven cases. Internal organ involvement was observed in two cases. In contrast, a single recurrence was found out of 61 patients with TEN/SJS. Incomplete recurrences with structurally unrelated culprit drugs are a frequent phenomenon in DRESS patients. © 2014 European Academy of Dermatology and Venereology.

  12. Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome.

    PubMed

    Fernando, Suran L

    2014-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing-remitting course despite withdrawal of the drug. The drugs that are most implicated include aromatic anticonvulsants, allopurinol, sulphonamides, antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of DRESS/DIHS is far from clear but probably involves a combination of impaired pharmacokinetics and the accumulation of drug metabolites, the sequential reactivation of the herpesvirus family and genetic susceptibility conferred by the association with certain human leukocyte antigen (HLA) class I alleles. The strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics screening to be employed successfully to minimise the occurrence of hypersensitivity. A prolonged course of oral corticosteroids is required to treat DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v. immunoglobulin and valgangciclovir reserved for refractory or life-threatening cases. © 2013 The Australasian College of Dermatologists.

  13. The Clinical Course of a Drug-induced Acute Dystonic Reaction in the Emergency Room

    PubMed Central

    Marano, Massimo; di Biase, Lazzaro; Salomone, Gaetano; Di Santo, Alessandro; Montiroli, Annalisa; Di Lazzaro, Vincenzo

    2016-01-01

    Background Acute dystonic reactions following the administration of safe, reliable drugs can occur and must be promptly recognized and treated in the emergency room. Phenomenology Shown The entire clinical course of an acute dystonic reaction due to metoclopramide, from early motor signs to full-blown clinical symptoms and resolution. Educational Value Providing elements for early recognition of a drug-induced movement disorder phenomenology. PMID:28105387

  14. [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.

  15. Pharmacogenomics of drug-induced hypersensitivity reactions: challenges, opportunities and clinical implementation.

    PubMed

    Sukasem, Chonlaphat; Puangpetch, Apichaya; Medhasi, Sadeep; Tassaneeyakul, Wichittra

    2014-06-01

    Drug hypersensitivity reactions affect many patients leading to a variety of clinical manifestations, mainly the cutaneous adverse reactions ranging from milder skin reactions to severe cutaneous adverse reactions (SCARs). Hypersensitivity reactions are unpredictable and are thought to have an underlying genetic etiology, as suggested by case reports. With the scientific knowledge of pharmacogenomics and the evidence based on the genomic testing, it is possible to identify genetic predisposing factors for these serious adverse reactions and personalize drug therapy. The most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes encoded for human leukocyte antigens (HLA) alleles. Drugs associated with hypersensitivity reactions with strong genetic predisposing factors include abacavir, nevirapine, carbamazepine, and allopurinol. In this review, strong genetic associations of drug-induced SCARs are highlighted so as to improve drug safety and help to select optimal drugs for individual patients. Further investigation, however, is essential for the characterization of other genes involved in the hypersensitivity reactions with the use of several genetic strategies and technologies.

  16. 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

  17. 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.

  18. 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

  19. Cetirizine-induced acute generalized exanthematous pustulosis: a serious reaction to a commonly used drug.

    PubMed

    Badawi, Ahmed H; Tefft, Kimberly; Fraga, Garth R; Liu, Deede Y

    2014-05-16

    Acute generalized exanthematous pustulosis (AGEP) is an abrupt cutaneous adverse reaction usually in response to medications. It is generally a self-limiting disease if diagnosed promptly and the offending agent discontinued. Cetirizine, a commonly used anti-histamine medication for the treatment of allergic diseases has few reported side effects and is normally well-tolerated and effective. Herein, the first reported case of cetirizine induced AGEP is presented, followed by a discussion of the clinical and pathological aspects of this adverse cutaneous reaction to a widely used drug. Awareness of this reaction is vital owing to the extensive use of cetirizine and the importance of drug cessation once the reaction is identified. Lastly, other pustular cutaneous reactions may present similarly and therefore accurate identification of this disease can prevent unnecessary diagnostic testing.

  20. Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome: clinical features of 27 patients.

    PubMed

    Avancini, J; Maragno, L; Santi, C G; Criado, P R

    2015-12-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) [also called drug-induced hypersensitivity syndrome (DIHS)] includes severe reactions to drugs that need to be promptly recognized by physicians. To explore heterogeneity in the clinical presentation of DRESS/DIHS at a large academic hospital in Latin America, using the criteria defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system. A retrospective medical record review of 60 patients with diagnostic suspicion of DRESS/DIHS admitted to our hospital between July 2008 and April 2012 was performed, including demographic data, clinical features, laboratory findings and treatment. Of the 60 patients, 27 fulfilled the criteria for DRESS/DIHS. Maculopapular exanthema (85.1%), fever (96.2%) and hepatic involvement (85.1%) were the most common features. Anticonvulsants were the most common causal drugs (77.7%); Phenytoin was the most common individual drug (44.4%), followed by carbamazepine (29.6%). All patients were treated initially with prednisone 1 mg/kg/day. Mortality rate was 4%. The major findings of this study (to our knowledge the largest collection of data on DRESS/DIHS in Latin America) include a positive statistical association between presence of atypical lymphocytes and higher levels of alanine aminotransferase (P < 0.001) and reinforce the importance of anticonvulsants in the pathogenesis of this severe reaction. © 2015 British Association of Dermatologists.

  1. Drug Reaction with Eosinophilia and Systemic Symptom Syndrome Induced by Lamotrigine

    PubMed Central

    Han, Song Hee; Hur, Min Seok; Youn, Hae Jeong; Roh, Nam Kyung; Lee, Yang Won; Choe, Yong Beom

    2017-01-01

    Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a type of severe adverse drug-induced reaction. Dermatologists should make a quick diagnosis and provide appropriate treatment for DRESS syndrome to reduce mortality rates, which can be as high as 10%. We present the case of a 47-year-old man with schizoaffective disorder treated with lamotrigine who developed DRESS syndrome to emphasize the importance of close observation of patients with drug eruption. He was consulted for erythematous maculopapular rashes on the trunk that developed 3 weeks after starting lamotrigine. A few days later, he developed generalized influenza-like symptoms. The skin rashes spread over his entire body, and the sense of itching was rapidly aggravated within a few days. Increased liver enzyme levels and significant eosinophilia were found on laboratory test results. His condition was diagnosed as DRESS syndrome, and he was treated with systemic and topical corticosteroids for 2 weeks. PMID:28392649

  2. Sulthiame-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

    PubMed

    Fong, Choong Yi; Hashim, Nurmaira; Gan, Chin Seng; Chow, Tak Kuan; Tay, Chee Geap

    2016-11-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening acute drug-induced hypersensitivity reaction. Antiepileptic drugs (AEDs) predominantly aromatic AEDs are commonly reported in DRESS. To date there are no reports of sulthiame AED causing DRESS syndrome. We report a 10-year-old girl of Indian descent with AED resistant epilepsy on maintenance sodium valproate and clonazepam. Sulthiame AED was initiated to try to improve her seizure control. Five weeks after commencing sulthiame, she developed fever with a diffuse erythematous morbilliform maculopapular rash, elevated transaminases and atypical lymphocytes. At day 3 of illness, she deteriorated with worsening elevation of liver transaminases, thrombocytopenia, progression of rash, hepatosplenomegaly, pneumonitis and markedly elevated inflammatory markers. Immunomodulatory treatment of pulse methylprednisolone was given from day 7 which was associated with improvement inflammatory markers and complete resolution of rash from day 30 of illness. The diagnosis of sulthiame-induced DRESS syndrome was made based on clinical, laboratory and skin histology findings. She was HLA-B heterozygous for HLA-B(∗)15:123 and 15:240 and HLA-A homozygous for HLA-A(∗)11:01:09. Both these HLA-A and HLA-B typing has not been reported before in cutaneous drug reactions. This is the first reported case of sulthiame-induced DRESS syndrome. Our case expands the list of possible susceptible HLA alleles associated with cutaneous drug reactions. It also raises the awareness of possible DRESS syndrome among patients commenced on sulthiame who will require immediate discontinuation of sulthiame and consideration of prompt treatment of corticosteroids. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Drug Reaction With Eosinophilia and Systemic Symptoms Induced by Valproic Acid: A Case Report

    PubMed Central

    Darban, Mahboubeh; Bagheri, Bahador

    2016-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but life-threatening reaction to drugs such as carbamazepine and allopurinol. The condition is characterized by skin rashes, fever, hematological disturbances, lymphadenopathy, and organ failure, most probably hepatic dysfunction. To date, only a few cases of valproate-induced DRESS syndrome have been reported. Case Presentation We report on the case of a 60-year-old man who had been treated with valproic acid some time before being referred to Kowsar Hospital, Semnan, Iran in December 2015. He was given valproic acid 1000 mg PO, and after 20 days, he had developed widespread rashes, fever, esophagitis, cervical lymphadenopathy, and tender hepatomegaly. Laboratory results at Kowsar showed a drop in hemoglobin, in addition to lymphocytosis, thrombocytopenia, and elevated serum transaminases. DRESS was diagnosed, and corticosteroid therapy was initiated. Administration of the culprit drug to the patient was also stopped. Intravenous immunoglobulin (IVIG) improved the general condition of the patient. Conclusions Only a small number of case reports have described valproic acid-induced DRESS syndrome; therefore, the condition is difficult to prevent. Rechallenge with valproic acid should be avoided in patients with a history of reaction to the drug. PMID:28144463

  4. 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

  5. Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts.

    PubMed

    Criado, Paulo Ricardo; Criado, Roberta Fachini Jardim; Avancini, João de Magalhães; Santi, Claudia Giuli

    2012-01-01

    The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

  6. Raltegravir-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome - implications for clinical practice and patient safety.

    PubMed

    Perry, Melissa E O; Almaani, Noor; Desai, Nemesha; Larbalestier, Nick; Fox, Julie; Chilton, Daniella

    2013-08-01

    This case report describes two severe antiretroviral drug adverse reactions that occurred in the same patient. A 55-year-old HIV-positive African woman received a single epidural triamcinolone injection for pain relief of postherpetic neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's syndrome due to the drug-drug interaction between triamcinolone and her boosted protease inhibitor therapy. The patient's antiretroviral regimen was thus changed to replace her protease inhibitor with the integrase inhibitor raltegravir. Shortly after commencing the drug, the patient developed a severe adverse drug reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity syndrome presents with severe skin reaction as well as fever, rash, lymphadenopathy and internal organ involvement with marked eosinophilia. Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the potential for drug-drug interactions due to protease inhibitor-based therapy.

  7. Drug-induced hypersensitivity reactions and pharmacogenomics: past, present and future.

    PubMed

    Alfirevic, Ana; Pirmohamed, Munir

    2010-04-01

    Drug-induced hypersensitivity reactions represent a major concern for clinicians, patients, regulators and drug developers. Severe hypersensitivity is associated with high morbidity and mortality, it cannot be predicted from the known pharmacology of the drug and it is usually detected post-marketing when a large number of patients have been exposed to a particular drug. Recent success in developing clinically useful genetic tests that have allowed us to predict the risk of abacavir-induced hypersensitivity has helped to pave the path for a pharmacogenetic approach. However, the loop from identifying a genetic association to improving clinical outcome is still lacking for many drugs. In this commentary, we discuss the progress of hypersensitivity pharmacogenomics over the last decade and point out what remains to be done in the future. The current efforts of the international community are focused on the development of consortia, which aim to standardize disease phenotypes, but also to collect larger numbers of well-phenotyped patients and to pool biological samples through these collaborations. In addition, it is necessary to advance our knowledge of hypersensitivity mechanisms through functional studies, which will lead to the development of predictive and diagnostic tests.

  8. 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

  9. Severe cutaneous adverse drug reactions

    PubMed Central

    Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran

    2013-01-01

    Severe cutaneous drug reactions are one of the commonest medical challenges presenting to an emergency room in any hospital. The manifestations range from maculopapular rash to severe systemic symptoms like renal failure and cardiovascular compromise. Toxic epidermal necrolysis, erythroderma, drug rash with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis and drug induced vasculitis are the common cutaneous drug reactions which can have severe morbidity and even mortality. Careful history taking of the lag period after drug intake and associated symptoms, along with detailed examination of the skin, mucosa and various systems, help in early diagnosis of these reactions. Early stoppage of the incriminating drug, specific therapy including corticosteroids, cyclosporine and intravenous immunoglobulin depending on the case along with supportive therapy and local measures help in salvaging most patients. An overview of these important cutaneous drug reactions along with their management is being reviewed in this article. PMID:24600147

  10. Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

    PubMed

    Lehloenya, R J; Todd, G; Wallace, J; Ngwanya, M R; Muloiwa, R; Dheda, K

    2016-07-01

    The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied. To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection. Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated. Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions. In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings. © 2016 British Association of Dermatologists.

  11. Drug hypersensitivity reactions involving skin.

    PubMed

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  12. Drug reaction with eosinophilia and systemic symptoms syndrome probably induced by a lamotrigine-ginseng drug interaction.

    PubMed

    Myers, Amy P; Watson, Troy A; Strock, Steven B

    2015-03-01

    The likelihood of a drug reaction with lamotrigine is increased by dose escalation that is too rapid or drug interactions that increase the concentration of lamotrigine. There is a well-documented interaction between valproic acid and lamotrigine in which lamotrigine levels are increased, subsequently increasing the risk of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. This syndrome is characterized by fever, lymphadenopathy, diffuse maculopapular rash, multivisceral involvement, eosinophilia, and atypical lymphocytes and has a mortality rate of 10-40%. We describe the first case, to our knowledge, of DRESS syndrome that was probably induced by a drug interaction between lamotrigine and ginseng. A 44-year-old white man presented to the emergency department after experiencing a possible seizure. His medical history included two other lifetime events concerning for seizures at ages 14 and 29 years old. After referral to the neurology clinic, he was diagnosed with generalized tonic-clonic seizure disorder, and lamotrigine was started with up-titration according to the drug's package insert to a goal dosage of 150 mg twice/day. The patient had also been taking deer antler velvet and ginseng that he continued during his lamotrigine therapy. On day 43 of therapy, the patient presented to the emergency department with a pruritic rash that had started on his extremities and spread to his torso. He was thought to have experienced a drug reaction to lamotrigine, and the drug was discontinued. Thirteen days later, the patient was admitted from the acute care clinic for inpatient observation due to laboratory abnormalities in the setting of continued rash, headache, and myalgias. His admission laboratory results on that day were remarkable for leukocytosis, with a white blood cell count up to 17.6 × 10(3) /mm(3) , with a prominent eosinophilia of 3.04 × 10(3) /mm(3) ; his liver enzyme levels were also elevated, with an aspartate

  13. [Bullous drug reactions].

    PubMed

    Hertl-Yazdi, M S; Hertl, M

    2005-01-01

    Bullous drug exanthems are clinically characteristic, usually severe cutaneous and mucosal drug hypersensitivity reactions. Commonly, they appear 5-14 days after onset of drug treatment. Therapy of choice is to avoid the culprit drug and systemic administration of glucocorticoids. A key element in the immune pathogenesis of bullous drug exanthems is presumably the activation of cytotoxic CD8(+) T lymphocytes which recognize drug metabolites as nominal antigens. These compounds form spontaneously (e.g. penicillins) or are metabolized by cytochrome P450-dependent enzymes (sulfonamides). The diagnosis of bullous drug exanthems is primarily based on skin tests and in vitro-techniques. Among the skin tests, prick as well as patch tests are important. Patch tests can be also applied at the former skin lesion in fixed drug eruption. In vitro techniques include analysis of drug-specific IgE (only available for anti-penicillin, anti-sulfamethoxazole) and cellular tests with the patients' lymphocytes (lymphocyte transformation test-LTT).

  14. [Occurrence of drug reactions].

    PubMed

    Pastorello, E; Qualizza, R M; Luraghi, M T; Ispano, M; Villa, A M; Ortolani, C; Zanussi, C

    1986-01-01

    The aim of this prospective study was to evaluate the incidence of allergic reactions to drugs compared to other kinds of medical emergencies admitted to the main Hospital in Milan during a 6 months period. At the same time we drew a list of drugs most frequently involved in allergic reactions, and a list of the most frequent symptoms. Using special forms, the medical staff collected patients' data: age, history of atopy, identification of the drug causing the reaction, and any previous reactions. Among 11,407 cases of medical emergencies, we found 163 (1.43%) patients showing drug reactions: the mean age was 27.3; 58.90% were female; atopy was present in 16.56%. The drugs most frequently involved were: pyrazon group (22%); ASA (20.86%); penicillin and derivatives (9.20%); sulfa drugs (6.14%); group B vitamins (4.30%); tetanus toxoid (4.30%); hyposensitizing extracts (3.68%); propionic acid derivatives (2.46%); paracetamol (1.84%); indomethacin (1.23%); rifampicin (1.23%); erythromycin (1.23%); glafenine (1.23%); others (17.80%). Urticaria and/or angioedema were the most frequent symptoms (86.51%), then anaphylactic shock (9.81%) and asthma (3.68%) with regard to anaphylactic shock only 6.20% of the patients had had a previous reaction to the same drug. From these data we can see that the incidence of drug reactions is very low compared to other medical emergencies; penicillin evidenced fewer reactions than expected, while the pyrazon group and ASA confirmed the data from literature.

  15. Pharmacogenetics of hypersensitivity drug reactions.

    PubMed

    Negrini, Simone; Becquemont, Laurent

    2017-04-01

    Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  16. Drug dangers and reactions.

    PubMed

    WEILERSTEIN, R W

    1961-01-01

    The protection of the consumer against dangerous, adulterated, and misbranded drugs provided by the Federal Food, Drug, and Cosmetic Act has failed in some instances. A general program of reporting adverse drug reactions has been initiated on a pilot basis. Arrangements are being made to extend this program into larger hospitals. Better and more complete reporting of adverse drug reactions together with tightening of the Food and Drug law regarding new drugs will improve this situation. Recently the president of the National Academy of Sciences appointed a committee at the request of the Secretary of Health, Education, and Welfare to review the policies and procedures used by the Food and Drug Administration in reaching decisions and to present recommendations. This committee has completed its work and has made specific recommendations that would give the Food and Drug Administration authority to require proof of efficacy as well as safety of all new drugs, and would provide it with sufficient resources to meet the responsibilities assigned to it.

  17. DRUG DANGERS AND REACTIONS

    PubMed Central

    Weilerstein, Ralph W.

    1961-01-01

    The protection of the consumer against dangerous, adulterated, and misbranded drugs provided by the Federal Food, Drug, and Cosmetic Act has failed in some instances. A general program of reporting adverse drug reactions has been initiated on a pilot basis. Arrangements are being made to extend this program into larger hospitals. Better and more complete reporting of adverse drug reactions together with tightening of the Food and Drug law regarding new drugs will improve this situation. Recently the president of the National Academy of Sciences appointed a committee at the request of the Secretary of Health, Education, and Welfare to review the policies and procedures used by the Food and Drug Administration in reaching decisions and to present recommendations. This committee has completed its work and has made specific recommendations that would give the Food and Drug Administration authority to require proof of efficacy as well as safety of all new drugs, and would provide it with sufficient resources to meet the responsibilities assigned to it. PMID:13783849

  18. Adverse cutaneous drug reaction.

    PubMed

    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.

  19. Pustular-type drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement.

    PubMed

    Matsuda, Haruna; Saito, Kanami; Takayanagi, Yoshikazu; Okazaki, Toshio; Kashima, Kenji; Ishikawa, Kazushi; Kai, Yoshitaka; Takeo, Naoko; Hatano, Yutaka; Okamoto, Osamu; Fujiwara, Sakuhei

    2013-02-01

    Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe reaction usually associated with maculopapular eruptions and systemic involvement. Here we report the first case, to our knowledge, of DIHS/DRESS due to carbamazepine with acute generalized pustular bacterid-like (AGPB-like) eruptions and skeletal muscle involvement. Reviewing our case and the published work, we discuss pustular-type DIHS/DRESS which, in most cases, involves acute generalized exanthematous pustulosis (AGEP)-like skin eruptions in response to carbamazepine. Pustular eruptions may appear in relatively few cases of DIHS/DRESS, in particular, when the causative drug is carbamazepine and, even in cases of intractable pustular bacterid-like eruptions, a reaction to a drug should be suspected. Skeletal muscle involvement may be associated with DIHS/DRESS as one of its systemic manifestations. © 2012 Japanese Dermatological Association.

  20. Probable Griseofulvin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms in a Child.

    PubMed

    Smith, Robert J; Boos, Markus D; McMahon, Patrick

    2016-09-01

    A 9-year-old boy presented with fever, rash, anterior cervical lymphadenopathy, high liver enzymes, atypical lymphocytosis, and eosinophilia (drug reaction with eosinophilia and systemic symptoms [DRESS]). His history was notable for having taken griseofulvin for 3 weeks prior to onset of these findings. He improved after treatment with oral prednisone. We present a rare case of probable DRESS secondary to griseofulvin. © 2016 Wiley Periodicals, Inc.

  1. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review.

    PubMed

    E L omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug.

  2. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    PubMed Central

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  3. 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.

  4. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  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. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    PubMed

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson

    2013-01-01

    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  7. Drug-induced exanthems.

    PubMed

    Yawalkar, Nikhil

    2005-04-15

    Cutaneous adverse reactions to drugs can comprise a broad spectrum of clinical and histopathological features. Recent evidence from immunohistological and functional studies of drug-reactive T cells suggest that distinct T-cell functions may be responsible for this broad spectrum of different clinical reactions. Maculopapular exanthems represent the most commonly encountered cutaneous drug eruption. Previous studies on maculopapular exanthems indicate that drug-specific CD4+ T cells expressing cytotoxic granule proteins such as perforin and granzyme B are critically involved in killing activated keratinocytes. These cells are particularly found at the dermo-epidermal junction and may contribute to the generation of vacuolar alteration and destruction of basal keratinocytes, which are typical found in drug-induced maculopapular exanthems. In contrast to maculopapular exanthems, the preferential activation of drug-specific cytotoxic CD8+ T cells may lead to more severe reactions like bullous drug eruptions. Furthermore, activation of drug-specific T with distinct cytokine and chemokines profiles may also explain the different clinical features of drug-induced exanthems. IL-5 and eotaxin are upregulated in maculopapular exanthems and explain the eosinophilia often found in these reactions.

  8. Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome Induced by Levetiracetam in a Pediatric Patient.

    PubMed

    Bayram, Ayşe Kaçar; Canpolat, Mehmet; Çınar, Salih Levent; Tahan, Fulya; Gumus, Hakan; Kumandaş, Sefer; Per, Hüseyin

    2016-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, life-threatening hypersensitivity drug reaction. Patients present with cutaneous rash, fever, lymphadenopathy, hematologic abnormalities with eosinophilia and atypical lymphocytes, and visceral organ involvement. The prognosis of DRESS syndrome is related to the degree of end-organ damage, and the mortality rate is approximately 10%. We report a 9-year-old girl treated with only levetiracetam because of intracranial space occupying mass-related seizures. The patient developed pharyngitis accompanied by exudative membrane, bilateral cervical lymphadenopathy, tender hepatomegaly, skin rash, and fever after 19 days of levetiracetam therapy. Laboratory findings revealed leukocytosis, lymphocytosis with an atypical lymphocytosis, eosinophilia, thrombocytopenia, and elevated serum transaminases. Serologic studies of viruses were negative. The patient was diagnosed with DRESS syndrome and antiepileptic therapy was ceased immediately. The systemic signs and symptoms of the patient were improved after systemic steroid and antihistamine therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important that emergency physicians be aware of the possibility of DRESS syndrome when attending children that present with clinical viral infections. We would like to emphasize that obtaining a careful and detailed medication history is an essential part of clinical assessment for the diagnosis of DRESS syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children.

    PubMed

    Manuyakorn, Wiparat; Siripool, Khanitha; Kamchaisatian, Wasu; Pakakasama, Samart; Visudtibhan, Anannit; Vilaiyuk, Soamarat; Rujirawat, Thidarat; Benjaponpitak, Suwat

    2013-05-01

    Aromatic anticonvulsant-induced severe cutaneous adverse drug reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502 has also been demonstrated to be associated with carbamazepine-induced SJS-TEN. Forty case patients who were diagnosed with SCARs after initiation of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty control patients who received PB, PHT, or CBZ at least 2 months with no adverse drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2, and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction technique. Clinical characteristics of SCARs patients who used different drugs were also analyzed. There was no significant difference in sex, onset of symptoms, laboratory results, treatment, and length of stay among patients with SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to have a likelihood to develop SCARs more than the patients with CYP2C19 wild type (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p < 0.03). There was no association between the HLA-B*1502 and aromatic anticonvulsant-induced severe cutaneous adverse reactions (SCARs). CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. Protective effect of antiasthma drugs on late asthmatic reactions and increased airway responsiveness induced by toluene diisocyanate in sensitized subjects.

    PubMed

    Mapp, C; Boschetto, P; dal Vecchio, L; Crescioli, S; de Marzo, N; Paleari, D; Fabbri, L M

    1987-12-01

    To determine whether 4 drugs used in the treatment of asthma inhibit the late asthmatic reaction and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 24 sensitized subjects divided into 4 groups. Beclomethasone aerosol (1 mg bid), slow-release theophylline (6.5 mg/kg bid), slow-release verapamil (120 mg bid), and cromolyn (20 mg qid via spinhaler), were administered for 7 days, respectively, to 1 of the 4 groups, according to a double-blind, crossover, placebo-controlled study design. When the subjects were treated with placebo, verapamil, or cromolyn, FEV1 markedly decreased and airway responsiveness increased after exposure to TDI. By contrast, beclomethasone prevented the late asthmatic reaction and the associated increase in airway responsiveness to methacholine induced by TDI. Slow-release theophylline partially inhibited both the immediate and the late asthmatic reactions but had no effect on airway hyperresponsiveness to methacholine. These results suggest that only high-dose inhaled steroids can completely block TDI-induced late asthmatic reactions.

  11. 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.

  12. 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…

  13. Management of nonimmediate hypersensitivity reactions to drugs.

    PubMed

    Roujeau, Jean-Claude; Haddad, Cynthia; Paulmann, Maren; Mockenhaupt, Maja

    2014-08-01

    Nonimmediate hypersensitivity to drugs has a huge diversity of clinical presentations affecting exclusively or predominantly a single organ (most often the skin) or multiple organs. The latter is the rule with drug reaction with eosinophilia and systemic symptoms, and with drug-induced vasculitis. The management includes a dozen successive steps. Finally, the patient should be provided clear information on the suspected cause of the reaction, recommendations for follow-up after severe reactions associated with a risk of sequelae, and clear recommendations for future use of medications. Pharmacovigilance networks should be informed.

  14. Drug-induced lupus.

    PubMed

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  15. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  16. Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients.

    PubMed

    Low, Siew-Kee; Kiyotani, Kazuma; Mushiroda, Taisei; Daigo, Yataro; Nakamura, Yusuke; Zembutsu, Hitoshi

    2009-10-01

    Cyclophosphamide (CPA)-based combination treatment has known to be effective for breast cancer, but often causes adverse drug reactions (ADRs). Hence, the identification of patients at risk for toxicity by CPA is clinically significant. In this study, a stepwise case-control association study was conducted using 403 patients with breast cancer who received the CPA combination therapy. A total of 143 genetic polymorphisms in 13 candidate genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, ALDH3A1, GSTA1, GSTM1, GSTP1, GSTT1, ABCC2 and ABCC4), possibly involved in the activation, metabolism and transport of CPA, were genotyped using 184 cases who developed either > or =grade 3 leukopenia/neutropenia or > or =grade 2 gastrointestinal toxicity and 219 controls who did not show any ADRs throughout the treatment. The association study revealed that one SNP, rs9561778 in ABCC4, showed a significant association with CPA-induced ADRs (Cochran-Armitage trend's P-value=0.00031; odds ratio (OR)=2.06). Subgroup analysis also indicated that the SNP rs9561778 was significantly associated with two major ADR subgroups; gastrointestinal toxicity and leukopenia/neutropenia (Cochran-Armitage trend's P-value=0.00019 and 0.014; OR=2.31 and 1.83). Furthermore, the SNP rs9561778 showed an association with breast cancer patients who were treated with CA(F) drug regimen-induced ADR (Cochran-Armitage trend's P-value=0.00028; OR=3.13). The SNPs in ABCC4 might be applicable in predicting the risk of ADRs in patients receiving CPA combination chemotherapy.

  17. Cicatrizing Conjunctivitis in a Patient Diagnosed With Drug Reaction With Eosinophilia and Systemic Symptoms/Drug-Induced Hypersensitivity Syndrome but With Features of Stevens-Johnson Syndrome.

    PubMed

    Bohm, Kelley J; Ciralsky, Jessica B; Harp, Joanna L; Bajaj, Shirin; Sippel, Kimberly C

    2016-06-01

    Severe cutaneous adverse reactions to drugs (SCARs) such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) serve as one of the main reasons for inpatient ophthalmic consultation. Although it is well-recognized that SJS/TEN is associated with severe ocular mucosal inflammation and cicatrizing, potentially blinding, sequelae, this association has not been described in relation to other SCARs. We present a patient fulfilling the diagnostic criteria for probable DRESS/DIHS but not for SJS/TEN, yet exhibiting the severe ocular surface involvement characteristic of SJS/TEN. Case report. A 64-year-old man presented with bilateral pseudomembranous conjunctivitis and conjunctival denudation (sloughing) in the setting of a maculopapular rash, fever, liver dysfunction, and hematologic abnormalities 1 month after initiating several medications. A skin biopsy was not consistent with SJS/TEN. The patient was diagnosed with probable DRESS/DIHS and treated with high-dose systemic corticosteroids. The ocular surface inflammation was addressed with intensive topical corticosteroid ointment. The pseudomembranes resolved over a 6-week period, but the patient exhibited residual conjunctival scarring of all palpebral surfaces. The development of severe ocular surface mucosal inflammation and denudation with cicatrizing sequelae in a patient carrying a diagnosis of DRESS/DIHS has diagnostic and therapeutic implications for the ophthalmologist. Careful ophthalmic assessment is indicated in any SCAR patient with ophthalmic symptoms, regardless of formal diagnosis. Furthermore, the early therapeutic interventions recently recommended in SJS/TEN to limit the ophthalmic cicatricial sequelae, such as systemic or topical corticosteroids, may be indicated.

  18. Drug-induced lupus.

    PubMed

    Rubin, Robert L

    2015-03-01

    Drug-induced lupus (DIL) refers to an idiosyncratic side effect of numerous, apparently unrelated, medications, in which symptoms overlap with those of systemic lupus erythematosus. DIL is reversible by discontinuation of the medication. The etiological mechanism underlying DIL is linked to the inherent susceptibility of the adaptive immune system to lapse into auto-reactivity. Clinical and laboratory features of DIL will be compared with those of idiopathic systemic lupus and with other types of drug reactions with overlapping features. Formerly commonly-used drugs conferred very high risk of developing DIL, although the probability of developing DIL has not been established with most lupus-inducing drugs. Pharmacological or physiochemical properties of the parent compounds are uninformative, but the importance of reactive drug metabolites in initiating autoimmunity will be discussed. As with most systemic autoimmune diseases, the pathogenesis of DIL is complex and obscure. The role of complement and human leukocyte allotypes as well as drug acetylator phenotype inform the underlying mechanism, and several of these non-mutually exclusive concepts will be described. The pros and cons of proposed mechanisms for DIL will be discussed in the context of current understanding of autoimmunity and immune tolerance to self.

  19. Delayed drug hypersensitivity reactions - new concepts.

    PubMed

    Posadas, S J; Pichler, W J

    2007-07-01

    Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications

  20. Stevens-Johnson syndrome and toxic epidermal necrolysis: an update on pharmacogenetics studies in drug-induced severe skin reaction.

    PubMed

    Rufini, Sara; Ciccacci, Cinzia; Politi, Cristina; Giardina, Emiliano; Novelli, Giuseppe; Borgiani, Paola

    2015-11-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening drug reactions involving skin and membranes mucous, which are associated with significant morbidity and mortality and triggered, especially by drug exposure. Different studies have demonstrated that drug response is a multifactorial character and that the interindividual variability in this response depends on both environmental and genetic factors. The last ones have a relevant significance. In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice.

  1. 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

  2. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS): 11 years retrospective study in Thailand.

    PubMed

    Hiransuthikul, Akarin; Rattananupong, Thanapoom; Klaewsongkram, Jettanong; Rerknimitr, Pawinee; Pongprutthipan, Marisa; Ruxrungtham, Kiat

    2016-10-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but life-threatening adverse drug reaction. Several criteria have been established to aid the diagnosis. However, patients with DRESS remained underdiagnosis and undertreatment. Medical records of hospitalized patients at the King Chulalongkorn Memorial Hospital from January 2004-December 2014 due to DRESS were enrolled retrospectively using RegiSCAR diagnostic criteria. A total of 52 patients were included. Thirty-seven patients (71.2%) were female. The four most common causative agents were phenytoin (23.1%), nevirapine (17.3%), allopurinol (15.4%), and cotrimoxazole (13.5%). The overall prevalence was 9.63 cases per 100,000 inpatients. Median onset time (IQR) was 16 (9-27) days. Allopurinol was associated with longer onset time than others (p = 0.014). skin rash 100%, fever 78.8%, and lymphadenopathy 50%. The majority (84.6%) had single internal organ involvement. The most common internal organ involvement was liver (94.2%). Allopurinol was associated with higher incidence of renal involvement (p = 0.01). Up to 60% of patients had eosinophilia. Allopurinol was associated with higher eosinophilia (p = 0.003). A half of patients received systemic corticosteroids. Two mortality cases were reported (omeprazole-fulminant hepatitis and phenytoin-nosocomial infection). DRESS is associated with severe morbidity and mortality. Phenytoin, nevirapine, allopurinol, and cotrimoxazole were the major causes. Allopurinol-induced DRESS had the longest onset time, and was associated with higher eosinophilia and incidence of renal involvement. Raising awareness among both health care providers and public for early detection and withdrawal of the causative agent is critical to save life and reduce morbidity. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  3. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).

    PubMed

    Kano, Yoko; Tohyama, Mikiko; Aihara, Michiko; Matsukura, Setsuko; Watanabe, Hideaki; Sueki, Hirohiko; Iijima, Masafumi; Morita, Eishin; Niihara, Hiroyuki; Asada, Hideo; Kabashima, Kenji; Azukizawa, Hiroaki; Hashizume, Hideo; Nagao, Keisuke; Takahashi, Hayato; Abe, Riichiro; Sotozono, Chie; Kurosawa, Michiko; Aoyama, Yumi; Chu, Chia-Yu; Chung, Wen-Hung; Shiohara, Tetsuo

    2015-03-01

    Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up. © 2015 Japanese Dermatological Association.

  4. Mechanisms of drug hypersensitivity reactions and the skin.

    PubMed

    Kuljanac, Ilko

    2008-01-01

    The skin is an organ most often affected by adverse drug reactions. Because of limited reactivity of the skin, different drugs may induce the same reactions on the skin, even if the same drug may induce different adverse drug reactions. Many of these adverse drug reactions do not include immunological mechanisms, most of them are non-immunological processes. Adverse drug reactions which involve an immune system, may appear different times after drug administration. The severity of reactions is not dependent on the time at which adverse drug reaction appeared, even if some life threatening adverse drug reactions appear immediately after a drug administration. Four types of immunological reactions, (according to Cooms and Gell), may be involved in a drug adverse reaction. The first type of reaction (anaphylactic reaction) begins early after drug administration and different severities of the reactions could exist. The second type, known as cytotoxic hypersensitivity, begins after some minutes to a few hours after a drug administration. Third and fourth types of immunological reactions begin usually hours to days after drug administration. Some types of immunological reactions may begin days to weeks after drug administration. Sensitization to the drugs must be happen early, since re-exposition to the drug leads to the adverse drug reactions. The way of sensitization sometimes determines which immune mechanism will be involved and which clinical reaction will appear. Tests in vivo and in vitro can be used in the diagnosis of adverse drug reactions. All these tests are more or less limited to a false positive or false negative reaction and possibilities of serious reactions in tests. Provocations tests give the most satisfactory results but they may be dangerous and life threatening. We must carefully choose the skin tests and apply them according to the suspected pathomechanism of adverse drug reaction geneses and estimate the usefulness and the risks of the tests

  5. Adverse reactions to drug additives.

    PubMed

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  6. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  7. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  8. Drug-induced nephropathies.

    PubMed

    Paueksakon, Paisit; Fogo, Agnes B

    2017-01-01

    Drugs are associated frequently with the development of various types of acute and chronic kidney diseases. Nephrotoxicity is associated most commonly with injury in the tubulointerstitial compartment manifested as either acute tubular injury or acute interstitial nephritis. A growing number of reports has also highlighted the potential for drug-induced glomerular disease, including direct cellular injury and immune-mediated injury. Recognition of drug-induced nephropathies and rapid discontinuation of the offending agents are critical to maximizing the likelihood of renal function recovery. This review will focus on the pathology and pathogenesis of drug-induced acute interstitial nephritis and drug-induced glomerular diseases.

  9. Animal models of idiosyncratic drug reactions.

    PubMed

    Ng, Winnie; Lobach, Alexandra R M; Zhu, Xu; Chen, Xin; Liu, Feng; Metushi, Imir G; Sharma, Amy; Li, Jinze; Cai, Ping; Ip, Julia; Novalen, Maria; Popovic, Marija; Zhang, Xiaochu; Tanino, Tadatoshi; Nakagawa, Tetsuya; Li, Yan; Uetrecht, Jack

    2012-01-01

    If we could predict and prevent idiosyncratic drug reactions (IDRs) it would have a profound effect on drug development and therapy. Given our present lack of mechanistic understanding, this goal remains elusive. Hypothesis testing requires valid animal models with characteristics similar to the idiosyncratic reactions that occur in patients. Although it has not been conclusively demonstrated, it appears that almost all IDRs are immune-mediated, and a dominant characteristic is a delay between starting the drug and the onset of the adverse reaction. In contrast, most animal models are acute and therefore involve a different mechanism than idiosyncratic reactions. There are, however, a few animal models such as the nevirapine-induced skin rash in rats that have characteristics very similar to the idiosyncratic reaction that occurs in humans and presumably have a very similar mechanism. These models have allowed testing hypotheses that would be impossible to test in any other way. In addition there are models in which there is a delayed onset of mild hepatic injury that resolves despite continued treatment similar to the "adaptation" reactions that are more common than severe idiosyncratic hepatotoxicity in humans. This probably represents the development of immune tolerance. However, most attempts to develop animal models by stimulating the immune system have been failures. A specific combination of MHC and T cell receptor may be required, but it is likely more complex. Animal studies that determine the requirements for an immune response would provide vital clues about risk factors for IDRs in patients.

  10. Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore.

    PubMed

    Chong, Kok Wee; Chan, Derrick W S; Cheung, Yin Bun; Ching, Leng Kee; Hie, Szu Liang; Thomas, Terrence; Ling, Simon; Tan, Ene Choo

    2014-06-01

    To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7-12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Drug-induced blood consumption: the impact of adverse drug reactions on demand for blood components in German departments of internal medicine.

    PubMed

    Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Thuermann, Petra A; Hasford, Joerg

    2012-10-01

    Therapy for adverse drug reactions (ADRs) often results in the application of blood components. This study aims to assess the demand for blood components and the resulting economic burden (hospital perspective) in German hospitals induced by ADRs leading to admissions to departments of internal medicine. In this prospective study, ADRs leading to hospitalization were surveyed in four regional pharmacovigilance centres in Germany during the years 2000-2007. ADRs assessed as 'possible', 'likely' or 'very likely' were included. Market prices for blood components and hospitalization data were determined by desktop research. A probabilistic sensitivity analysis was performed. A total of 6099 patients were admitted to internal medicine departments because of an outpatient ADR of whom 1165 patients (19.1%; mean age, 73.0 ± 13.0 years) required treatment with blood components owing to major bleeding events. Overall consumption was 4185 erythrocyte concentrates (EC), 426 fresh frozen plasma (FFP) and 48 thrombocyte (TC) units. On the basis of statistical hospital data, we estimated a nationwide demand of approximately 132,020 EC, 13,440 FFP and 1515 TC units, resulting in total costs of €12.66 million per year for all German hospitals. Some 19.2% of all ADR cases were assessed as preventable. Theoretically, a nationwide decreased demand for blood components and a savings potential of €2.43 million per year could be achieved by preventing ADRs in Germany. Blood components are used in one-fifth (mainly gastrointestinal bleeding) of all ADRs, leading to hospitalizations in internal medicine departments. Both blood demand and hospital procurement costs can be significantly lowered by preventing ADRs.

  12. Oxazolone-induced delayed type hypersensitivity reaction in the adult yucatan pigs. A useful model for drug development and validation.

    PubMed

    Nuhaily, Samer; Damaj, Bassam B; Maghazachi, Azzam A

    2009-09-01

    The purpose of this study was to establish a model of delayed type hypersensitivity (DTH) reaction in the ear skin of large animals such as adult Yucatan pigs, which may aid in evaluating the efficacy of therapeutic modalities of newly developed anti-inflammatory drugs. The pigs were sensitized with oxazolone, re-challenged with the same irritant six days later, and dosed with either vehicle or with cyclosporine A (CsA) before and after challenge. CsA reduced the redness, inhibited the accumulation of ear fluid and inflammatory cells, as well as the release of the inflammatory mediators. Further, CsA inhibited the proliferation of T cells collected from the spleens or PBMCs of CsA-treated pigs when these cells were stimulated in vitro with PMA plus Ionomycin. These results indicate that pig skin can be used to evaluate modalities for the purpose of developing drugs that may be used to treat DTH in humans.

  13. Drug-induced photosensitivity.

    PubMed

    Dawe, Robert S; Ibbotson, Sally H

    2014-07-01

    Drug-induced photosensitivity is common. The principal mechanism of systemic drug photosensitivity is phototoxicity and the principal mechanism of topical drug photosensitivity is photoallergy. Photopatch testing is helpful to determine suspected topical agent photoallergies (eg, from ultraviolet filters in sunscreens) but generally not helpful in detecting systemic drug photosensitivity. Drug-induced photosensitivity is usually best managed by stopping the suspected drug. Other measures, including phototherapy using wavelengths that do not elicit the response, are sometimes necessary. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Drug-induced mania.

    PubMed

    Peet, M; Peters, S

    1995-02-01

    Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.

  15. [Drug-induced bronchospasm (author's transl)].

    PubMed

    Strumeliev, S

    1978-01-01

    A detailed review of drug-induced bronchospasm is presented. Four types of reactions are described. Furthermore, pathogenesis, clinical picture, treatment and prophylaxis of the "Aspirin-induced asthma" are demonstrated.

  16. Tenofovir induced lichenoid drug eruption.

    PubMed

    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.

  17. Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms.

    PubMed

    Takehara, A; Aoyama, Y; Kurosawa, M; Shirafuji, Y; Umemura, H; Kamiya, K; Ushigome, Y; Kano, Y; Shiohara, T; Iwatsuki, K

    2016-11-01

    The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses. © 2016 British Association of Dermatologists.

  18. Drug-induced taste and smell alterations: a case/non-case evaluation of an italian database of spontaneous adverse drug reaction reporting.

    PubMed

    Tuccori, Marco; Lapi, Francesco; Testi, Arianna; Ruggiero, Elisa; Moretti, Ugo; Vannacci, Alfredo; Bonaiuti, Roberto; Antonioli, Luca; Fornai, Matteo; Giustarini, Giulio; Scollo, Carla; Corona, Tiberio; Ferrazin, Fernanda; Sottosanti, Laura; Blandizzi, Corrado

    2011-10-01

    The frequency and clinical features of drug-related taste and/or smell impairments are currently unclear. The aim of this study was to identify major drug classes associated with taste and smell alterations reported to the Italian spontaneous adverse drug reaction (ADR) reporting database. The association between drug and altered taste or smell was investigated by case/non-case methodology. The reporting odds ratio (ROR) was used as a measure of disproportionality. Cases were defined as patients with at least one ADR related to taste or smell impairments. The non-cases included all patients without any ADRs related to taste or smell alterations. According to the selection criteria, 52 166 reports were included in the analysis. Overall, 182 cases of drug-related taste and/or smell dysfunctions were identified. Statistically significant unadjusted RORs were reported for macrolides (n = 31; 7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n = 17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n = 15; 1.7; 95% CI 1.0, 2.8) and protein kinase inhibitors (n = 10; 4.0; 95% CI 2.1, 7.7). When RORs were adjusted for sex and age category, the disproportion remained statistically significant for all of the previously mentioned drug classes. Taste and/or smell abnormalities are common, sometimes unexpected and often persistent complaints of patients during pharmacological treatments. Physicians should be aware of the impact of these ADRs on patients' quality of life.

  19. 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.

  20. Pharmacogenetics of adverse reactions to antiepileptic drugs.

    PubMed

    Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M

    2015-05-11

    Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions

    PubMed Central

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted. PMID:27818635

  2. Drug-induced hypokalaemia.

    PubMed

    Ben Salem, Chaker; Hmouda, Houssem; Bouraoui, Kamel

    2009-01-01

    Hypokalaemia (defined as a plasma potassium concentration<3.5 mEq/L) is a common electrolyte abnormality in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hypokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic disease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diagnosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.

  3. 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 and depigmented, but maintains the ...

  4. Drug-induced catatonia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-09-01

    Catatonia is a heterogeneous syndrome that varies in etiology, presentation, course and sequelae. Initially conceptualized as a subtype of schizophrenia, catatonia is now recognized to occur not only with other psychiatric conditions but also with medical conditions and drug-induced and toxic states. While drug-induced catatonia is now a recognized entity, most studies club it with catatonia due to general medical conditions or organic catatonia, thus precluding any meaningful interpretation of such cases. The literature on drug-induced catatonia mostly draws from scattered case reports. This article attempts to review the available literature in this realm and integrate the information in an attempt to explore the epidemiology, etiology, mechanism and treatment of drug-induced catatonia.

  5. Drug-induced diarrhoea.

    PubMed

    Chassany, O; Michaux, A; Bergmann, J F

    2000-01-01

    Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several

  6. [Drug-induced oral ulcerations].

    PubMed

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  7. Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4(+)CD25(+)CD134(+) lymphocytes.

    PubMed

    Klaewsongkram, Jettanong; Thantiworasit, Pattarawat; Sodsai, Pimpayao; Buranapraditkun, Supranee; Mongkolpathumrat, Pungjai

    2016-11-01

    Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common. To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4(+)CD25(+)CD134(+) T-lymphocyte percentages. Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4(+)CD25(+)CD134(+) T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis. By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4(+)CD25(+)CD134(+) T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively. Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4(+)CD25(+)CD134(+) T cells in these patients may be associated with immune tolerance. Copyright © 2016 American College of Allergy, Asthma

  8. Influence of chemical structure on skin reactions induced by antiepileptic drugs--the role of the aromatic ring.

    PubMed

    Wang, Xiang-Qing; Shi, Xiao-Bing; Au, Ran; Chen, Fu-Shun; Wang, Fang; Lang, Sen-Yang

    2011-05-01

    Here we assessed whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain skin reaction. We found that 164 cases of skin reactions associated with the use of AEDs were reported. Aromatic AEDs were suspected in 88.41% (145/164) of patients with skin reactions versus 59.80% (2316/3873) of patients without skin reactions. The presence of an aromatic ring in the chemical structure was associated with a significant increased risk of skin reactions (adjusted ROR 3.50; 95% CI 2.29, 5.35). Among the aromatic AEDs, skin reactions were significantly associated with carbamazepine, lamotrigine, and oxarbazepine. These results confirm that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains AED-skin reactions. Skin reactions were reported triple as frequently with aromatic AEDs than with non-aromatic AEDs.

  9. [Drug-induced dyschromatopsias].

    PubMed

    Perdriel, G; Manent, P J

    1982-01-01

    Drug-induced dyschromatopsias are defined as functional or objective alterations of color sense following drug treatment. Drug induced chromatopsias are characterized by a perception of white surfaces as colored and occur following modifications of normally transparent structures or alterations of the chorioretina or higher centers. Digitalic intoxication is responsible for incorrect perception of yellow or blue; the retinal origin of the disorder is confirmed by electroretinograms and histologic modifications in the photoreceptor synapses. Santonin in doses exceeding 1 cg is associated with various color misperceptions due to injury to a peripheral neuron or problems of rhodopsin formation. Some sulfas and antibiotics may cause misperception of yellow, and the anticonvulsant drug Tridione may cause an almost complete disappearance of some colors. Chromotopsias of central origin due to direct action on cerebral neurons are rare but may follow use of phenacetine or atropine. Drug induced dyschromatopsias are more common and may be the initial symptoms of various kinds of drug intoxication. Various simple and reliable tests enable the practicing clinician to detect such disorders at an early stage. Synthetic antimalarial drugs derived from chloroquine and used in longterm treatment of rheumatism or during antimalarial prophylaxis, indomethacine, and the phenotiazins may cause dyschromatopsias due to retinal intoxication. Oral contraceptives diminish the chromatic perception in 20% of cases according to 1 author, and often cause deficits of blue-yellow perception. Disulfiram, certain antibiotics such as chloramphenicol, nystatin, isoniazide, and other drugs may cause dyschromatopsias due to alterations in the optical fibers. Ethambutol is the most harmful to color perception; its effects are usually but not always reversible on discontinuation of the drug. Systematic tests of color perception should be administered prior to and during treatment with any drug known to

  10. 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.

  11. 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

  12. Recognizing and reporting adverse drug reactions.

    PubMed Central

    Lucas, L. M.; Colley, C. A.

    1992-01-01

    Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067

  13. 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

  14. Drug-induced gynecomastia.

    PubMed

    Eckman, Ari; Dobs, Adrian

    2008-11-01

    Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

  15. Pharmacogenetics of antiepileptic drug-induced hypersensitivity.

    PubMed

    Bloch, Katarzyna M; Sills, Graeme J; Pirmohamed, Munir; Alfirevic, Ana

    2014-04-01

    Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future.

  16. Drug-induced uveitis

    PubMed Central

    2013-01-01

    A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates. PMID:23522744

  17. [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.

  18. Adverse drug reaction cards carried by patients.

    PubMed

    Hannaford, P C

    1986-04-26

    Five hundred patients were asked whether they were allergic to any medicines. The description given of any stated reaction was assessed to see whether an important adverse drug reaction was likely to have occurred. The patients' records were also examined for collaborative evidence. Poor documentation often made it difficult to confirm the patient's claim of drug sensitivity. A total of 89 patients may have suffered from important adverse reactions to 113 drugs. Full documentation of adverse reactions is important, but only eight patients carried any information to warn others of their sensitivities. Patients should be asked about any drug sensitivities and, if appropriate, given written confirmation of them. A quick, simple method of doing this would be to provide patients' with a plastic card, similar to a credit card, with instructions and details of the reaction written on it with an indelible pen.

  19. 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

  20. Adverse drug reactions in hospitalized Colombian children

    PubMed Central

    Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-01-01

    Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Results: Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Conclusions: Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics. PMID:27821893

  1. Adverse drug reactions in hospitalized Colombian children.

    PubMed

    de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-09-30

    The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

  2. Antiepileptic drugs and adverse skin reactions: An update.

    PubMed

    Błaszczyk, Barbara; Lasoń, Władysław; Czuczwar, Stanisław Jerzy

    2015-06-01

    This paper summarizes current views on clinical manifestation, pathogenesis, prognosis and management of antiepileptic drug (AED)-induced adverse skin reactions. Cochrane Central Register of Controlled Trials, MEDLINE (PubMed) and ISI Web of Knowledge were searched. The recent classification, among drug-induced skin injuries, points to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis and hypersensitivity syndrome (HSS), which may be also recognized as a drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The use of aromatic AEDs, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, zonisamide, and lamotrigine is more frequently associated with cutaneous eruption and other signs or symptoms of drug hypersensitivity. There is a high degree of cross-reactivity (40-80%) in patients with hypersensitivity or allergic reactions to AEDs. Pharmacogenetic variations in drug biotransformation may also play a role in inducing these undesired effects. It is suggested that avoidance of specific AEDs in populations at special risk, cautious dose titration and careful monitoring of clinical response and, if applicable, laboratory parameters can minimize the serious consequences of idiosyncratic reactions.

  3. 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

  4. Domino Reactions in Drug Design and Discovery.

    PubMed

    Bhar, Shanta; Ramana, Mucheli M V

    2016-01-01

    With reference to challenges in developing varied and exceedingly complex scaffolds expeditiously through atom economy, domino reactions have assumed a significant role in several transformative endeavors towards established pharmaceuticals and new chemical entities across diverse therapeutic classes such as HIV integrase inhibitors, DPP4 [dipeptidyl peptidase IV] inhibitors, GSK- 3 (Glycogen Synthase Kinase 3) inhibitors, neoplastic drugs and microtubule antagonists. The very large chemical space of Domino Reactions can be leveraged for the design strategy of drugs and drug- like candidates with leading examples like Indinavir (Crixivan), Trandolapril (Mavik), Biyouyanagin A, endo pyrrolizidinone diastereomer [GSK] and several others. Domino reactions therefore constitute an integral part of both creative and functional aspects of drug design and discovery, contributing both enhanced efficiency as well as synthetic versatility to pharmaceutical drug design.

  5. Doxycycline-induced drug fever: a case report.

    PubMed

    Yuan, Hai-Ling; Lu, Ning-Wei; Xie, Hua; Zheng, Yuan-Yuan; Wang, Qiu-Hong

    2016-01-01

    Drug fever is a febrile reaction induced by a drug without additional clinical symptoms. This adverse reaction is not rare but under diagnosed and under reported. Doxycycline is a tetracycline compound with broad-spectrum antibiotic activity. Drug fever induced by doxycycline is rarely reported. In this study, we describe a patient in whom doxycycline induced drug fever after 17 days of therapy for brucellosis.

  6. Reaction phenotyping to assess victim drug-drug interaction risks.

    PubMed

    Di, Li

    2017-08-18

    Reaction phenotyping provides critical information regarding the fraction metabolized (fm) of drug candidates. It has become increasingly important in drug discovery and development as it can be used to assess victim drug-drug interaction potential, guide structural modification to reduce fm, inform clinical study design, predict individual variability in pharmacokinetics, and evaluate the impact of genetic polymorphisms. Areas covered: The currently available in vitro and in vivo methods for reaction phenotyping are summarized along with their advantages, limitations and timings for application during the different stages of drug discovery and development. Challenges of reaction phenotyping for low clearance compounds, non-Cytochrome P450 (CYP) enzymes, extrahepatic contribution and atypical kinetics are highlighted and various approaches are discussed. Expert opinion: Certain areas of reaction phenotyping remain challenging with the current state of the science. In order to better define fm in this challenging space, there needs to be future advances in selective inhibitors and specific substrate reactions for non-CYP enzymes, availability of high quality and low cost recombinant enzymes, tissue distribution and in vitro-in vivo correlation, scaling factors for extrahepatic enzymes and the next generation of low clearance tools.

  7. Patch testing for adverse drug reactions.

    PubMed

    Sekhon, Sahil; Nedorost, Susan T

    2017-01-01

    Adverse drug reactions result in a substantial number of hospital admissions and inpatient events. Diagnosis usually is made with clinical judgment and circumstantiality without diagnostic testing. Furthermore, even in situations where diagnostic testing is performed, no safe gold standard tests exist. Oral rechallenge is currently the gold standard but carries the risk of recrudescence of severe allergic symptoms. Other tests include skin prick tests, the lymphocyte transformation test, immunohistochemistry, and patch testing. This article provides a review of patch testing in cases of adverse drug reactions and presents new data on this topic.

  8. Vibrational excitation induces double reaction.

    PubMed

    Huang, Kai; Leung, Lydie; Lim, Tingbin; Ning, Zhanyu; Polanyi, John C

    2014-12-23

    Electron-induced reaction at metal surfaces is currently the subject of extensive study. Here, we broaden the range of experimentation to a comparison of vibrational excitation with electronic excitation, for reaction of the same molecule at the same clean metal surface. In a previous study of electron-induced reaction by scanning tunneling microscopy (STM), we examined the dynamics of the concurrent breaking of the two C-I bonds of ortho-diiodobenzene physisorbed on Cu(110). The energy of the incident electron was near the electronic excitation threshold of E0=1.0 eV required to induce this single-electron process. STM has been employed in the present work to study the reaction dynamics at the substantially lower incident electron energies of 0.3 eV, well below the electronic excitation threshold. The observed increase in reaction rate with current was found to be fourth-order, indicative of multistep reagent vibrational excitation, in contrast to the first-order rate dependence found earlier for electronic excitation. The change in mode of excitation was accompanied by altered reaction dynamics, evidenced by a different pattern of binding of the chemisorbed products to the copper surface. We have modeled these altered reaction dynamics by exciting normal modes of vibration that distort the C-I bonds of the physisorbed reagent. Using the same ab initio ground potential-energy surface as in the prior work on electronic excitation, but with only vibrational excitation of the physisorbed reagent in the asymmetric stretch mode of C-I bonds, we obtained the observed alteration in reaction dynamics.

  9. Chemotherapy and biotherapy-induced hypersensitivity reactions.

    PubMed

    Van Gerpen, Ruth

    2009-01-01

    Nearly all chemotherapy and biotherapy drugs used in cancer treatment today can cause hypersensitivity reactions. Certain groups of drugs frequently associated with these reactions include the asparaginases, taxanes, platinum compounds, epipodophyllotoxins, and the monoclonal antibodies. Recognizing and managing hypersensitivity reactions are critical when caring for patients receiving these drugs because the reactions are potentially life-threatening. A thorough understanding of the drugs is necessary to assist the nurse in prevention, early recognition, and timely management.

  10. [Drug-induced asterixis].

    PubMed

    Rittmannsberger, H; Leblhuber, F

    1994-04-22

    A 54-year-old woman with acute schizoaffective psychosis was treated with lithium carbonate (1,350 mg daily) and zuclopenthixol. On admission, clozapine was added (250 mg daily). Because extrapyramidal symptoms (rigor, akinesia) developed, she was additionally given biperiden retard (4 mg daily) from the fourth hospital day onwards. Eleven days after admission she began to complain of "unsteadiness" and "tremors" in her arms and she had asterixis (flapping tremor) on holding up her arms. The electromyogram showed electrical pauses of 60-120 ms, typical for asterixis. There were no significant metabolic or organic cerebral changes that could have accounted for the symptoms which presumably had been induced by the drugs even though their dosage was not unusual. The symptoms in fact regressed completely after the clozapine dose had been reduced, at first to 125 mg then to 50 mg. Previous experience has suggested that the risk of asterixis is particularly high when lithium and clozapine are taken together.

  11. Drug induced exfoliative dermatitis: state of the art.

    PubMed

    Yacoub, Mona-Rita; Berti, Alvise; Campochiaro, Corrado; Tombetti, Enrico; Ramirez, Giuseppe Alvise; Nico, Andrea; Di Leo, Elisabetta; Fantini, Paola; Sabbadini, Maria Grazia; Nettis, Eustachio; Colombo, Giselda

    2016-01-01

    Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Overall, T cells are the central player of these immune-mediated drug reactions. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED.

  12. Drug hypersensitivity syndrome induced by meglumine antimoniate.

    PubMed

    Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

    2009-06-01

    We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS.

  13. 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

  14. Spallation-induced fission reactions

    NASA Astrophysics Data System (ADS)

    Benlliure, J.; Rodríguez-Sánchez, J. L.

    2017-03-01

    During the last decade spallation-induced fission reactions have received particular attention because of their impact in the design of spallation-neutron sources or radioactive beam facilities, but also in the understanding of the fission process at high excitation energy. In this paper, we review the main progress brought by modern experimental techniques, in particular those based in the inverse kinematic, as well as the achievements in modelling these reactions. We will also address future possibilities for improving the investigation of fission dynamics.

  15. Adverse drug reactions related to drug administration in hospitalized patients.

    PubMed

    Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

    2017-06-15

    Drug treatment may be related with the development of adverse drug reactions (ADRs). Here, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During this time, we analyzed 2870 clinical records and 11,138 prescriptions and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6± 1.2 days) respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescription on 11,138 (27.4%), with a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) respect to patients that not experienced ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and treated as new disease. In conclusion, we documented that age and gender are risk factors for the development of ADRs, that in some patients are under-diagnosed. Therefore, it is important to motivate healthcare to report the ADRs in order optimize the patient safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. 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

  17. Drug-induced hair loss.

    PubMed

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  18. Involvement of anticancer drugs in the relief system for adverse drug reactions in Japan.

    PubMed

    Maeda, Hideki; Kurokawa, Tatsuo

    2013-12-01

    The compensation scheme for adverse drug reactions in Japan was implemented more than three decades ago as relief system by regulatory agencies. Because of the high frequency of adverse drug reactions, anticancer drugs have been excluded from coverage by the relief system since its implementation. Requests have recently been made by some patient advocates for the expansion of relief coverage to include anticancer drugs. In response to these requests, the Ministry of Health, Labor and Welfare of Japan established a committee to discuss relief from anticancer drug-induced health damages in June 2011. We conducted comprehensive research into the compensation scheme for adverse drug reactions in the world. We also investigated the situation of compensation and the committee for discussing inclusion of anticancer drugs into the relief system in Japan. Many countries including the United States and UK do not have relief or compensation schemes for no-fault compensation. We investigated whether a no-fault compensation system exists in Nordic countries (Sweden, Denmark, Norway and Finland), France, Germany, New Zealand and Taiwan in the world, although they offer different services from Japan. We also reviewed current situation and the fundamental difficulties associated with including anticancer drugs in the systems in Japan. The present study investigated the current situation and the fundamental difficulties associated with including anticancer drugs in the systems in Japan and pointed out part of the reason why the committee could not conclude involvement of anticancer drugs in the relief system.

  19. Adverse drug reactions in the oral cavity.

    PubMed

    Lo Russo, Lucio; Guida, Laura; Di Masi, Maria; Buccelli, Claudio; Giannatempo, Giovanni; Di Fede, Olga; Di Lorenzo, Pierpaolo; Lo Muzio, Lorenzo

    2012-01-01

    Several drugs may have a number of adverse reactions (ADRs) involving the oro-facial region. The dose of the drug and the time required for the reaction to take place are relevant parameters; nonetheless, ADRs mechanisms are not always known and ADRs are not always predictable since aspects other than drug pharmacodynamics and/or pharmacokinetics, as well as various interacting variables contribute to the final outcome. All tissues and many functions of the oral cavity can be affected. In particular, salivary function is frequently involved and hypo-salivation is the main manifestation; several mucosal lesions with different morphology (ulcerations, vesiculobullous lesions, white lesions, pigmentations, swelling) are also possible. Taste, sensation and trigeminal function alterations have been reported and the recent evidence regarding the occurrence of jawbones osteonecrosis, especially in bisphosphonates treated patients, is increasing. Clinical management may be quite difficult due to the multiplicity of involved classes of drugs and substances (dental materials, foods), the variety of affected tissues and functions, the type of produced lesions and disturbances, the complexity of related pathogenetic mechanisms (if known), the difficulties in assessing causality and managing drug withdrawal and/or dose adjustment, as well as in establishing specific treatments, if any. In this paper the most common and significant oral ADRs, their related aspects and importance (including medico-legal implications) for health care providers will be discussed.

  20. Role of peripheral eosinophilia in adverse cutaneous drug reactions.

    PubMed

    Drago, F; Cogorno, L; Agnoletti, A F; Parodi, A

    2015-01-01

    The objective of this retrospective study was to verify whether peripheral eosinophilia (PE) may be a marker of severity for adverse cutaneous drug reactions (ACDR). We investigated for PE in sixty-three patients diagnosed as adverse cutaneous drug reactions. All the patients underwent blood tests at baseline visit. Only patients that showed a very likely connection between ACDR and the suspected causative drug were induced in the study. We found that 11 out of 63 patients (17%) presented PE for values ≥ 0.6 x 10(9) cells/l or for a percentage of total leukocytes ≥ 6%. These 11 patients compared to patients without eosinophilia had a longer recovery time, they showed diffuse severe cutaneous reactions and they all needed a systemic therapy compared to the 41% of patients without eosinophilia. These outcomes prompt us to believe that peripheral eosinophilia may be an index of severity for adverse cutaneous drug reactions. Therefore, we suggest physicians to always detect the presence of peripheral eosinophilia in order to not underestimate the reaction and to promptly start an appropriate therapy.

  1. New concepts in the management of adverse drug reactions.

    PubMed

    Bahna, Sami L; Khalili, Barzin

    2007-01-01

    Our understanding of drug reactions and their management has changed markedly in recent years with the development of several new concepts. Epidermal cell death seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG) contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to healing. Furthermore, several studies have dispelled the myth of sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial sulfonamides are directed against two unique side chains that non-antibacterial sulfonamides do not contain. Certain patients seem to have a genetic predisposition for "multiple drug sensitivities." Hence, they may react to several drugs that are not necessarily cross-reacting. Also, multiple studies have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross-reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that results in pseudoallergic reactions to multiple NSAIDs. Several studies have indicated that selective COX-2 inhibitors can be safely administered in patients with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous reactions, although their use has been curtailed by their cardiovascular side effects. Biological agents, such as infliximab, are being increasingly used for a variety of diseases and have caused adverse reactions in some patients. Studies differ as to whether concomitant immunosuppressive use with infliximab affects the development of drug-specific antibodies and infusion reactions. Successful desensitization protocols have been developed for reactions to some of these agents.

  2. 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

  3. Modafinil-induced Fixed Drug Eruption.

    PubMed

    Gaikwad, Girish Vasant; Dhuri, Chetali Vijay

    2012-10-01

    Modafinil is a stimulant drug widely used to promote wakefulness in a variety of psychiatric and neurological conditions. Modafinil-induced severe dermatologic reactions are uncommon but serious side effects. We report a patient who developed fixed drug eruption after exposure to a single dose of tablet modafinil. On assessment using the Naranjo scale, the score was five, which made us conclude that modafinil was the "probable" cause of the patient's adverse drug event. This case report highlights the need to be alert toward the emergence of dermatologic side effects among patients taking modafinil.

  4. Drug Induced Hypersensitivity and the HLA Complex

    PubMed Central

    Alfirevic, Ana; Pirmohamed, Munir

    2011-01-01

    Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity.

  5. Drug-induced liver injury and drug development: industry perspective.

    PubMed

    Regev, Arie

    2014-05-01

    Despite intensive ongoing research, drug-induced live injury (DILI) remains a serious issue for care providers and patients, and has been a major cause of drug withdrawal and non-approval by regulatory authorities in the past 50 years. Consequently, DILI remains a major concern for the pharmaceutical industry and a leading cause for attrition during drug development. In most instances, severe DILI is an uncommon idiosyncratic reaction, which typically does not present during preclinical phases or early clinical phases of drug development. In the majority of cases, drugs that caused severe DILI in humans have not shown clear and consistent hepatotoxic signals in preclinical assessment including animal studies, cell cultures, or other methods. Despite intensive efforts to develop better biomarkers that would help in predicting DILI risk in earlier phases of drug development, such biomarkers are currently not supported by sufficient evidence and are not yet available for routine use by drug makers. Due to the lack of effective and accurate methods for prediction of idiosyncratic DILI during preclinical phases of drug development, different drug makers have adopted different approaches, which are often not supported by strong systematic evidence. Based on growing experience, it is becoming increasingly evident that milder forms of liver injury occurring during clinical development, when assessed correctly, may significantly enhance our ability to predict the drug's potential to cause more severe liver injury postmarketing. Strategies based on this concept have been adopted by many drug makers, and are being increasingly implemented during drug development. Meticulous causality assessment of individual hepatic cases and adherence to strict hepatic discontinuation rules are critical components of this approach and have to rely on thorough clinical evaluation and occasionally on assessment by liver experts experienced with DILI and drug development.

  6. Thromobocytopenia - drug-induced

    MedlinePlus

    ... to treat arthritis Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Quinidine Quinine Ranitidine Sulfonamides Linezolid and other antibiotics ... Hadjiliadis, MD, MHS, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University ...

  7. Drug-induced hypertension

    MedlinePlus

    ... desipramine) Caffeine (including the caffeine in coffee and energy drinks) Corticosteroids Cyclosporine Ephedra and many other herbal products Erythropoietin Estrogens (including birth control pills) and other ... drugs Yohimbe Rebound hypertension occurs when blood ...

  8. Drug-induced lupus erythematosus

    MedlinePlus

    ... Causes Drug-induced lupus erythematosus is similar to systemic lupus erythematosus (SLE). It is an autoimmune disorder. This means ... 2015:chap 132. Wright B, Bharadwaj S, Abelson A. Systemic lupus erythematosus. In: Carey WD, ed. Cleveland Clinic: Current Clinical ...

  9. [Drug-induced lung diseases].

    PubMed

    Camus, Philippe

    2007-12-31

    Drug-induced interstitial pneumonias are systematically considered in the differential diagnosis of the interstitial pneumonias. The presentation may be acute, sub-acute or chronic, with the same drug possibly leading to either acute or subacute/chronic interstitial lung disease (e.g. amiodarone). There is no definite diagnostic criterion, the final diagnosis relying on the clinical and imaging features, the chronology of pulmonary manifestations, and the prevalence of reported cases with the suspected drug.

  10. Drug-induced rash: nuisance or threat?

    PubMed

    Wick, Jeannette Y

    2013-03-01

    Drug-induced rash is the most commonly reported drug reaction and occurs in a dizzying array of presentations. Changes in lean and fat body tissue, gastrointestinal acid and mucosal permeability, cardiac output, and renal and hepatic metabolism can affect drug absorption, distribution, metabolism, and elimination. Elders may develop cutaneous eruptions from drugs or biologics and be more sensitive to topical medications. Almost all medications have been associated with rash to some degree. Consultant pharmacists should be able to distinguish between the rashes that are uncomfortable from those that are potentially life-threatening. Some drug therapies tend to induce or aggravate "companion" rashes. With select medications, rash is a clinical indicator that the medication is working. Extensive or unusually painful drug-induced skin conditions are rare, but often require fast action by health care providers to direct the patient to life-saving help. Many of these rashes are associated with high mortality, severe complications, and potential chronic disability. Awareness of the drugs that are most likely to cause a rash can help consultant pharmacists work with the clinical team to arrange appropriate care.

  11. Human leukocyte antigen and idiosyncratic adverse drug reactions.

    PubMed

    Usui, Toru; Naisbitt, Dean J

    2017-02-01

    A clinical association between a specific human leukocyte antigen (HLA) allele and idiosyncratic adverse drug reactions (IADRs) is a strong indication that IADRs are mediated by the adaptive immune system. For example, it is well-established that HLA-B*15:02 and HLA-B*57:01 are associated with carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, respectively. Drug-specific T-cells whose response is restricted by specific HLA risk alleles have been detected from IADR patients, also suggesting an adaptive immune pathogenesis. T-cells from carbamazepine SJS/TEN patients are activated by direct pharmacological interaction between carbamazepine and HLA-B*15:02 expressed on antigen presenting cells (APCs). Abacavir-specific, HLA-B*57:01-restricted T-cells are activated by APCs presenting peptides which are only displayed by the HLA molecule when abacavir is bound during peptide loading. Finally, HLA-B*57:01-restricted activation of T-cells from patients with flucloxacillin-induced liver injury is dependent on processing of drug protein adducts. Based on these observations, it is now possible to utilize blood from healthy drug-naïve volunteers to study the priming of naïve T-cells to drugs. Future development of these methodologies may lead to the development of assays that predict intrinsic immunogenicity of drugs and chemicals at the preclinical stage of drug development. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  12. Drug-induced urinary calculi.

    PubMed

    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.

  13. 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

  14. Evaluation of drug-related hypersensitivity reactions in children.

    PubMed

    Martín-Muñoz, F; Moreno-Ancillo, A; Domínguez-Noche, C; Díaz-Pena, J M; García-Ara, C; Boyano, T; Ojeda, J A

    1999-01-01

    Patients with drug reactions are often referred to allergists for "allergy". Skin testing and clinical history seem to have a good negative predictive value, however, although drug challenge could be dangerous, it is the only way to confirm the diagnosis. We aimed to demonstrate that most children with a history of non-life-threatening drug reactions do not have a true drug allergy and examined the use of drug challenge in childhood. Patients with reactions were referred to our clinic by pediatricians. In 1 year, 354 reactions were studied in 239 children. Patients were classified according to their positive or negative history of drug allergy. Skin prick testing was done in all cases. Exclusion criteria for challenge included drug anaphylaxis, Stevens-Johnson syndrome, systemic reactions with severe concomitant illness, beta-inhibitor drug therapy or positive skin test to the implicated drug with a positive history. It was found that the beta-lactam antibiotics were involved in 50% of suspected reactions, aspirin in 10% and sulfonamides in 9%. Histories were considered positive only in 25%. Drug challenges confirmed only 4% of all reactions. It was concluded that drug challenge may be the gold standard for most childhood reactions that are considered to be allergic, non-life-threatening and drug-related. Only 4% of these suspected reactions were exclusively caused by drug allergy.

  15. 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

  16. Drug-induced yawning--a review.

    PubMed

    Patatanian, Edna; Williams, Nancy Toedter

    2011-10-01

    To review the current literature on drug-induced yawning. Literature was accessed through MEDLINE/PubMed (1996-July 2011), International Pharmaceutical Abstracts (1997-July 2011), and EMBASE, using the search terms yawning, drug-induced yawning, and adverse drug reactions. Relevant clinical trials and case reports were selected and included to present background information. Bibliographies of all relevant articles were reviewed for additional citations. Yawning is a common stereotype behavior with unknown physiologic function that occurs in most vertebrates and humans as early as 15 weeks of intrauterine life. Yawning is under the control of several neurotransmitters and neuropeptides, including dopamine, serotonin, oxytocin, and acetylcholine. Among drugs, antidepressants, opioids, dopaminergic agents, benzodiazepines, and induction agents are the main pharmacologic classes associated with yawning. Yawning is rarely a serious adverse reaction and is not frequently listed in the drug summary. Most available data are based on case reports, small studies, and older literature. Clinicians should be aware of the agents commonly triggering this behavior.

  17. Mechanisms of adverse drug reactions to biologics.

    PubMed

    Clarke, Janet B

    2010-01-01

    Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs.

  18. Drug-induced Liver Injury

    PubMed Central

    David, Stefan; Hamilton, James P

    2011-01-01

    Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

  19. Drug hypersensitivity reactions during hematopoietic stem cell transplantation.

    PubMed

    Bircher, Andreas J; Scherer Hofmeier, Kathrin

    2012-01-01

    Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthema, urticaria and angioedema. More rarely pustular, vesiculobullous, vasculitic and lichenoid lesions may be observed. Apart from the morphology, also the chronology of the occurrence and the evolution of the single skin lesions and the exanthema are paramount in the clinical diagnosis. Often, the skin is the only affected organ; however, it may herald a systemic involvement of internal organs, such as in severe drug-induced hypersensitivity syndromes or anaphylaxis. Cutaneous manifestations, particularly maculopapular exanthemas have a high incidence among patients treated with hematopoietic stem cell transplantation. In many cases, a virus- or drug-induced origin or a combination of both is responsible. However, the transplantation itself may also induce similar skin changes. These exanthemas include most often graft-versus-host disease, and rarely engraftment syndrome or eruption of lymphocyte recovery. The elucidation of the underlying cause of the exanthemas occurring in immune compromised patients and the determination of the correct diagnosis remain challenging. An extensive differential diagnosis has to be put forward. This includes several groups of disorders with sometimes very similar cutaneous manifestations. Manifestations form the underlying disease, complications from therapy, infections and drug reactions are the most common differential diagnoses.

  20. [Nursing role in reporting adverse drug reactions].

    PubMed

    Zurita-Garaicoechea, Ana; Reis-Carvalho, Joana; Ripa-Aisa, Irantzu; Jiménez-Mendoza, Ana; Díaz-Balén, Almudena; Oroviogoicoechea, Cristina

    2015-01-01

    The spontaneous report system, in which suspected adverse drug reaction (ADR) are reported by healthcare workers, is currently one of the primary methods to prevent and discover new and serious ADR to marketed medicinal products. The collaboration of nursing professionals with this task makes it possible to improve patient safety and to reduce ADR costs. Although a total of 781 cases of ADR cases were reported in Navarra in 2011, only 7.33% were reported by nurses. The objectives werw to determine the factors that influence nurses in reporting of ADR, and second, to devise strategies which help to increase reporting. A bibliographic search for articles that included the words: reacciones adversas medicamentosas (adverse drug reactions), notificación (reporting) and enfermería (nursing) was conducted using the PubMed and Cinhal databases. A total of 107 articles were retrieved, of which 27 were selected according to inclusion and exclusion criteria. The conclusion learned by reading and analyzing the selected articles was that the factors that affect the notification depend on the attitude of the notifier, as well as personal and professional factors. The main strategies to encourage notification are education and training, motivation, and the availability of facilitating tools. The main factors that have an influence on under-notification are the lack of knowledge and motivation among professionals. To solve the problem of under-notification, the main actions and strategies to undertake are education, motivation and persistence. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

    2012-01-01

    With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

  2. Analysis of adverse drug reactions using drug and drug target interactions and graph-based methods.

    PubMed

    Lin, Shih-Fang; Xiao, Ke-Ting; Huang, Yu-Ting; Chiu, Chung-Cheng; Soo, Von-Wun

    2010-01-01

    The purpose of this study was to integrate knowledge about drugs, drug targets, and topological methods. The goals were to build a system facilitating the study of adverse drug events, to make it easier to find possible explanations, and to group similar drug-drug interaction cases in the adverse drug reaction reports from the US Food and Drug Administration (FDA). We developed a system that analyses adverse drug reaction (ADR) cases reported by the FDA. The system contains four modules. First, we integrate drug and drug target databases that provide information related to adverse drug reactions. Second, we classify drug and drug targets according to anatomical therapeutic chemical classification (ATC) and drug target ontology (DTO). Third, we build drug target networks based on drug and drug target databases. Finally, we apply topological analysis to reveal drug interaction complexity for each ADR case reported by the FDA. We picked 1952 ADR cases from the years 2005-2006. Our dataset consisted of 1952 cases, of which 1471 cases involved ADR targets, 845 cases involved absorption, distribution, metabolism, and excretion (ADME) targets, and 507 cases involved some drugs acting on the same targets, namely, common targets (CTs). We then investigated the cases involving ADR targets, ADME targets, and CTs using the ATC system and DTO. In the cases that led to death, the average number of common targets (NCTs) was 0.879 and the average of average clustering coefficient (ACC) was 0.067. In cases that did not lead to death, the average NCTs was 0.551, and the average of ACC was 0.039. We implemented a system that can find possible explanations and cluster similar ADR cases reported by the FDA. We found that the average of ACC and the average NCTs in cases leading to death are higher than in cases not leading to death, suggesting that the interactions in cases leading to death are generally more complicated than in cases not leading to death. This indicates that our system

  3. [Research advances in drug-induced autoimmune hepatitis].

    PubMed

    Li, C M; Zhang, J Y; Tang, Y Y; Mao, Y M

    2016-11-20

    Drug induced autoimmune hepatitis (DIAIH) refers to the liver injury mediated by drug-induced autoimmune reaction. Since it has similar clinical features as idiopathic autoimmune hepatitis, it is often difficult to make differential diagnosis in clinical practice. A deep understanding of the development, pathogenesis, related drugs, risk factors, and clinical and histological features of DIAIH helps with the correct diagnosis and treatment of DIAIH.

  4. Hyperthermia-induced drug targeting.

    PubMed

    May, Jonathan P; Li, Shyh-Dar

    2013-04-01

    Specific delivery of a drug to a target site is a major goal of drug delivery research. Using temperature-sensitive liposomes (TSLs) is one way to achieve this; the liposome acts as a protective carrier, allowing increased drug to flow through the bloodstream by minimizing clearance and non-specific uptake. On reaching microvessels within a heated tumor, the drug is released and quickly penetrates. A major advance in the field is ThermoDox® (Celsion), demonstrating significant improvements to the drug release rates and drug uptake in heated tumors (∼ 41°C). Most recently, magnetic resonance-guided focused ultrasound (MRgFUS) has been combined with TSL drug delivery to provide localized chemotherapy with simultaneous quantification of drug release within the tumor. In this article the field of hyperthermia-induced drug delivery is discussed, with an emphasis on the development of TSLs and their combination with hyperthermia (both mild and ablative) in cancer therapy. State-of-the-art image-guided heating technologies used with this combination strategy will also be presented, with examples of real-time monitoring of drug delivery and prediction of efficacy. The specific delivery of drugs by combining hyperthermia with TSLs is showing great promise in the clinic and its potential will be even greater as the use of image-guided focused ultrasound becomes more widespread - a technique capable of penetrating deep within the body to heat a specific area with improved control. In conjunction with this, it is anticipated that multifunctional TSLs will be a major topic of study in this field.

  5. Clinical applications of pharmacogenomics to adverse drug reactions.

    PubMed

    Issa, Amalia M

    2008-03-01

    The problem of adverse drug reactions is a well-documented global public health problem. Recent withdrawals of several widely used prescription medications in the USA and other countries have raised concerns among patients, clinicians, scientists and policy makers. The increasing interest and concern regarding withdrawal of previously approved prescription medications and drug safety has prompted renewed research efforts aimed at improving surveillance of approved drugs and reducing adverse drug reactions. Pharmacogenomics research is increasingly directed at developing genomic diagnostics and tests with predictive ability for adverse drug reactions. This paper focuses on the problem of adverse drug reactions and reviews the evidence and the state of the science for the application of pharmacogenomics to adverse drug reactions.

  6. 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

  7. 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

  8. 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. © The Author(s) 2015. Published by Oxford University Press.

  9. A review and assessment of drug-induced parotitis.

    PubMed

    Brooks, Krista G; Thompson, Dennis F

    2012-12-01

    To review the current literature on drug-induced parotitis. Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other

  10. Drug-Induced Sleep Endoscopy.

    PubMed

    Charakorn, Natamon; Kezirian, Eric J

    2016-12-01

    Drug-induced sleep endoscopy (DISE) is an upper airway evaluation technique in which fiberoptic examination is performed under conditions of unconscious sedation. Unique information obtained from this 3-dimensional examination of the airway potentially provides additive benefits to other evaluation methods to guide treatment selection. This article presents recommendations regarding DISE technique and the VOTE Classification system for reporting DISE findings and reviews the evidence concerning DISE test characteristics and the association between DISE findings and treatment outcomes.

  11. [Drug-induced hypersensitivity syndrome and HHV-6 reactivation].

    PubMed

    Tohyama, Mikiko; Hashimoto, Koji

    2009-06-01

    Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash, and internal organ involvement. The culprit drugs of DIHS are limited to several drugs such as carbamazepine, phenytoin, phenobarbital, zonisamide, allopurinol, salazosulfapyridine, diaphenylsulphone, and mexiletine. The association of HHV-6 reactivation with DIHS has been known. Flaring of symptoms such as fever and hepatitis is closely related to HHV-6 reactivation. A combination of immunologic reaction to a drug and HHV-6 reactivation results in the severe course of DIHS.

  12. Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of Serious or Fatal 'Slow Gut' Reactions, and Comparison with International Drug Safety Advice.

    PubMed

    Every-Palmer, Susanna; Ellis, Pete M

    2017-08-01

    Clozapine is the preferred antipsychotic for treatment-resistant schizophrenia, but has significant adverse effects, including gastrointestinal hypomotility or 'slow gut', which may result in severe constipation, ileus, bowel obstruction, and even death. These gastrointestinal effects remain inadequately recognized. We reviewed all reports of serious clozapine-induced gastrointestinal hypomotility (CIGH) submitted to the Australian Therapeutic Goods Administration and New Zealand Pharmacovigilance Centre between 1992 and 2013. We extracted relevant demographic, clinical, and outcome data and derived a numerator from clozapine registries. We examined whether clozapine drug safety information in Australia, New Zealand, the US, and the UK was adequate and consistent with pharmacoepidemiologic evidence. A total of 43,132 people commenced clozapine over the study period. 160 were reported as having serious gastrointestinal hypomotility with clozapine the suspected cause (37/10,000 clozapine users). Of these, 66.3% were male, age range was 17-76 years, clozapine dose range 25-1000 mg/day (mean 439 mg/day) and median duration of clozapine treatment 2.5 years. Few had received laxatives. At least 29 patients died (7/10,000 clozapine users), a reported case fatality rate of 18%. The CIGH prevalence, while similar to other smaller studies, differs significantly from clozapine prescribing information issued by regulators and pharmaceutical companies, none of which mention CIGH, and which report serious gastrointestinal complications at rates of <1/10,000, almost a 40-fold difference. This is the largest study to date of serious CIGH. The reported prevalence of serious CIGH was 37/10,000, a likely underestimation of true prevalence. Current prescribing guidelines provide inadequate information on CIGH. This may be contributing to poor awareness and high associated morbidity and mortality. It is time regulators and manufacturers update their guidance.

  13. SNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese.

    PubMed

    Gui, H; Kwok, M; Baum, L; Sham, P C; Kwan, P; Cherny, S S

    2017-04-11

    Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation. The performance of our new panel was compared to a recent Han Chinese panel. Finally, genetic associations of HLA variants with mild skin rash were performed on the combined sample of 408 patients. Common SNPs rs2571375 and rs144295468 were found to successfully tag HLA risk alleles A*31:01 and B*13:01, respectively. HLA-B*15:02 can be predicted by rs144012689 with >95% sensitivity and specificity. The imputation reference panel for the Hong Kong population had comparable performance to the Han Chinese panel due to the large sample size for common HLA alleles, though it retained discordance for imputing rare alleles. No significant genetic associations were found between HLA genetic variants and mild skin rash induced by aromatic antiepileptic drugs. This study provides new information on the genetic structure of HLA regions in the Hong Kong population by identifying tagging SNPs and serving as a reference panel. Moreover, our comprehensive genetic analyses revealed no significant association between HLA alleles and mild skin rash in Hong Kong Han Chinese.The Pharmacogenomics Journal advance online publication, 11 April 2017; doi:10.1038/tpj.2017.11.

  14. Drug hypersensitivity reactions targeting the skin in dogs and cats.

    PubMed

    Voie, K L; Campbell, K L; Lavergne, S N

    2012-01-01

    Adverse drug reactions (ADRs) can be dose dependent or idiosyncratic. Most idiosyncratic reactions are believed to be immune-mediated; such drug hypersensitivities and allergies are unpredictable. Cutaneous reactions are the most common presentation of drug allergies. In veterinary medicine it can be difficult to assess the true prevalence of adverse drug reactions, although reports available suggest that they occur quite commonly. There are multiple theories that attempt to explain how drug allergies occur, because the pathogenesis is not yet well understood. These include the (pro)-hapten hypothesis, the Danger Theory, the pi concept, and the viral reactivation theory. Cutaneous drug allergies in veterinary medicine can have a variety of clinical manifestations, ranging from pruritus to often fatal toxic epidermal necrolysis. Diagnosis can be challenging, as the reactions are highly pleomorphic and may be mistaken for other dermatologic diseases. One must rely heavily on history and physical examination to rule out other possibilities. Dechallenge of the drug, histopathology, and other diagnostic tests can help to confirm the diagnosis. New diagnostic tools are beginning to be used, such as antibody or cellular testing, and may be used more in the future. There is much yet to learn about drug allergies, which makes future research vitally important. Treatment of drug allergies involves supportive care, and additional treatments, such as immunosuppressive medications, depend on the manifestation of the disease. Of utmost importance is to avoid the use of the incriminating drug in future treatment of the patient, as subsequent reactions can be worse, and ultimately can prove fatal.

  15. Toxins and adverse drug reactions affecting the equine nervous system.

    PubMed

    Dawson, Dominic R

    2011-12-01

    This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.

  16. Reactions Induced by Platelet Transfusions

    PubMed Central

    Kiefel, Volker

    2008-01-01

    Summary Platelet transfusions play a central role in therapeutic regimens for patients with hematologic/oncologic diseases who develop severe thrombocytopenia either in the course of their disease or following cytostatic therapy. Like other blood components, platelet transfusions have achieved a high degree of safety as far as transmission of viral diseases is concerned. However, transfusion of platelet concentrates is accompanied by a high frequency of febrile and anaphylactoid reactions. In rare cases, recipients of platelet concentrates are threatened by severe reactions as septic complications due to bacterial contamination of platelet concentrates, transfusion-related acute lung injury and severe anaphylactic episodes. PMID:21512624

  17. Laser-induced tissue reactions and dermatology.

    PubMed

    Weber, Rebecca J; Taylor, Brent R; Engelman, Dendy E

    2011-01-01

    Knowledge of laser tissue reactions and tissue properties allows the practitioner to tailor a treatment to an individual patient's need and goals. A laser's power, spot size and pulse duration may be manipulated to yield different tissue reactions. Five tissue reactions, each the result of varying laser pulse durations and energy densities, may be achieved. They are photochemical, photothermal, photoablation, plasma-induced ablation and photomechanical. Of these, photothermal reactions are most utilized in dermatology. When higher powered pulses are applied, tissue often undergoes multiple reactions simultaneously. An understanding of these reactions allows their effects to be predicted. In this chapter, the various reactions are reviewed, and the reactions caused by many of the most commonly used lasers in dermatology are discussed.

  18. Oral Muscle Relaxant May Induce Immediate Allergic Reactions

    PubMed Central

    Hur, Gyu-Young; Hwang, Eui Kyung; Moon, Jae-Young; Ye, Young-Min; Shim, Jae-Jeong; Kang, Kyung-Ho

    2012-01-01

    Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully. PMID:22665359

  19. Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical update and review of current thinking.

    PubMed

    Walsh, S A; Creamer, D

    2011-01-01

    Summary Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a severe medication-induced adverse reaction, which has cutaneous, haematological and solid-organ features. It is one of the triad of life-threatening drug hypersensitivity dermatoses, along with acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this article, we discuss several controversies that surround DRESS, including problems with nomenclature and the lack of consensus in diagnostic criteria.

  20. 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

  1. Ofloxacin Induced Cutaneous Reactions in Children.

    PubMed

    Ramani, Yerramalli Roja; Mishra, Sailen Kumar; Rath, Bandana; Rath, Saroj Sekhar

    2015-06-01

    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.

  2. Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study

    PubMed Central

    Sasidharanpillai, Sarita; Riyaz, Najeeba; Khader, Anza; Rajan, Uma; Binitha, Manikoth P; Sureshan, Deepthi N

    2015-01-01

    Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR. PMID:25657416

  3. Drug-induced liver injury.

    PubMed

    Katarey, Dev; Verma, Sumita

    2016-12-01

    Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identified by genetic risk determined by human leukocyte antigen variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, although recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued, especially in the presence of elevated transaminases (aspartate aminotransferase/alanine aminotransferase ratio ≥5 times the upper limit of normal) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in the early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory.

  4. [Adverse reactions induced by food additives: sulfites].

    PubMed

    Montaño García, M L

    1989-01-01

    Many chemicals are used to preserve, color and flavor foods and drugs. There have been numerous reports of adverse reactions, including urticaria, angioneurotic edema, asthma an anaphylaxis following the ingestion of food additives such as tartrazine, monosodium glutamate and benzoic acid. Recently the food and drug additives reaching medical awareness as a cause of sensitivity are the sulfiting agents. Sulfites are widely used in the food and beverage industry as preservatives and antioxidants. They are also used by the pharmaceutical industry. This work describes the common uses of sulfiting agents, the mechanisms of sulfite sensitivity, the diagnosis, prevention and treatment of adverse reactions to sulfites.

  5. Drug-induced status epilepticus.

    PubMed

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  6. 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

  7. Erythropoietin-induced iritis-like reaction.

    PubMed

    Beiran, I; Krasnitz, I; Mezer, E; Meyer, E; Miller, B

    1996-01-01

    The present report describes an iritis-like reaction found in 13 patients treated with recombinant human erythropoietin (Eprex), a drug given to hemodialysis patients for their chronic anemia. Among 120 patients being treated by hemodialysis in two centers affiliated with our medical center, ten out of 30 Eprex-treated patients but none of 90 not being treated with Eprex developed this reaction. The observations described support a causal relation between Eprex treatment and the iritis-like reaction. Further investigative effort is needed to establish the mechanism.

  8. Role of dermatology in pharmacogenomics: drug-induced skin injury.

    PubMed

    Borroni, Riccardo G

    2015-01-01

    Different individuals may respond diversely to the same drug, in terms of efficacy and toxicity. Adverse drug reactions cause about 6% of all hospital admissions and account for up to 9% of hospitalization costs. Drug-induced skin injury (DISI) is the most common presentation of adverse drug reactions, ranging from maculopapular eruptions to severe adverse cutaneous drug reactions (SCARs) with mortality of up to 40%. Specific genetic polymorphisms confer susceptibility to different types of DISI. Identifying patients genetically at risk for SCARs is one of the goals of pharmacogenomics. In this article, the aspects of clinical dermatology relevant to the pharmacogenetics of DISI are reviewed. Many SCARs are now preventable, with consequent reduction of morbidity, mortality and healthcare costs.

  9. Histopathological and immunohistochemical features of drug-induced exanthems.

    PubMed

    Lisi, P; Pelliccia, S; Bellini, V

    2014-04-01

    Exanthematic eruptions, together with urticaria-angioedema syndrome and fixed drug eruption, are the most frequent cutaneous adverse drug reactions. Among the drug-induced exanthems (DIEs), erythematous maculopapular eruptions are the most common. Their management, especially when retrospective, is often not easy, and it is based on the use of clinical criteria, history, results of some laboratory tests, drug elimination test, skin tests, and oral challenge test. The superficial perivascular and spongiotic dermatitis, which is the prevalent histopathological features of DIEs, is not very useful in the differential diagnosis with virus- and bacteria-induced exanthems (VBIEs). On the contrary, some immune-histochemical findings (interleukin-5 overexpression, concomitant enhancement of perforin, interleukin-5, and granzyme B production, positivity for fatty acid synthase-ligand-L in amoxicillin-induced exanthems) seem to be more important. These data justifie the inclusion of DIEs in the subtypes IVb and IVc of delayed hypersensitivity reactions.

  10. Drug-induced hair colour changes.

    PubMed

    Ricci, Francesco; De Simone, Clara; Del Regno, Laura; Peris, Ketty

    2016-12-01

    Hair colour modifications comprise lightening/greying, darkening, or even a complete hair colour change, which may involve the scalp and/or all body hair. Systemic medications may cause hair loss or hypertrichosis, while hair colour change is an uncommon adverse effect. The rapidly increasing use of new target therapies will make the observation of these side effects more frequent. A clear relationship between drug intake and hair colour modification may be difficult to demonstrate and the underlying mechanisms of hair changes are often unknown. To assess whether a side effect is determined by a specific drug, different algorithms or scores (e.g. Naranjo, Karch, Kramer, and Begaud) have been developed. The knowledge of previous similar reports on drug reactions is a key point of most algorithms, therefore all adverse events should be recognised and reported to the scientific community. Furthermore, even if hair colour change is not a life-threatening side effect, it is of deep concern for patient's quality of life and adherence to treatment. We performed a review of the literature on systemic drugs which may induce changes in hair colour.

  11. 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.

  12. Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.

    PubMed

    Mathuram, Alice J; George, Renu E

    2014-06-01

    Drug induced hypersensitivity syndrome has been reported to a variety of drugs. Reactivation of herpes viruses is associated with relapse of symptoms even as late as five weeks after stopping the inciting drug. We report here a case of drug hypersensitivity with CMV reactivation which was treated successfully.

  13. Predicting and managing adverse reactions of psychotropic drugs.

    PubMed

    Ilyina, Rosa Yu; Pasynkova, Olga O; Ziganshina, Lilia E

    2013-01-01

    Neuroleptic induced extrapyramidal disorders are often presented in a form of orofacial hyperkinesias and dystonia. Rational use of neuroleptic drugs requires individualised approach to a patient, however simple criteria for determining individual, "personalised" dosage regimen have not been fully developed for routine practice in resource-limited hospital settings. To study the tonus of tongue muscles as a measure of orofacial dystonia and the total hepatic oxidative capacity as a potential predictor of excessive vulnerability to neuroleptic-induced dystonia in psychiatric patients. We measured the maximal force of the tongue manoeuvre (F, g/cm2), the total (integral) hepatic oxidative capacity by the antipyrine-test and used chlorpromazine equivalent to calculate the total daily neuroleptic load in 283 psychiatric patients and 30 healthy volunteers. The tonus of tongue muscles depends on the total daily neuroleptic dose and the length of antipsychotic treatment. The higher the total daily neuroleptic dose and the longer the treatment history, the greater the tongue muscles' tonus is. The tongue muscles' tonus was greater in patients with low rate of oxidative antipyrine metabolism. Antidepressants contributed to the increased tonus of the tongue muscles in "slow metabolisers" of antipyrine. The simple and cheap measurements of total hepatic oxidative capacity and of muscle tonus of the tongue could be used to predict and manage neuroleptic-induced adverse reactions.

  14. Falls: the adverse drug reaction of the elderly and the impact of pharmacogenetics.

    PubMed

    Just, Katja Susanne; Schneider, Katharina Luise; Schurig, Marlen; Stingl, Julia Carolin; Brockmöller, Jürgen

    2017-08-01

    Falls is a frequent type of adverse drug reactions causing significant morbidity and mortality in the elderly. We reviewed, with which drugs the risk of falls is relevant and might depend on genomic variation. Pharmacogenetic variability may contribute to drug-induced falls for instance mediated by impaired drug elimination due to inherited deficiency in enzymes like CYP2C9, CYP2C19 and CYP2D6. The relative role of specific genes and polymorphisms in old age may differ from younger people. Biomarkers for frailty, but also genomic biomarkers might help identifying patients at high risk for drug-induced falls. Many other factors including disease and drug-drug interactions also contribute to risk of falls. Further studies analyzing the impact of genomic variation on the medication-related fall risk in the older adult are urgently needed.

  15. Age-related trends in injection site reaction incidence induced by the tumor necrosis factor-α (TNF-α) inhibitors etanercept and adalimumab: the Food and Drug Administration adverse event reporting system, 2004-2015

    PubMed Central

    Matsui, Toshinobu; Umetsu, Ryogo; Kato, Yamato; Hane, Yuuki; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Abe, Junko; Fukuda, Akiho; Naganuma, Misa; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2017-01-01

    Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS database contains 7,561,254 reports from January 2004 to December 2015. Adjusted reporting odds ratios (RORs) (95% Confidence Intervals) were obtained for interaction terms for age-stratified groups treated with etanercept (ETN) and adalimumab (ADA). The adjusted RORs for ETN* ≥ 70 and ADA* ≥ 70 groups were the lowest among the age-stratified groups undergoing the respective monotherapies. Furthermore, we found that crude RORs for ETN + methotrexate (MTX) combination therapy and ADA + MTX combination therapy were lower than those for the respective monotherapies. This study was the first to evaluate the relationship between aging and ISR using the FAERS database. PMID:28260984

  16. Pediatric bupropion-induced serum sicknesslike reaction.

    PubMed

    Hack, Sabine

    2004-01-01

    This reports the first 2 cases of serum sicknesslike reaction to bupropion in children (age 12 and 14). Serum sicknesslike reactions are an example of immune-complex medicated disease. The cardinal symptoms of serum sickness are fever, lymphadenopathy, arthralgias or arthritis, and urticaria. Symptoms usually resolve without long-term sequela following discontinuation of the exogenous antigen. It is likely that serum sicknesslike reactions to bupropion are either relatively rare or underrecognized and underreported. Between May 1998 and May 2001, GlaxoSmith Kline received 172 reports of seizures (a well-known adverse drug reaction) and only 37 reports of serum sicknesslike reactions (Wooltorton 2002). We do not know if children and adolescents are more prone than adults to develop serum sicknesslike reactions to bupropion. Luckily, the reported cases of serum sicknesslike reactions to bupropion have not caused irreversible morbidity or mortality. Nevertheless, the symptoms are painful, temporarily disfiguring and disabling, and warrant prompt medical attention. Parents and patients should be educated about this potential side effect at the onset of treatment, because symptoms are similar to many infectious childhood illnesses, and the treatment of serum sicknesslike reactions to bupropion should include the discontinuation of bupropion.

  17. Adverse drug reactions from birth to early childhood.

    PubMed

    Gupta, A; Waldhauser, L K

    1997-02-01

    Neonates and older infants are a diverse group of children, quite different from their older counterparts. Adverse drug reactions may have profound immediate, delayed, and long-term implications for their neurologic and somatic development. The intrauterine, neonatal, and infancy periods are the only stages in life in which one is exposed to and affected by drugs administered to another person, the mother. In addition, because of the fragility of the neonate and the complexity of their illnesses, their pharmacotherapy is frequently complicated with misadventure and adverse drug reactions that are unavoidable or difficult to assess. Because of their differences in morphology and disease process and treatments, infants and children experience a different range of adverse drug reactions. These reactions are not necessarily predictable from the adult experience. Despite the advances made in the field of pediatric adverse drug reactions and the lessons learned through the misfortunes involving children, children continue to suffer. Sixty years after the Elixir of Sulfanilamide-Massengill disaster, children continue to be given medications with diethylene glycol in developing countries. Pediatricians, pharmacologists, and others must continue to be vigilant and active in preventing, monitoring, and treating adverse drug reactions in children. Learning from mistakes of the past will improve the health of children by preventing mistakes in the future.

  18. 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.

  19. MULTICOMPONENT REACTIONS IN ALKALOID-BASED DRUG DISCOVERY

    PubMed Central

    Magedov, I. V.; Kornienko, A.

    2016-01-01

    Multicomponent reactions are emerging as a powerful tool in alkaloid-based drug discovery. This Highlight describes several recent (all published in 2011) examples of the employment of multicomponent reactions for the synthesis of biologically active alkaloids and their medicinally relevant analogues. PMID:27917001

  20. Drug-Induced Liver Injury.

    PubMed

    Hamilton, Leslie A; Collins-Yoder, Angela; Collins, Rachel E

    2016-10-01

    Drug-induced liver injury (DILI) can result from both idiosyncratic and intrinsic mechanisms. This article discusses the clinical impact of DILI from a broad range of medications as well as herbal and dietary supplements. Risk factors for idiosyncratic DILI (IDILI) are the result of multiple host, environmental, and compound factors. Some triggers of IDILI often seen in critical care include antibiotics, antiepileptic medications, statins, novel anticoagulants, proton pump inhibitors, inhaled anesthetics, nonsteroidal anti-inflammatory agents, methotrexate, sulfasalazine, and azathioprine. The mechanism of IDILI due to these medications varies, and the resulting damage can be cholestatic, hepatocellular, or mixed. The primary treatment of IDILI is to discontinue the causative agent. DILI due to acetaminophen is intrinsic because the liver damage is predictably aligned with the dose ingested. Acute acetaminophen ingestion can be treated with activated charcoal or N-acetylcysteine. Future areas of research include identification of mitochondrial stress biomarkers and of the patients at highest risk for DILI.

  1. Terbinafine-induced lichenoid drug eruption.

    PubMed

    Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

    2017-03-01

    Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

  2. Acute and subacute drug-induced movement disorders.

    PubMed

    Burkhard, Pierre R

    2014-01-01

    Many pharmacological agents may induce a variety of movement disorders, including dystonia, tremor, parkinsonism, myoclonus and dyskinesia, with an acute, subacute or more chronic time course. Motor symptoms may be isolated or part of a more extensive cerebral or systemic condition, such as the neuroleptic malignant syndrome or the serotonin syndrome. Drug-induced movement disorders share a number of features that should make them easy to identify, including a clear temporal relationship between medication initiation and symptom onset, a dose-effect, and, with the exception of tardive syndromes, complete resolution after discontinuation of the offending agent. Diagnosis relies on a thorough medication history. Medications commonly involved include dopamine receptor blockers, antidepressants and anti-epileptics, among many others. Mechanisms underlying drug-induced movement disorders involve blockade, facilitation or imbalance of dopamine, serotonin, noradrenaline and cholinergic neurotransmission in the basal ganglia. The present review focuses on drug-induced movement disorders that typically develop as an acute (hours to days) or subacute (days to weeks) event, including acute dystonic reactions, akathisia, drug-induced parkinsonism, neuroleptic malignant syndrome, serotonin syndrome, parkinsonism-hyperpyrexia syndrome, drug-induced tremor, drug-induced hyperkinesias and movement disorders associated with the use of recreational drugs.

  3. Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (–141 C Ins/Del) and 5HTR2C (–759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

    PubMed Central

    Alladi, Charanraj Goud; Mohan, Anbarasan; Shewade, Deepak Gopal; Rajkumar, Ravi Philip; Adithan, Surendiran; Subramanian, Karthick

    2017-01-01

    Objective: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. Materials and Methods: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively. Results: Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89, P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms. Conclusion: Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone. PMID:28405133

  4. Bullous Fixed Drug Eruption Induced by Paracetamol: Report of a Pediatric Case

    PubMed Central

    Nino, Massimiliano; Francia, Maria Grazia; Costa, Claudia; Scalvenzi, Massimiliano

    2009-01-01

    Drug eruptions are among the most common adverse drug reactions, affecting approximately 3% of hospitalized patients. A fixed drug eruption (FDE) is a distinct drug-induced reaction pattern that characteristically recurs at the same skin or mucosal site. We report a case of a 2-year-old girl with bullous FDE due to Tachipirina syrup, a preparation containing paracetamol, a commonly used nonsteroidal anti-inflammatory drug in Italy. PMID:20652116

  5. Adverse drug reactions and their measurement in the rheumatic diseases.

    PubMed

    Day, R O; Quinn, D I; Conaghan, P G; Tett, S E

    1995-05-01

    Drugs administered as therapy for rheumatological disorders are a relatively common cause of adverse events. Important data regarding the effects of drugs on patients with rheumatological conditions is being lost or rendered inaccessible because of deficiencies in classification, measurement, and collection methods for adverse drug reactions. A significant number of adverse reactions to drugs will not be known before marketing, and hence vigilance on the part of clinicians and patients in observing and documenting these reactions is paramount in building our knowledge and modifying our practice accordingly. A variety of systems and methods for detecting adverse drug reactions are described, critically evaluated, and compared for cost, potential bias, ethical concerns, and subject recruitment required for necessary statistical power. Systems need to be developed to give access to the wealth of clinical experimental data available in the individual practices of a broad spectrum of clinicians. To facilitate this, representative organizations need to make adverse drug reactions a high priority as well as contributing expertise and finance to database formulation and accessibility.

  6. The role of haptic macrophages in regulation of idiosyncratic drug reactions.

    PubMed

    Ju, Cynthia

    2009-01-01

    Idiosyncratic drug reactions (IDR) account for approximately 6%-10% of all adverse drug reactions. The unpredictable and serious nature of these reactions makes them a significant economic burden and safety concern to the health care community and the pharmaceutical industry. Clinical and laboratory evidence suggests that adverse immune responses against drug-protein adducts play a role in the pathogenesis of IDR. However, it remains unclear why only a small percentage of patients are susceptible to developing these reactions. We hypothesized that most patients develop immunological tolerance against drug-protein adducts as a default mechanism, and that IDRs can only occur when this tolerance is deficient or abrogated in susceptible individuals. Using a murine model of 2,4-dinitrochlorobenzene (DNCB)-induced delayed type hypersensitivity (DTH) reaction, our previously published data demonstrated that intravenous pretreatment of mice with dinitrophenyl-bovine serum albumin (DNP-BSA) induced immunological tolerance to subsequent DNCB sensitization, and that hepatic macrophages (Kupffer cells, KC) played an important role in mediating such tolerance. Further mechanistic investigation revealed that KC, acting as incompetent antigen-presenting cells, cannot elicit strong T cell reactions, and that they actively suppress T cell activation through production of prostaglandins. These findings suggest that KCs may play a critical role in regulating immune reactions within the liver and contributing to liver-mediated systemic immune tolerance.

  7. Multinational experience with hypersensitivity drug reactions in Latin America.

    PubMed

    Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

    2014-09-01

    Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), β-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Profile of adverse drug reactions in drug resistant tuberculosis from Punjab.

    PubMed

    Bhushan, Bharat; Chander, Ramesh; Kajal, N C; Ranga, Vikrant; Gupta, Ajay; Bharti, Heena

    2014-10-01

    The aim of the study was to elucidate the profile of adverse drug reactions (ADRs) associated with second-line anti-tubercular treatment for drug-resistant tuberculosis. ADR profile of diagnosed drug-resistant tuberculosis cases on supervised second-line anti-tubercular drug regimen under Programmatic Management of Drug-resistant Tuberculosis under Revised National Tuberculosis Control Programme, were studied over two years' period. Adverse reactions were categorised into mild, moderate and severe types with subsequent systematic data-analysis. Out of total 207 patients in the study, 81.16% reported with adverse drug reactions. Out of total 195 adverse events, 63.58%, 18.46% and 17.94% were of mild, moderate and severe types respectively. Gastrointestinal events, hepatitis, hearing impairment, arthralgia, psychosis, hypothyroidism, visual disturbances, giddiness, peripheral neuropathy, skin reactions, swelling or pain at injection site, anorexia and sleep disturbances were important amongst these. High proportion of drug and/or alcohol abuse was an important observation. The offending drug(s) had to be terminated in 12.08% of the patients. Early detection, management and pharmaco-vigilance reporting of ADRs remain key factors in the management of drug-resistant tuberculosis with remarkable relevance of the need for early diagnosis and treatment of 'drug-sensitive tuberculosis', to prevent emergence of drug-resistant tuberculosis.

  9. iADRs: towards online adverse drug reaction analysis.

    PubMed

    Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

    2012-12-01

    Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

  10. Adverse reactions to oncologic drugs: spontaneous reporting and signal detection.

    PubMed

    Tuccori, Marco; Montagnani, Sabrina; Capogrosso-Sansone, Alice; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado

    2015-01-01

    Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting.

  11. Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions

    PubMed Central

    KARIMZADEH, Parvaneh; BAKRANI, Vahid

    2013-01-01

    Objective According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. Material & Methods In this descriptive study, children less than 14 years old with AED side effects referred to the Children’s Medical Center and Mofid Childeren’s Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. Results A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). Conclusion In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions. PMID:24665302

  12. Antiepileptic drug-related adverse reactions and factors influencing these reactions.

    PubMed

    Karimzadeh, Parvaneh; Bakrani, Vahid

    2013-01-01

    According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. In this descriptive study, children less than 14 years old with AED side effects referred to the Children's Medical Center and Mofid Childeren's Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions.

  13. Drug-induced restless legs syndrome.

    PubMed

    2010-08-01

    Restless legs syndrome can be very troublesome but it has no serious physical complications. The underlying causes are unknown, but it can be triggered or aggravated by a drug. In early 2010, about 60 cases of drug-induced restless legs syndrome had been published in detail. The drugs implicated were mainly psychotropics, especially antidepressants and neuroleptics. Some drugs used to treat restless legs syndrome, especially dopaminergic drugs, can in fact aggravate symptoms. Drug-induced restless legs syndrome generally resolves when the dose is reduced or the drug is withdrawn. Dysfunction of the dopaminergic system has been implicated in some cases. In practice, when a patient presents with restless legs syndrome, the role of a drug, especially a psychotropic, should be considered. Drug withdrawal or a dose reduction may be beneficial.

  14. Ф-order kinetics of photoreversible-drug reactions.

    PubMed

    Maafi, Mounir; Maafi, Wassila

    2014-08-25

    Drug photodegradation data are usually treated by zero-, first- or second-order kinetic equations. Such treatments would lack reliability since the aforementioned equations have been originally developed for pure thermal reactions. In this respect, it has recently been shown that unimolecular photodegradations obey Ф-order kinetics (Maafi and Maafi, 2013). However, no similar information is, thus far, available for other reactions including photoreversible AB(2Ф) systems. This paper aims at filling this gap for AB(2Ф) kinetics. Runge-Kutta numerical integration data for photoreversible reactions traces were combined with a template equation in order to derive an optimized (semi-empirical) integrated rate-law equation for AB(2Ф) reactions. The proposed model equation was test by examining its ability to fit synthetic Runge-Kutta data that have not been used for the optimization. The obtained fitting parameters are then compared to their theoretical counterparts. Both an integrated rate-law and an analytical equation for the overall reaction rate-constant were set for photoreversible drug reactions. The values of overall reaction rate-constant and initial velocity obtained theoretically correlated well with those obtained by fitting the kinetic traces of reactions with the derived integrated rate-law. AB(2Ф) photodegradation reactions have been proven to obey Ф-order kinetics. The equation proposed describes faithfully their kinetic behaviour in solution. The formula of the overall rate-constant involves both reagents' characteristics and experimental parameters. These equations facilitated the rationalisation and prediction of the individual effects of each reaction parameter. Specially, our results proved a self-photostabilisation with increasing initial drug-concentration and demonstrated the potential for actinometry of drugs obeying AB(2Ф) mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Drug rechallenge following drug-induced liver injury.

    PubMed

    Hunt, Christine M; Papay, Julie I; Stanulovic, Vid; Regev, Arie

    2017-08-01

    Drug-induced hepatocellular injury is identified internationally by alanine aminotransferase (ALT) levels equal to or exceeding 5× the upper limit of normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decrease by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT level of 3-5× ULN or greater. Nearly 50 drugs are associated with positive rechallenge after drug-induced liver injury (DILI): antimicrobials; and central nervous system, cardiovascular and oncology therapeutics. Drugs associated with high rates of positive rechallenge exhibit multiple risk factors: daily dose >50 mg, an increased incidence of ALT elevations in clinical trials, immunoallergic clinical injury, and mitochondrial impairment in vitro. These drug factors interact with personal genetic, immune, and metabolic factors to influence positive rechallenge rates and outcomes. Drug rechallenge following drug-induced liver injury is associated with up to 13% mortality in prospective series of all prescribed drugs. In recent oncology trials, standardized systems have enabled safer drug rechallenge with weekly liver chemistry monitoring during the high-risk period and exclusion of patients with hypersensitivity. However, high positive rechallenge rates with other innovative therapeutics suggest that caution should be taken with rechallenge of high-risk drugs. For critical medicines, drug rechallenge may be appropriate when 1) no safer alternatives are available, 2) the objective benefit exceeds the risk, and 3) patients are fully informed and consent, can adhere to follow-up, and alert providers to hepatitis symptoms. To better understand rechallenge outcomes and identify key risk factors for positive rechallenge, additional data are needed from controlled clinical trials, prospective registries, and large health care databases. (Hepatology 2017;66:646-654).

  16. An update on drug-induced arthritis.

    PubMed

    Adwan, Marwan H

    2016-08-01

    A large and heterogeneous group of drugs can cause drug-induced arthritis. No single pathogenetic mechanism or drug class unifies these diverse culprits. Recognizing that joint symptoms may, in fact, be drug-related not only saves time and unnecessary investigations but can also prevent needless suffering and morbidity due to late recognition of a drug-induced arthritic condition. The extent of drug-induced arthritis is variable and ranges from minor short-lived and reversible arthralgia to a prolonged and occasionally destructive arthritis. The onset of arthritis due to various medications in relation to the timing of drug initiation is also variable and may range from a few days to several months.

  17. Ceftriaxone-induced fixed drug eruption: first report.

    PubMed

    Ozkaya, Esen; Mirzoyeva, Leyla; Jhaish, Mohammed S H

    2008-01-01

    Fixed drug eruption (FDE) is an unusual type of cutaneous adverse drug reaction that is characterized by recurrent site-specific lesions each time the drug responsible is taken. FDE from cephalosporins has been rarely reported, and to the best of our knowledge there is no published report of ceftriaxone-induced FDE in the literature. We report the first case of a 54-year-old Turkish woman who presented with ceftriaxone-induced FDE. Topical provocation with ceftriaxone sodium salt (1% in water [aq.], 5% aq., 10% in petrolatum [pet.], 20% pet.) remained negative both at previously affected sites and in the unaffected skin of the back. Therapeutic re-exposure with intravenous ceftriaxone 1 g confirmed the diagnosis. The patient tolerated amoxicillin and cefazolin, suggesting that the sensitizing portion was not the beta-lactam ring. Identification of the antigenic determinants of FDE-inducing drugs will make predicting safe alternatives in patients with FDE an easier task.

  18. Drug reactions affecting the nail unit: diagnosis and management.

    PubMed

    Piraccini, Bianca Maria; Iorizzo, Matilde

    2007-04-01

    Several drugs may be responsible for the development of nail abnormalities, but only a few classes are consistently associated with nail symptoms. Drug-induced nail abnormalities result from toxicity to the matrix, the nail bed, the periungual tissues, or the digit blood vessels. Pharmacologic agents that most frequently produce nail abnormalities include retinoids, indinavir, and cancer chemotherapeutic agents.

  19. Nuclear Reactions Induced by a Pyroelectric Accelerator

    SciTech Connect

    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)].

  20. Debatable evidence for the adverse drug reactions to local anaesthetics.

    PubMed

    Maitland, Ronald I

    2013-01-01

    Medline, Embase, Chinese National Knowledge Infrastructure VIP Database for Chinese Technical Periodicals (and Chinese Biomedical Literature Database. Randomised controlled trials (RCTs), non-RCTs, case-control studies, case reports, case series and cross-sectional studies that focused on adverse drug reactions of local anaesthetics were considered. Data abstraction was conducted independently by two reviewers, and summary data and a meta-analysis presented. One hundred and one studies reporting 1645 events were included. Seven of these were deaths. Lidocaine (43.17%) and bupivacaine (16.32%) were the most often involved local anaesthetics. According to the meta-analysis, the risk of using LA alone was lower than when combined with epinephrine. The present study demonstrated that the adverse drug reactions of local anaesthetics could not be ignored, especially in oral and ophthalmologic treatments. Some adverse drug reactions could be avoided by properly evaluating the conditions of patients and correctly applying local anaesthetics.

  1. Severe Drug Hypersensitivity Reactions: Clinical Pattern, Diagnosis, Etiology and Therapeutic Options.

    PubMed

    Paulmann, Maren; Mockenhaupt, Maja

    2016-01-01

    Severe cutaneous adverse reactions (SCAR) are known for a high morbidity and mortality. They may be life-threatening for the affected patient and difficult to accomplish for the patient's family and the treating physician. Such conditions include not only bullous reactions like toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Since clinical pattern, etiology, prognosis and treatment differ among these severe skin reactions, a clear diagnosis based on a comprehensive clinical examination, skin biopsy, and specific laboratory tests is necessary. Because most of these reactions are caused by drug intake, a thorough history of medication use has to be obtained. However, there are cases with an infectious or idiopathic cause. In any case it is crucial to identify the most likely cause and rapidly discontinue the inducing agent, if a drug cause is suspected. This is associated with the patient`s prognosis which is often poor for bullous reaction. In addition, patient's age, underlying conditions, and the extent of skin detachment play a major role in terms of prognosis. Severe cutaneous adverse reactions are T-cell-mediated reactions, and certain alleles of human leukocyte antigens (HLA) are involved in the activation of T-cells with cytotoxic effect. The therapeutic options depend on the clinical diagnosis. For all reactions a symptomatic and adequate supportive therapy is necessary, in some cases a systemic immunomodulating therapy can be useful.

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

    PubMed

    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

    2014-11-11

    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.

  3. Prediction of drug-induced liver injury using keratinocytes.

    PubMed

    Hirashima, Rika; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2017-01-31

    Drug-induced liver injury (DILI) is one of the most common adverse drug reactions. DILI is often accompanied by skin reactions, including rash and pruritus. However, it is still unknown whether DILI-associated genes such as S100 calcium-binding protein A and interleukin (IL)-1β are involved in drug-induced skin toxicity. In the present study, most of the tested hepatotoxic drugs such as pioglitazone and diclofenac induced DILI-associated genes in human and mouse keratinocytes. Keratinocytes of mice at higher risk for DILI exhibited an increased IL-1β basal expression. They also showed a higher inducibility of IL-1β when treated by pioglitazone. Mice at higher risk for DILI showed even higher sums of DILI-associated gene basal expression levels and induction rates in keratinocytes. Our data suggest that DILI-associated genes might be involved in the onset and progression of drug-induced skin toxicity. Furthermore, we might be able to identify individuals at higher risk of developing DILI less invasively by examining gene expression patterns in keratinocytes. Copyright © 2017 John Wiley & Sons, Ltd.

  4. 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

  5. Points of view on adverse drug reactions terminology.

    PubMed

    Benichou, C; Castle, W

    1998-01-01

    Global management of drug safety data is the best way to make the detection and validation of adverse drug reactions (ADRs) earlier. Centralization needs a previous standardization, of which terminology is a crucial component. ADR terminology must be designed so as to enable users to know exactly what is covered by each term regarding the nature of the reaction and its significance for public health. A worldwide standardized terminology for all drug reporting purposes is currently being developed by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. However, practical definitions of medical terms will be necessary and could be developed by specialists on drug safety in collaboration with specialists of different system organs, as has already been achieved for some of them.

  6. 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.

  7. Adverse drug reactions in neonates: could we be documenting more?

    PubMed

    Hawcutt, Daniel B; O'Connor, Olya; Turner, Mark A

    2014-11-01

    Neonates are vulnerable to adverse drug reactions but reports of these events are relatively infrequent. Reporting can be increased by adapting a number of standard techniques to the unique features of neonatal care and pathology. However, clinicians and parents will be reluctant to report information about harms in the absence of mechanisms to ensure that reports affect clinical practice. Improved reporting will depend on education and cultural change that are informed by research about pharmacovigilance in neonatal settings. The efficient use of neonatal adverse drug reaction reports will require harmonization of terminology and interoperable databases.

  8. Postmarketing surveillance of adverse drug reactions: problems and solutions.

    PubMed Central

    Lortie, F M

    1986-01-01

    The surveillance of adverse drug reactions (ADRs) is an unqualified must. However, the optimal means of surveillance is still unclear. Although anecdotal reports are the backbone of an ADR surveillance system, they are not enough. The pharmaceutical industry, academics and regulatory agencies need to expand their efforts in monitoring ADRs. The author discusses the various techniques for counting and evaluating adverse reactions and suggests ways in which the system could be improved. PMID:3719483

  9. Acetaminophen-induced cellulitis-like fixed drug eruption.

    PubMed

    Fathallah, Neila; Ben Salem, Chaker; Slim, Raoudha; Boussofara, Lobna; Ghariani, Najet; Bouraoui, Kamel

    2011-03-01

    Acetaminophen is a widely used analgesic drug. Its adverse reactions are rare but severe. An 89-year-old man developed an indurated edematous and erythematous plaque on his left arm 1 day after acetaminophen ingestion. Cellulitis was suspected and antibiotictherapy was started but there was no improvement of the rash; there was a spectacular extension of the lesion with occurrence of flaccid vesicles and blisters in the affected sites. The diagnosis of generalized-bullous-fixed drug eruption induced by acetaminophen was considered especially with a reported history of a previous milder reaction occurring in the same site. Acetaminophen was withdrawn and the rash improved significantly. According to the Naranjo probability scale, the eruption experienced by the patient was probably due to acetaminophen. Clinicians should be aware of the ability of acetaminophen to induce fixed drug eruption that may clinically take several aspects and may be misdiagnosed.

  10. Drug-induced hypersensitivity syndrome due to carbapenem antibiotics.

    PubMed

    Goto, Mizuki; Shimizu, Fumiaki; Takeo, Naoko; Okamoto, Osamu; Katagiri, Kazumoto; Ikewaki, Junji; Ogata, Masao; Kadota, Jun-ichi; Fujiwara, Sakuhei

    2010-04-01

    Drug-induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3-6-week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV-6 in particular, has been reported in patients with DIHS. We report the case of a 64-year-old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV-6 and cytomegalovirus (CMV) was demonstrated by real-time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte-stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.

  11. 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.

  12. [Surveillance of severe cutaneous drug reactions: experience REACT-Lombardia].

    PubMed

    Gamba, Chiara; Schroeder, Jan; Citterio, Antonella; Cazzaniga, Simone; Rivolta, Alma Lisa; Vighi, Giuseppe

    2014-10-01

    Adverse drug reactions affecting the skin have particular relevance as they may cause significant mortality and a possible modification of the benefit/risk profile of the concerned drug. The following entities are of special importance: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug rash with eosinophilia and systemic symptoms (DRESS). On the above mentioned reactions we focused our surveillance programme in the Lombardy region, the REACT-Lombardia project. The REACT registry involved 22 hospital-based dermatological centres, collecting, from April 2009 up to March 2014, a total of 72 cases of SJS-TEN, 17 cases of AGEP and 9 cases of DRESS. Allopurinol was the drug associated with the largest number of cases of SJS/TEN (21 cases) followed by paracetamol (8 cases), levofloxacine (6 cases) and carbamazepine (4 cases). The risk for specific drug exposures was estimated by employing drug utilization data expressed as Defined Daily Doses (DDD). Mortality rate from SJS-TEN was 21%. Together with the registry, a "hub and spoke" clinical network for the management of severe cutaneous reactions was established with the Burn Unit of Niguarda Ca' Granda Hospital as the reference center for the most critical patients.

  13. Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

    PubMed

    Ding, Wen Yi; Lee, Chew Kek; Choon, Siew Eng

    2010-07-01

    Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens-Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA-B*1502 and HLA-B*5801 which are genetic markers for carbamazepine-induced SJS/TEN and allopurinol-induced SJS/TEN/DRESS respectively. The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine

  14. 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.

  15. Drug-induced hyperuricaemia and gout.

    PubMed

    Ben Salem, C; Slim, Raoudha; Fathallah, Neila; Hmouda, Houssem

    2016-08-07

    Hyperuricaemia is a common clinical condition that can be defined as a serum uric acid level >6.8 mg/dl (404 µmol/l). Gout, a recognized complication of hyperuricaemia, is the most common inflammatory arthritis in adults. Drug-induced hyperuricaemia and gout present an emergent and increasingly prevalent problem in clinical practice. Diuretics are one of the most important causes of secondary hyperuricaemia. Drugs raise serum uric acid level by an increase of uric acid reabsorption and/or decrease in uric acid secretion. Several drugs may also increase uric acid production. In this review, drugs leading to hyperuricaemia are summarized with regard to their mechanism of action and clinical significance. Increased awareness of drugs that can induce hyperuricaemia and gout, and monitoring and prevention are key elements for reducing the morbidity related to drug-induced hyperuricaemia and gout.

  16. [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.

  17. 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.

  18. 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

  19. Adverse drug reactions and off-label drug use in paediatric outpatients

    PubMed Central

    Horen, Benjamin; Montastruc, Jean-Louis; Lapeyre-mestre, Maryse

    2002-01-01

    Aims To investigate the potential relationship between off-label drug use and increased risk of adverse drug reactions in paediatric outpatients. Methods A prospective pharmacovigilance survey of drug prescribing in office based paediatricians was carried out in Haute-Garonne County (south west of France). Results The study involved a sample of 1419 children under 16 years old. Forty-two percent of patients were exposed to at least one off-label prescription. The incidence of adverse drug reactions was 1.41% (95% CI 0.79, 2.11). Off-label drug use was significantly associated with adverse drug reactions (relative risk 3.44; 95% CI 1.26, 9.38), particularly when it was due to an indication different than that defined in the Summary Product Characteristics (relative risk 4.42; 95% CI 1.60, 12.25). Conclusions Our data suggest an increasing risk of adverse drug reactions related to off-label drug use. This risk would be acceptable if further studies prove the potential benefit of such a drug use. PMID:12492616

  20. Adverse drug reactions in Sjögren's syndrome. Frequent allergic reactions and a specific trimethoprim-associated systemic reaction.

    PubMed

    Antonen, J A; Markula, K P; Pertovaara, M I; Pasternack, A I

    1999-01-01

    Trimethoprim-associated systemic reactions, including aseptic meningitis, have been reported to be very rare adverse drug reactions. Patients with Sjögren's syndrome have been overrepresented, but no epidemiological surveys of the reaction have been conducted. To study the overall frequency of adverse drug reactions, and especially trimethoprim-associated reactions, we interviewed 85 primary Sjögren's syndrome patients and compared the results with those of 45 similarly interviewed osteoarthritis patients. Antimicrobial allergy was more common among Sjögren's syndrome patients than in osteoarthritis patients (46% vs. 27%). Eleven Sjögren's syndrome patients (13%), but no osteoarthritis patient, had experienced at least a partial, non-allergic systemic reaction with trimethoprim. Of them five (6%) had had a full-blown systemic reaction including both chills/fever and headache/backache and at least one of the following: malaise, vomiting, dizziness, confusion or meningeal irritation. Our findings confirm that allergic reactions to antimicrobials are frequent in Sjögren's syndrome. In addition to allergic reactions Sjögren's syndrome patients are prone to a specific trimethoprim-associated systemic reaction. This should be remembered when prescribing antimicrobials.

  1. [Reported adverse reactions of veterinary drugs and vaccines in 2005].

    PubMed

    Müntener, C R; Bruckner, L; Gassner, B; Demuth, D C; Althaus, F R; Zwahlen, R

    2007-02-01

    We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future.

  2. Role of Oxidative Stress in Drug-Induced Kidney Injury

    PubMed Central

    Hosohata, Keiko

    2016-01-01

    The kidney plays a primary role in maintaining homeostasis and detoxification of numerous hydrophilic xenobiotics as well as endogenous compounds. Because the kidney is exposed to a larger proportion and higher concentration of drugs and toxins than other organs through the secretion of ionic drugs by tubular organic ion transporters across the luminal membranes of renal tubular epithelial cells, and through the reabsorption of filtered toxins into the lumen of the tubule, these cells are at greater risk for injury. In fact, drug-induced kidney injury is a serious problem in clinical practice and accounts for roughly 20% of cases of acute kidney injury (AKI) among hospitalized patients. Therefore, its early detection is becoming more important. Usually, drug-induced AKI consists of two patterns of renal injury: acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). Whereas AIN develops from medications that incite an allergic reaction, ATN develops from direct toxicity on tubular epithelial cells. Among several cellular mechanisms underlying ATN, oxidative stress plays an important role in progression to ATN by activation of inflammatory response via proinflammatory cytokine release and inflammatory cell accumulation in tissues. This review provides an overview of drugs associated with AKI, the role of oxidative stress in drug-induced AKI, and a biomarker for drug-induced AKI focusing on oxidative stress. PMID:27809280

  3. [Adverse drug reactions reporting is helping "non substituable" prescription!].

    PubMed

    Jacquot, Julien; Bagheri, Haleh; Montastruc, Jean-Louis

    2014-01-01

    In August 2012, general practitioners of Haute- Garonne received a letter from Health insurance system, informing that prescriptions could be endorsed by "not substituable" after reporting an adverse drug reactions (ADR). Compared to an equivalent period before this letter, we observed an increase of ADRs reports for generics, mainly concerning gastrointestinal ADR and lack of efficacy.

  4. Using Drug Similarities for Discovery of Possible Adverse Reactions

    PubMed Central

    Muñoz, Emir; Nováček, Vít; Vandenbussche, Pierre-Yves

    2016-01-01

    We propose a new computational method for discovery of possible adverse drug reactions. The method consists of two key steps. First we use openly available resources to semi-automatically compile a consolidated data set describing drugs and their features (e.g., chemical structure, related targets, indications or known adverse reaction). The data set is represented as a graph, which allows for definition of graph-based similarity metrics. The metrics can then be used for propagating known adverse reactions between similar drugs, which leads to weighted (i.e., ranked) predictions of previously unknown links between drugs and their possible side effects. We implemented the proposed method in the form of a software prototype and evaluated our approach by discarding known drug-side effect links from our data and checking whether our prototype is able to re-discover them. As this is an evaluation methodology used by several recent state of the art approaches, we could compare our results with them. Our approach scored best in all widely used metrics like precision, recall or the ratio of relevant predictions present among the top ranked results. The improvement was as much as 125.79% over the next best approach. For instance, the F1 score was 0.5606 (66.35% better than the next best method). Most importantly, in 95.32% of cases, the top five results contain at least one, but typically three correctly predicted side effect (36.05% better than the second best approach). PMID:28269889

  5. 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.

  6. 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

  7. Drug-induced pulmonary disease

    MedlinePlus

    ... mediastinitis ) Abnormal buildup of fluid in the lungs ( pulmonary edema ) Buildup of fluid between the layers of tissue ... reactions Cardiovascular Chemotherapy Interstitial lung disease Pleural effusion Pulmonary edema Respiratory Systemic lupus erythematosus Patient Instructions Interstitial lung ...

  8. 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.

  9. Drug-induced tardive syndromes.

    PubMed

    Ortí-Pareja, M; Jiménez-Jiménez, F J; Vázquez, A; Catalán, M J; Zurdo, M; Burguera, J A; Martínez-Martín, P; Molina, J A

    1999-04-01

    We reviewed the database of five Movement Disorders Units to establish drugs responsible for tardive syndromes or TS (tardive dyskinesia, dystonia, akathisia, tremor, tics or tourettism, and myoclonus). The diagnostic criteria for TS included: (1) appearance of persistent dyskinesia, dystonia, akathisia, tremor, tics or tourettism, or myoclonus, related to prolonged drug exposure, (2) exclusion of other possible causes of these movement disorders. One-hundred patients fulfilled the diagnostic criteria for TS (26 males, 74 females, mean age 69.4+/-15.8 years). TS were related to 1, 2, 3, 4 and 5 drugs in 58, 27, 9, 5 and 1 patients, respectively. The most frequently offending drugs were antipsychotic drugs, substituted benzamides, thietylperazine and calcium-channel blockers. Seventy-two patients had buccolinguomasticatory syndrome, 30 had tremor, 22 akathisia and 16 dystonia (35 patients had a combination of at least two of these TS). Forty-two patients had coexistent parkinsonism. The TS disappeared following withdrawal of the offending drug in 40 cases. Old age and being female were more frequently associated with TS, with the exception of tardive dystonia. Substituted benzamides, calcium-channel blockers and thiethylperazine (a neuroleptic used for vertigo) were a frequent cause of TS in our series.

  10. Drug-induced low blood sugar

    MedlinePlus

    Drug-induced low blood sugar is low blood glucose that results from taking medicine. ... Low blood sugar (hypoglycemia) is common in people with diabetes who are taking insulin or other medicines to control their diabetes. ...

  11. 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.

  12. [Introduction of "the manual for handling disorders due to adverse drug reactions"--focus on the antibiotics related severe adverse drug reactions].

    PubMed

    Saito, Mitsuo

    2008-08-01

    Because the drug-induced severe adverse reaction (SAR) is rare and often occur in the unexpected organs, the physician could be unfamiliar to SAR. In that case the early stage of the SAR is easy to overlook. So the Ministry of the Health and Welfare of Japan (MHLW) started the "Comprehensive project to deal with the disorders due to adverse drug reactions" as a four years plan since 2005. In this project, the MHLW published "the manual for handling disorders due to adverse drug reactions" in corporation with the academia. This manual is constituted by two parts, one is intended for the parents, and the other is for the general healthcare providers. In this article, the aim and the progress of the manuals and the brief summary of the SAR induced by the antibiotics will be explained. By the end of the June 2008, 29 manuals have been released, and 16 of them are antibiotics-related. It is needless to say that antibiotics are essential in the modern medical care, close monitoring of the symptom of SAR in untargeted organ is required in use of the antibiotics.

  13. Azithromycin induced bullous fixed drug eruption.

    PubMed

    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.

  14. Acemetacin-induced fixed drug eruption.

    PubMed

    Cebeci, Filiz; Yaşar, Şirin; Aytekin, Sema; Güneş, Pembegül

    2016-01-01

    Fixed drug eruption (FDE) is an adverse effect observed with various drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and various antibiotics. Acemetacin, a prodrug of indomethacin, is an NSAID licensed for use in rheumatic disease and other musculoskeletal disorders. We present a case of acemetacin-induced FDE in a 49-year-old woman. To the best of our knowledge, this is the second case report detailing clinical and histopathological findings of a patient with FDE caused by acemetacin.

  15. 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

  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. Drug-induced photosensitivity: culprit drugs, management and prevention.

    PubMed

    Drucker, Aaron M; Rosen, Cheryl F

    2011-10-01

    Photo-induced drug eruptions are cutaneous adverse events due to exposure to a drug and either ultraviolet or visible radiation. Based on their pathogenesis, they can be classified as phototoxic or photoallergic drug eruptions, although in many cases it is not possible to determine whether a particular eruption is due to a phototoxic or photoallergic mechanism. In this review, the diagnosis, prevention and management of drug-induced photosensitivity are discussed. Diagnosis is based primarily on the history of drug intake and the clinical appearance of the eruption, primarily affecting sun-exposed areas of the skin. Phototesting and photopatch testing can be useful adjuncts in making a diagnosis. The mainstay of management is prevention, including informing patients of the possibility of increased sun sensitivity and the use of sun protective measures. However, once the eruption has occurred, it may be necessary to discontinue the culprit medication and treat the eruption with a potent topical corticosteroid. Drugs that have been implicated in causing photosensitive eruptions are reviewed. Tetracycline, doxycycline, nalidixic acid, voriconazole, amiodarone, hydrochlorothiazide, naproxen, piroxicam, chlorpromazine and thioridazine are among the most commonly implicated medications. We review the medical literature regarding evidence for the culpability of each drug, including the results of phototesting, photopatch testing and rechallenge testing.

  18. 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

  19. In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.

    PubMed

    Mayorga, C; Sanz, M L; Gamboa, P; Garcia-Aviles, M C; Fernandez, J; Torres, M J

    2013-01-01

    Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

  20. Risk factors associated with adverse reactions to antituberculosis drugs*

    PubMed Central

    Resende, Laíse Soares Oliveira; dos Santos-Neto, Edson Theodoro

    2015-01-01

    This review sought to identify the available scientific evidence on risk factors associated with adverse reactions to antituberculosis drugs. We performed a systematic review of studies published in the 1965-2012 period and indexed in the MEDLINE and LILACS databases. A total of 1,389 articles were initially selected. After reading their abstracts, we selected 85 studies. Of those 85 studies, 16 were included in the review. Risk factors for adverse reactions to antituberculosis drugs included age > 60 years, treatment regimens, alcoholism, anemia, and HIV co-infection, as well as sodium, iron, and albumin deficiency. Protective factors against hepatic adverse effects of antituberculosis drugs included being male (combined OR = 0.38; 95% CI: 0.20-0.72) and showing a rapid/intermediate N-acetyltransferase 2 acetylator phenotype (combined OR = 0.41; 95% CI: 0.18-0.90). There is evidence to support the need for management of adverse reactions to antituberculosis drugs at public health care facilities. PMID:25750677

  1. Risk factors associated with adverse reactions to antituberculosis drugs.

    PubMed

    Resende, Laíse Soares Oliveira; Santos-Neto, Edson Theodoro Dos

    2015-01-01

    This review sought to identify the available scientific evidence on risk factors associated with adverse reactions to antituberculosis drugs. We performed a systematic review of studies published in the 1965-2012 period and indexed in the MEDLINE and LILACS databases. A total of 1,389 articles were initially selected. After reading their abstracts, we selected 85 studies. Of those 85 studies, 16 were included in the review. Risk factors for adverse reactions to antituberculosis drugs included age > 60 years, treatment regimens, alcoholism, anemia, and HIV co-infection, as well as sodium, iron, and albumin deficiency. Protective factors against hepatic adverse effects of antituberculosis drugs included being male (combined OR = 0.38; 95% CI: 0.20-0.72) and showing a rapid/intermediate N-acetyltransferase 2 acetylator phenotype (combined OR = 0.41; 95% CI: 0.18-0.90). There is evidence to support the need for management of adverse reactions to antituberculosis drugs at public health care facilities.

  2. HLA and Delayed Drug-Induced Hypersensitivity.

    PubMed

    Sousa-Pinto, Bernardo; Correia, Cláudia; Gomes, Lídia; Gil-Mata, Sara; Araújo, Luís; Correia, Osvaldo; Delgado, Luís

    2016-01-01

    Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B*57:01 (abacavir), HLA-B*15:02/HLA-A*31:01 (carbamazepine), and HLA-B*58:01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.

  3. Theory of photon and electron induced reactions

    SciTech Connect

    Onley, D.S.; Wright, L.E.

    1992-01-01

    During the first year and half of the current grant from the Department of Energy we have made considerable progress on the following aspects of the general investigation of electron and photon induced reactions: (1) photo- and electro-production of mesons; (2) Coulomb distortion effects on (e,e{prime}{gamma}) and (e,e{prime}) and (e,e{prime}p) in the quasi-elastic region, (3) studies involving the relativistic shell model, and (4) quark models. We will report on each of these developments in this paper.

  4. The discovery of drug-induced illness.

    PubMed

    Jick, H

    1977-03-03

    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.

  5. [Drug-induced interstitial lung diseases].

    PubMed

    Bonniaud, Philippe; Georges, Marjolaine; Favrolt, Nicolas; Camus, Philippe

    2014-09-01

    Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia, organising pneumonia, pulmonary edema, or sarcoidosis. A large amount of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin converting enzyme inhibitors), antibiotics (minocycline, nitrofurantoin), most of anticancer drugs (and especially chemotherapy and chest radiation), treatment of rheumatoid arthritis, as well as more recent drugs. A high index of suspicion is therefore required in any patient with infiltrative lung disease and the web-based tool www.pneumotox.com will help to list possible causative drugs. The following steps are necessary: history and timing of drug exposure, clinical and imaging pattern, exclusion of other causes of infiltrative lung disease, improvement following drug discontinuation. Rechallenge, dangerous, is not recommended.

  6. [Drug-induced extrapyramidal disorders].

    PubMed

    Horga, J F; Navarro, M; Peiró, V; Hernández, M

    1995-01-01

    We analyze 402 drug-adverse events consisting of movement disorders or aggravation of parkinsonisms, submitted to Sistema Español de Farmacovigilancia until 1994. Our aim is to know patient characteristics and the drugs related with these submissions. Most of them (64) belong to calcium-entry blocker group (31%) and benzamides (27%). Case age intervals more frequent were 11-30 and 60-80 years-old and the events affect predominantly females. The percentage of serious adverse events were near 80%. We think that drug-related parkinsonisms have high prevalence rate and that the role of calcium-entry blockers in these events should be considered at the moment to prescribe groups.

  7. 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

  8. Tranexamic Acid-Induced Fixed Drug Eruption

    PubMed Central

    Matsumura, Natsuko; Hanami, Yuka; Yamamoto, Toshiyuki

    2015-01-01

    A 33-year-old male showed multiple pigmented patches on his trunk and extremities after he took tranexamic acid for common cold. He stated that similar eruptions appeared when he was treated with tranexamic acid for influenza 10 months before. Patch test showed positive results at 48 h and 72 h by 1% and 10% tranexamic acid at the lesional skin only. To our knowledge, nine cases of fixed drug eruption induced by tranexamic acid have been reported in Japan. Tranexamic acid is a safe drug and frequently used because of its anti-fibrinolytic and anti-inflammatory effects, but caution of inducing fixed drug eruption should be necessary. PMID:26288438

  9. Tranexamic Acid-Induced Fixed Drug Eruption.

    PubMed

    Matsumura, Natsuko; Hanami, Yuka; Yamamoto, Toshiyuki

    2015-01-01

    A 33-year-old male showed multiple pigmented patches on his trunk and extremities after he took tranexamic acid for common cold. He stated that similar eruptions appeared when he was treated with tranexamic acid for influenza 10 months before. Patch test showed positive results at 48 h and 72 h by 1% and 10% tranexamic acid at the lesional skin only. To our knowledge, nine cases of fixed drug eruption induced by tranexamic acid have been reported in Japan. Tranexamic acid is a safe drug and frequently used because of its anti-fibrinolytic and anti-inflammatory effects, but caution of inducing fixed drug eruption should be necessary.

  10. 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.

  11. Ayurvedic management of adverse drug reactions with Shvitrahara Varti

    PubMed Central

    Jadav, Hasmukh R.; Ghetiya, Hitesh; Prashanth, B.; Galib; Patgiri, B. J.; Prajapati, P. K.

    2013-01-01

    Adverse drug reactions (ADR) are an expression that describes harm associated with the use of medications at therapeutic dose. Traditional medicines also can develop ADRs due to their improper use. Shvitrahara Varti, one of such medicines holds Bakuchi as a component and is to be used judiciously. Furanocoumarins like psoralen present in Bakuchi makes skin hypersensitive and causes phytophotodermatitis in few cases. Hence, one should be careful while using medicines that contain Bakuchi. One such case is observed, where extensive reactions with application of Shvitrahara Varti were noticed and managed with Ayurvedic treatment. PMID:24250129

  12. Quality of case reports of adverse drug reactions with psychotropic drugs: a 25-year review.

    PubMed

    Talat, Bilal; Mayers, Andrew; Baldwin, David S

    2013-09-01

    Case reports of adverse reactions with psychotropic drugs can be useful in raising hypotheses, to be tested with more rigorous study designs. However such reports have significant methodological drawbacks, making it hard to determine causality. We undertook a systematic assessment of the quality of case reports and small case series published within Human Psychopharmacology over 25 years. For reports of adverse drug reactions, modified Bradford Hill criteria for causality (for consistency, strength, specificity, temporal relationship and plausibility) were used to ascertain the quality of the account. Reports which had been cited at least 10 times by December 2010 were examined in detail, to assess their overall contribution in extending understanding and influencing clinical practice. Of 40 reports of adverse drug reactions, only seven were sufficiently robust for confidence in probable or possible causality. Nine reports had been cited more than 10 times: the five most frequently cited reports of adverse drug reactions described movement disorders, suicidal thoughts and discontinuation symptoms with SSRIs: clinical relevance was high, but their quality was not markedly greater than less frequently cited reports. Nearly all reports of adverse drug reactions, published in a single journal over 25 years, were insufficiently robust to demonstrate probable causality. Reports that are cited frequently become influential because of their potential clinical relevance, rather than due to their methodological quality. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Fixed drug eruption induced by atenolol

    PubMed Central

    Belhadjali, H; Trimech, O; Youssef, M; Elhani, I; Zili, J

    2008-01-01

    Fixed drug eruption (FDE) is characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. We report here a case of multiple FDE induced by atenolol in a 48-year-old woman confirmed by positive patch test in previously affected sites. Beta-blockers-induced FDE are very rare. Only two cases had been reported in the literature. To the best of our knowledge, this is the first case reported of atenolol-induced FDE confirmed by a positive patch test. PMID:21437137

  14. Fixed drug eruption induced by atenolol.

    PubMed

    Belhadjali, H; Trimech, O; Youssef, M; Elhani, I; Zili, J

    2009-04-24

    Fixed drug eruption (FDE) is characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. We report here a case of multiple FDE induced by atenolol in a 48-year-old woman confirmed by positive patch test in previously affected sites. Beta-blockers-induced FDE are very rare. Only two cases had been reported in the literature. To the best of our knowledge, this is the first case reported of atenolol-induced FDE confirmed by a positive patch test.

  15. [Dealing with adverse drug reactions in dentistry. Procedures on encountering adverse drug reactions and goal of the Swiss Pharmacovigilance system].

    PubMed

    Egger, Sabin S; Krähenbühl, Stephan; Schlienger, Raymond G

    2005-01-01

    Dentists may be confronted with adverse drug reactions (ADRs) in their dental practice, and are--like other health professionals--obliged to report certain ADRs. The aim of this article is to sensitise dentists for this topic, to show how to proceed in case of a supposed ADR, and to emphasise the importance of spontaneous reporting of ADRs. ADRs may not always be clearly distinguished from symptoms of underlying diseases, and in cases of polypharmacy multiple drugs may be responsible for the reaction. It is therefore important to get a detailed medical history, and to establish a temporal relationship between start of a therapy and appearance of the symptom. Information from the medical literature, exclusion of other possible causes, and identification of risk factors help to confirm a causal relationship between a suspected drug and an observed reaction. In Switzerland severe and unexpected ADRs have to be reported to one of the regional Pharmacovigilance centres with the yellow ADR reporting form from Swissmedic. The spontaneous reports of ADRs help to early identify new problems of a drug therapy, and permit to take measures to minimise the risk.

  16. 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.

  17. Adverse drug reactions: a hospital pharmacy-based reporting scheme.

    PubMed Central

    Winstanley, P A; Irvin, L E; Smith, J C; Orme, M L; Breckenridge, A M

    1989-01-01

    A pharmacy-based adverse drug reaction (ADR) reporting scheme, using pharmacists, nurses and medical practitioners as initiators of reports, was set up at the end of 1984 in the Royal Liverpool Hospital in order to encourage reporting. New reports were inspected at weekly intervals by a staff pharmacist, and a clinical pharmacologist. Reports were forwarded to the Committee on Safety of Medicines if the reaction was considered to be serious by the clinicians, or the ADR team or involved 'black triangle' drugs. The total number of ADR reports was increased eightfold by the introduction of the scheme (from 14 in 1984 to 76, 102 and 94 in 1985, 1986 and 1987 respectively), and this rate of reporting has been sustained. PMID:2775609

  18. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    PubMed Central

    Jönsson, Anna K.; Lövborg, Henrik; Lohr, Wolfgang; Ekman, Bertil; Rocklöv, Joacim

    2017-01-01

    Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA). Methods: All individual adverse drug reactions (ADR) reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR) with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72). Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia. PMID:28737683

  19. Neutrino-induced reactions on nuclei

    NASA Astrophysics Data System (ADS)

    Gallmeister, K.; Mosel, U.; Weil, J.

    2016-09-01

    Background: Long-baseline experiments such as the planned deep underground neutrino experiment (DUNE) require theoretical descriptions of the complete event in a neutrino-nucleus reaction. Since nuclear targets are used this requires a good understanding of neutrino-nucleus interactions. Purpose: Develop a consistent theory and code framework for the description of lepton-nucleus interactions that can be used to describe not only inclusive cross sections, but also the complete final state of the reaction. Methods: The Giessen-Boltzmann-Uehling-Uhlenbeck (GiBUU) implementation of quantum-kinetic transport theory is used, with improvements in its treatment of the nuclear ground state and of 2p2h interactions. For the latter an empirical structure function from electron scattering data is used as a basis. Results: Results for electron-induced inclusive cross sections are given as a necessary check for the overall quality of this approach. The calculated neutrino-induced inclusive double-differential cross sections show good agreement data from neutrino and antineutrino reactions for different neutrino flavors at MiniBooNE and T2K. Inclusive double-differential cross sections for MicroBooNE, NOvA, MINERvA, and LBNF/DUNE are given. Conclusions: Based on the GiBUU model of lepton-nucleus interactions a good theoretical description of inclusive electron-, neutrino-, and antineutrino-nucleus data over a wide range of energies, different neutrino flavors, and different experiments is now possible. Since no tuning is involved this theory and code should be reliable also for new energy regimes and target masses.

  20. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    PubMed

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  1. Lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome.

    PubMed

    Thakur, B K; Verma, S; Mishra, J

    2015-06-01

    Human immunodeficiency virus-infected patients are at increased risk of drug reactions because of immune dysregulation and multiple drug intake. Lichenoid drug reactions to isoniazid have been reported previously in the literature. However, for lichenoid drug reaction to isoniazid to be so extensive to present as exfoliative dermatitis is rare. We report here a rare case of lichenoid drug reaction to isoniazid presenting as exfoliative dermatitis in a patient with acquired immunodeficiency syndrome.

  2. Reaction induced fractures in 3D

    NASA Astrophysics Data System (ADS)

    Ulven, Ole Ivar; Malthe-Sørenssen, Anders

    2014-05-01

    The process of fracture formation due to volume changing processes has been studied numerically in a variety of different settings, e.g. fracture initiation in general volume increasing reactions by Ulven et al.[4], weathering of dolerites by Røyne et al.[2], and volume reduction during chemical decomposition prosesses by Malthe-Sørenssen et al.[1]. Common to many previous works is that the simulations were performed in a 2D setting, due to computational limitations. Fractures observed both in field studies and in experiments are in many cases three dimensional. It remains an open question in what cases the simplification to 2D systems is applicable, and when a full 3D simulation is necessary. In this study, we use a newly developed 3D code combining elements from the discrete element model (DEM) with elements from Peridynamics[3]. We study fracture formation in fully three dimensional simulations, and compare them with simulation results from 2D DEM, thus gaining insight in both qualitative and quantitative differences between results from 2D and 3D simulations. References [1] Malthe-Sørenssen, A., Jamtveit, B., and Meakin, P., 'Fracture Patterns Generated by Diffusion Controlled Volume Changing Reactions,' Phys. Rev. Lett. 96, 2006, pp. 245501-1 - 245501-4. [2] Røyne, A., Jamtveit, B., and Malthe-Sørenssen, A., 'Controls on rock weathering rates by reaction-induced hierarchial fracturing,' Earth Planet. Sci. Lett. 275, 2008, pp. 364 - 369. [3] Silling, S. A., 'Reformulation of elasticity theory for discontinuities and long-range forces,' J. Mech. Phys. Solids, 48, Issue 1, 2000, pp. 175 - 209 [4] Ulven, O. I., Storheim, H., Austrheim, H., and Malthe-Sørenssen, A., 'Fracture Initiation During Volume Increasing Reactions in Rocks and Applications for CO2 Sequestration', Earth Planet. Sci. Lett. 389C, 2014, pp. 132 - 142.

  3. Drug reaction with eosinophilia and systemic symptoms (DRESS): incidence, pathogenesis and management.

    PubMed

    Shiohara, Tetsuo; Kano, Yoko

    2017-02-01

    Drug-induced hypersensitivity syndrome(DiHS), often referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a life-threatening multi-organ system reaction induced by drugs and associated with sequential reactivations of herpesviruses. This syndrome has several unique features, creating uncertainty over whether it represents true drug eruption. Areas covered: A literature review of all the cases was made by a Pub Med search. The delayed onset, paradoxical worsening of clinical symptoms after withdrawal of the causative drug and unexplained cross-reactivity to multiple drugs are unique features of this syndrome, which could prompt infection to be an initial consideration. Regulatory T cells (Tregs) are expanded at the acute stage but, upon clinical resolution, their function become gradually defective. Because such a gradual loss of Treg function occurring after resolution of DiHS/DRESS could increase the risk of developing autoimmune sequelae, systemic corticosteroids administered during the acute stage may serve to prevent not only tissue damage but also the gradual loss of Treg function by restoring the impaired Treg activity. Expert opinion: Systemic corticosteroids give promising results in terms of not only alleviating a variety of clinical symptoms at the acute stage but also of preventing the generation of autoimmune responses occurring at the resolution stage.

  4. 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.

  5. Clinical association between pharmacogenomics and adverse drug reactions.

    PubMed

    Zhou, Zhi-Wei; Chen, Xiao-Wu; Sneed, Kevin B; Yang, Yin-Xue; Zhang, Xueji; He, Zhi-Xu; Chow, Kevin; Yang, Tianxin; Duan, Wei; Zhou, Shu-Feng

    2015-04-01

    Adverse drug reactions (ADRs) are a major public health concern and cause significant patient morbidity and mortality. Pharmacogenomics is the study of how genetic polymorphisms affect an individual's response to pharmacotherapy at the level of a whole genome. This article updates our knowledge on how genetic polymorphisms of important genes alter the risk of ADR occurrence after an extensive literature search. To date, at least 244 pharmacogenes identified have been associated with ADRs of 176 clinically used drugs based on PharmGKB. At least 28 genes associated with the risk of ADRs have been listed by the Food and Drug Administration as pharmacogenomic biomarkers. With the availability of affordable and reliable testing tools, pharmacogenomics looks promising to predict, reduce, and minimize ADRs in selected populations.

  6. Remission-inducing drugs in rheumatoid arthritis.

    PubMed Central

    Anastassiades, T. P.

    1980-01-01

    The administration of certain drugs to patients with established rheumatoid arthritis frequently results in improvement that is slow to appear but persists for long periods, even after the drug is discontinued. The three main drugs with this effect, whose efficacy and toxicity are reviewed in this paper, are gold salts, D-penicillamine and chloroquine. The cytotoxic agents used to treat rheumatoid arthritis, which likely have nonspecific anti-inflammatory actions and have serious long-term side effects, are also briefly reviewed. A new drug, levamisole, is currently being tested in patients with rheumatoid arthritis. It is suggested that the time for considering the introduction of a remission-inducing drug in patients with progressive rheumatoid arthritis is after an adequate trial of therapy with salicylates or other nonsteroidal anti-inflammatory agents, or both, and before the oral administration of steroids. It is difficult, however, on the basis of rigorous clinical comparisons, to recommend which of the three main remission-inducing drugs should be tried first, although gold salts have been used the most. Patients who have improved with 6 months of chrysotherapy may continue treatment for at least 3 years, during which time the frequency of mucocutaneous and renal toxic effects will steadily decrease. Some aspects of the medical economics of therapy with remission-inducing drugs for rheumatoid arthritis are discussed. PMID:6768438

  7. Adverse Drug Reactions in Children—A Systematic Review

    PubMed Central

    Smyth, Rebecca Mary Diane; Gargon, Elizabeth; Kirkham, Jamie; Cresswell, Lynne; Golder, Su; Smyth, Rosalind; Williamson, Paula

    2012-01-01

    Background Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided. Methods and Findings We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable. Conclusions There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further

  8. Drug-induced taste disorders.

    PubMed

    Naik, B Sadananda; Shetty, Nagaraj; Maben, E V S

    2010-06-01

    Taste and smell are critical components to a person's overall sense of well-being and quality of life. Taste related problems can cause pain and discomfort and can hinder the maintenance of a satisfying and nutritious diet. Loss of taste interferes with pleasure derived from food and food-related activities. Many drugs can affect this special sense and contribute significantly to the morbidity of the associated illness. This article gives a brief account of this problem and emphasizes the need for more awareness of the clinicians about this problem. Copyright 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  9. The mechanobiology of drug-induced cardiac valve disease.

    PubMed

    Lam, Ngoc Thien; Balachandran, Kartik

    2015-01-01

    Drug-related adverse reactions leading to valve disease or valvulopathy were first identified in the 1960s. These were associated with patients taking anti-migraine ergot-derivative drugs, anti-anorectics, anti-Parkinson's drugs, or other anti-depressant drugs. In general, these drugs have serotonergic, dopaminergic, or β-adrenergic activity, being either agonists or reuptake inhibitors of the aforementioned neurotransmitter pathways. Recent work has focused on several possible mechanisms for valvulopathy, specifically highlighting the serotonin or 5-hydroxy-trypta-mine-2B (5-HT2B) receptor subtype and the 5-HT transporter as mediators that cause expression of myofibroblast phenotype, excessive cell proliferation, leading to valve fibrosis. Most of these studies and reviews, however, were not reported in the context of the mechanical environment of the valve, which by itself is an important factor in the initiation and progression of valve disease. It is also not known whether patients who have altered mechanical environments in their cardiovascular system, such as those who are hypertensive or have functional cardiac disease, such as ischemic ventricular dilation, or those who have an increased propensity for developing drug-induced valvulopathy. In the present review, we highlight the potential role of hemodynamics and the mechanical environment in influencing these drug-induced valvulopathies, focusing on serotonin-mediated disease and the need for further study of this topic.

  10. Drug-induced hperpigemntation: a systematic review.

    PubMed

    Krause, Walter

    2013-07-01

    Acquired hyperpigmentation of the skin is sometimes interpreted as an adverse effect of drugs. Systematic studies are rare in the literature; predominantly case reports have been published. The present review provides evaluates the evidence for a causal relation. The reports on a relationship between hyperpigmentation and drugs from 1970 until June 2012 found in MEDLINE and EMBASE were rated according to the SIGN grading system for clinical studies. In this system, the grade of evidence of each report is rated. The highest grade of evidence for each drug is cited. 306 publications were included. They were predominantly case reports; only a small number of case series was available. Only very few case-control-studies and randomized controlled trials (RCT) were found. For the majority of drugs, there was a low level of evidence for a causal relationship in drug-induced hyperpigmentation. A causal relationship is likely only for prostaglandins, minocycline, phenothiazine, nicotine, and antimalarial drugs. There is little evidence for drug-induced hyperpigmentation. A causal relationship appears liklely only for a limited number of drugs. © The Author • Journal compilation © Blackwell Verlag GmbH, Berlin.

  11. 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

  12. Drug-induced immune haemolytic anaemia caused by levofloxacin.

    PubMed

    Sukhal, Shashvat; Gupta, Shweta

    2014-08-01

    Drug-induced immune haemolytic anaemia (DIIHA) is extremely rare. We herein report a case of life-threatening DIIHA due to levofloxacin. This is the second case reported in the literature. A 51-year-old woman presented with complaints of fatigue after 4-5 days of levofloxacin therapy for a lung infection. At presentation, she was found to have haemolysis with a positive Coombs test and IgG autoantibodies. Levofloxacin was identified as the probable culprit, using the Naranjo adverse drug reaction probability scale. Upon discontinuation of the drug and initiation of steroids, the patient's haematological parameters stabilised. Diagnosis of DIIHA is made through a history of intake of levofloxacin, clinical and laboratory features of haemolysis and a positive Coombs test. An autoantibody screen is most commonly positive for warm antibodies (IgG type). It is essential for clinicians to recognise this rare complication caused by a commonly prescribed medication, discontinue the offending drug and initiate treatment.

  13. 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

  14. Fluconazole-induced Fixed Drug Eruption.

    PubMed

    Gaiser, Cory Allen; Sabatino, Dominick

    2013-03-01

    Triazole antifungals are commonly used in the treatment of oral, esophageal, and vaginal candidiasis. Fluconazole is frequently prescribed as the therapy modality for vaginal fungal infections. On rare occasions, fluconazole has been shown to cause fixed drug eruptions. Lesions of fixed drug eruptions vary in size and number, but have the same general appearance and symptoms. The authors report a case of fluconazole-induced fixed drug eruption in a 24-year-old woman with recurrent vaginal candidiasis. The lesion was initially diagnosed as a spider bite. Topical and oral provocation tests with fluconazole were performed. Topical provocation with petroleum/fluconazole and dimethyl sulfoxide/fluonazole were both negative. Oral provocation was positive, thus confirming the diagnosis of fluconazole-induced fixed drug eruption.

  15. Risk factors for adverse drug reactions--epidemiological approaches.

    PubMed

    Hoigné, R; Lawson, D H; Weber, E

    1990-01-01

    Age by itself is not an important risk factor for ADRs. Age-related changes are the consequence of a number of individual factors, for example morbidity associated with polypharmacy, decline in renal or liver function in the elderly, hypoalbuminaemia, reduced body weight, etc. The relationship between gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be assessed globally in large cohort studies with access to computerized data, but complete accuracy requires access to the original patient records. The increase in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in non-users. About a quarter of ADRs in hospitalized patients seem not to arise from purely pharmacological mechanisms. They are mainly due to allergic, anaphylactoid, or idiosyncratic reactions and to intolerance. In such non-pharmacological reactions, the time of exposure, reaction time, and even dosage may be important factors in identification of the causal drug. The use of benzodiazepines can be optimized by taking into account potency, time of action and the different syndromes encountered after withdrawal. Following long-term use problems of relapse and rebound are being increasingly recognized, in addition to organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due to neuroleptics are common. The rates of these ADRs differ markedly between various drugs, even after dosages and co-medications are taken into account. Epidemiological screening for potentially carcinogenic drugs can only be done in large cohorts of patients with pre-recorded full information sets as may be found in an HMO (Health Maintenance Organization). The findings of several such studies have been published in specialist cancer journals.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Mechanistic Review of Drug-Induced Steatohepatitis

    PubMed Central

    Schumacher, Justin; Guo, Grace

    2015-01-01

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. PMID:26344000

  17. Drug-induced metabolic syndrome.

    PubMed

    Wofford, Marion R; King, Deborah S; Harrell, T Kristopher

    2006-02-01

    The metabolic syndrome is a cluster of risk factors associated with an increased risk for cardiovascular disease and type 2 diabetes. Based on data from 1988 to 1994, it is estimated that 24% of adults in the United States meet the criteria for diagnosis of the metabolic syndrome. The use of certain medications may increase the risk of the metabolic syndrome by either promoting weight gain or altering lipid or glucose metabolism. Health providers should recognize and understand the risk associated with certain medications and appropriately monitor for changes related to the metabolic syndrome. Careful attention to drug choices should be paid in patients who are overweight or have other risk factors for diabetes or cardiovascular disease.

  18. 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.

  19. Patient knowledge on reporting adverse drug reactions in Poland

    PubMed Central

    Staniszewska, Anna; Dąbrowska-Bender, Marta; Olejniczak, Dominik; Duda-Zalewska, Aneta; Bujalska-Zadrożny, Magdalena

    2017-01-01

    Aim The aim of the study was to assess patient knowledge on reporting of adverse drug reactions. Materials and methods A prospective study was conducted among 200 patients. The study was based on an original survey composed of 15 single- and multiple-choice questions. The study involved individuals who have experienced adverse reactions as well as individuals who have never experienced any adverse reactions; people over the age of 18; literate; residing in Mazowieckie Voivodeship, who have not been diagnosed with any disease that could compromise their logical thinking skills. Results The respondents who lived in the city had a greater knowledge compared to the respondents who lived in the countryside (Pearson’s χ2=47.70, P=0.0013). The respondents who lived in the city were also more statistically likely to provide a correct answer to the question about the type of adverse reactions to be reported (Pearson’s χ2=50.66, P=0.012). Statistically significant associations were found between the place of residence of the respondents and the correct answer to the question about the data that must be included in the report on adverse reactions (Pearson’s χ2=11.7, P<0.0001). PMID:28096661

  20. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management.

    PubMed

    Moore, Douglas E

    2002-01-01

    The interaction of sunlight with drug medication leads to photosensitivity responses in susceptible patients, and has the potential to increase the incidence of skin cancer. Adverse photosensitivity responses to drugs occur predominantly as a phototoxic reaction which is more immediate than photoallergy, and can be reversed by withdrawal or substitution of the drug. The bias and inaccuracy of the reporting procedure for these adverse reactions is a consequence of the difficulty in distinguishing between sunburn and a mild drug photosensitivity reaction, together with the patient being able to control the incidence by taking protective action. The drug classes that currently are eliciting a high level of adverse photosensitivity are the diuretic, antibacterial and nonsteroidal anti-inflammatory drugs (NSAIDs). Photosensitising chemicals usually have a low molecular weight (200 to 500 Daltons) and are planar, tricyclic, or polycyclic configurations, often with heteroatoms in their structures enabling resonance stabilisation. All absorb ultraviolet (UV) and/or visible radiation, a characteristic that is essential for the chemical to be regarded as a photosensitiser. The photochemical and photobiological mechanisms underlying the adverse reactions caused by the more photoactive drugs are mainly free radical in nature, but reactive oxygen species are also involved. Drugs that contain chlorine substituents in their chemical structure, such as hydrochlorthiazide, furosemide and chlorpromazine, exhibit photochemical activity that is traced to the UV-induced dissociation of the chlorine substituent leading to free radical reactions with lipids, proteins and DNA. The photochemical mechanisms for the NSAIDs that contain the 2-aryl propionic acid group involve decarboxylation as the primary step, with subsequent free radical activity. In aerated systems, the reactive excited singlet form of oxygen is produced with high efficiency. This form of oxygen is highly reactive towards

  1. 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.

  2. 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

  3. Adverse drug reactions experience in a teaching hospital in Jordan.

    PubMed

    Alsbou, Mohammed; Alzubiedi, Sameh; Alzobi, Hamed; Samhadanah, Nawal Abu; Alsaraireh, Yousef; Alrawashdeh, Omar; Aqel, Amin; Al-Salem, Khalil

    2015-12-01

    Adverse drug reactions (ADRs) represent a major health care problem. To identify the most common ADRs, drugs implicated in ADRs, and to assess their causality, severity, preventability and risk factors predisposing to reported ADRs in Jordan. Al-Karak teaching hospital, southern of Jordan. Method A cross sectional observational study was carried out for 11 months from January to November 2013. Suspected ADRs were recorded in ADRs report forms and analyzed for causality, severity, and preventability. Most common ADRs, drugs involved in these ADRs, causality, severity, and preventability of suspected ADRs. A total of 64 reports were received. Some patients suffered more than one ADR. The total number of ADRs identified was 108. Forty one drugs were involved in causing these ADRs. About 2/3 of adverse reactions (73.4 %) did not cause admission to the hospital, whereas 26.6 % of the ADRs resulted in admission. Majority of the ADRs were type A (62.5 %). Most of ADRs (92.2 %) were assessed as probable. Nearly, 65.6 % of ADRs were categorized as mild. Majority of ADRs were assessed as "not preventable" (75 %). The most common classes of drugs involved in ADRs were antibiotics, analgesics, vaccines and antiepileptics. The most commonly identified ADRs were abdominal pain, skin rash, shortness of breath, fever, upper gastrointestinal bleeding and vomiting. Risk factors contributed to ADRs were age and polypharmacy. Jordanian healthcare providers should be aware of the importance of detecting and reporting ADRs, in order to prevent and reduce the incidence of ADRs. Awareness of risk factors predisposing to ADRs may help in identifying patients with higher risk and therefore reducing the risk of these ADRs and improving patient outcome.

  4. A review of drug-induced hypernatraemia

    PubMed Central

    Liamis, George; Milionis, Haralampos J.; Elisaf, Moses

    2009-01-01

    Drug-induced electrolyte abnormalities have been increasingly reported and may be associated with considerable morbidity and/or mortality. In clinical practice, hypernatraemia (serum sodium higher than 145 mmol/L) is usually of multifactorial aetiology and drug therapy not infrequently is disregarded as a contributing factor for increased serum sodium concentration. Strategies to prevent this adverse drug effect involve careful consideration of risk factors and clinical and laboratory evaluation in the course of treatment. Herein, we review evidence-based information via PubMed and EMBASE and the relevant literature implicating pharmacologic treatment as an established cause of hypernatraemia and discuss its incidence and the underlying pathophysiologic mechanisms. PMID:25949338

  5. Acemetacin-induced fixed drug eruption

    PubMed Central

    Cebeci, Filiz; Yaşar, Şirin; Aytekin, Sema; Güneş, Pembegül

    2016-01-01

    Fixed drug eruption (FDE) is an adverse effect observed with various drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and various antibiotics. Acemetacin, a prodrug of indomethacin, is an NSAID licensed for use in rheumatic disease and other musculoskeletal disorders. We present a case of acemetacin-induced FDE in a 49-year-old woman. To the best of our knowledge, this is the second case report detailing clinical and histopathological findings of a patient with FDE caused by acemetacin. PMID:27114641

  6. Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features.

    PubMed

    Pedrós, Consuelo; Formiga, Francesc; Corbella, Xavier; Arnau, Josep Maria

    2016-02-01

    To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥ 65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥ 65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥ 65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1-3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes (p = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. One out of every 30 urgent admissions of patients aged ≥ 65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.

  7. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    PubMed

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology.

  8. Systematic review of NSAID-induced adverse reactions in patients with rheumatoid arthritis in Japan.

    PubMed

    Tomita, Tetsuya; Ochi, Takahiro; Sugano, Kentaro; Uemura, Shinichi; Makuch, Robert W

    2003-06-01

    Abstract A systematic review of randomized controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis (RA) patients was conducted to evaluate the risk of NSAID-induced adverse reactions. Double-blind, randomized, controlled trials with 6-week treatments for RA patients were included in the study. The endpoints for the analysis included any adverse reactions, digestive adverse reactions, and upper gastrointestinal (GI) adverse reactions. A fixed-effect model was used for estimation of the risk. Time-to-event analysis of the incidence of adverse reactions was also conducted. A total of 28 trials was included for the analysis, and a total of 30 NSAIDs were used in the trials. The proportion of patients who experienced any adverse reaction was as follows: piroxicam 18.9% (3 trials), diclofenac 18.8% (4 trials), indomethacin 22.1% (14 trials), and aspirin 25.0% (4 trials). The proportion of patients who experienced digestive adverse reactions was as follows: piroxicam 10.2%, diclofenac 10.6%, indomethacin 13.1%, and aspirin 14.1%. Most withdrawals due to adverse reaction occurred during the first 3 weeks after administration of the NSAID. Although the risk of NSAID-induced adverse reaction was different from drug to drug, the risk of adverse reaction was clinically significant.

  9. Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

    PubMed

    Silva, Soraia Aparecida da; Figueiredo, Mariana Maciel Pereira de; Carneiro, Lauro; Reiss, Débora Borowiak; Damásio, Mariana Amaranto de Souza

    2016-01-01

    To review the hypersensitivity reaction to drugs known as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), based on a case report. We also intend to discuss the difficulty and importance of disease recognition, since none of the changes is pathognomonic of this disease and failure to identify it may have disastrous consequences for the patient. To describe this case report, in addition to the information collected for clinical assessment, a literature review was performed in the PubMed and Bireme databases in order to retrieve the latest information published in literature on DRESS syndrome. The case of a 20-year old patient is reported. After anamnesis, physical examination and laboratory tests a diagnosis of DRESS syndrome was performed, characterized by rash, hematologic alterations, lymphadenopathy and lesions in target organ. This is a rare syndrome, whose frequency varies according to the drug used and the immune status of the patient, being more often associated with the use of anticonvulsants. The approach and discussion of the topic are of paramount importance, in view of the potential lethality of this treatable syndrome. Recognizing the occurrence of DRESS syndrome and starting treatment as soon as possible is crucial to reduce the risk of mortality and improve prognosis.

  10. Adverse Drug Reactions and quality deviations monitored by spontaneous reports

    PubMed Central

    Visacri, Marília Berlofa; de Souza, Cinthia Madeira; Sato, Catarina Miyako Shibata; Granja, Silvia; de Marialva, Mécia; Mazzola, Priscila Gava; Moriel, Patricia

    2014-01-01

    Objectives The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases. PMID:25972731

  11. Impact of depression mood disorder on the adverse drug reaction incidence rate of anticancer drugs in cancer patients.

    PubMed

    Zhou, T; Duan, J J; Zhou, G P; Cai, J Y; Huang, Z H; Zeng, Y T; Xu, F

    2010-01-01

    The aim of this study was to explore the impact of depression mood disorder on the incidence of adverse drug reactions of anticancer drugs in cancer patients. The Hamilton Depression Scale 17 was used to evaluate the depression mood disorder level in 73 cancer patients before chemotherapy. Pharmacists monitored adverse drug reactions during the chemotherapy period. The relationship between depression mood disorder level and the incidence of adverse drug reactions was analysed. The frequency and extent of total adverse drug reactions were not related to depression mood disorder level. The frequency and extent of subjectively experienced adverse drug reactions such as anorexia, nausea and fatigue were related to depression mood disorder level. In conclusion, psychological support and intervention should be provided to cancer patients in order to improve patient adherence and cancer chemotherapy effectiveness, and to decrease the incidence of adverse drug reactions.

  12. [Patterns of drug consumption and the occurrence of adverse drug reactions among students of public health].

    PubMed

    Plichta, Danuta; Doryńska, Agnieszka; Spiewak, Radosław

    2012-04-01

    The research of drug consumption is focused mainly upon the elderly, while the knowledge of drug consumption patterns among young people remains insufficient. Public health students (PHS) seem of particular interest as future opinion leaders and drug policy makers. The aim of the study was to analyze opinions and patterns of drug consumption, and adverse drug reactions (ADR) in this group. 130 PHS took part in the anonymous questionnaire survey. All students admitted to using some drug at least once in their lives. While purchasing over-the-counter (OTC) drugs, 51.6% students trusted their own knowledge and experience. Women more often relied on a pharmacist's recommendation (47.2% vs 21.7% men; p = 0.045), while men were more influenced by advertising (34.8% vs 12.3% women, p = 0.008). Strict adherence to recommended dosage of OTC and prescription drugs (Rx) was declared by 41.1% and 71.9% students, respectively. Every fourth student (24.8%) admitted to having purchased a Rx drug at least once without having the prescription. Past episodes of ADR to OTC were reported by 7.8% students and to Rx by 38.4% (p < 0.001). Respectively 27.2% and 34.4% students were never, or hardly ever asked about past ADR by prescribing physicians. According to 89.2% students, drug advertising should be subject to regulation and policing, and 66.1% considered it inaccurate and unreliable. Forty-five percent of students had an OTC drug on them while responding the questionnaire, 20.0% had a prescription drug. Students of public health seem to be notorious consumers of drugs and their attitude seems not fully rational.

  13. Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

    PubMed

    Sevene, Esperança; Mariano, Alda; Mehta, Ushma; Machai, Maria; Dodoo, Alexander; Vilardell, David; Patel, Sam; Barnes, Karen; Carné, Xavier

    2008-01-01

    The roll out of various public health programmes involving mass administration of medicines calls for the deployment of responsive pharmacovigilance systems to permit identification of signals of rare or even common adverse reactions. In developing countries in Africa, these systems are mostly absent and their performance under any circumstance is difficult to predict given the known shortage of human, financial and technical resources. Nevertheless, the importance of such systems in all countries is not in doubt, and research to identify problems, with the aim of offering pragmatic solutions, is urgently needed. To examine the impact of training and monitoring of healthcare workers, making supervisory visits and the availability of telecommunication and transport facilities on the implementation of a pharmacovigilance system in Mozambique. This was a descriptive study enumerating the lessons learnt and challenges faced in implementing a spontaneous reporting system in two rural districts of Mozambique - Namaacha and Matutuíne - where remote location, poor telecommunication services and a low level of education of health professionals are ongoing challenges. A 'yellow card' system for spontaneous reporting of adverse drug reactions (ADRs) was instituted following training of health workers in the selected districts. Thirty-five health professionals (3 medical doctors, 2 technicians, 24 nurses, 4 basic healthcare agents and 2 pharmacy agents) in these districts were trained to diagnose, treat and report ADRs to all medicines using a standardized yellow card system. There were routine site visits to identify and clarify any problems in filling in and sending the forms. One focal person was identified in each district to facilitate communication between the health professionals and the National Pharmacovigilance Unit (NPU). The report form was assessed for quality and causality. The availability of telecommunications and transport was assessed. Fourteen months after

  14. Doxycycline induced generalized bullous fixed drug eruption - A case report.

    PubMed

    Nitya, Selvaraj; Deepa, Kameswari; Mangaiarkkarasi, Adhimoolam; Karthikeyan, Kaliaperumal

    2013-12-01

    Adverse drug reactions are a major hazard of modern medicine. Fixed drug eruption, which is a cutaneous adverse drug reaction, is commonly seen with antimicrobials and analgesics. Here we report 37-year-old female with bullous fixed drug eruptions due to doxycycline administration.

  15. [Hypersensitivity reactions to non-steroidal anti-inflammatory drugs and tolerance to alternative drugs].

    PubMed

    Calvo Campoverde, K; Giner-Muñoz, M T; Martínez Valdez, L; Rojas Volquez, M; Lozano Blasco, J; Machinena, A; Plaza, A M

    2016-03-01

    Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6 to 5.7% in general population, but there are no data available in children. The aim of this study is to determine the frequency of patients diagnosed with hypersensitivity to NSAIDs, and describe their clinical characteristics, type of hypersensitivity, and tolerance to alternative drugs. Retrospective study was conducted on children with suspected hypersensitivity to NSAIDs from January 2012 to December 2013. The diagnosis was confirmed by oral drug provocation test (DPT) to the drug involved in the group with a history of one episode, while in the group with a history of more than one episode with the same drug the diagnosis was based on clinical data. Subsequently, a DPT with acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into selective or multiple. In those cases with a positive result, a DPT was performed with alternative drugs. Out of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. More than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  16. Characteristics of drug-induced anaphylaxis in children and adolescents.

    PubMed

    Cavkaytar, Ozlem; Karaatmaca, Betül; Cetinkaya, Pınar Gur; Esenboga, Saliha; Arik Yilmaz, Ebru; Sahiner, Umit M; Sekerel, Bulent E; Soyer, Ozge

    2017-09-01

    Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals <18 years old. Patients with a history of drug hypersensitivity reaction (DHR) referred to our center between January 2012 and February 2016 were included. After the collection of European Network for Drug Allergy questionnaire results, initial skin tests and/or provocation tests were performed for the offending drug. Among 561 children and adolescents referred due to a suspected DHR, 113 (19%) (median age [interquartile range], 9.6 years [5.4-13.8 years]; 55% boys) had anaphylaxis in their history. At the end of diagnostic evaluation of the patients, 84 (74% of the patients with a history of DIA) were actually hypersensitive to the offending drug. Major drugs that resulted in DIA were antibiotics (33%), nonsteroidal anti-inflammatory drugs (25%), and chemotherapeutics (19%). The majority of patients reported grade 2 (moderate) (45%) and grade 3 (severe) (33%) anaphylactic reactions. A history of systemic illness (41.7 versus 7.1%; p = 0.001), concomitant intake of other drugs regularly (36.9 versus 10.3%; p = 0.007), and the use of chemotherapeutics as the culprit drug (19 versus 0%; p = 0.011) were more frequent, whereas the use of antibiotics was less frequent (34.5 versus 75.9%; p < 0.001) among patients with actual DIA compared to drug tolerant patients. Three-fourths of the children and adolescents referred due to a suspected history of DIA were found to actually be drug hypersensitive. Prediagnosed systemic illness and different types of drugs would have an impact on the risk of DIA; however, atopic disease or a family history of drug hypersensitivity did not have an impact on actual DIA.

  17. Constipation and diarrhoea - common adverse drug reactions? A cross sectional study in the general population

    PubMed Central

    2011-01-01

    Background Constipation and diarrhoea are common complaints and often reported as adverse drug reactions. This study aimed at finding associations between drugs and constipation and diarrhoea in a general population. Methods A selection of inhabitants in Oppland County, Norway participated in a cross-sectional survey. Information about demographics, diseases including gastrointestinal complaints classified according to the Rome II criteria and use of drugs were collected on questionnaires. Constipation was defined as functional constipation and constipation predominant Irritable Bowel Syndrome (IBS), and diarrhoea as functional diarrhoea and diarrhoea predominant IBS. Associations between drugs and constipation and diarrhoea were examined with multivariable logistic regression models. Based on the multivariable model, the changes in prevalence (risk difference) of the abdominal complaints for non-users and users of drugs were calculated. Results In total 11078 subjects were invited, 4622 completed the questionnaires, 640 (13.8%) had constipation and 407 (8.8%) had diarrhoea. To start using drugs increased the prevalence of constipation and diarrhoea with 2.5% and 2.3% respectively. Polypharmacy was an additional risk factor for diarrhoea. Use of furosemide, levothyroxine sodium and ibuprofen was associated with constipation, and lithium and carbamazepine with diarrhoea. The excess drug related prevalence varied from 5.3% for the association between ibuprofen and constipation to 27.5% for the association between lithium and diarrhoea. Conclusions Use of drugs was associated with constipation and diarrhoea in the general population. The associations are most likely adverse drug reactions and show that drug-induced symptoms need to be considered in subjects with these complaints. PMID:21332973

  18. Isorefractive high internal phase emulsion organogels for light induced reactions.

    PubMed

    Zhang, Tao; Guo, Qipeng

    2016-03-25

    Isorefractive high internal phase emulsion (HIPE) organogels have been fabricated and investigated for light induced reactions. High transparency facilitates both the UV and visible light induced reactions within HIPE organogels. Transparent HIPE organogels are advantageous for light induced polymerizations, accelerating such polymerizations and enabling the preparation of large polyHIPE monoliths.

  19. [DRESS syndrome or reaction to drugs with eosinophilia and systemic symptoms associated to anti-tuberculosis drugs].

    PubMed

    Fernández de Córdova-Rodríguez1, Luis René; Guzmán-Guillén, Karol Andrea; Fernández de Córdova-Aguirre, Juan Carlos

    2015-01-01

    Tuberculosis has increased all over the world. This paper reports the case of a male patient with tuberculous meningitis, spinal tuberculosis (Pott's disease) and severe adverse reactions to antituberculosis drugs. He had skin rash, hepatitis, eosinophilia and fever; all these signs make the diagnosis of DRESS syndrome. This syndrome is caused by a severe hypersensitivity reaction to different drugs. It is usually caused by anticonvulsants, sulfonamides and some antiviral drugs, among other drugs. Anti-tuberculosis drugs can also cause this potentially fatal syndrome. The importance of surveillance for early detection and treatment of adverse drug reactions is emphasized.

  20. Risk of drug-induced congenital defects.

    PubMed

    De Santis, Marco; Straface, Gianluca; Carducci, Brigida; Cavaliere, Anna Franca; De Santis, Lidia; Lucchese, Angela; Merola, Anna Maria; Caruso, Alessandro

    2004-11-10

    Defects attributable to drug therapy represent about 1% of congenital defects of known aetiology. This means that a precautionary attitude and correct use of drugs in fertile, and especially pregnant, women is a feasible form of prevention. Drugs currently in use with proven teratogenic effect number approximately 25, but new pharmaceutical drugs are constantly in preparation. Recognition of a drug-induced teratogenic effect is a complex procedure taking into account not only experimental animal data but also experience in humans. Considering that 40% of pregnancies are not planned, it follows that any drug with known or suspected teratogenic potential must be used only under strict medical control. Also, adequate knowledge on potential teratogenicity of a drug permits modification of therapy before conception. It goes without saying that any drug should be used during pregnancy only if it is essential, and it would be prudent to use only those where adequate information is provided and prior clinical experience is available. Teratology Information Services can assist both physicians and patients when any doubt exists.

  1. [Induced drug prescription in oncology patients].

    PubMed

    Mas Arcas, C; Pascual Plá, F; Escrivá Muñz, J J; Boscas Mayans, R

    2004-01-01

    To study drug prescription generated by cancer patients treated at the Emergency Service (ES) of the Instituto Valenciano de Oncología (IVO) in their Primary Health Care Centre (PHCC). A descriptive prospective study has been carried out with patients treated and discharged from the ES of the IVO in November (n=207) and December (n=239) of 2001. 446 patients were treated and discharged; one out of five patients was contacted by telephone 48 hours after discharge to confirm drug prescriptions from the ES. In November, drug prescription was based on brand-name products, while, in December, generic drugs were prescribed. All patients were discharged with a detailed report that included: patient's medical records, consultation reason, physical exploration performed, diagnostic test results, discharge diagnosis and prescribed treatment. When a brand-name drug was prescribed, the majority of patients received the same product at the PHCC (92.5%), while the rest of them received the same active drug with a different brand name. When a generic drug was prescribed, patients received a prescription for the same active substance at the PHCC in 98% of cases (46% generic drug and 54% brand-name). As to length of treatment, 96% were short treatments (less than 2 weeks), while the rest of them were on-going. 80% needed one prescription; 15%, two, and 5% three or more prescriptions. In terms of therapeutic groups, the most commonly prescribed drugs were anti-infectious, analgesics, digestive-metabolism, respiratory, cardiovascular, neurological and miscellaneous. 1. There is a high level of induced drug prescription at PHCC in cancer patients, since primary care physicians usually maintain active substances prescribed by the ES of IVO, with few variations. 2. Promoting a good relationship between Hospital Care and Primary Health Care Centres helps control and reduce pharmaceutical costs. 3. A high correlation can be found between most frequently prescribed drugs in oncological

  2. Immunohistology of drug-induced exanthema: clues to pathogenesis.

    PubMed

    Yawalkar, N; Pichler, W J

    2001-08-01

    Hypersensitivity reactions to drugs can cause a variety of different skin disorders, the most frequent being maculopapular eruptions. In recent years increasing evidence has indicated the important involvement of T cells in this drug reaction. Histopathological changes typically show a dominant T-cell infiltration together with vacuolar interface dermatitis. Immunohistochemical studies demonstrate the presence of cytotoxic CD4+ and CD8+ T cells, which contain perforin and granzyme B, in close proximity to keratinocytes showing signs of cell destruction. Expression of Fas ligand is barely detectable, which suggests that cytotoxic granule exocytosis may be the dominant pathway leading to keratinocyte cell damage. In addition, drug-specific T cells may orchestrate the inflammatory skin reaction through the release and induction of various cytokines (i.e. IL-5, IL-6, TNF-alpha, IFN-gamma) and chemokines (i.e. regulated on activation, normal T-cell expressed and secreted; eotaxin). These mediators contribute to the generation of eosinophilia, which may amplify the underlying immune response through the release of further proinflammatory mediators in drug-induced maculopapular exanthema.

  3. Drug reaction with eosinophilia and systemic symptoms: observations from a tertiary care institution.

    PubMed

    Sasidharanpillai, Sarita; Riyaz, Najeeba; Rajan, Uma; Binitha, Manikoth P; Khader, Anza; Mariyath, Olasseri K Reena; John, Rajiv; Puravoor, Jayasree

    2014-01-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction which can mimic a viral infection, an autoimmune disease or a neoplastic disease. To study the clinical and epidemiological aspects of DRESS and to identify the precipitating drugs. All patients admitted to the dermatology ward of our tertiary care hospital from 1 st October 2010 to 30 th September 2013 with probable or definite DRESS as per the RegiSCAR scoring system were included in this prospective study. The clinical manifestations observed in the study population were studied and the common offending drugs were identified. During the 3 year study period, 26 patients fulfilled criteria for probable or definite DRESS. In more than 50% of cases, the culprit drug was phenytoin. Most common symptoms observed were fever, rash and facial edema. Liver was the most common internal organ affected. Most of the patients responded to withdrawal of the drug and administration of steroids for 3-6 weeks. One patient with dapsone-induced DRESS died. Intense facial erythema and edema and an elevated eosinophil count were not found to be bad prognostic factors. In most instances the flare ups during the course of the disease could be managed with a slower tapering of steroids. More prospective studies on DRESS are required to assess the prognostic factors and to formulate better diagnostic criteria.

  4. Cutaneous Adverse Drug Reactions with Antimalarials and Allergological Skin Tests.

    PubMed

    Soria, Angèle; Barbaud, Annick; Assier, Haudrey; Avenel-Audran, Martine; Tétart, Florence; Raison-Peyron, Nadia; Amarger, Stéphanie; Girardin, Pascal; Francès, Camille

    2015-01-01

    Currently used antimalarial drugs (AM) are hydroxychloroquine and chloroquine, which are prescribed for many autoimmune disorders. The value of skin tests on cutaneous adverse drug reactions (CADR) with AM remains unknown. The main objective of this retrospective study is to know whether skin tests for AM are useful and how to manage the recovery of AM therapy in these patients. All patients referred for suspected CADR secondary to AM between 2001 and 2014 in eight French dermatology centers were retrospectively reviewed. We report herein a retrospective series of 20 patients with CADR and AM involvement. Skin tests, performed in 14/20 patients, were negative in all cases. Six patients had an oral provocation test with recurrence of CADR in 1 case. We encourage dermatologists to perform oral provocation tests in nonsevere CADR in order to allow AM rechallenge at progressive doses. © 2015 S. Karger AG, Basel.

  5. Drug induced acute pancreatitis: incidence and severity.

    PubMed Central

    Lankisch, P G; Dröge, M; Gottesleben, F

    1995-01-01

    To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

  6. 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

  7. Adverse drug reactions in therapeutic hypothermia after cardiac arrest

    PubMed Central

    Witcher, Robert; Dzierba, Amy L.; Kim, Catherine; Smithburger, Pamela L.; Kane-Gill, Sandra L.

    2016-01-01

    Background: Therapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs). Methods: A retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres. Medications commonly used during TH were screened for association with significant ADRs (grade 3 or greater per Common Terminology Criteria for Adverse Events) using three published ADR detection instruments. Results: A total of 229 patients were included, the majority being males with median age of 62 presenting with an out-of-hospital cardiac arrest in pulseless electrical activity or asystole. The most common comorbidities were hypertension, coronary artery disease, and diabetes mellitus. There were 670 possible ADRs and 69 probable ADRs identified. Of the 670 possible ADRs, propofol, fentanyl, and acetaminophen were the most common drugs associated with ADRs. Whereas fentanyl, insulin, and propofol were the most common drugs associated with a probable ADR. Patients were managed with TH for a median of 22 hours, with 38% of patients surviving to hospital discharge. Conclusions: Patients undergoing TH after cardiac arrest frequently experience possible adverse reactions associated with medications and the corresponding laboratory abnormalities are significant. There is a need for judicious use and close monitoring of drugs in the setting of TH until recommendations for dose adjustments are available to help prevent ADRs.

  8. A case of allopurinol-induced fixed drug eruption confirmed with a lymphocyte transformation test.

    PubMed

    Kim, Min-Hye; Shim, Eun-Jin; Jung, Jae-Woo; Sohn, Seong-Wook; Kang, Hye-Ryun

    2012-09-01

    Allopurinol is one of the causative drugs that induce fixed drug eruption (FDE). The lymphocyte transformation test (LTT) is a safe and reliable diagnostic procedure for drug allergy, but is reported to be rarely positive in patients with FDE. In the current case, we performed an LTT and successfully confirmed allopurinol as the offending drug. This case report suggests that an LTT should be an optional diagnostic tool for FDE or delayed reaction due to allopurinol.

  9. A Case of Allopurinol-Induced Fixed Drug Eruption Confirmed With a Lymphocyte Transformation Test

    PubMed Central

    Kim, Min-Hye; Shim, Eun-Jin; Jung, Jae-Woo; Sohn, Seong-Wook

    2012-01-01

    Allopurinol is one of the causative drugs that induce fixed drug eruption (FDE). The lymphocyte transformation test (LTT) is a safe and reliable diagnostic procedure for drug allergy, but is reported to be rarely positive in patients with FDE. In the current case, we performed an LTT and successfully confirmed allopurinol as the offending drug. This case report suggests that an LTT should be an optional diagnostic tool for FDE or delayed reaction due to allopurinol. PMID:22950038

  10. Drug-induced subacute cutaneous lupus erythematosus.

    PubMed

    Callen, J P

    2010-08-01

    Subacute cutaneous lupus erythematosus (SCLE) is a subset of cutaneous lupus erythematosus with unique immunologic and clinical features. The first description dates back to 1985 when a series of five patients were found to have hydrochlorothiazide-induced SCLE. Since that time, at least 40 other drugs have been implicated in the induction of SCLE.

  11. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review.

    PubMed

    Rodrigues, Maria Cristina Soares; Oliveira, Cesar de

    2016-09-01

    to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a

  12. Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking phenytoin and levetiracetam: a case report.

    PubMed

    Hall, David Jeffrey; Fromm, Jason Steven

    2013-01-03

    Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.

  13. Drug-induced, factitious, & idiopathic diarrhoea.

    PubMed

    Abraham, Bincy P; Sellin, Joseph H

    2012-10-01

    The aetiology of diarrhoea can often be simple to identify, but in some cases may pose a challenge. The diagnosis of drug-induced diarrhoea can easily be sorted based on timing of the symptom with onset of a new drug. Treatment can vary from simply monitoring and eventual resolution with continuation of the drug, to discontinuation of the offending agent. In cases where a drug cannot always be stopped, additional medications can help control the symptom. Factitious diarrhoea can present a diagnostic challenge if the evaluating physician does not suspect its possibility. Typically a careful history, and in some cases, stool testing can provide clues. The diagnosis of idiopathic diarrhoea is often made when exhaustive testing provides no definite aetiology and the goal of management is supportive care and symptomatic treatment.

  14. 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

  15. Knowledge and attitudes to reporting adverse drug reactions.

    PubMed

    Pulford, Andrew; Malcolm, William

    The reporting of adverse drug reactions (ADRs) by health professionals forms an important component of ongoing surveillance of post-marketing drug safety. The extension of responsibility for all health professionals to report ADRs has coincided with national immunization programmes, such as the national childhood immunization, human papillomavirus (HPV), and seasonal and H1N1 influenza programmes. The study objective was to evaluate knowledge of, and attitudes to, reporting ADRs among the professional groups most likely to see suspected reactions to vaccines. This included nursing professionals, whose views have not been included in previous studies. A survey of 91 practice nurses, health visitors, school nurses and GPs working in Ayrshire and Arran during June, July and August 2007 was undertaken. The respondents' knowledge of ADR reporting varied considerably. Although the majority of respondents recognized that it is the responsibility of health professionals to report suspected ADRs, there were lower levels of knowledge about the purpose of the Yellow Card system specifically; less than 50% of the respondents reported good knowledge about the system. The study suggests implications for practice with regard to the implementation of large-scale immunization programmes and potential solutions to under-reporting among these professional groups.

  16. Epidemiology, Mechanisms, and Diagnosis of Drug-Induced Anaphylaxis

    PubMed Central

    Montañez, Maria Isabel; Mayorga, Cristobalina; Bogas, Gador; Barrionuevo, Esther; Fernandez-Santamaria, Ruben; Martin-Serrano, Angela; Laguna, Jose Julio; Torres, Maria José; Fernandez, Tahia Diana; Doña, Inmaculada

    2017-01-01

    Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators by mast cells and basophils. Although anaphylaxis is often under-communicated and thus underestimated, its incidence appears to have risen over recent decades. Drugs are among the most common triggers in adults, being analgesics and antibiotics the most common causal agents. Anaphylaxis can be caused by immunologic or non-immunologic mechanisms. Immunologic anaphylaxis can be mediated by IgE-dependent or -independent pathways. The former involves activation of Th2 cells and the cross-linking of two or more specific IgE (sIgE) antibodies on the surface of mast cells or basophils. The IgE-independent mechanism can be mediated by IgG, involving the release of platelet-activating factor, and/or complement activation. Non-immunological anaphylaxis can occur through the direct stimulation of mast cell degranulation by some drugs, inducing histamine release and leading to anaphylactic symptoms. Work-up of a suspected drug-induced anaphylaxis should include clinical history; however, this can be unreliable, and skin tests should also be used if available and validated. Drug provocation testing is not recommended due to the risk of inducing a harmful reaction. In vitro testing can help to confirm anaphylaxis by analyzing the release of mediators such as tryptase or histamine by mast cells. When immunologic mechanisms are suspected, serum-sIgE quantification or the use of the basophil activation test can help confirm the culprit drug. In this review, we will discuss multiple aspects of drug-induced anaphylaxis, including epidemiology, mechanisms, and diagnosis. PMID:28611774

  17. 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. © 2015 The British Pharmacological Society.

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

    PubMed Central

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

    2015-01-01

    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

  19. Adverse drug reactions in older people: detection and prevention.

    PubMed

    Petrovic, Mirko; van der Cammen, Tischa; Onder, Graziano

    2012-06-01

    Adverse drug reactions (ADRs) in older adults are an important healthcare problem since they are frequently a cause of hospitalization, occur commonly during admission, and are an important cause of morbidity and mortality. Older adults are particularly susceptible to ADRs because they are usually on multiple drug regimens and because age is associated with changes in pharmacokinetics and pharmacodynamics. The presentation of an ADR in older adults is often atypical, which further complicates its recognition. One potential strategy for improving recognition of ADRs is to identify those patients who are at risk of an ADR. The recently developed GerontoNet ADR Risk Score is a practical tool for identification of older patients who are at increased risk for an ADR and who may represent a target for interventions aimed at reducing ADRs. Provision of adequate education in the domain of clinical geriatric pharmacology can improve recognition of ADRs. Besides formal surveillance systems, built-in computer programs with electronic prescribing databases and clinical pharmacist involvement in patient care within multidisciplinary geriatric teams might help to minimize the occurrence of ADRs. In addition, a number of actions can be taken in hospitals to stimulate appropriate prescribing and to assure adequate communication between primary and hospital care. In older adults with complex medical problems and needs, a global evaluation obtained through a comprehensive geriatric assessment may be helpful in simplifying drug prescription and prioritizing pharmacological and healthcare needs, resulting in an improvement in quality of prescribing.

  20. Adverse drug reactions to herbal and synthetic expectorants.

    PubMed

    Ernst, E; Sieder, C; März, R

    1995-01-01

    Our knowledge relating to adverse drug reactions (ADRs) of phytomedicines is highly fragmentary. The aim of this study was to define the prevalence of ADRs following medication with herbal or synthetic expectorants. In a multicentre, comparative post-marketing surveillance study of more than 3000 patients with acute bronchitis, about half were treated with a herbal remedy (SinupretR) and the other half with various other expectorants. In ascending order of incidence, ADRs were noted during mono-medication of SinupretR (0.8%), Ambroxol (1.0%) and acetylcysteine (4.3%). When concomitant drugs were used, this rank order was unchanged but incidence rates were markedly increased (3.4, 6.5 and 8.2%, respectively). The most frequent ADRs were gastrointestinal symptoms. It is concluded that expectorants are associated with ADRs in roughly 1-5% of cases undergoing single drug treatment and in 3-10% when more than one medication is being used. Amongst the expectorants used in this study, the herbal preparation SinupretR is associated with the lowest incidence of ADRs.

  1. Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug-drug interactions: a PharmacoVigilance study in France.

    PubMed

    Danton, Anne Charlotte; Montastruc, François; Sommet, Agnès; Durrieu, Geneviève; Bagheri, Haleh; Bondon-Guitton, Emmanuelle; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis

    2013-04-01

    Our aim was to characterize Adverse Drug Reactions (ADRs) related to drug-drug interactions (DDIs) related to involvement of cytochrome P450 (CYP450) isoenzymes in a pharmacovigilance database. ADRs recorded by Midi-Pyrénées PharmacoVigilance center (France) between 1 January and 31 August 2008 were extracted from the French PharmacoVigilance Database (FPVD). Among the 1,205 reported ADRs, 16 (1.3 %), can be explained by involvement of CYP450 isoenzymes (including 4 "serious"). All interactions involved CYP inhibitors, mainly for CYP3A4/5. The percentage of ADRs reported in the pharmacovigilance database and related to CYP450-induced DDIs appears to be relatively low (~ 1-2 %).

  2. Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity.

    PubMed

    Wiley, Laura K; Moretz, Jeremy D; Denny, Joshua C; Peterson, Josh F; Bush, William S

    2015-01-01

    It is unclear the extent to which best practices for phenotyping disease states from electronic medical records (EMRs) translate to phenotyping adverse drug events. Here we use statin-induced myotoxicity as a case study to identify best practices in this area. We compared multiple phenotyping algorithms using administrative codes, laboratory measurements, and full-text keyword matching to identify statin-related myopathy from EMRs. Manual review of 300 deidentified EMRs with exposure to at least one statin, created a gold standard set of 124 cases and 176 controls. We tested algorithms using ICD-9 billing codes, laboratory measurements of creatine kinase (CK) and keyword searches of clinical notes and allergy lists. The combined keyword algorithms produced were the most accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms, addition of ICD9 codes or laboratory data did not appreciably increase algorithm accuracy. We conclude that phenotype algorithms for adverse drug events should consider text based approaches.

  3. 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.

  4. [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.

  5. Antiepileptic Drugs-induced Stevens–Johnson syndrome: A case Series

    PubMed Central

    Trivedi, Bhavi S.; Darji, Nishita H.; Malhotra, Supriya D.; Patel, Pankaj R.

    2016-01-01

    Stevens–Johnson syndrome (SJS) is an acute life-threatening mucocutaneous reaction, characterized by extensive necrosis and detachment of the epidermis from the skin. The overall incidence of SJS is seen in five cases per million people per year. SJS is typically caused by drugs and is a kind of idiosyncratic reaction. Adverse drug reactions such an SJS have a remarkable effect on patient's safety issues. We encountered nine cases of antiepileptic drug (AED)-induced SJS, specifically with carbamazepine, oxcarbazepine, and phenytoin. To manage the reaction, the clinician withdrew the drug in all 8 cases, and in 1 case, the patient was shifted to valproate and symptomatic treatment was provided. There is still a controversy whether or not all AEDs can cause SJS. Recent studies have investigated the role of genetic factors - HLAB*502 allele in the development of AED-induced SJS in patients of Asian ancestry. PMID:28104975

  6. Drug-induced liver injury due to antibiotics.

    PubMed

    Björnsson, Einar S

    Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

  7. Allergic reactions to oral drugs: A case/non-case study from an Italian spontaneous reporting database (GIF).

    PubMed

    Salvo, Francesco; Polimeni, Giovanni; Cutroneo, Paola Maria; Leone, Roberto; Confortic, Anita; Moretti, Ugo; Motola, Domenico; Tuccori, Marco; Caputi, Achille Patrizio

    2008-01-01

    Despite the wide number of studies investigating on drug-induced allergy, limited data focused on allergies associated with orally administered drugs are available. The aim of the study is to evaluate allergic drug reactions associated with oral drug use, using an Italian spontaneous reporting database of adverse drug reactions (ADRs). Spontaneous reports associated with oral drugs retrieved from seven Italian regions (GIF research group), collected from 1988 to 2006, were analysed. Association between drugs and allergic adverse reactions was assessed using the case/non-case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. Overall, 27,175 reports of adverse reactions related to oral drug use were analysed; of these, 3143 (11.6%) were judged as allergy cases. Paediatric patients (Drugs (NSAIDs) were the only two drug classes associated with a significant increase of ROR. Regarding antibiotics, cinoxacin (6.88; 95%CI 4.19-11.29) and moxifloxacin (4.20; 95% CI 3.19-5.55) were related to the highest ROR values, while propionic acid derivates (ROR 2.75; 95% CI 2.30-3.28), and in particular ibuprofen (4.20; 95% CI 3.13-5.63), have shown the highest ROR values among NSAIDs. The results of the present paper confirm the higher frequency of allergic reactions with oral antibiotics and NSAIDs, although more data are needed. Given the widespread use of these drug classes (some of them being purchased as over the counter drugs), awareness should be raised among patients and prescribers about these risks.

  8. Epidemiology of drug exposure and adverse drug reactions in two Swiss departments of internal medicine

    PubMed Central

    Fattinger, Karin; Roos, Malgorzata; Vergères, Patrice; Holenstein, Clemens; Kind, Brigitt; Masche, Urspeter; Stocker, David N; Braunschweig, Suzanne; Kullak-Ublick, Gerd A; Galeazzi, Renato L; Follath, Ferenc; Gasser, Theo; Meier, Peter J

    2000-01-01

    Aims To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. Methods Structured data regarding patient characteristics, ‘events’ (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by ‘event monitoring’ to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. Results The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1) and 9 (Q3) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8.6% of hospital days. Conclusions These data demonstrate the feasibility of the developed ‘event monitoring’ system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients. PMID:10671911

  9. Idiosyncratic Drug-Induced Liver Injury: Is Drug-Cytokine Interaction the Linchpin?

    PubMed

    Roth, Robert A; Maiuri, Ashley R; Ganey, Patricia E

    2017-02-01

    Idiosyncratic drug-induced liver injury continues to be a human health problem in part because drugs that cause these reactions are not identified in current preclinical testing and because progress in prevention is hampered by incomplete knowledge of mechanisms that underlie these adverse responses. Several hypotheses involving adaptive immune responses, inflammatory stress, inability to adapt to stress, and multiple, concurrent factors have been proposed. Yet much remains unknown about how drugs interact with the liver to effect death of hepatocytes. Evidence supporting hypotheses implicating adaptive or innate immune responses in afflicted patients has begun to emerge and is bolstered by results obtained in experimental animal models and in vitro systems. A commonality in adaptive and innate immunity is the production of cytokines, including interferon-γ (IFNγ). IFNγ initiates cell signaling pathways that culminate in cell death or inhibition of proliferative repair. Tumor necrosis factor-α, another cytokine prominent in immune responses, can also promote cell death. Furthermore, tumor necrosis factor-α interacts with IFNγ, leading to enhanced cellular responses to each cytokine. In this short review, we propose that the interaction of drugs with these cytokines contributes to idiosyncratic drug-induced liver injury, and mechanisms by which this could occur are discussed. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Drug-Provoked Psoriasis: Is It Drug Induced or Drug Aggravated?

    PubMed Central

    Kim, Grace K.

    2010-01-01

    Psoriasis is a commonly encountered dermatosis with a variety of internal and external paradoxical factors contributing to the clinical course of the disease. There are several drugs described in the literature that have been associated with the initiation, exacerbation, and aggravation of psoriasis. Understanding the pathophysiology can provide clues to treatment and management of drug-induced and drug-aggravated psoriasis, which may be indistinguishable from idiopathic psoriasis. The clinical manifestations of drug-associated psoriasis can range from plaque-type psoriasis to severe erythroderma, thus warranting astute and sustained clinical observation. PMID:20725536

  11. 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.

  12. [DRUGS-INDUCED URTICARIA AND ANGIOEDEMA].

    PubMed

    Braire-Bourrel, Marion; Augey, Frédéric; Doutre, Marie-Sylvie

    2015-09-01

    Drug-induced urticaria and/or angioedema is a frequent issue encountered in family medicine. A specific collection of the anamnesis and of the general context is very important to appreciate the involved mechanism, allergic or not, and potential cofactors. If in doubt about an allergic mechanism, tests will be conducted, mostly under a hospital setting. Bradykinin-mediated angioedema, so much rare than histamine-mediated one, has to be known, because it is potentially lethal. It is often iatrogenic (ACE inhibitors especially). At the end of the allergology work-up, a course of action is proposed to the patient and his family practitioner as far as the rechallenge of the drug is concerned, In case of non-allergic urticaria, much more frequent than allergy, taking the drug is possible with a premedication with antihistamines.

  13. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation.

    PubMed

    Riyaz, Najeeba; Sarita, S; Arunkumar, G; Sabeena, S; Manikoth, Neeraj; Sivakumar, C P

    2012-01-01

    A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR) on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6). Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS) was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  14. Drug-induced Angle-Closure Glaucoma

    PubMed Central

    Khurana, Aruj K; Khurana, Bhawna

    2012-01-01

    Drug-induced angle-closure glaucoma is an important entity for the ophthalmologist as well as the general physician as it represents a preventable cause of potential blindness. This brief review highlights the fact that a high index of suspicion, in a susceptible individual followed by confirmation on appropriate imaging modality (UBM, ultrasound or anterior segment OCT) can alleviate the threat to sight and also help to institute appropriate therapy. PMID:27990064

  15. Drug-induced mitochondrial dysfunction and cardiotoxicity

    PubMed Central

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

    2015-01-01

    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

  16. [Iatrogenic and drug-induced hypertension].

    PubMed

    Mounier-Vehier, Claire; Boudghène, Fanny; Claisse, Gonzague; Delsart, Pascal

    2015-06-01

    Various toxic or drug agents can induce arterial hypertension, aggravate or limit the efficiency of anti-hypertensive drugs. Iatrogenic and drug-induced hypertension should be well known by the clinicians and the pharmacists, given the impact for driving the management of patients. In the food, an excessive alcohol consumption (more than 30 g per day) and more rarely glycerizine (active ingredient of the licorice) should be systematically looked for in front of a recent hypertension or do not respond to usual treatment. In the list of offending medicines, we must remember ethinyl estradiol contained in the contraception (oral, vaginal ring or transcutaneous patch), non steroidal anti-inflammatory drugs, immunosuppressants (cyclosporine, tacrolimus), vascular endothelial growth factor and its receptor R2 (avastin, inhibitors of receptor tyrosine kinases), recombinant human erythropoietin, sympathomimetics (nasal decongestants), anabolic steroids, bromocriptine (inhibitor of lactation), psychotropes (tricyclics antidepressants, monoamine oxydase inhibitors). The diagnosis of iatrogenic hypertensions should be systematically suspected in front of a suggestive clinical context with a meticulous food questioning because these hypertensions are partially or fully reversible after exposure stops.

  17. Muscle spasms: an unexpected adverse drug reaction of pemetrexed?

    PubMed Central

    de Rouw, Hendrika J. A.; Jessurun, Naomi T.; Masen-Poos, Lucie J. P.; Derijks, Hieronymus J.

    2016-01-01

    In this report we describe a 53-year-old woman with advanced non-small cell lung cancer, treated with pemetrexed and cisplatin combination therapy, followed by pemetrexed monotherapy. The patient developed severe muscle spasms at least twice, shortly after administration of pemetrexed monotherapy. A possible explanation for this observation is that in combination with cisplatin therapy, the patient was hyperhydrated before administration to promote renal excretion and reduce toxicity. Pemetrexed is also renally excreted, which supports the finding that toxicity did not occur when the patient was hyperhydrated. After discontinuation of pemetrexed the symptoms did not reoccur. All aspects of this case point to a possible relationship between pemetrexed and an adverse drug reaction (ADR). We conclude that muscle spasms are a rare, but possibly dose-related ADR of pemetrexed-based therapy. PMID:28203304

  18. Mechanistic review of drug-induced steatohepatitis.

    PubMed

    Schumacher, Justin D; Guo, Grace L

    2015-11-15

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Drug Induced Hearing Loss: Researchers Study Strategies to Preserve Hearing

    MedlinePlus

    ... JavaScript on. Feature: Drug-Induced Hearing Loss Researchers Study Strategies to Preserve Hearing Past Issues / Spring 2016 Table ... Read More "Drug Induced Hearing Loss" Articles Researchers Study Strategies to Preserve Hearing / What Is Ototoxicity? Spring 2016 ...

  20. Improving the reporting of adverse drug reactions in the hospital setting.

    PubMed

    Pushkin, Richard; Frassetto, Lynda; Tsourounis, Candy; Segal, Eleanor S; Kim, Stephanie

    2010-11-01

    The US Food and Drug Administration (FDA) is perceived by the public as having a substantial responsibility to ensure drug safety; however, the FDA has limited resources for active surveillance and relies on voluntary reporting of adverse events and potential adverse drug reactions. Studies have shown that underreporting of adverse events and adverse drug reactions is widespread. Furthermore, a review of several studies demonstrates that most adverse drug reactions are reported by pharmacists and nurses, with physicians reporting the fewest. The hospital setting, with its clearly defined patient population observed around the clock, is an ideal setting in which to identify potential adverse drug reaction signals and to report them to either the drug manufacturer or the FDA. In this article we describe the present system for addressing adverse events, obstacles to reporting them, and the important role any hospital physician could play in reporting adverse events and potential adverse drug reactions.

  1. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Teicoplanin: A Case Report.

    PubMed

    Ebrahimpour, Sholeh; Mohammadi, Mehdi; Gholami, Kheirollah

    2017-12-01

    Intramuscular teicoplanin (400 mg every 12 h for three doses, then 400 mg daily, intramuscularly) was prescribed for a 37-year-old woman with presumptive diagnosis of cellulitis. On the 14th day of treatment, she developed generalized maculopapular rash, accompanied by fever, wheezing, shortening of breath, and lymphadenopathy. Lab tests revealed abnormal liver enzymes, leukocytosis, and eosinophilia. The treatment was interrupted with suspicion of drug reaction. Fever subsided after 48 h. Skin eruption and respiratory symptoms began to resolve within 2 weeks. The follow-up lab tests performed 1 month later indicated resolution of liver dysfunction. With respect to delayed onset of symptoms including fever, generalized rash, lymphadenopathy, and organ involvement, drug reaction with eosinophilia and systemic symptoms (DRESS) was highly suspected. The causality was evaluated by conventional scoring systems. The reaction was rated as probable (score = 5) according to RegiSCAR and possible (score = 5) based on Kardaun et al.'s scoring system. However, DRESS was not confirmed by the Japanese group's criteria for diagnosis of DRESS/drug-induced hypersensitivity syndrome (DIHS).

  2. 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.

  3. Adverse drug reactions in special populations – the elderly

    PubMed Central

    Davies, E A; O’Mahony, M S

    2015-01-01

    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

  4. Early identification of adverse drug reactions from search log data.

    PubMed

    White, Ryen W; Wang, Sheng; Pant, Apurv; Harpaz, Rave; Shukla, Pushpraj; Sun, Walter; DuMouchel, William; Horvitz, Eric

    2016-02-01

    The timely and accurate identification of adverse drug reactions (ADRs) following drug approval is a persistent and serious public health challenge. Aggregated data drawn from anonymized logs of Web searchers has been shown to be a useful source of evidence for detecting ADRs. However, prior studies have been based on the analysis of established ADRs, the existence of which may already be known publically. Awareness of these ADRs can inject existing knowledge about the known ADRs into online content and online behavior, and thus raise questions about the ability of the behavioral log-based methods to detect new ADRs. In contrast to previous studies, we investigate the use of search logs for the early detection of known ADRs. We use a large set of recently labeled ADRs and negative controls to evaluate the ability of search logs to accurately detect ADRs in advance of their publication. We leverage the Internet Archive to estimate when evidence of an ADR first appeared in the public domain and adjust the index date in a backdated analysis. Our results demonstrate how search logs can be used to detect new ADRs, the central challenge in pharmacovigilance.

  5. 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

  6. A perspective of nanotechnology in hypersensitivity reactions including drug allergy.

    PubMed

    Montañez, Maria Isabel; Ruiz-Sanchez, Antonio J; Perez-Inestrosa, Ezequiel

    2010-08-01

    We provide an overview of the application of the concepts of nanoscience and nanotechnology as a novel scientific approach to the area of nanomedicine related to the domain of the immune system. Particular emphasis will be paid to studies on drug allergy reactions. Several well defined chemical structures arranged in the dimension of the nanoscale are currently being studied for biomedical purposes. By interacting with the immune system, some of these show promising applications as vaccines, diagnostic tools and activators/effectors of the immune response. Even a brief listing of some key applications of nanostructured materials shows how broad and intense this area of nanomedicine is. As a result of the development of nanoscience and nanotechnology applied to medicine, new approaches can be envisioned for problems related to the modulation of the immune response, as well as in immunodiagnosis, and to design new tools to solve related medical challenges. Nanoparticles offer unique advantages with which to exploit new properties and for materials to play a major role in new diagnostic techniques and therapies. Fullerene-C60 and multivalent functionalized gold nanoparticles of various sizes have led to new tools and opened up new ways to study and interact with the immune system. Some of the most versatile nanostructures are dendrimers. In their interaction with the immune system they can naturally occurring macromolecules, taking advantage of the fact that dendrimers can be synthesized into nanosized structures. Their multivalence can be successfully exploited in vaccines and diagnostic tests for allergic reactions.

  7. Mining unexpected temporal associations: applications in detecting adverse drug reactions.

    PubMed

    Jin, Huidong Warren; Chen, Jie; He, Hongxing; Williams, Graham J; Kelman, Chris; O'Keefe, Christine M

    2008-07-01

    In various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. The MUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.

  8. Electron-induced hydration of an alkene: alternative reaction pathways.

    PubMed

    Warneke, Jonas; Wang, Ziyan; Swiderek, Petra; Bredehöft, Jan Hendrik

    2015-03-27

    Electron-induced reactions in condensed mixtures of ethylene and water lead to the synthesis of ethanol, as shown by post-irradiation thermal desorption spectrometry (TDS). Interestingly, this synthesis is not only induced by soft electron impact ionization similar to a previously observed electron-induced hydroamination but also, at low electron energy, by electron attachment to ethylene and a subsequent acid/base reaction with water.

  9. Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches.

    PubMed

    Matsuno, Osamu

    2012-05-31

    Drug-induced interstitial lung disease (DILD) is not uncommon and has many clinical patterns, ranging from benign infiltrates to life-threatening acute respiratory distress syndrome. There are two mechanisms involved in DILD, which are probably interdependent: one is direct, dose-dependent toxicity and the other is immune-mediated. Cytotoxic lung injury may result from direct injury to pneumocytes or the alveolar capillary endothelium. Drugs can induce all types of immunological reactions described by Gell and Coombs; however, most reactions in immune-mediated DILD may be T cell-mediated. DILD can be difficult to diagnose; diagnosis is often possible by exclusion alone. Identifying the causative drug that induces an allergy or cytotoxicity is essential for preventing secondary reactions. One method to confirm the diagnosis of a drug-induced disease is re-exposure or re-test of the drug. However, clinicians are reluctant to place patients at further risk of illness, particularly in cases with severe drug-induced diseases. Assessment of cell-mediated immunity has recently increased, because verifying the presence or absence of drug-sensitized lymphocytes can aid in confirmation of drug-induced disease. Using peripheral blood samples from drug-allergic patients, the drug-induced lymphocyte stimulation test (DLST) and the leukocyte migration test (LMT) can detect the presence of drug-sensitized T cells. However, these tests do not have a definite role in the diagnosis of DILD. This study explores the potential of these new tests and other similar tests in the diagnosis of DILD and provides a review of the relevant literature on this topic.

  10. Pharmacogenomics and active surveillance for serious adverse drug reactions in children.

    PubMed

    Loo, Tenneille T; Ross, Colin J D; Sistonen, Johanna; Visscher, Henk; Madadi, Parvaz; Koren, Gideon; Hayden, Michael R; Carleton, Bruce C

    2010-09-01

    Juxtaposing clinical pharmacology with human genetics, pharmacogenomics utilizes a patient's genetic information to identify genetic variants that have the potential to provide clinically relevant predictions of toxicity and efficacy. The goal is to develop personalized and genetic-based predictions of an individual's drug response and likelihood of experiencing an adverse drug reaction. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has implemented active adverse drug reaction surveillance to monitor and discover genetic markers related to serious adverse drug reactions in the pediatric population. Evidence-based pharmacogenomics research will inform public policy and influence drug benefit-risk decision-making. Regulatory processes and future challenges in pharmacogenomics research will be discussed.

  11. Reactions of buffers in cyanogen bromide-induced ligations.

    PubMed

    Vogel, Heike; Gerlach, Claudia; Richert, Clemens

    2013-01-01

    Rapid, template-directed ligation reactions between a phosphate-terminated oligonucleotide and an unphosphorylated reaction partner may be induced by cyanogen bromide (BrCN). Frequently, however, the reaction is low yielding, and even a large excess of the condensing agent can fail to induce quantitative conversions. In this study, we used BrCN to induce chemical primer extension reactions. Here, we report that buffers containing hydroxyl groups react with short oligodeoxynucleotides in the presence of BrCN. One stable adduct between HEPBS buffer and cytosine was characterized by mass spectrometry and NMR after HPLC purification, indicating that a side reaction occurred at this nucleobase. Further, a first example of a primer extension reaction between an unmodified oligodeoxynucleotide as primer and dGMP is reported. Together, our results shed light on the potency, as well as the drawbacks of BrCN as a highly reactive condensing reagent for the ligation of unmodified nucleic acids.

  12. 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

  13. Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India.

    PubMed

    Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha

    2016-01-01

    The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society.

  14. Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India

    PubMed Central

    Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha

    2016-01-01

    Objectives: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Materials and Methods: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. Results: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. Conclusions: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society. PMID:27721535

  15. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    PubMed

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Awareness among nurses about reporting of adverse drug reactions in Sweden

    PubMed Central

    Ekman, Elisabet; Petersson, Göran; Tågerud, Sven; Bäckström, Martin

    2012-01-01

    Background The purpose of this study was to investigate awareness among nurses regarding their new role as reporters of adverse drug reactions in Sweden and factors that may influence reporting by nurses. Methods In 2007, all nurses were included in the adverse drug reaction reporting scheme in Sweden. A questionnaire was sent to 753 randomly selected nurses in September 2010. Results Of the 453 (60%) responding nurses, 265 (58%) were aware that nurses were included in the reporting of adverse drug reactions. Sixty-one nurses (14%) stated that they had reported an adverse drug reaction. Fifteen percent (n = 70) of the respondents had received training about reporting of adverse drug reactions. Almost one third of these (n = 21, 30%) had reported an adverse drug reaction on at least one occasion. Among nurses without training, a smaller proportion (n = 40, 11%, P < 0.05) had reported an adverse drug reaction on at least one occasion. The two factors considered most important by nurses for reporting were the severity of the adverse drug reaction and if the reaction was to a newly approved drug. A majority of the nurses (n = 397, 88%) were interested in a training course in pharmacology as part of their ongoing professional development. One third (32%) of all nurses stated that one reason for not reporting a suspected adverse drug reaction was that the physician responsible did not regard the reaction necessary to report. Conclusion We found that more than half of the study population of nurses in Sweden were aware of their new role as reporters of adverse drug reactions, but few of the responding nurses had reported an adverse drug reaction. Given that training seems to be associated with high reporting frequency, we suggest more training in pharmacovigilance for nurses. PMID:22826643

  17. Advances in understanding drug-induced neuropathies.

    PubMed

    Peltier, Amanda C; Russell, James W

    2006-01-01

    Many commonly used medications have neurotoxic adverse effects; the most common of these is peripheral neuropathy. Neuropathy can be a dose-limiting adverse effect for many medications used in life-threatening conditions, such as malignancy and HIV-related disease. Epidemiological evidence supports previous case reports of HMG-CoA reductase inhibitors (or 'statins') causing an axonal sensorimotor neuropathy or a purely small-fibre neuropathy in some patients. The neuropathy improves when the medication is withdrawn. Despite the association between HMG-CoA reductase inhibitors and neuropathy, the risk is low compared with the significant vascular protective benefits. Oxaliplatin, a new platinum chemotherapy agent designed to have fewer adverse effects than other such agents, has been shown to cause a transient initial dysaesthesia in addition to an axonal polyneuropathy. Thalidomide, an old therapy currently being utilised for new therapeutic indications (e.g. treatment of haematological malignancies), is associated with a painful, axonal sensorimotor neuropathy that does not improve on withdrawal of the drug. Nucleoside reverse transcriptase inhibitors are important components of highly active antiretroviral therapy, but are associated with a sensory neuropathy that is likely to be due to a direct effect of these drugs on mitochondrial DNA replication. New research demonstrates that lactate levels may help discriminate between neuropathy caused by nucleoside analogues and HIV-induced neuropathy. Understanding the mechanism of drug-induced neuropathy has led to advances in preventing this disabling condition.

  18. Drug-Induced Anaphylaxis in Latin American Countries.

    PubMed

    Jares, Edgardo José; Baena-Cagnani, Carlos E; Sánchez-Borges, Mario; Ensina, Luis Felipe C; Arias-Cruz, Alfredo; Gómez, Maximiliano; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos; Monsell, Silvana; Schuhl, Juan; Cardona-Villa, Ricardo

    2015-01-01

    Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P < .01). Severe DIA was less frequent with underlying asthma (N = 22 vs 35 [38.6% vs 61.4%], P < .05) or atopy (N = 62 vs 71 [43% vs 59% ], P < .01). Nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 178 [57.8%]), beta-lactam antibiotics (N = 44 [14.3%]), and other antibiotics (N = 16 [5.2%]) were the most frequently implicated drug classes. Anaphylaxis was rated as severe in N = 133 (50.4%) and anaphylactic shock (AS) was present in N = 90 (34.1%). Epinephrine was only used in N = 73 (27.6%) overall, but in N = 70 (77.8%) of patients with AS. In Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve

  19. 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.

  20. Morphological changes of amphiphilic molecular assemblies induced by chemical reactions.

    PubMed

    Nakagawa, Koh M; Noguchi, Hiroshi

    2015-02-04

    Shape transformations of amphiphilic molecular assemblies induced by chemical reactions are studied using coarse-grained molecular simulations. A binding reaction between hydrophilic and hydrophobic molecules is considered. It is found that the reaction induces transformation of an oil droplet to a tubular vesicle via bicelles and vesicles with discoidal arms. The discoidal arms close into vesicles, which are subsequently fused into the tubular vesicle. Under the chemical reaction, the bicelle-to-vesicle transition occurs at smaller sizes than in the absence of the hydrophobic molecules. It is revealed that the enhancement of this transition is due to embedded hydrophobic particles that reduce the membrane bending rigidity.

  1. Evaluation of the Effects of Pharmacist Intervention for Adverse Drug Reaction Detection and Exacerbation Avoidance.

    PubMed

    Imaura, Masaharu; Yamaya, Takeshi; Uehara, Nozomi; Mano, Narutoshi; Nagase, Satoshi; Kimura, Koji; Kanno, Hiroshi; Yamada, Yasuhiko

    2017-01-01

     We evaluated the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, as well as the severity and outcome of reactions based on analyses of pharmacist involvement in a collaborative approach to medicine. Of 5436 cases with pharmacist involvement, adverse drug reaction prevention was seen in 440, accounting for 8.1%, and exacerbation avoidance in 213, accounting for 3.9%. We concluded that pharmacist involvement contributes to detect adverse drug reactions and avoid exacerbation, and improves pharmacotherapy safety. We also analyzed 131 cases in which the course after intervention was followed. When categorized by adverse drug reaction severity, Grade 1 and 2 were the same at 45.8%, Grade 3 at 8.4%, respectively. Those findings suggested that pharmacist intervention contributes to early detection of an adverse drug reaction. Also, the relationship between clues for detecting adverse drug reactions by a pharmacist and their severity showed that objective evaluations such as clinical laboratory test results, physical assessments and medication history were important for detecting reactions that became more serious. Patients recovered or recovering from an adverse reaction comprised 76.4%, indicating that pharmacist intervention contributed to exacerbation avoidance and improvement. Our findings revealed the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, and for safety improvement of pharmacotherapy. Additionally, we considered it necessary for the future pharmacist intervention to improve skills of assessing an adverse drug reaction objectively.

  2. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

    Drug hypersensitivity represents an immune-mediated reaction to a drug. Although several drug hypersensitivity reactions are confined to the skin and rather mild, some may be life threatening and also involve further organs such as liver, kidney and bone marrow. The exact pathogenesis of many drug hypersensitivity reactions is still obscure. In this review the concepts on how small molecular drugs can activate the immune system are discussed and the hapten, prohapten and p-i concept are explained. Furthermore, the classification of drug hypersensitivity reactions and some common and severe clinical manifestations of drug-induced T cell mediated reactions are presented.

  3. Postmarket Drug Surveillance Without Trial Costs: Discovery of Adverse Drug Reactions Through Large-Scale Analysis of Web Search Queries

    PubMed Central

    Gabrilovich, Evgeniy

    2013-01-01

    Background Postmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; hence, less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery. Objective Here we propose a low cost, fully automated method for continuous monitoring of adverse drug reactions in single drugs and in combinations thereof, and demonstrate the discovery of heretofore-unknown ones. Methods We used aggregated search data of large populations of Internet users to extract information related to drugs and adverse reactions to them, and correlated these data over time. We further extended our method to identify adverse reactions to combinations of drugs. Results We validated our method by showing high correlations of our findings with known adverse drug reactions (ADRs). However, although acute early-onset drug reactions are more likely to be reported to regulatory agencies, we show that less acute later-onset ones are better captured in Web search queries. Conclusions Our method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials. PMID:23778053

  4. 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

  5. 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.

  6. Drug-induced hyponatremia: an updated review.

    PubMed

    Ramos-Levi, A M; Duran Rodriguez-Hervada, A; Mendez-Bailon, M; Marco-Martinez, J

    2014-03-01

    Hyponatremia, defined as serum sodium concentrations <135 mmol/L, is the most frequent electrolyte disturbance observed in both hospitalized and ambulatory patients, and has been associated to relevant negative consequences regarding morbidity and mortality. Drug-induced hyponatremia has been widely observed. However, since it may be clinically symptomatic or asymptomatic, it is frequently an underdiagnosed condition. This review aims to highlight the main drugs involved in the pathophysiology of hyponatremia, which should be considered in the differential diagnosis when approaching a patient with hyponatremia. We discuss their impact and relative importance. In order to prevent undesirable negative consequences we also emphasize the need for awareness of this clinically-relevant adverse effect, and we suggest how clinical management of patients may be approached.

  7. Artificial Force Induced Reaction Method for Systematic Determination of Complex Reaction Mechanisms.

    PubMed

    Sameera, W M C; Kumar Sharma, Akhilesh; Maeda, Satoshi; Morokuma, Keiji

    2016-10-01

    Nowadays, computational studies are very important for the elucidation of reaction mechanisms and selectivity of complex reactions. However, traditional computational methods usually require an estimated reaction path, mainly driven by limited experimental implications, intuition, and assumptions of stationary points. However, the artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy can be used for unbiased and automatic reaction path searches for complex reactions. In this account, we highlight applications of the AFIR method to a variety of reactions (organic, organometallic, enzymatic, and photochemical) of complex molecular systems. In addition, the AFIR method has been successfully used to rationalise the origin of stereo- and regioselectivity. The AFIR method can be applied from small to large molecular systems, and will be a very useful tool for the study of complex molecular problems in many areas of chemistry, biology, and material sciences.

  8. 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

  9. Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

    PubMed Central

    Bracken, Louise E.; Nunn, Anthony J.; Kirkham, Jamie J.; Peak, Matthew; Arnott, Janine; Smyth, Rosalind L.; Pirmohamed, Munir; Turner, Mark A.

    2017-01-01

    Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than

  10. Imputation of adverse drug reactions: Causality assessment in hospitals.

    PubMed

    Varallo, Fabiana Rossi; Planeta, Cleopatra S; Herdeiro, Maria Teresa; Mastroianni, Patricia de Carvalho

    2017-01-01

    Different algorithms have been developed to standardize the causality assessment of adverse drug reactions (ADR). Although most share common characteristics, the results of the causality assessment are variable depending on the algorithm used. Therefore, using 10 different algorithms, the study aimed to compare inter-rater and multi-rater agreement for ADR causality assessment and identify the most consistent to hospitals. Using ten causality algorithms, four judges independently assessed the first 44 cases of ADRs reported during the first year of implementation of a risk management service in a medium complexity hospital in the state of Sao Paulo (Brazil). Owing to variations in the terminology used for causality, the equivalent imputation terms were grouped into four categories: definite, probable, possible and unlikely. Inter-rater and multi-rater agreement analysis was performed by calculating the Cohen´s and Light´s kappa coefficients, respectively. None of the algorithms showed 100% reproducibility in the causal imputation. Fair inter-rater and multi-rater agreement was found. Emanuele (1984) and WHO-UMC (2010) algorithms showed a fair rate of agreement between the judges (k = 0.36). Although the ADR causality assessment algorithms were poorly reproducible, our data suggest that WHO-UMC algorithm is the most consistent for imputation in hospitals, since it allows evaluating the quality of the report. However, to improve the ability of assessing the causality using algorithms, it is necessary to include criteria for the evaluation of drug-related problems, which may be related to confounding variables that underestimate the causal association.

  11. Imputation of adverse drug reactions: Causality assessment in hospitals

    PubMed Central

    Mastroianni, Patricia de Carvalho

    2017-01-01

    Background & objectives Different algorithms have been developed to standardize the causality assessment of adverse drug reactions (ADR). Although most share common characteristics, the results of the causality assessment are variable depending on the algorithm used. Therefore, using 10 different algorithms, the study aimed to compare inter-rater and multi-rater agreement for ADR causality assessment and identify the most consistent to hospitals. Methods Using ten causality algorithms, four judges independently assessed the first 44 cases of ADRs reported during the first year of implementation of a risk management service in a medium complexity hospital in the state of Sao Paulo (Brazil). Owing to variations in the terminology used for causality, the equivalent imputation terms were grouped into four categories: definite, probable, possible and unlikely. Inter-rater and multi-rater agreement analysis was performed by calculating the Cohen´s and Light´s kappa coefficients, respectively. Results None of the algorithms showed 100% reproducibility in the causal imputation. Fair inter-rater and multi-rater agreement was found. Emanuele (1984) and WHO-UMC (2010) algorithms showed a fair rate of agreement between the judges (k = 0.36). Interpretation & conclusions Although the ADR causality assessment algorithms were poorly reproducible, our data suggest that WHO-UMC algorithm is the most consistent for imputation in hospitals, since it allows evaluating the quality of the report. However, to improve the ability of assessing the causality using algorithms, it is necessary to include criteria for the evaluation of drug-related problems, which may be related to confounding variables that underestimate the causal association. PMID:28166274

  12. Pharmacokinetic patterns of risperidone-associated adverse drug reactions.

    PubMed

    Schoretsanitis, Georgios; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Schruers, Koen R J; Walther, Sebastian; Lammertz, Sarah E; Haen, Ekkehard; Paulzen, Michael

    2016-09-01

    The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398). Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64 mg/day) than patients without ADRs (4.40 mg/day). No differences were found for active moiety plasma concentrations between the groups (p = 0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by-dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78 ng/mL/mg) than in patients without ADRs (4.3 ng/mL/mg) (p = 0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p = 0.697). Our findings are consistent with previous data supporting a prominent role of 9-hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis.

  13. A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital

    PubMed Central

    MARTÍNEZ-MIR, I.; GARCÍA-LÓPEZ, M.; PALOP, V.; FERRER, J. M.; ESTAÑ, L.; RUBIO, E.; MORALES-OLIVAS, F. J.

    1996-01-01

    1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42). 5The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group. PMID:8877022

  14. 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

  15. [Drug-induced interstitial lung disease].

    PubMed

    Gemma, Akihiko

    2008-10-01

    There was limited knowledge about drug-induced ILD(DILD), when safety reports of acute ILD-type events in gefitinib-treated patients appeared in Japan. There is a need to better understand DILD including event incidence on different treatments and risk factors for developing DILD. Some studies using recent advances in imaging, molecular examination, and pathology are designed and conducted by an independent academic team to define the risk and increase understanding of ILD of various agents in a postmarketing surveillance. These studies may help to shed light on the underlying mechanisms of DILD and appropriate strategies for such events.

  16. Drug-Induced Liver Disease: Clinical Course.

    PubMed

    Saithanyamurthi, Hemamala; Faust, Alison Jazwinski

    2017-02-01

    Drug-induced liver injury (DILI) is a term used to describe a spectrum of clinical presentations and severity that ranges from mild elevation of liver enzymes on routine blood work to acute liver failure and death. Approximately 10% of all patients with DILI develop acute liver failure resulting in death or liver transplantation. DILI may be prolonged with persistence of elevated liver enzymes for longer than 6 months in approximately 5% to 20% of cases. Cirrhosis and long-term liver-related morbidity and mortality have also been described but are rare, occurring in 1% to 3% of cases.

  17. 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.

  18. 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.

  19. Alcohol and Drugs in Schools: Teachers' Reactions to the Problem

    ERIC Educational Resources Information Center

    Finn, Kristin V.; Willert, H. Jeannette

    2006-01-01

    Although schools are places for learning and growth, they are also places where students engage in alcohol and drug use. This study showed that most teachers were aware of drugs in their schools, but did not regard drug use as an interference in their own classrooms. Many teachers were knowledgeable about their schools' drug policy, but did not…

  20. 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.

  1. Adverse drug reactions in hospitals: a narrative review.

    PubMed

    Davies, Emma C; Green, Christophe F; Mottram, David R; Pirmohamed, Munir

    2007-01-01

    The serious nature of adverse drug reactions (ADRs) has been highlighted in a number of instances over the last forty years, the most recent of these being the occurrence of serious thrombotic events with the use of COX-2 inhibitors. ADRs are estimated to be between the 4(th) and 6(th) leading cause of death in the USA, with fatal ADRs occurring in 0.32% of patients. A recent UK study showed that 6.5% of hospital admissions were related to ADRs. ADRs can therefore be regarded as a significant public health and economic problem. There is an urgent need to develop better preventive strategies to reduce the burden of ADRs. Because ADRs can affect any bodily system, can have many different clinical presentations, and are of widely variable severity, prevention will not be easy and will have to be multifactorial in its approach. This paper reviews the epidemiology of ADRs in hospitals and evaluates the research that has been undertaken to date to prevent ADRs.

  2. Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

    PubMed Central

    Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M.; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

    2013-01-01

    Introduction: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. Materials and Methods: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. Results: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Discussion and Conclusion: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health. PMID:24347986

  3. Drug-induced liver injury in children.

    PubMed

    Amin, Mansi D; Harpavat, Sanjiv; Leung, Daniel H

    2015-10-01

    Drug-induced liver injury (DILI) is an underrecognized cause of pediatric liver disease, accounts for almost 20% of pediatric acute liver failure cases, and is a major reason for liver transplantation in the USA. This article reviews the pathogenesis of DILI, approach to diagnosis and management, and highlights recent pediatric DILI case series. Select individuals have an increased propensity to develop DILI. Known genetic polymorphisms of enzymes and host factors play an important role in medication management and influence the clinical outcome in 20-25% of all drug therapies. Children are more likely to have mitochondrial dysfunction from drugs, increasing their susceptibility to severe liver injury or acute liver failure. Antibiotics and central nervous system agents account for the majority of pediatric DILI in the West, although herbals are becoming more common. Clinical features of DILI vary and overlap so exclusion of other conditions, identification of latency period and risk factors, and use of a searchable database can aid evaluation. Treatment consists of cessation of the offending agent and supportive care. Areas needing further research include elucidating mechanisms, identifying at risk individuals, and therapeutic interventions.

  4. Drug-induced abnormalities of potassium metabolism.

    PubMed

    Kokot, Franciszek; Hyla-Klekot, Lidia

    2008-01-01

    Pharmacotherapy has progressed rapidly over the last 20 years with the result that general practioners more and more often use drugs which may influence potassium metabolism at the kidney or gastrointestinal level, or the transmembrane transport of potassium at the cellular level. Potassium abnormalities may result in life-theatening clinical conditions. Hypokalemia is most frequently caused by renal loss of this electrolyte (thiazide, thiazide-like and loop diuretics, glucocorticoids) and the gastrointestinal tract (laxatives, diarrhea, vomiting, external fistula), and may be the result of an increased intracellular potassium influx induced by sympathicomimetics used mostly by patients with asthma, or by insulin overdosage in diabetic subjects. The leading symptoms of hypokalemia are skeletal and smooth muscle weakness and cardiac arrhythmias. Hyperkalemia may be caused by acute or end-stage renal failure, impaired tubular excretion of potassium (blockers of the renin-angiotensin-aldosterone system, nonsteroidal anti-inflammatory drugs, cyclosporine, antifungal drugs, potassium sparing diuretics), acidemia, and severe cellular injury (tumor lysis syndrome). Hyperkalemia may be the cause of severe injury of both skeletal and smooth muscle cells. The specific treatment counteracting hyperkalemia is a bolus injection of calcium salts and, when necessary, hemodialysis.

  5. Drug-induced regeneration in adult mice

    PubMed Central

    Zhang, Yong; Strehin, Iossif; Bedelbaeva, Khamilia; Gourevitch, Dmitri; Clark, Lise; Leferovich, John; Messersmith, Phillip B.; Heber-Katz, Ellen

    2015-01-01

    Whereas amphibians regenerate lost appendages spontaneously, mammals generally form scars over the injury site through the process of wound repair. The MRL mouse strain is an exception among mammals because it shows a spontaneous regenerative healing trait and so can be used to investigate proregenerative interventions in mammals. We report that hypoxia-inducible factor 1α (HIF-1α) is a central molecule in the process of regeneration in adult MRL mice. The degradation of HIF-1α protein, which occurs under normoxic conditions, is mediated by prolyl hydroxylases (PHDs). We used the drug 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), a PHD inhibitor, to stabilize constitutive expression of HIF-1α protein. A locally injectable hydrogel containing 1,4-DPCA was designed to achieve controlled delivery of the drug over 4 to 10 days. Subcutaneous injection of the 1,4-DPCA/hydrogel into Swiss Webster mice that do not show a regenerative phenotype increased stable expression of HIF-1α protein over 5 days, providing a functional measure of drug release in vivo. Multiple peripheral subcutaneous injections of the 1,4-DPCA/hydrogel over a 10-day period led to regenerative wound healing in Swiss Webster mice after ear hole punch injury. Increased expression of the HIF-1α protein may provide a starting point for future studies on regeneration in mammals. PMID:26041709

  6. Drug-induced erythrocyte membrane internalization.

    PubMed

    Ben-Bassat, I; Bensch, K G; Schrier, S L

    1972-07-01

    In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) 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.

  7. 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

  8. Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

    PubMed

    Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

    2016-11-01

    Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions.

  9. Drug Induced Pneumonitis Secondary to Treatment with Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK®) for Chronic Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction

    PubMed Central

    Faire, Bridget; Gane, Edward

    2017-01-01

    VIEKIRA PAK (ritonavir-boosted paritaprevir/ombitasvir and dasabuvir) is an approved treatment for compensated patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection. This oral regimen has minimal adverse effects and is well tolerated. Cure rates are 97% in patients infected with HCV GT 1a and 99% in those with HCV GT 1b. We report the first case of life-threatening allergic pneumonitis associated with VIEKIRA PAK. This unexpected serious adverse event occurred in a 68-year-old Chinese female with genotype 1b chronic hepatitis C and Child-Pugh A cirrhosis. One week into treatment with VIEKIRA PAK without ribavirin, she was admitted to hospital with respiratory distress and acute kidney injury requiring intensive care input. She was initially diagnosed with community acquired pneumonia and improved promptly with intravenous antibiotics and supported care. No bacterial or viral pathogens were cultured. Following complete recovery, she recommenced VIEKIRA PAK but represented 5 days later with more rapidly progressive respiratory failure, requiring intubation and ventilation, inotropic support, and haemodialysis. The final diagnosis was drug induced pneumonitis. PMID:28408931

  10. 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

  11. Plasmapheresis for Refractory Pruritus due to Drug-Induced Cholestasis

    PubMed Central

    Al-Azzawi, Hasan; Patel, Ruchi; Sood, Gagan; Kapoor, Sumit

    2016-01-01

    Pruritus can be a distressing symptom seen in various cholestatic disorders. It is treated with medications like bile acid sequestrants. Drug-induced cholestasis usually resolves with withdrawal of the causative medication. We describe a case of refractory pruritus due to drug-induced cholestasis, not improved with withdrawal of the drug, managed effectively with multiple sessions of plasmapheresis. PMID:28203129

  12. Plasmapheresis for Refractory Pruritus due to Drug-Induced Cholestasis.

    PubMed

    Al-Azzawi, Hasan; Patel, Ruchi; Sood, Gagan; Kapoor, Sumit

    2016-01-01

    Pruritus can be a distressing symptom seen in various cholestatic disorders. It is treated with medications like bile acid sequestrants. Drug-induced cholestasis usually resolves with withdrawal of the causative medication. We describe a case of refractory pruritus due to drug-induced cholestasis, not improved with withdrawal of the drug, managed effectively with multiple sessions of plasmapheresis.

  13. 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

  14. Drug bioactivation and protein adduct formation in the pathogenesis of drug-induced toxicity.

    PubMed

    Park, B K; Laverty, H; Srivastava, A; Antoine, D J; Naisbitt, D; Williams, D P

    2011-06-30

    Adverse drug reactions (ADRs) remain a major complication of drug therapy and can be classified as 'on-target' or 'off-target' (idiosyncratic) reactions. On-target reactions can be predicted from the known primary or secondary pharmacology of the drug and often represent an exaggeration of the pharmacological effect of the drug. In contrast, off-target adverse reactions cannot be predicted from knowledge of the basic pharmacology of the drug. The exact mechanisms of idiosyncratic drug reactions are still unclear; however it is believed that they can be initiated by chemically reactive drug metabolites. It is well known that xenobiotics can undergo metabolic bioactivation reactions which have the potential to cause cellular stress and damage. Bioactivation of drugs is thought to have the potential of initiating covalent linkages between cellular protein and drugs which can be recognised by the adaptive immune system in the absence of detectable cellular stress. This process cannot yet be predicted in pre-clinical models or discovered in clinical trials. Because of this hazard perception, the formation of chemically reactive metabolites in early drug discovery remains a serious impediment to the development of new medicines and can lead to withdrawal of an otherwise effective therapeutic agent. The fear of such reactions occurring at the post-licensing stage - when such problems first become evident - is a major contribution to drug attrition. The first step towards such methodology has been the development of chemically reactive metabolite screens. The chemical basis of drug bioactivation can usually be rationalised and synthetic strategies put in place to prevent such bioactivation. However, there is no simple correlation between drug bioactivation in vitro and adverse drug reactions in the clinic. Such a chemical approach is clearly limited by the facts that (a) not all drugs that can undergo bioactivation by human drug-metabolising enzymes are associated with

  15. [Active drug monitoring of adverse drug reactions in pediatric emergency department].

    PubMed

    Planchamp, F; Nguyen, K-A; Vial, T; Nasri, S; Javouhey, E; Gillet, Y; Ranchin, B; Villard, F; Floret, D; Cochat, P; Gueyffier, F; Kassaï, B

    2009-02-01

    The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period. The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated. During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations. Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.

  16. Trojan Horse Method for neutrons-induced reaction studies

    NASA Astrophysics Data System (ADS)

    Gulino, M.; Asfin Collaboration

    2017-09-01

    Neutron-induced reactions play an important role in nuclear astrophysics in several scenario, such as primordial Big Bang Nucleosynthesis, Inhomogeneous Big Bang Nucleosynthesis, heavy-element production during the weak component of the s-process, explosive stellar nucleosynthesis. To overcome the experimental problems arising from the production of a neutron beam, the possibility to use the Trojan Horse Method to study neutron-induced reactions has been investigated. The application is of particular interest for reactions involving radioactive nuclei having short lifetime.

  17. An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions.

    PubMed

    Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne; Darsø, Perle; Christophersen, Anette Kvindebjerg; Borck, Bille; Christensen, Catrine; Hansen, Melissa Voigt; Halladin, Natalie Monica Løvland; Christensen, Mikkel Bring; Harboe, Kirstine Moll; Lund, Marie; Jimenez-Solem, Espen

    2017-01-01

    Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region of Denmark. The ADEM assists healthcare professionals in reporting suspected ADRs to the Danish Health Authority. The aim of this retrospective observational study was to quantify and describe ADRs reported via the ADEM in 2014. All ADR reports handled by the ADEM in 2014 were recorded anonymously and analysed descriptively. A total of 484 ADRs were reported through the ADEM in 2014 (the median number of reports per month was 37; range: 17-78). The majority of the reports came from departments of internal medicine (61%), psychiatry (14%) and dermatology, ophthalmology or otorhinolaryngology (11%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR reporting and helps raise awareness about ADRs, including how and why they should be reported. Hopefully, this will assist national and European spontaneous reporting systems in their work to increase patient safety nationally and abroad. none. not relevant. .

  18. 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. Copyright © 2016 John Wiley & Sons, Ltd.

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

    PubMed

    Sriratanaviriyakul, Narin; Nguyen, Lam-Phuong; Henderson, Mark C; Albertson, Timothy E

    2014-10-08

    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. 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 × 10(9)/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. We report the first adult case of drug reaction with eosinophilia and

  1. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review 1

    PubMed Central

    Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

    2016-01-01

    ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380

  2. Noise-induced transition in human reaction times

    NASA Astrophysics Data System (ADS)

    Medina, José M.; Díaz, José A.

    2016-09-01

    The human reaction/response time can be defined as the time elapsed from the onset of stimulus presentation until a response occurs in many sensory and cognitive processes. A reaction time model based on Piéron’s law is investigated. The model shows a noise-induced transition in the moments of reaction time distributions due to the presence of strong additive noise. The model also demonstrates that reaction times do not follow fluctuation scaling between the mean and the variance but follow a generalized version between the skewness and the kurtosis. The results indicate that noise-induced transitions in the moments govern fluctuations in sensory-motor transformations and open an insight into the macroscopic effects of noise in human perception and action. The conditions that lead to extreme reaction times are discussed based on the transfer of information in neurons.

  3. Varenicline-induced acute dystonic reaction: a case report.

    PubMed

    Uca, Ali Ulvi; Kozak, Hasan Hüseyin; Uguz, Faruk

    2014-01-01

    Dystonia is a syndrome characterized by sustained muscle contractions frequently causing twisting and repetitive movements or abnormal postures. Dystonic reactions may be a complication of many drugs such as antipsychotics, anti-emetics and antidepressants. This report presents a 25-year-old patient who was admitted to an emergency department with acute dystonia following the use of varenicline, a pharmacological agent used for the treatment of nicotine addiction. Dystonic reactions may be related to the dopaminergic deficiency caused by the use of varenicline. In conclusion, this report suggests that varenicline can cause dystonic reaction in at least some patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. On laser-induced harpooning reactions

    NASA Astrophysics Data System (ADS)

    Weiner, J.

    1980-05-01

    In the present paper, the switching of chemical reactivity by a nonresonant laser field in simple gas-phase collisions of the type A + BC to AB + C is discussed in terms of a second-order optical/collision perturbation. A simple expression relating laser-induced harpooning cross sections to the laser power density is derived and is applied to Hg/Cl2 collisions.

  5. A multicenter study of the point prevalence of drug-induced hypotension in the ICU.

    PubMed

    Kane-Gill, Sandra L; LeBlanc, Jaclyn M; Dasta, Joseph F; Devabhakthuni, Sandeep

    2014-10-01

    To determine the point prevalence of drug-induced hypotension episodes in critically ill patients, to assess the episodes resulting from error, and to describe how episodes are treated. Multicenter observational, 24-hour snapshot study. Forty-seven ICUs in 27 institutions located in the United States, Canada, and Singapore. A total of 688 ICU patients were evaluated. None. Patients were included in the study if they had an episode of hypotension in the 24 hours prior to the clinical pharmacists' evaluation. The definition for a hypotensive episode is either a systolic blood pressure less than 90 mm Hg or a decrease in systolic blood pressure of 30 mm Hg over a 2-hour period. Each episode of unintentional hypotension was assessed for suspected drug-related causes. When a drug-related cause was suspected, an objective assessment tool, the modified Kramer, was used to determine causality. A score of at least "possible" was considered drug induced, referred to as a "drug-related hazardous condition." A drug-related hazardous condition is the temporal gap (intermediate stage) between the identification of an adverse drug reaction and the subsequent onset of drug-induced injury, known as an "adverse drug event." Drug-induced episodes were evaluated for medication errors and treatment. One hundred fifty-eight patients experienced 204 hypotensive episodes that were considered unintentional and drug related. Common drugs implicated included propofol, fentanyl, metoprolol, lorazepam, hydralazine, and furosemide. A total of 54 episodes (26.5%) resulted from medication errors. Common error types were improper dose/quantity (46%) and prescribing (25%). A total of 56.9% episodes were treated. Many hypotensive episodes in the ICU are drug related and require treatment. A substantial portion of these episodes result from errors and are therefore preventable. This presents opportunities to improve prescribing including optimizing drug dosing to avoid possible patient harm from drug-induced

  6. A web-based quantitative signal detection system on adverse drug reaction in China.

    PubMed

    Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan

    2009-07-01

    To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.

  7. Capture and documentation of coded data on adverse drug reactions: an overview.

    PubMed

    Paul, Lindsay; Robinson, Kerin M

    2012-01-01

    Allergic responses to prescription drugs are largely preventable, and incur significant cost to the community both financially and in terms of healthcare outcomes. The capacity to minimise the effects of repeated events rests predominantly with the reliability of allergy documentation in medical records and computerised physician order entry systems (CPOES) with decision support such as allergy alerts. This paper presents an overview of the nature and extent of adverse drug reactions (ADRs) in Australia and other developed countries, a discussion and evaluation of strategies which have been devised to address this issue, and a commentary on the role of coded data in informing this patient safety issue. It is not concerned with pharmacovigilance systems that monitor ADRs on a global scale. There are conflicting reports regarding the efficacy of these strategies. Although in many cases allergy alerts are effective, lack of sensitivity and contextual relevance can often induce doctors to override alerts. Human factors such as user fatigue and inadequate adverse drug event reporting, including ADRs, are commonplace. The quality of and response to allergy documentation can be enhanced by the participation of nurses and pharmacists, particularly in medication reconciliation. The International Classification of Diseases (ICD) coding of drug allergies potentially yields valuable evidence, but the quality of local and national level coded data is hampered by under-documenting and under-coding.

  8. 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

  9. Factors that affect adverse drug reaction reporting among hospital pharmacists in Western China.

    PubMed

    Liu, Jun; Zhou, Zhongliang; Yang, Shimin; Feng, Bianling; Zhao, Jun; Liu, Hua; Huang, Haiyan; Fang, Yu

    2015-06-01

    Hospital pharmacists can make a considerable contribution to the spontaneous reporting system of adverse drug reactions. The factors that influence adverse drug reaction reporting among hospital pharmacists remain largely unknown in China. This study aims to identify factors that affect hospital pharmacist-led adverse drug reaction reporting in Xi'an, and to obtain suggestions from pharmacists about how to improve the current adverse drug reaction reporting system. Hospital settings throughout Xi'an, a region of Western China. A matched case-control study was conducted on a population of 2,814 hospital pharmacists in Xi'an during 2011. Cases included all pharmacists who had reported at least one adverse drug reaction between 2008 and 2010 and agreed to participate in the study (186/204; 91.2 %); controls (n = 372) were pharmacists who had not reported any adverse drug reaction during the same period. A self-administered questionnaire was distributed to the participants. Logistic regression was performed to evaluate the association between indicator variables and the outcome of having reported at least one adverse drug reaction. Pharmacists' knowledge, attitude and practice towards adverse drug reaction reporting and factors affecting reporting. Higher professional title (adjusted OR 1.44; 95 % CI 1.07-1.94; p = 0.018), having received training about adverse drug reaction reporting (1.64; 1.04-2.57; p = 0.032), better knowledge about reporting (1.53; 1.12-2.08; p = 0.007), "lack of access to adverse drug reaction reporting form" (0.29; 0.12-0.72; p = 0.008) was independently associated with adverse drug reaction reporting. Clinical pharmacists were more likely to report an adverse drug reaction than dispensary pharmacists (1/adjusted OR 5.26; p < 0.001), pharmacy administrators (5.00; p = 0.003), and other technicians (5.56; p = 0.001). Higher professional title, having received training, mastering knowledge about reporting, and being a clinical pharmacist were

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

    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.

  12. Oxcarbazepine-induced drug rash with eosinophilia and systemic symptoms syndrome presenting as exfoliative dermatitis.

    PubMed

    Saha, Mahimanjan; Gorai, Surajit; Madhab, Vaswatee

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a type of severe adverse cutaneous drug reaction characterized by fever, skin eruption, hematological abnormalities, and internal organ involvement. Although anticonvulsant drugs are mainly implicated in DRESS, newer anticonvulsants such as oxcarbazepine-induced definite cases of DRESS syndrome are rare and oxcarbazepine-induced DRESS syndrome presenting as exfoliative dermatitis is even rarer. We report a case of a 35-year-old male who developed DRESS syndrome presenting as exfoliative dermatitis after taking oxcarbazepine for 3 weeks.

  13. Phenotypes and Pathology of Drug-Induced Liver Disease.

    PubMed

    Goodman, Zachary D

    2017-02-01

    Drug hepatotoxicity can simulate nearly any clinical syndrome or pathologic lesion that may occur in the liver, so clinical and histopathologic diagnosis of drug-induced liver injury may be difficult. Nevertheless, most drugs that are known to idiosyncratic liver injury tend to cause patterns of injury that produce characteristic phenotypes. Recognition of these patterns or phenotypes in liver biopsy material is helpful in evaluation of clinical cases of suspected drug-induced liver injury.

  14. How Does This Happen? Part I: Mechanisms of Adverse Drug Reactions Associated with Psychotropic Medications

    PubMed Central

    Elbe, Dean; Savage, Robert

    2010-01-01

    Objective: To review the background and mechanisms behind how certain psychotropic medications cause adverse drug reactions. Methods: A literature review pertaining to several interesting and unusual adverse drug reactions attributed to selected psychotropic medications was conducted. These include: 1) QTc interval prolongation secondary to ziprasidone, pimozide, and other antipsychotic agents. 2) Nephrogenic diabetes insipidus and hypernatremia secondary to lithium. 3) Hypothyroidism secondary to lithium. 4) Erectile dysfunction secondary to selective serotonin and serotonin/norepinephrine reuptake inhibitors (SSRIs/SNRIs). Results: Biochemical mechanisms of how certain psychotropic medications cause adverse drug reactions were reviewed. Specific interventions and monitoring recommendations to prevent or reduce the impact of these adverse reactions are discussed briefly. Conclusion: Knowledge of risk factors and mechanisms of adverse drug reactions with psychotropic medications can help to guide medication prescribing, monitoring and interventions to prevent or mitigate these reactions. PMID:20119566

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

    PubMed

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

    2014-01-01

    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. 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. 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. 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.

  17. 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

  18. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.

    PubMed

    Aronson, Jeffrey K

    2013-03-01

    The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

  19. Measuring Neutron-Induced Reaction Cross Sections without Neutrons

    NASA Astrophysics Data System (ADS)

    Bernstein, L. A.; Schiller, A.; Cooper, J. R.; Hoffman, R. D.; McMahan, M. A.; Fallon, P.; Macchiavelli, A. O.; Mitchell, G.; Tavukcu, E.; Guttormsen, M.

    2003-04-01

    Neutron-induced reactions on radioactive nuclei play a significant role in nuclear astrophysics and many other applied nuclear physics topics. However, the majority of these cross sections are impossible to measure due to the high-background of the targets and the low-intensity of neutron beams. We have explored the possibility of using charged-particle transfer reactions to form the same "pre-compound" nucleus as one formed in a neutron-induced reaction in order to measure the relative decay probabilities of the nucleus as a function of energy. Multiplying these decay probabilities by the neutron absorption cross section will then produce the equivalent neutron-induced reaction cross section. In this presentation I will explore the validity of this "surrogate reaction" technique by comparing results from the recent 157Gd(3He,axng)156-xGd experiment using STARS (Silicon Telescope Array for Reaction Studies) at GAMMASPHERE with reaction model calculations for the 155Gd(n,xng)156-xGd. This work was funded by the US Department of Energy under contracts number W-7405-ENG-48 (LLNL), AC03-76SF00098 (LBNL) and the Norwegian Research Council (Oslo).

  20. Drug-induced methaemoglobinaemia. Treatment issues.

    PubMed

    Coleman, M D; Coleman, N A

    1996-06-01

    In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug

  1. Management of serious adverse drug reactions: proposals from a victims' organisation.

    PubMed

    2012-09-01

    Amalyste is a French patient-advocacy group for victims of two very serious adverse drug reactions: Lyell and Stevens-Johnson syndromes. The aims of this organisation are to represent the interests of patients who have experienced these syndromes; to better inform the public about these syndromes; to provide analyses of drug-related risks; and to demand collective compensation for victims of serious adverse drug reactions. The following text is our translation of an Amalyste position statement on drug-related risks. It provides valuable food for thought, both for healthcare professionals and for drug regulatory agencies, and has the potential to improve practice (a).

  2. Metoclopramide induced acute dystonic reaction: a case report.

    PubMed

    Tianyi, Frank-Leonel; Agbor, Valirie Ndip; Njim, Tsi

    2017-01-07

    Metoclopramide is a commonly used anti-emetic drug known to cause extrapyramidal symptoms as adverse effects, amongst which are dystonic reactions. These reactions are more frequent at high doses of metoclopramide, in female patients, children and adults less than 30 years of age. We hereby present the case of a 16 year old female who had dystonic reactions from metoclopramide, highlighting its unpredictable nature and the shortcomings of the management in resource-limited settings. A 16 year old female Muslim from the Extreme North of Cameroon with no significant past history, was treated for severe malaria and associated refractory vomiting using intravenous quinine and metoclopramide respectively. She developed dystonic reactions after being administered her second dose of metoclopramide. The drug was discontinued and she was administered 8 mg of chlorpheniramine by mouth. Her symptoms resolved after 4 h. She was discharged 2 days later with no further complaints. Metoclopramide causes dystonic reactions which are often unpredictable and is frequently prescribed by health providers. This creates an environment of anxiety for the patient and the caregiver, and can result in life threatening consequences. Patients on metoclopramide should be monitored closely to detect these reactions early, and health facilities should be equipped to cope with the adverse effects before administration.

  3. 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

  4. Adverse drug reactions reported to the drug and poison information center of Tehran, Iran.

    PubMed

    Saheb Sharif-Askari, Fatemeh; Saheb Sharif-Askari, Narjes; Javadi, Mohammadreza; Gholami, Kheirollah

    2017-01-01

    Burden of adverse drug reactions (ADRs), in home-environment and domestic settings, is unknown. To discuss the epidemiology of reported ADRs to 13-Aban drug and poison information center (DPIC) and to discuss the burden of hospitalization caused by these ADRs from commonly implicated therapeutic groups. A retrospective analysis of the yellow card schemes of suspected ADRs reported to the 13-Aban DPIC was conducted from 21 March 2013 to 21 November 2016 inclusive. Characteristics of the ADRs, such as the sex and age of the patient, the therapeutic group involved, and the medical outcome of the exposure, were examined. ADR Hospitalization (ADRH) index was calculated for each drug group by dividing the number of ADR-related hospitalizations with total number of reported ADR cases (n = 748), and then multiplying by 100. ADRs were reported for 748 patients representing 5 cases per 1000 enquiries to the 13-Aban DPIC over almost 4-years of the study period. Public were responsible for reporting every 4 out of 5 ADR cases (n = 651, 87%) and the remaining 1 out of 5 ADR cases was reported by the health care professionals (n = 97, 13%). Most of the ADRs had a medical outcome documented as having a minor effect or were minimally bothersome to the patients (n = 509, 68%), and less than 4.9% (n = 37) were documented as having a major effect or were life-threatening. Overall, 7.4% (n = 55) of ADRs were resulted in hospitalization. Antibacterials for systemic use represented the therapeutic group with the highest hospitalization index (1.7%). The study concluded that ADRs to antibiotics are common and some of them resulted in hospitalization.

  5. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2015-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Influence of regulatory measures on the rate of spontaneous adverse drug reaction reporting in Italy.

    PubMed

    Motola, Domenico; Vargiu, Antonio; Leone, Roberto; Conforti, Anita; Moretti, Ugo; Vaccheri, Alberto; Velo, Giampaolo; Montanaro, Nicola

    2008-01-01

    The reporting of adverse drug reactions (ADRs) is the mainstay of post-marketing surveillance systems. Under-reporting and selective reporting are considered the main limitations of a spontaneous reporting-based pharmacovigilance system. However, excessive reporting induced by external events may also impair signal detection by increasing the noise level. The aim of this study was to examine the influence of regulatory measures and other external factors on the rate of ADR reporting in Italy, focusing on four situations occurring in the last 10 years: ACE inhibitor-induced cough; HMG-CoA reductase inhibitors ('statins') and rhabdomyolysis; nimesulide and hepatic toxicity; and cyclo-oxygenase (COX)-2 selective inhibitors ('coxibs') and increase in cardiovascular risk. The study was based on data from spontaneous reporting in six Italian regions collected from January 1995 to December 2005. We analysed a 10-year period as a reasonable time interval around the four situations of interest, highlighting the influence of regulatory measures on the rate of ADR reporting (number of reports per million inhabitants). Chi-squared tests were used to assess the statistical significance of any changes in ADR reporting. Drug sales data were also studied to examine possible changes in drug use. Sales data were expressed as daily defined dose per 1000 inhabitants per day. ACE inhibitors: a 5-fold increase in the reporting rate of ACE inhibitor-induced cough was observed in 1998 and 1999 following a restriction on reimbursement for angiotensin receptor blockers introduced in 1998 and removed at the end of 1999. Statins: after the withdrawal of cerivastatin in 2001, the ADR reporting rate increased more than 4-fold, with musculoskeletal ADRs representing about 60% of all the ADRs reported in that year, and progressively decreased in the following years. Nimesulide: an increase in hepatic ADR reporting was observed after withdrawal of the drug from the Finnish and Spanish markets in

  7. 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.

  8. 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.

  9. Locomotion of electrocatalytic nanomotors due to reaction induced charge autoelectrophoresis

    NASA Astrophysics Data System (ADS)

    Moran, J. L.; Wheat, P. M.; Posner, J. D.

    2010-06-01

    Bimetallic rod-shaped nanomotors swim autonomously in hydrogen peroxide solutions. Here, we present a scaling analysis, computational simulations, and experimental data that show that the nanomotor locomotion is driven by fluid slip around the nanomotor surface due to electrical body forces. The body forces are generated by a coupling of charge density and electric fields induced by electrochemical reactions occurring on the nanomotor surface. We describe the dependence of nanomotor motion on the nanomotor surface potential and reaction-driven flux.

  10. Bullous Fixed Drug Eruption Probably Induced by Paracetamol.

    PubMed

    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.

  11. 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.

  12. 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.

  13. [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.

  14. Drug-induced neurobehavioral plasticity: the role of environmental context.

    PubMed

    Badiani, A; Robinson, T E

    2004-09-01

    Repeated administrations of addictive drugs produce long-lasting changes in brain and behavior. However, drug-induced neurobehavioral plasticity is not a mere function of the neuropharmacological actions of drugs, but the result of complex drug-environment interactions. In the present review we summarize results obtained in a series of studies using an animal model of drug-environment interaction, showing that environmental context and past drug history interact to modulate the effects of amphetamine, cocaine and morphine on behavior, gene expression and structural plasticity. These findings may help shed some light on the conditions necessary for addictive drugs to enduringly alter brain and behavior.

  15. 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.

  16. Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2.

    PubMed

    Zhang, Tao; Che, Delu; Liu, Rui; Han, Shengli; Wang, Nan; Zhan, Yingzhuan; Pundir, Priyanka; Cao, Jiao; Lv, Yanni; Yang, Liu; Wang, Jue; Ding, Meiwen; Dong, Xinzhong; He, Langchong

    2017-07-08

    Mast cells are unique immune cells that function as sentinels in host defence reactions, including immediate hypersensitivity responses and allergic responses. The mast cell-specific receptor named MAS-related G protein-coupled receptor X2 (MRGPRX2) triggers mast-cell degranulation, a key process in anaphylactoid reactions. It is widely observed that antimicrobials can induce pseudo-allergic reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin inflammation to life-threatening systemic anaphylaxis. However, their direct involvement and the mechanisms underlying anaphylactoid reactions caused by antimicrobials have not been demonstrated. Structurally different antimicrobials were screened by Ca(2+) imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated by body temperature drop and mast cell degranulation assays. We showed that MRGPRX2 is involved in allergic-like reactions to three types of antimicrobials in a dose-dependent manner. However, mast cells lacking the receptor show reduced degranulation. Furthermore, mice without MAS-related G protein-coupled receptor B2 (the orthologous gene of MRGPRX2) exhibited reduced substance-induced inflammation. Interestingly, β-lactam and antiviral nucleoside analogues did not induce anaphylactic reactions, which were also observed in vitro. These results should alarm many clinicians that such drugs might induce anaphylactoid reactions and provide guidance on safe dosage of these drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Cavitation-induced reactions in high-pressure carbon dioxide.

    PubMed

    Kuijpers, M W A; van Eck, D; Kemmere, M F; Keurentjes, J T F

    2002-12-06

    The feasibility of ultrasound-induced in situ radical formation in liquid carbon dioxide was demonstrated. The required threshold pressure for cavitation could be exceeded at a relatively low acoustic intensity, as the high vapor pressure of CO2 counteracts the hydrostatic pressure. With the use of a dynamic bubble model, the formation of hot spots upon bubble collapse was predicted. Cavitation-induced radical formation was used for the polymerization of methyl methacrylate in CO2, yielding high-molecular-weight polymers. These results show that sonochemical reactions can be performed in dense-phase fluids, which allows the environmentally benign CO2 to replace conventional organic solvents in many reaction systems.

  18. Effects of midazolam and phenobarbital on brain oxidative reactions induced by pentylenetetrazole in a convulsion model.

    PubMed

    Arai, Yukiko; Maeda, Shigeru; Higuchi, Hitoshi; Tomoyasu, Yumiko; Shimada, Masahiko; Miyawaki, Takuya

    2012-04-01

    Brain oxidative reactions are involved in epilepsy as well as neurodegenerative diseases. In animal convulsion models, some anticonvulsants have been found to suppress oxidative reactions associated with convulsions. However, the effect of anticonvulsants on brain oxidative reactions has not fully been clarified. Midazolam and phenobarbital are often used as an intravenous anesthetic, and are known to have anticonvulsive effect, but antioxidative effect of these drugs has rarely been studied. Thus, the purpose of this study was to evaluate the effects of these drugs on the degree of convulsions and brain oxidative reactions in an animal convulsion model. In order to evaluate brain oxidative reactions, we measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression level in the brain of mice in a convulsion model generated by a single injection of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and phenobarbital on the degree of PTZ-induced convulsions and on the changes in brain MDA level and HO-1 mRNA expression level. After PTZ injection, severe convulsions were observed in all mice. MDA level was increased in the whole brain, while HO-1 mRNA expression level was increased only in the hippocampus. Both midazolam and phenobarbital prevented the convulsions and suppressed the increase in both MDA level and HO-1 mRNA expression level in the brain. In this study, both midazolam and phenobarbital suppressed PTZ-induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit brain oxidative reactions in a convulsion model.

  19. 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

  20. Clinical and endoscopic characteristics of drug-induced esophagitis.

    PubMed

    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

    2014-08-21

    To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. 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. 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. 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%.

  1. Severe exfoliative dermatitis caused by strontium ranelate: two cases of a new drug reaction.

    PubMed

    Smith, Emma V; Shipley, Debbie R V

    2010-05-01

    Strontium ranelate is a relatively new drug used as a second-line treatment for osteoporosis, often targeted at older patients. It is known to cause skin rash and rarely drug reaction with eosinophilia and systemic symptoms, but there are no reports of exfoliative dermatitis as a reaction in the literature. We present the first two cases of this adverse effect of the drug, combined with eosinophilia but no systemic symptoms. We illustrate the significant morbidity involved and use of systemic steroid treatment required, highlighting the need for awareness of this reaction in medical and particularly in elderly care communities.

  2. Patients' Perspectives on Adverse Drug Reaction Reporting in a Developing Country: A Case Study from Ghana.

    PubMed

    Sabblah, George Tsey; Darko, Delese Mimi; Mogtari, Hudu; Härmark, Linda; van Puijenbroek, Eugène

    2017-06-26

    Recent efforts to introduce direct patient reporting into pharmacovigilance systems have proved that patient reports contribute significantly to medicine safety, but there is a paucity of information relating to patients' perspectives regarding adverse drug reaction reporting in developing countries. The objective of this study was to explore patients' knowledge, attitudes, behaviours and opinions on spontaneous adverse drug reaction reporting in Ghana. A cross-sectional study using questionnaires administered through face-to-face interviews was carried out from 25 August, 2016 to 20 September, 2016 with 442 patients aged 18 years and above selected by convenience sampling from two community pharmacies in urban and rural Ghana. Reasons and opinions on patients' reporting on adverse drug reactions were surveyed using a 5-point Likert scale. The Pearson chi-square test was used to determine associations between background variables and responses on knowledge of adverse drug reaction reporting. Responses from 434 patients (86.7%) were included in the analysis. Among those interviewed, there was a high level of awareness regarding the existence of the National Pharmacovigilance Centre (81.6%). Approximately half of the respondents (49.5%) were aware that patients were able to report adverse drug reactions associated with medicinal products directly to the National Pharmacovigilance Centre. Of the respondents, 46.3% stated that they had an adverse drug reaction to their medicines in the past; of these, 53.2% reported to healthcare professionals and 36.9% failed to report because they stopped their medication. The three main reasons for patients' reporting were desire for extra information (92.4%), desire to share experiences with other people (91.7%) and expectation for the National Pharmacovigilance Centre to inform others about the possible adverse drug reactions (88.0%). Patients' opinions were to contribute to research/knowledge (96.5%) and improvements in drug

  3. [Research on foreign countries laws and regulations on surveillance and reporting of postmarketing drugs adverse reactions].

    PubMed

    Tian, Feng; Xie, Yanming

    2009-06-01

    Following more and more new drugs are authorized into market, new, serious or unexpected adverse drug reactions appear frequently, which is a serious threat to people health and life. Through making laws and guidelines, governments of various countries aim to strengthen and standardize the surveillance and reporting of postmarketing drugs. The drugs management department of our country are doing related jobs positively, but there are some problems, such as drug risk-menagement is not emphasized well, and the management department lacks clarity on operating related regulations. This article tries to explore foreign countries' laws and regulations on the surveillance and reporting of postmarketing drugs, aiming to provide reference for our courtry.

  4. Noncovalent chirality sensing ensembles for the detection and reaction monitoring of amino acids, peptides, proteins, and aromatic drugs.

    PubMed

    Biedermann, Frank; Nau, Werner M

    2014-05-26

    Ternary complexes between the macrocyclic host cucurbit[8]uril, dicationic dyes, and chiral aromatic analytes afford strong induced circular dichroism (ICD) signals in the near-UV and visible regions. This allows for chirality sensing and peptide-sequence recognition in water at low micromolar analyte concentrations. The reversible and noncovalent mode of binding ensures an immediate response to concentration changes, which allows the real-time monitoring of chemical reactions. The introduced supramolecular method is likely to find applications in bioanalytical chemistry, especially enzyme assays, for drug-related analytical applications, and for continuous monitoring of enantioselective reactions, particularly asymmetric catalysis.

  5. A theoretical study of deuteron-induced surrogate reactions

    NASA Astrophysics Data System (ADS)

    Carlson, B. V.; Capote, R.; Sin, M.

    2017-09-01

    We use the zero-range post-form DWBA approximation to calculate deuteron elastic and nonelastic breakup cross sections and estimate the breakup-fusion cross section that could serve as a surrogate for a neutron-induced reaction cross section. We compare the angular momentum dependence of the breakup-fusion compound nucleus formation cross section with that of the corresponding neutron-induced cross section.

  6. A Theoretical Study of Deuteron-induced Surrogate Reactions

    NASA Astrophysics Data System (ADS)

    Carlson, B. V.; Capote, R.; Sin, M.

    2017-06-01

    We use the zero-range post-form DWBA approximation to calculate deuteron elastic and nonelastic breakup cross sections and estimate the breakup-fusion cross section that could serve as a surrogate for a neutron-induced reaction cross section. We compare the angular momentum dependence of the breakup-fusion compound nucleus formation cross section with that of the corresponding neutron-induced cross section.

  7. 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

  8. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    PubMed

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to <20,000 platelets/pL). Diagnosis of DIIT is complicated by its similarity to other non-drug-induced immune thrombocytopenias, including autoimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal

  9. Photoscratch testing in systemic drug-induced photosensitivity.

    PubMed

    Conilleau, V; Dompmartin, A; Michel, M; Verneuil, L; Leroy, D

    2000-04-01

    Because of numerous false-negative results, photopatch testing is seldom relevant in systemic drug-induced photosensitivity. These false-negative photopatch test results can be attributed to the inability of the drug to penetrate into the epidermis. In order to enhance the penetration of the tested drug into the epidermis, some authors proposed to breach the cutaneous barrier. We performed a prospective study comparing photopatch and photoscratch testing. Fifteen patients presenting with a systemic drug-induced photosensitivity, proved by a favourable outcome after discontinuing the drug, were tested. For each drug, photopatch and photoscratch tests were performed. Two-thirds of the patients had negative photopatch and photoscratch tests with the suspected drugs. Photopatch and photoscratch tests were positive and relevant, respectively, in 3 and 4 patients. Photoscratch tests induced more false-positive results due to irritation confirmed on control subjects. Our study proves that photoscratch tests do not change the sensitivity of phototesting.

  10. Antituberculosis drug-induced hepatotoxicity in children

    PubMed Central

    Donald, Peter R

    2011-01-01

    Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, RMP and PZA only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. ADIH can occur in children at any age or at any dosage of INH, RMP or PZA, but the incidence of.ADIH is is considerably lower in children than in adults. Children with disseminated forms of disease are at greater risk of ADIH. The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children. PMID:21772953

  11. Psychotic disorders induced by antiepileptic drugs in people with epilepsy.

    PubMed

    Chen, Ziyi; Lusicic, Ana; O'Brien, Terence J; Velakoulis, Dennis; Adams, Sophia J; Kwan, Patrick

    2016-10-01

    Antiepileptic drug treatment can induce psychosis in some patients. However, there are no agreed definitions or diagnostic criteria for antiepileptic drug-induced psychotic disorder in the classification systems of either epileptology or psychiatry. In this study we investigated the clinical spectrum of antiepileptic drug-induced psychotic disorder in patients with epilepsy. The medical records of all patients with epilepsy who were diagnosed by a neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital from January 1993 to June 2015 were reviewed. Data were extracted regarding epilepsy and its treatment, psychotic symptoms profile and outcome. The diagnosis of epilepsy was established in accordance to the classification system of the International League Against Epilepsy while that of psychotic disorder was made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposal on neuropsychiatric disorders in epilepsy. Patients with antiepileptic drug-induced psychotic disorder were compared to those with psychotic disorders unrelated to antiepileptic drugs assessed over the same period (non-antiepileptic drug induced psychotic disorder group). Univariate comparisons were performed and variables with a value of P < 0.1 were selected for the multivariate logistic regression analysis. The records of 2630 in-patients and outpatients with epilepsy were screened, from which 98 (3.7%) with psychotic disorders were identified. Among these, 14 (14.3%) were diagnosed to have antiepileptic drug-induced psychotic disorder. Excluding one patient who developed psychosis after valproate withdrawal, 76.9% in the antiepileptic drug induced psychotic disorder group were female and the percentage of temporal lobe involvement was higher in the antiepileptic drug induced psychotic disorder group (69.2% versus 38.1%, P < 0.05). Current use of levetiracetam was higher in antiepileptic drug-induced psychotic disorder group (84

  12. Genetic predisposition to adverse drug reactions in the intensive care unit.

    PubMed

    Empey, Philip E

    2010-06-01

    Adverse drug reactions are a significant public health problem that leads to mortality, hospital admissions, an increased length of stay, increasing healthcare costs, and withdrawal of drugs from market. Intensive care unit patients are particularly vulnerable and are at an elevated risk. Critical care practitioners, regulatory agencies, and the pharmaceutical industry aggressively seek biomarkers to mitigate patient risk. The rapidly expanding field of pharmacogenomics focuses on the genetic contributions to the variability in drug response. Polymorphisms may explain why some groups of patients have the expected response to pharmacotherapy whereas others experience adverse drug reactions. Historically, genetic association studies have focused on characterizing the effects of variation in drug metabolizing enzymes on pharmacokinetics. Recent work has investigated drug transporters and the variants of genes encoding drug targets, both intended and unintended, that comprise pharmacodynamics. This has led to an appreciation of the role that genetics plays in adverse drug reactions that are either predictable extensions of a drug's known therapeutic effect or idiosyncratic.This review presents the evidence for a genetic predisposition to adverse drug reactions, focusing on gene variants producing alterations in drug pharmacokinetics and pharmacodynamics in intensive care unit patients. Genetic biomarkers with the strongest associations to adverse drug reaction risk in the intensive care unit are presented along with the medications involved. Variant genotypes and phenotypes, allelic frequencies in different populations, and clinical studies are discussed. The article also presents the current recommendations for pharmacogenetic testing in clinical practice and explores the drug, patient, research study design, regulatory, and practical issues that presently limit more widespread implementation.

  13. 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. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Improving the quality of adverse drug reaction reporting by 4th-year medical students.

    PubMed

    Rosebraugh, Curtis J; Tsong, Yi; Zhou, Feng; Chen, Min; Mackey, Ann Corken; Flowers, Charlene; Toyer, Denise; Flockhart, David A; Honig, Peter K

    2003-03-01

    Evaluate whether a 15-minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms. Seventy-eight 4th-year medical students were randomized to intervention 'Group-A' or non-intervention 'Group-B' on the first day of a required five-day clinical pharmacology rotation. Group-A participants attended a 15-minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group-B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA. Seventy-eight MedWatch forms were evaluated (Group-A = 40, Group B = 38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non-intervention group (p < 0.004). As little as a 15-minute intervention can significantly improve the quality of adverse drug reaction reporting by 4th-year medical students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students.

  15. Toxic Epidermal Necrolysis induced by rarely implicated drugs.

    PubMed

    Rajagopalan, Sujit; Kaur, Sharonjeet; Dogra, Sunil; Shafiq, Nusrat; Bhalla, Ashish; Pandhi, Promila; Malhotra, Samir

    2012-03-01

    Toxic Epidermal Necrolysis (TEN) and Steven-Johnson Syndrome (SJS) are serious disorders commonly caused as idiosyncratic reactions to drugs, the most common ones being oxicams, anticonvulsants, allopurinol, and sulfonamides. We present a case of TEN in a patient who developed the lesions after ingesting multiple drugs including paracetamol, metoclopramide, antihistamines, and multivitamins. These drugs have rarely been implicated in this disorder. The suspected drugs in this case were paracetamol and metoclopramide. However, the role of other drugs could not be ruled out definitely. The patient was managed with antibiotics, corticosteroids, and parenteral fluids and recovered well.

  16. Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs.

    PubMed

    Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra

    2016-01-01

    Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT

  17. 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. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Reactions and enzymes in the metabolism of drugs and other xenobiotics.

    PubMed

    Testa, Bernard; Pedretti, Alessandro; Vistoli, Giulio

    2012-06-01

    In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Mechanisms of shock-induced reactions in high explosives

    NASA Astrophysics Data System (ADS)

    Kay, Jeffrey J.

    2017-01-01

    Understanding the mechanisms by which shock waves initiate chemical reactions in explosives is key to understanding their unique and defining property: the ability to undergo rapid explosive decomposition in response to mechanical stimulus. Although shock-induced reactions in explosives have been studied experimentally and computationally for decades, the nature of even the first chemical reactions that occur in response to shock remain elusive. To predictively understand how explosives respond to shock, the detailed sequence of events that occurs - mechanical deformation, energy transfer, bond breakage, and first chemical reactions - must be understood at the quantum-mechanical level. This paper reviews recent work in this field and ongoing experimental and theoretical work at Sandia National Laboratories in this important area of explosive science.

  20. 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

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Identification of drugs inducing phospholipidosis by novel in vitro data.

    PubMed

    Muehlbacher, Markus; Tripal, Philipp; Roas, Florian; Kornhuber, Johannes

    2012-11-01

    Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design process. PLD has been reported to be a side effect of many commonly used drugs, especially those with cationic amphiphilic properties. To predict drug-induced PLD in silico, we established a high-throughput cell-culture-based method to quantitatively determine the induction of PLD by chemical compounds. Using this assay, we tested 297 drug-like compounds at two different concentrations (2.5 μM and 5.0 μM). We were able to identify 28 previously unknown PLD-inducing agents. Furthermore, our experimental results enabled the development of a binary classification model to predict PLD-inducing agents based on their molecular properties. This random forest prediction system yields a bootstrapped validated accuracy of 86 %. PLD-inducing agents overlap with those that target similar biological processes; a high degree of concordance with PLD-inducing agents was identified for cationic amphiphilic compounds, small molecules that inhibit acid sphingomyelinase, compounds that cross the blood-brain barrier, and compounds that violate Lipinski's rule of five. Furthermore, we were able to show that PLD-inducing compounds applied in combination additively induce PLD.

  3. Identification of Drugs Inducing Phospholipidosis by Novel in vitro Data

    PubMed Central

    Muehlbacher, Markus; Tripal, Philipp; Roas, Florian; Kornhuber, Johannes

    2012-01-01

    Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design process. PLD has been reported to be a side effect of many commonly used drugs, especially those with cationic amphiphilic properties. To predict drug-induced PLD in silico, we established a high-throughput cell-culture-based method to quantitatively determine the induction of PLD by chemical compounds. Using this assay, we tested 297 drug-like compounds at two different concentrations (2.5 μm and 5.0 μm). We were able to identify 28 previously unknown PLD-inducing agents. Furthermore, our experimental results enabled the development of a binary classification model to predict PLD-inducing agents based on their molecular properties. This random forest prediction system yields a bootstrapped validated accuracy of 86 %. PLD-inducing agents overlap with those that target similar biological processes; a high degree of concordance with PLD-inducing agents was identified for cationic amphiphilic compounds, small molecules that inhibit acid sphingomyelinase, compounds that cross the blood–brain barrier, and compounds that violate Lipinski’s rule of five. Furthermore, we were able to show that PLD-inducing compounds applied in combination additively induce PLD. PMID:22945602

  4. Natural Inhibitors of Cholinesterases: Implications for Adverse Drug Reactions

    PubMed Central

    Krasowski, Matthew D.; McGehee, Daniel S.

    2010-01-01

    Purpose Acetylcholinesterase and butyrylcholinesterase are two closely related enzymes important in the metabolism of acetylcholine and anaesthetic drugs, including succinylcholine, mivacurium, and cocaine. The solanaceous glycoalkaloids (SGAs) are naturally occurring steroids in potatoes and related plants that inhibit both acetylcholinesterase and butyrylcholinesterase. There are many clinical examples of direct SGA toxicity due to cholinesterase inhibition. The aim of this study was to review the hypotheses that (1) SGAs may be the evolutionary driving force for atypical butyrylcholinesterase alleles and that (2) SGAs may adversely influence the actions of anaesthetic drugs that metabolized by acetylcholinesterase and butyrylcholinesterase. Source The information was obtained by Medline search and consultation with experts in the study of SGAs and cholinesterases. Principal findings The SGAs inhibit both acetylcholinesterase and butyrylcholinesterase in numerous in vitro and in vivo experiments. Although accurate assays of SGA levels are difficult, published data indicate human serum SGA concentrations at least ten-fold lower than required to inhibit acetylcholinesterase and butyrylcholinesterase in vitro. However, we review evidence that suggests the dietary ingestion of SGAs can initiate a cholinergic syndrome in humans. This syndrome occurs at SGA levels lower than those which interfere with anaesthetic drug catabolism. The world distribution of solanaceous plants parallels the distribution of atypical alleles of butyrylcholinesterase and may explain the genetic diversity of the butyrylcholinesterase gene. Conclusion Correlative evidence suggests that dietary SGAs may be the driving force for atypical butyrylcholinesterase alleles. In addition, SGAs may influence the metabolism of anaesthetic drugs and this hypothesis warrants experimental investigation. PMID:9161749

  5. [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.

  6. Systematic measurements of proton-induced reactions on enriched molybdenum

    NASA Astrophysics Data System (ADS)

    Lamere, Edward; Gilardy, Gwenaelle; Meisel, Zach; Moran, Michael; Seymore, Christopher; Skulski, Michael; Simonetti, Antonio; Couder, Manoel

    2016-09-01

    Between 2008 and 2010, shortages in the world-wide supply of Mo highlighted weaknesses in the current fission-based production method of mTc, a critical medical isotope. This crisis sparked interest in developing the direct production of mTc from proton-induced reactions on enriched Mo targets as an alternative. One complication with this method is that mTc must be chemically extracted from the irradiated target. Therefore, radiopharmaceuticals produced from proton bombardment will contain a mixture of all Tc-species with open production channels, affecting radiochemical purity, specific activity and total production yield of mTc-factors critical for the feasibility of this production method. Reactions on trace impurities in the enriched targets have been shown to impact these factors dramatically. Precise cross-section measurements for all Mo +p reactions that lead to Tc or Mo species are required for proper assessment of this production technique. Cross-section measurements for the main reaction of interest, mTc(p,2n), have been performed in recent years, however, other reactions producing Tc have been mostly neglected. We will introduce a systematic study of proton-induced reactionson 92, 94-98, 100 Mo currently being performed at Notre Dame. Preliminary results will be presented. NRC-HQ-12-G-38-0073.

  7. Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children.

    PubMed

    Arikoglu, Tuğba; Aslan, Gulen; Yildirim, Didem Derici; Batmaz, Sehra Birgul; Kuyucu, Semanur

    2017-07-01

    Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. All patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. We evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA(2)LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50-10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. This study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity. Copyright

  8. 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

  9. Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.

    PubMed

    Illing, Patricia T; Mifsud, Nicole A; Purcell, Anthony W

    2016-10-01

    It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01(+) individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.

  10. Needs for an expanded ontology-based classification of adverse drug reactions and related mechanisms.

    PubMed

    Zhichkin, P E; Athey, B D; Avigan, M I; Abernethy, D R

    2012-06-01

    The growing significance of bioinformatics and systems biology in drug safety research requires a system of adverse-event classification that goes beyond a simple vocabulary. This opinion piece outlines the need for development of an ontology-based framework of describing adverse drug reactions (ADRs) and describes the potential applications for such a framework.

  11. Family Communication Patterns, Rebelliousness, and Adolescent Reactions to Anti-Drug PSAs.

    ERIC Educational Resources Information Center

    Skinner, Ellen R.; Slater, Michael D.

    A study investigated the proposition that the ability of family communication patterns (FCP) and related measures to predict reactions to anti-drug messages is in part contingent on adolescent rebelliousness. Fifty-one adolescents (ages 15-18) in high school health classes saw six anti-drug PSAs, and indicated the extent to which they considered…

  12. Control of serpentinisation rate by reaction-induced cracking

    NASA Astrophysics Data System (ADS)

    Malvoisin, Benjamin; Brantut, Nicolas; Kaczmarek, Mary-Alix

    2017-10-01

    Serpentinisation of mantle rocks requires the generation and maintenance of transport pathways for water. The solid volume increase during serpentinisation can lead to stress build-up and trigger cracking, which ease fluid penetration into the rock. The quantitative effect of this reaction-induced cracking mechanism on reactive surface generation is poorly constrained, thus hampering our ability to predict serpentinisation rate in geological environments. Here we use a combined approach with numerical modelling and observations in natural samples to provide estimates of serpentinisation rate at mid-ocean ridges. We develop a micromechanical model to quantify the propagation of serpentinisation-induced cracks in olivine. The maximum crystallisation pressure deduced from thermodynamic calculations reaches several hundreds of megapascals but does not necessary lead to crack propagation if the olivine grain is subjected to high compressive stresses. The micromechanical model is then coupled to a simple geometrical model to predict reactive surface area formation during grain splitting, and thus bulk reaction rate. Our model reproduces quantitatively experimental kinetic data and the typical mesh texture formed during serpentinisation. We also compare the model results with olivine grain size distribution data obtained on natural serpentinised peridotites from the Marum ophiolite and the Papuan ultramafic belt (Papua New Guinea). The natural serpentinised peridotites show an increase of the number of olivine grains for a decrease of the mean grain size by one order of magnitude as reaction progresses from 5 to 40%. These results are in agreement with our model predictions, suggesting that reaction-induced cracking controls the serpentinisation rate. We use our model to estimate that, at mid-ocean ridges, serpentinisation occurs up to 12 km depth and reaction-induced cracking reduces the characteristic time of serpentinisation by one order of magnitude, down to values

  13. Antitubercular drug-induced violent suicide of a hospitalised patient

    PubMed Central

    Behera, C; Krishna, Karthik; Singh, H R

    2014-01-01

    We present a case where a young adult male, on treatment for multidrug-resistance tuberculosis (MDR-TB), developed drug-induced psychosis. The psychiatric symptoms were ascribed to the anti-TB drug and were duly withdrawn by the treating doctors and supplemented with other drugs. However, the victim continued to have psychiatric symptoms and committed suicide in the hospital. He ended his life in a violent manner by stabbing and cutting himself with a kitchen knife. The case is briefly reported in this paper with a discussion on anti-TB drug-induced psychiatric effects leading to suicide. PMID:24395874

  14. Incidence of cutaneous adverse drug reactions among medical inpatients of Sultanah Aminah Hospital Johor Bahru.

    PubMed

    Latha, S; Choon, S E

    2017-06-01

    Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. A prospective study was conducted among medical inpatients from July to December 2014. A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.

  15. Evolution of a predator-induced, nonlinear reaction norm.

    PubMed

    Carter, Mauricio J; Lind, Martin I; Dennis, Stuart R; Hentley, William; Beckerman, Andrew P

    2017-08-30

    Inducible, anti-predator traits are a classic example of phenotypic plasticity. Their evolutionary dynamics depend on their genetic basis, the historical pattern of predation risk that populations have experienced and current selection gradients. When populations experience predators with contrasting hunting strategies and size preferences, theory suggests contrasting micro-evolutionary responses to selection. Daphnia pulex is an ideal species to explore the micro-evolutionary response of anti-predator traits because they face heterogeneous predation regimes, sometimes experiencing only invertebrate midge predators and other times experiencing vertebrate fish and invertebrate midge predators. We explored plausible patterns of adaptive evolution of a predator-induced morphological reaction norm. We combined estimates of selection gradients that characterize the various habitats that D. pulex experiences with detail on the quantitative genetic architecture of inducible morphological defences. Our data reveal a fine scale description of daphnid defensive reaction norms, and a strong covariance between the sensitivity to cues and the maximum response to cues. By analysing the response of the reaction norm to plausible, predator-specific selection gradients, we show how in the context of this covariance, micro-evolution may be more uniform than predicted from size-selective predation theory. Our results show how covariance between the sensitivity to cues and the maximum response to cues for morphological defence can shape the evolutionary trajectory of predator-induced defences in D. pulex. © 2017 The Authors.

  16. Current Concepts of Mechanisms in Drug-Induced Hepatotoxicity

    PubMed Central

    Russmann, Stefan; Kullak-Ublick, Gerd A; Grattagliano, Ignazio

    2009-01-01

    Drug-induced liver injury (DILI) has become a leading cause of severe liver disease in Western countries and therefore poses a major clinical and regulatory challenge. Whereas previously drug-specific pathways leading to initial injury of liver cells were the main focus of mechanistic research and classifications, current concepts see these as initial upstream events and appreciate that subsequent common downstream pathways and their attenuation by drugs and other environmental and genetic factors also have a profound impact on the risk of an individual patient to develop overt liver disease. This review summarizes current mechanistic concepts of DILI in a 3-step model that limits its principle mechanisms to three main ways of initial injury, i.e. direct cell stress, direct mitochondrial impairment, and specific immune reactions. Subsequently, initial injury initiates further downstream events, i.e. direct and death receptor-mediated pathways leading to mitochondrial permeability transition, which then results in apoptotic or necrotic cell death. For all mechanisms, mitochondria play a central role in events leading to apoptotic vs. necrotic cell death. New treatment targets consequently focus on interference with downstream pathways that mediate injury and therefore determine the ultimate outcome of DILI. Genome wide and targeted pharmacogenetic as well as metabonomic approaches are now used in order to reach the key goals of a better understanding of mechanisms in hepatotoxicity, and to develop new strategies for its prediction and treatment. However, the complexity of interactions between genetic and environmental risk factors is considerable, and DILI therefore currently remains unpredictable for most hepatotoxins. PMID:19689281

  17. Drug-induced impairment of renal function

    PubMed Central

    Pazhayattil, George Sunny; Shirali, Anushree C

    2014-01-01

    Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies. PMID:25540591

  18. Chemical memory reactions induced bursting dynamics in gene expression.

    PubMed

    Tian, Tianhai

    2013-01-01

    Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

  19. 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/.

  20. 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