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Sample records for antimalaria drug mefloquine

  1. Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe.

    PubMed

    Schlagenhauf, Patricia; Hatz, Christoph; Behrens, Ron; Visser, Leo; Funk, Maia; Holzer, Benedikt; Beck, Bernhard; Bourquin, Cathérine; Etter, Hermann; Furrer, Hansjakob; Genton, Blaise; Landry, Pierre; Chappuis, Francois; Loutan, Louis; Stössel, Ulrich; Jeschko, Eva; Rossanese, Andrea; Nothdurft, Hans Dieter

    2015-01-01

    Since its introduction to the market in 1985, mefloquine has been used for malaria chemoprophylaxis by more than 35 million travellers. In Europe, in 2014, the European Medicines Agency (EMA) issued recommendations on strengthened warnings, prescribing checklists and updates to the product information of mefloquine. Some malaria prevention advisors question the scientific basis for the restrictions and suggest that this cost-effective, anti-malarial drug will be displaced as a first-line anti-malaria medication with the result that vulnerable groups such as VFR and long-term travellers, pregnant travellers and young children are left without a suitable alternative chemoprophylaxis. This commentary looks at the current position of mefloquine prescribing and the rationale of the new EMA recommendations and restrictions. It also describes the new recommendations for malaria prophylaxis that have been adapted by Switzerland, Germany, Austria and Italy where chemoprophylaxis use is restricted to high-risk malaria-endemic areas. PMID:25825015

  2. Mass administration of the antimalarial drug mefloquine to Guantánamo detainees: a critical analysis.

    PubMed

    Nevin, Remington L

    2012-10-01

    Recently, evidence has emerged from an unusual form of mass drug administration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use. PMID:22882560

  3. Prophylactic activity of mefloquine hydrochloride (WR 142 490) in drug-resistant malaria*

    PubMed Central

    Rieckmann, K. H.; Trenholme, G. M.; Williams, R. L.; Carson, P. E.; Frischer, H.; Desjardins, R. E.

    1974-01-01

    In preliminary studies with mefloquine (WR 142 490) a single dose exerted prolonged suppressive activity against a drug-resistant strain of Plasmodium falciparum. Development of patent parasitaemia was prevented when nonimmune persons were exposed to infected mosquitos 2 weeks after medication, and it was delayed when exposure occurred 3 weeks after drug administration. PMID:4619059

  4. Further studies on mefloquine and praziquantel alone or interaction of both drugs against Schistosoma japonicum in vitro.

    PubMed

    Xiao, Shu-hua; Xue, Jian; Zhang, Hao-bing

    2012-03-01

    The aim of the present study is to further understand and analyze the interaction of mefloquine with praziquantel against adult Schistosoma japonicum in vitro. Mice infected with S. japonicum cercariae for 35-37 days were sacrificed, and adult schistosomes were collected by perfusion. Schistosomes were placed to each of 12 wells of a Falcon plate and maintained in RPMI 1640 supplemented by 10% calf serum. For determination of 50% and 95% lethal concentration (LC50 and LC95) of the two drugs in vitro, schistosomes were exposed to mefloquine at concentrations of 1, 2, 3, 4, 5, 6, 7, and 10 μg/mL or praziquantel at concentrations of 0.001, 0.01, 0.05, 0.1, 0.2, 0.5, 1, 10, and 30 μg/mL. The plate was incubated at 37°C in 95% air + 5% CO₂ for 72 h. According to the half-life of oral mefloquine and praziquantel in mice, mefloquine combined with praziquantel simultaneously, mefloquine administered within 1 h after praziquantel and praziquantel administered within 17 h after mefloquine were used to evaluate the effect of mefloquine in combination with praziquantel against S. japonicum in vitro. The results showed that the LC50 and LC95 of mefloquine calculated by the Bliss method were 6.17 μg/mL (95% confidence limits, 5.84-6.517 μg/mL) and 8.703 μg/mL (95% confidence limits, 7.632-9.797 μg/mL), respectively. As to praziquantel, no worm death was seen when schistosomes were exposed to praziquantel at concentrations of 0.005-0.2 μg/mL for 72 h. While in the worms exposed to praziquantel 1, 10, and 30 μg/mL, strong spasmodic contractions of the worm body and vesiculation along the worm surface were observed, but 48-75% of the schistosomes survived the exposure in 72-h incubation. Meanwhile, the number of dead worms that emerged in each group was not proportion to the increasing concentrations. Therefore, it is not appropriate to calculate the LC50 and LC95 of praziquantel. For evaluation of the interaction with the two drugs, praziquantel 0.1 or 0.2

  5. The story of artesunate–mefloquine (ASMQ), innovative partnerships in drug development: case study

    PubMed Central

    2013-01-01

    Background The Drugs for Neglected Diseases initiative (DNDi) is a not-for profit organization committed to providing affordable medicines and access to treatments in resource-poor settings. Traditionally drug development has happened “in house” within pharmaceutical companies, with research and development costs ultimately recuperated through drug sales. The development of drugs for the treatment of neglected tropical diseases requires a completely different model that goes beyond the scope of market-driven research and development. Artesunate and mefloquine are well-established drugs for the treatment of uncomplicated malaria, with a strong safety record based on many years of field-based studies and use. The administration of such artemisinin-based combination therapy in a fixed-dose combination is expected to improve patient compliance and to reduce the risk of emerging drug resistance. Case description DNDi developed an innovative approach to drug development, reliant on strong collaborations with a wide range of partners from the commercial world, academia, government institutions and NGOs, each of which had a specific role to play in the development of a fixed dose combination of artesunate and mefloquine. Discussion and evaluation DNDi undertook the development of a fixed-dose combination of artesunate with mefloquine. Partnerships were formed across five continents, addressing formulation, control and production through to clinical trials and product registration, resulting in a safe and efficacious fixed dose combination treatment which is now available to treat patients in resource-poor settings. The south-south technology transfer of production from Farmanguinhos/Fiocruz in Brazil to Cipla Ltd in India was the first of its kind. Of additional benefit was the increased capacity within the knowledge base and infrastructure in developing countries. Conclusions This collaborative approach to drug development involving international partnerships and

  6. Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum

    PubMed Central

    Ibraheem, Zaid O.; Abd Majid, R.; Noor, S. Mohd.; Sedik, H. Mohd.

    2014-01-01

    Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs. PMID:25506039

  7. Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum.

    PubMed

    Ibraheem, Zaid O; Abd Majid, R; Noor, S Mohd; Sedik, H Mohd; Basir, R

    2014-01-01

    Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs. PMID:25506039

  8. Mefloquine and its oxazolidine derivative compound are active against drug-resistant Mycobacterium tuberculosis strains and in a murine model of tuberculosis infection.

    PubMed

    Rodrigues-Junior, Valnês S; Villela, Anne D; Gonçalves, Raoni S B; Abbadi, Bruno Lopes; Trindade, Rogério Valim; López-Gavín, Alexandre; Tudó, Griselda; González-Martín, Julian; Basso, Luiz Augusto; de Souza, Marcus V N; Campos, Maria Martha; Santos, Diógenes Santiago

    2016-08-01

    Repurposing of drugs to treat tuberculosis (TB) has been considered an alternative to overcome the global TB epidemic, especially to combat drug-resistant forms of the disease. Mefloquine has been reported as a potent drug to kill drug-resistant strains of Mycobacterium tuberculosis. In addition, mefloquine-derived molecules have been synthesised and their effectiveness against mycobacteria has been assessed. In this work, we demonstrate for the first time the activities of mefloquine and its oxazolidine derivative compound 1E in a murine model of TB infection following administration of both drugs by the oral route. The effects of associations between mefloquine or 1E with the clinically used antituberculosis drugs isoniazid, rifampicin, ethambutol, moxifloxacin and streptomycin were also investigated. Importantly, combination of mefloquine with isoniazid and of 1E with streptomycin showed a two-fold decrease in their minimum inhibitory concentrations (MICs). Moreover, no tested combinations demonstrated antagonist interactions. Here we describe novel evidence on the activity of mefloquine and 1E against a series of quinolone-resistant M. tuberculosis strains. These data show MICs against quinolone-resistant strains (0.5-8 µg/mL) similar to or lower than those previously reported for multidrug-resistant strains. Taking these results together, we can suggest the use of mefloquine or 1E in combination with clinically available drugs, especially in the case of resistant forms of TB. PMID:27364701

  9. Mefloquine and its oxazolidine derivative compound are active against drug-resistant Mycobacterium tuberculosis strains and in a murine model of tuberculosis infection.

    PubMed

    Rodrigues-Junior, Valnês S; Villela, Anne D; Gonçalves, Raoni S B; Abbadi, Bruno Lopes; Trindade, Rogério Valim; López-Gavín, Alexandre; Tudó, Griselda; González-Martín, Julian; Basso, Luiz Augusto; de Souza, Marcus V N; Campos, Maria Martha; Santos, Diógenes Santiago

    2016-08-01

    Repurposing of drugs to treat tuberculosis (TB) has been considered an alternative to overcome the global TB epidemic, especially to combat drug-resistant forms of the disease. Mefloquine has been reported as a potent drug to kill drug-resistant strains of Mycobacterium tuberculosis. In addition, mefloquine-derived molecules have been synthesised and their effectiveness against mycobacteria has been assessed. In this work, we demonstrate for the first time the activities of mefloquine and its oxazolidine derivative compound 1E in a murine model of TB infection following administration of both drugs by the oral route. The effects of associations between mefloquine or 1E with the clinically used antituberculosis drugs isoniazid, rifampicin, ethambutol, moxifloxacin and streptomycin were also investigated. Importantly, combination of mefloquine with isoniazid and of 1E with streptomycin showed a two-fold decrease in their minimum inhibitory concentrations (MICs). Moreover, no tested combinations demonstrated antagonist interactions. Here we describe novel evidence on the activity of mefloquine and 1E against a series of quinolone-resistant M. tuberculosis strains. These data show MICs against quinolone-resistant strains (0.5-8 µg/mL) similar to or lower than those previously reported for multidrug-resistant strains. Taking these results together, we can suggest the use of mefloquine or 1E in combination with clinically available drugs, especially in the case of resistant forms of TB.

  10. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    PubMed

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  11. Antimalarial Preclinical Drug Development: A Single Oral Dose of A 5-Carbon-linked Trioxane Dimer Plus Mefloquine Cures Malaria-Infected Mice.

    PubMed

    Moon, Deuk Kyu; Singhal, Vandana; Kumar, Nirbhay; Shapiro, Theresa A; Posner, Gary H

    2009-01-01

    Three new 5-carbon-linked trioxane dimer carboxylate esters have been prepared from the natural trioxane, artemisinin in only 3-steps and 40-50% overall yields. Each one of these new chemical entities is at least as efficacious as the clinically used trioxane antimalarial drug artemether when combined with mefloquine hydrochloride in a low single oral dose cure. PMID:20686674

  12. Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

    PubMed Central

    Shin, Ji Hyun; Bae, Dong-Jun; Kim, Eun Sung; Kim, Han Byeol; Park, So Jung; Jo, Yoon Kyung; Jo, Doo Sin; Jo, Dong-Gyu; Kim, Sang-Yeob; Cho, Dong-Hyung

    2015-01-01

    Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells. PMID:26157548

  13. 1993 Sir Henry Wellcome Medal and Prize recipient. The rise and fall of mefloquine as an antimalarial drug in South East Asia.

    PubMed

    Shanks, G D

    1994-04-01

    Mefloquine is an antimalarial drug developed by the U.S. Army Antimalarial Drug Program in conjunction with the World Health Organization and Hoffmann-La Roche to address the problem of chloroquine-resistant falciparum malaria encountered during the Vietnam War. Despite the expenditure of millions of dollars over a 20-year period, it is unlikely that mefloquine will ever be used for U.S. soldiers deployed to South East Asia. Although mefloquine met the specifications set by its developers, its usefulness is now limited by the rapid evolution of drug resistance following its release to the civilian population. Drug development for particular military needs was compromised by a rapid biological response from the parasite and commercial concerns. In an era of shrinking military budgets, military drug development programs will by necessity be more resource constrained, thus yielding fewer new drugs per decade. In the short-term, emphasis should be directed toward adapting available antimicrobial drugs for antimalarial purposes. PMID:20058419

  14. Suppression of autophagy exacerbates Mefloquine-mediated cell death.

    PubMed

    Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Kim, Eun Sung; Kang, Hee; Park, Ji-Ho; Lee, Eunjoo H; Cho, Dong-Hyung

    2012-05-01

    Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.

  15. Detection and cartography of the fluorinated antimalarial drug mefloquine in normal and Plasmodium falciparum infected red blood cells by scanning ion microscopy and mass spectrometry.

    PubMed

    Adovelande, J; Boulard, Y; Berry, J P; Galle, P; Slodzian, G; Schrével, J

    1994-01-01

    Due to the presence of fluorine atoms in its molecule, the antimalarial drug mefloquine (MQ) can be easily detected in normal and Plasmodium falciparum infected red blood cells (RBC) by scanning ion microscopy and mass spectrometry. The P falciparum infected RBC exhibited intense distribution of MQ inside the parasite. The main compartments of the parasite which accumulate the drug were the food vacuole and the cytoplasm. The correlation between fluorine (19F-) and phosphorus (31P-) as well as probes for the DNA synthesis (BrdU and IdU) emissions shows that the parasite nucleus is also accessible to the drug. This study demonstrates that SIMS technique on smear preparations is an efficient approach for the direct detection and cartography of fluorinated antimalarial drugs in normal and P falciparum infected RBC, without radioactive labelling.

  16. Psychiatric side effects of mefloquine: applications to forensic psychiatry.

    PubMed

    Ritchie, Elspeth Cameron; Block, Jerald; Nevin, Remington Lee

    2013-01-01

    Mefloquine (previously marketed in the United States as Lariam®) is an antimalarial medication with potent psychotropic potential. Severe psychiatric side effects due to mefloquine intoxication are well documented, including anxiety, panic attacks, paranoia, persecutory delusions, dissociative psychosis, and anterograde amnesia. Exposure to the drug has been associated with acts of violence and suicide. In this article, we discuss the history of mefloquine use and describe plausible mechanisms of its psychotropic action. Mefloquine intoxication has not yet been successfully advanced in legal proceedings as a defense or as a mitigating factor, but it appears likely that it eventually will be. Considerations for the application of claims of mefloquine intoxication in forensic settings are discussed.

  17. Mefloquine chemoprophylaxis of soldiers on the Thai-Cambodian border.

    PubMed

    Suriyamongkol, V; Timsaad, S; Shanks, G D

    1991-12-01

    Chemoprophylaxis of malaria on the Thai-Cambodian border is difficult due to the high level of drug resistance. Thirteen separate companies of Royal Thai Marine Militia were placed on 250 mg weekly mefloquine chemoprophylaxis from August 1989 to January 1990. A mean number of 722 soldiers received two or more doses of mefloquine per month for the five month study. The medication was well tolerated and compliance averaged 91%. Substantial numbers of prophylaxis breakthroughs were seen which resulted in 3.2 cases of malaria/100 man-months. Sixty-eight falciparum malaria cases were documented in men who had taken at least two mefloquine doses in the previous four weeks. No serious neuropsychiatric reactions occurred. Mefloquine chemoprophylaxis failures exist on the Thai-Cambodian border and are one sign of the spread of mefloquine resistance.

  18. Elucidation of the Enantiodiscrimination Properties of a Nonracemic Chiral Alignment Medium through Gel‐based Capillary Electrochromatography: Separation of the Mefloquine Stereoisomers

    PubMed Central

    Al‐Massaedh, “Ayat Allah”; Schmidt, Manuel

    2016-01-01

    Abstract Enantiodiscrimination and enantioseparation are two highly important processes in chemistry, often performed by using NMR spectroscopy and chromatography. For a better understanding of the mechanistic details, the same system should be studied by both methods. In addition, isotropic and anisotropic NMR parameters should be obtained, the latter using alignment media so that residual dipolar couplings and chemical‐shift anisotropies can be measured. Consequently, a chiral alignment medium was used for the first time in chiral gel‐based capillary electrochromatography with the four stereoisomers of the antimalaria drug mefloquine as test compounds. Chromatographic data verify that enantiodiscrimination obtained with this alignment gel is caused by differences in the equilibrium constants related to associate formation. Hence, the chromatographic separation provides physicochemical data that form a basis for the understanding and optimization of alignment processes, and vice versa. PMID:27777838

  19. Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine

    PubMed Central

    Quinn, Jane C.

    2015-01-01

    The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans. PMID:26576290

  20. Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.

    PubMed

    Mawson, Anthony

    2013-07-15

    Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

  1. Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice.

    PubMed

    Heshmati, Mitra; Golden, Sam A; Pfau, Madeline L; Christoffel, Daniel J; Seeley, Elena L; Cahill, Michael E; Khibnik, Lena A; Russo, Scott J

    2016-02-01

    Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors.

  2. A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

    PubMed Central

    2012-01-01

    Background Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. Methods A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. Results Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma concentrations ratio was 0.42. Conclusion Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring. PMID:22369125

  3. Praziquantel, Mefloquine-Praziquantel, and Mefloquine-Artesunate-Praziquantel against Schistosoma haematobium: A Randomized, Exploratory, Open-Label Trial

    PubMed Central

    Keiser, Jennifer; Silué, Kigbafori D.; Adiossan, Lukas K.; N'Guessan, Nicaise A.; Monsan, N'Chou; Utzinger, Jürg; N'Goran, Eliézer K.

    2014-01-01

    Background Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations. Methodology We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing. Principal Findings Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild. Conclusions/Significance The addition of mefloquine or mefloquine

  4. Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin.

    PubMed

    Küster, Tatiana; Stadelmann, Britta; Rufener, Reto; Risch, Corina; Müller, Joachim; Hemphill, Andrew

    2015-11-01

    This study investigated the effects of oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine (MEF) and identified proteins that bind to MEF in parasite extracts and human cells by affinity chromatography. In a pilot experiment, MEF treatment was applied 5 days per week and was intensified by increasing the dosage stepwise from 12.5 mg/kg to 200 mg/kg during 4 weeks followed by treatments of 100 mg/kg during the last 7 weeks. This resulted in a highly significant reduction of parasite weight in MEF-treated mice compared with mock-treated mice, but the reduction was significantly less efficacious compared with the standard treatment regimen of albendazole (ABZ). In a second experiment, MEF was applied orally in three different treatment groups at dosages of 25, 50 or 100 mg/kg, but only twice a week, for a period of 12 weeks. Treatment at 100 mg/kg had a profound impact on the parasite, similar to ABZ treatment at 200 mg/kg/day (5 days/week for 12 weeks). No adverse side effects were noted. To identify proteins in E. multilocularis metacestodes that physically interact with MEF, affinity chromatography of metacestode extracts was performed on MEF coupled to epoxy-activated Sepharose(®), followed by SDS-PAGE and in-gel digestion LC-MS/MS. This resulted in the identification of E. multilocularis ferritin and cystatin as MEF-binding proteins. In contrast, when human cells were exposed to MEF affinity chromatography, nicotinamide phosphoribosyltransferase was identified as a MEF-binding protein. This indicates that MEF could potentially interact with different proteins in parasites and human cells. PMID:26395219

  5. Rational Risk-Benefit Decision-Making in the Setting of Military Mefloquine Policy.

    PubMed

    Nevin, Remington L

    2015-01-01

    Mefloquine is an antimalarial drug that has been commonly used in military settings since its development by the US military in the late 1980s. Owing to the drug's neuropsychiatric contraindications and its high rate of inducing neuropsychiatric symptoms, which are contraindications to the drug's continued use, the routine prescribing of mefloquine in military settings may be problematic. Due to these considerations and to recent concerns of chronic and potentially permanent psychiatric and neurological sequelae arising from drug toxicity, military prescribing of mefloquine has recently decreased. In settings where mefloquine remains available, policies governing prescribing should reflect risk-benefit decision-making informed by the drug's perceived benefits and by consideration both of the risks identified in the drug's labeling and of specific military risks associated with its use. In this review, these risks are identified and recommendations are made for the rational prescribing of the drug in light of current evidence.

  6. Rational Risk-Benefit Decision-Making in the Setting of Military Mefloquine Policy

    PubMed Central

    Nevin, Remington L.

    2015-01-01

    Mefloquine is an antimalarial drug that has been commonly used in military settings since its development by the US military in the late 1980s. Owing to the drug's neuropsychiatric contraindications and its high rate of inducing neuropsychiatric symptoms, which are contraindications to the drug's continued use, the routine prescribing of mefloquine in military settings may be problematic. Due to these considerations and to recent concerns of chronic and potentially permanent psychiatric and neurological sequelae arising from drug toxicity, military prescribing of mefloquine has recently decreased. In settings where mefloquine remains available, policies governing prescribing should reflect risk-benefit decision-making informed by the drug's perceived benefits and by consideration both of the risks identified in the drug's labeling and of specific military risks associated with its use. In this review, these risks are identified and recommendations are made for the rational prescribing of the drug in light of current evidence. PMID:26579231

  7. Psoriasis triggered by mefloquine.

    PubMed

    Pace, Joseph L

    2010-01-01

    A 46-year-old Caucasian man living on the central Mediterranean island of Gozo (Malta) was started on mefloquine 250 mg once weekly before a trip to lower Egypt. He took his medication 1 week before starting his holiday and was advised to continue it for 4 weeks after returning. He did not take any other medication and enjoyed the holiday, which he initially intended to repeat in the near future. His medical history revealed a number of episodes of psoriasis for which he sought dermatologic advice. He had been given systemic therapy on at least one occasion, but the condition had been fairly quiescent for some time and he had not needed to consult a dermatologist for more than 4 years. Soon after the third tablet of mefloquine and effectively just after his return home to Gozo, the patient noticed that the psoriasis was "creeping back." He noted progressive deterioration in his skin problem but nevertheless finished the recommended course of therapy considering that "being sure about not developing malaria was far more important than a touch of psoriasis." The psoriasis worsened to the extent that he had taken off work for 2 weeks from his job as a self-employed carpenter at the time of referral. On examination, clearly there was a significant flare up of his psoriasis with severe involvement of the hands (Figure 1) and feet and less so over the rest of his body. He had been off work and matters were steadily getting worse in spite of topical treatment with a combination of calcipotriol-betamethasone ointment. Oral methotrexate 15 mg once weekly was commenced together with topical therapy with good results (Figure 2). PMID:21137644

  8. Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice.

    PubMed

    Abou-Shady, Omaima Mohammed; Mohammed, Soheir Sayed; Attia, Samar Sayed; Yusuf, Hebat-Allah Salah; Helmy, Dina Omar

    2016-06-01

    Schistosomiasis is one of the most prevalent parasitic infections worldwide. Praziquantel is the drug of choice for treatment of schistosomiasis for its high efficacy. The present work was carried out on 160 mice to evaluate the therapeutic effect of mefloquine on experimental schistosomiasis mansoni. Mice were classified into 3 groups; group I (20 infected non-treated mice), group II included 60 infected mice which were further divided into group IIm (20 mice treated with 400 mg/kg mefloquine), group IIp (20 mice treated with 1,000 mg/kg/2 days praziquantel) and group IIpm (20 mice treated with 200 mg/kg mefloquine and 500 mg/kg praziquantel), group III included 80 non-infected mice subdivided into group IIIn (20 non-treated mice), group IIIm (20 mice treated with 400 mg/kg mefloquine), group IIIp (20 mice treated with 1,000 mg/kg/2 days praziquantel), group IIIpm (20 mice treated with 200 mg mefloquine and 500 mg praziquantel). Mefloquine significantly reduced worm burden, tissue egg load, number of liver granulomas and increased the percent of dead ova within granulomas. Combination of mefloquine and praziquantel gave better curative effects than praziquantel or mefloquine given alone. PMID:27413290

  9. Mefloquine, a new type of compound against schistosomes and other helminthes in experimental studies.

    PubMed

    Xiao, Shu-hua

    2013-11-01

    Up to date, schistosomiasis is still prevalent worldwide. It is estimated that more than 200 million individuals are infected, and 120 million suffer from clinical morbidity. Facing such huge cases of schistosomiasis, only heavy reliance on a single praziquantel for schistosomiasis control does not adapt and may promote the selection and spread of drug-resistant parasites. Therefore, it is an urgent need to develop the new antischistosomal drug. In 2008-2009, the antimalarial drug mefloquine, an arylaminoalcohol compound, has been found to be effective against schistosomes. According to the experimental studies, the deepest impression on the antischistosomal properties of mefloquine can be summarized as following points: (1) single dose of mefloquine possesses potential effect against three major species of schistosomes (Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum) infecting humans; (2) the drug displays similar effects against developing stages of juvenile and adult schistosomes, which are superior to that of artemisinins and praziquantel; (3) in vitro mefloquine exerts direct killing effect on juvenile and adult schistosomes, while in vivo, the efficacy of the drug is independent to host immune response, (4) mefloquine causes extensive and severe morphological, histopathological, and ultrastructural damage to adult and juvenile schistosomes, particularly, the worm tegument, musculature, gut, and vitelline glands of female worms are the key sites attacked by the drug; (5) combined treatment with mefloquine and praziquantel, or artemisinins shows synergistic effect against schistosome in experimental therapy,while in initially clinical trial, mefloquine in combination with artesunate also exhibits higher cure rates against schistosomiasis hematobia and schistosomiasis mansoni, and (6) several mefloquine-related arylmethanols exhibit potential effect against schistosomes in vivo, which is a useful clue helpful for development of new

  10. New Recommendations for Mefloquine Use in Pregnancy

    MedlinePlus

    ... CDC Malaria Branch clinician. malaria@cdc.gov Update: New Recommendations for Mefloquine Use in Pregnancy Recommend on Facebook Tweet Share Compartir Update: New Recommendations for Mefloquine Use in Pregnancy The Centers ...

  11. In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine.

    PubMed

    Shalaby, Hatem A; El Namaky, Amira H; Kamel, Reem O A

    2016-03-01

    Emergence of drug-resistant Fasciola strains has drawn the attention of many authors to alternative drugs. The purpose of this study is to explore the in vitro effect of the antimalarial mefloquine against adult Fasciola gigantica. Light and scanning electron microscopic observations could be used to determine the target of the drug following 6 and 12 h of incubation in medium containing mefloquine at three different concentrations 10, 20 and 30 μg/mL, as morphological changes could be observed. These changes occurred in definite sequences in response to mefloquine, and were consisted of swelling, vacuolization that was later disrupted, leading to desquamation of the tegument, resulting in exposure and disruption of basal lamina and the dislodging of spines. It is concluded that mefloquine presented itself as a drug that might become important in trematode chemotherapy, with the tegument being an important drug target. PMID:27065615

  12. Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data

    PubMed Central

    2011-01-01

    Background Use of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data. Methods Data on the use of mefloquine in children, particularly in young children weighing less than 20 kg, were reviewed using PubMed literature and reports on file. Results Chemoprophylaxis data: Two studies with a total of 170 children were found. A simulated mefloquine plasma profile showed that doses to achieve protective chemoprophylaxis blood concentration of mefloquine of approximately 620 ng/mL (or 1.67 μmol/L) in children should be at least 5 mg/kg. This simulated plasma profile in children corresponds to that seen in adult travellers using a weekly prophylaxis dose of 250 mg. This reinforces current practice of using weight-based dosage for children. Clearance per body weight is higher in older children. For children who travel to malaria risk areas tablets can be broken and crushed as required. It is necessary to disguise the bitter taste of the drug. Treatment data: Mefloquine treatment (alone or in combination) data are available for more than 6000 children of all age and weight categories. The stereoselectivity and pharmacokinetic profile of mefloquine in children is similar to that observed in adults. There is higher clearance in older children (aged 5-12 years) compared to younger children (aged 6-24 months). Mefloquine treatment is well tolerated in infants (5-12 kg) but vomiting is a problem at high doses. This led to the use of a "split dose" regimen with 15 mg/kg initially, followed 12 hours later by 10 mg/kg. Mefloquine 125 mg has been used as intermittent preventive treatment (IPT) and was found to be efficacious in reducing episodes of malaria in a moderate-transmission setting but vomiting was a problem in 8% of children aged 2-11 months. Mefloquine is also used as a component of artemisinin combination therapy (ACT) in small children. The combination artesunate plus mefloquine is a WHO approved first

  13. Malaria Prevention, Mefloquine Neurotoxicity, Neuropsychiatric Illness, and Risk-Benefit Analysis in the Australian Defence Force.

    PubMed

    McCarthy, Stuart

    2015-01-01

    The Australian Defence Force (ADF) has used mefloquine for malaria chemoprophylaxis since 1990. Mefloquine has been found to be a plausible cause of a chronic central nervous system toxicity syndrome and a confounding factor in the diagnosis of existing neuropsychiatric illnesses prevalent in the ADF such as posttraumatic stress disorder and traumatic brain injury. Overall health risks appear to have been mitigated by restricting the drug's use; however serious risks were realised when significant numbers of ADF personnel were subjected to clinical trials involving the drug. The full extent of the exposure, health impacts for affected individuals, and consequences for ADF health management including mental health are not yet known, but mefloquine may have caused or aggravated neuropsychiatric illness in large numbers of patients who were subsequently misdiagnosed and mistreated or otherwise failed to receive proper care. Findings in relation to chronic mefloquine neurotoxicity were foreseeable, but this eventuality appears not to have been considered during risk-benefit analyses. Thorough analysis by the ADF would have identified this long-term risk as well as other qualitative risk factors. Historical exposure of ADF personnel to mefloquine neurotoxicity now also necessitates ongoing risk monitoring and management in the overall context of broader health policies.

  14. Malaria Prevention, Mefloquine Neurotoxicity, Neuropsychiatric Illness, and Risk-Benefit Analysis in the Australian Defence Force.

    PubMed

    McCarthy, Stuart

    2015-01-01

    The Australian Defence Force (ADF) has used mefloquine for malaria chemoprophylaxis since 1990. Mefloquine has been found to be a plausible cause of a chronic central nervous system toxicity syndrome and a confounding factor in the diagnosis of existing neuropsychiatric illnesses prevalent in the ADF such as posttraumatic stress disorder and traumatic brain injury. Overall health risks appear to have been mitigated by restricting the drug's use; however serious risks were realised when significant numbers of ADF personnel were subjected to clinical trials involving the drug. The full extent of the exposure, health impacts for affected individuals, and consequences for ADF health management including mental health are not yet known, but mefloquine may have caused or aggravated neuropsychiatric illness in large numbers of patients who were subsequently misdiagnosed and mistreated or otherwise failed to receive proper care. Findings in relation to chronic mefloquine neurotoxicity were foreseeable, but this eventuality appears not to have been considered during risk-benefit analyses. Thorough analysis by the ADF would have identified this long-term risk as well as other qualitative risk factors. Historical exposure of ADF personnel to mefloquine neurotoxicity now also necessitates ongoing risk monitoring and management in the overall context of broader health policies. PMID:26793391

  15. Malaria Prevention, Mefloquine Neurotoxicity, Neuropsychiatric Illness, and Risk-Benefit Analysis in the Australian Defence Force

    PubMed Central

    McCarthy, Stuart

    2015-01-01

    The Australian Defence Force (ADF) has used mefloquine for malaria chemoprophylaxis since 1990. Mefloquine has been found to be a plausible cause of a chronic central nervous system toxicity syndrome and a confounding factor in the diagnosis of existing neuropsychiatric illnesses prevalent in the ADF such as posttraumatic stress disorder and traumatic brain injury. Overall health risks appear to have been mitigated by restricting the drug's use; however serious risks were realised when significant numbers of ADF personnel were subjected to clinical trials involving the drug. The full extent of the exposure, health impacts for affected individuals, and consequences for ADF health management including mental health are not yet known, but mefloquine may have caused or aggravated neuropsychiatric illness in large numbers of patients who were subsequently misdiagnosed and mistreated or otherwise failed to receive proper care. Findings in relation to chronic mefloquine neurotoxicity were foreseeable, but this eventuality appears not to have been considered during risk-benefit analyses. Thorough analysis by the ADF would have identified this long-term risk as well as other qualitative risk factors. Historical exposure of ADF personnel to mefloquine neurotoxicity now also necessitates ongoing risk monitoring and management in the overall context of broader health policies. PMID:26793391

  16. Population pharmacokinetics of mefloquine, administered as a fixed-dose combination of artesunate-mefloquine in Indian patients for the treatment of acute uncomplicated Plasmodium falciparum malaria

    PubMed Central

    2014-01-01

    Background Fixed-dose combinations of artemisinin combination therapy are strongly recommended to facilitate drug administration and compliance. New fixed-dose combinations must nevertheless be evaluated in relevant populations in terms of efficacy and pharmacokinetics. Methods A single-arm, open-label, clinical trial was performed in Indian patients with acute uncomplicated Plasmodium falciparum malaria to investigate the efficacy and the pharmacokinetics of mefloquine when combined with artesunate in a fixed-dose combination (400/200 mg of mefloquine base/artesunate). The pharmacokinetic analysis was performed using a population approach. Results Seventy-seven patients were included in the study. Mefloquine pharmacokinetics obeys a two-compartment model with first-order absorption and elimination. Mean parameter estimates (% inter-individual variability) were as follows: 0.16 h-1 (75%) for the absorption rate constant, 1.13 L/h (30%) for the apparent plasma clearance, 271 L (21%) for the apparent central distribution volume, 344 L (54%) for the apparent peripheral distribution volume, and 1.43 L/h for the apparent distribution clearance. These values were consistent with the pharmacokinetic results described in Thai patients. No significant covariate was found for clearance. Body weight explained the inter-individual variability of the apparent central and peripheral distribution volumes. The PCR-adjusted efficacy of the treatment was 100%. Conclusions The lack of significant covariate explaining the inter-individual variability of mefloquine clearance, combined with the excellent efficacy, supports the use of the standard 200/400 mg of artesunate-mefloquine fixed-dose combination in Indian patients with uncomplicated P. falciparum malaria. Trial Registration Clinical Trial Registration: ISRCTN70618692 PMID:24886117

  17. In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis.

    PubMed

    Liu, Congshan; Zhang, Haobing; Yin, Jianhai; Hu, Wei

    2015-06-01

    Echinococcus granulosus is a cestode parasite. The metacestode stage causes cystic echinococcosis (CE) mainly in the human liver and lung. Current chemotherapy against CE is based on mebendazole and albendazole. However, benzimidazoles result in a low cure rate or are ineffective in many patients; therefore, novel compounds for the treatment of this disease have been studied. Mefloquine was reported to be dramatically effective on cultured Echinococcus multilocularis metacestodes in vitro. And, nitazoxanide has a prominent protoscolicidal effect. However, these compounds have no impact on the growth of cysts harbored in mice. In this study, we investigated the in vitro and in vivo efficacy of mebendazole, mefloquine, and nitazoxanide against E. granulosus protoscoleces, germinal cells, and infected mice. The effect of mebendazole on protoscoleces and germinal cell was proved to be dose-dependent in vitro. And, a reduction of the cyst weight was also the found after oral application of mebendazole to infected mice. Mefloquine (5 and 10 μg/ml) caused death within 24 h of protoscoleces and germinal cells in vitro, whereas a lower concentration of 1 μg/ml was ineffective. In mice infected with E. granulosus, oral mefloquine (200 and 400 mg/kg twice weekly for 2 weeks) showed no reduction in parasite weight. Without affecting the viability of germinal cells and the growth of hydatid cysts, nitazoxanide only showed protoscolicidal effects in infected mice. In conclusion, mebendazole, mefloquine, and nitazoxanide showed various effects on E. granulosus under different conditions. These drugs could be useful to some extent in the treatment of CE.

  18. Rifampicin/Cotrimoxazole/Isoniazid Versus Mefloquine or Quinine + Sulfadoxine- Pyrimethamine for Malaria: A Randomized Trial

    PubMed Central

    Genton, Blaise; Mueller, Ivo; Betuela, Inoni; Casey, Gerard; Ginny, Meza; Alpers, Michael P; Reeder, John C

    2006-01-01

    Objectives: Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea. Design: The trial design was open-label, block-randomised, comparative, and multicentric. Setting: The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea. Participants: Patients of all ages with recurrent uncomplicated malaria were included. Interventions: Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine–pyrimethamine (SP). Outcome Measures: Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded. Results: The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]). Conclusion: Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria. PMID:17192794

  19. Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine.

    PubMed

    Perez-Cortes, E J; Islas, A A; Arevalo, J P; Mancilla, C; Monjaraz, E; Salinas-Stefanon, E M

    2015-10-15

    The antimalarial drug mefloquine, is known to be a potassium channel blocker, although its mechanism of action has not being elucidated and its effects on the transient outward current (Ito) and the molecular correlate, the Kv4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular Ito and of CHO cells co-transfected with human Kv4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat Ito and hKv4.3+KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC50=8.9μM and 10.5μM for cardiac myocytes and Kv4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hKv4.3 steady-state inactivation and recovery from inactivation. The effects of this drug was compared with that of 4-aminopyridine (4-AP), a well-known potassium channel blocker and its binding site does not seem to overlap with that of 4-AP.

  20. Computational Study of Quinolone Derivatives to Improve their Therapeutic Index as Anti-malaria Agents: QSAR and QSTR

    PubMed Central

    Iman, Maryam; Davood, Asghar; Khamesipour, Ali

    2015-01-01

    Malaria is a parasitic disease caused by five different species of Plasmodium. More than 40% of the world’s population is at risk and malaria annual incidence is estimated to be more than two hundred million, malaria is one of the most important public health problems especially in children of the poorest parts of the world, annual mortality is about 1 million. The epidemiological status of the disease justifies to search for control measures, new therapeutic options and development of an effective vaccine. Chemotherapy options in malaria are limited, moreover, drug resistant rate is high. In spite of global efforts to develop an effective vaccine yet there is no vaccine available. In the current study, a series of quinolone derivatives were subjected to quantitative structure activity relationship (QSAR) and quantitative structure toxicity relationship (QSTR) analyses to identify the ideal physicochemical characteristics of potential anti-malaria activity and less cytotoxicity. Quinolone with desirable properties was built using HyperChem program, and conformational studies were performed through the semi-empirical method followed by the PM3 force field. Multi linear regression (MLR) was used as a chemo metric tool for quantitative structure activity relationship modeling and the developed models were shown to be statistically significant according to the validation parameters. The obtained QSAR model reveals that the descriptors PJI2, Mv, PCR, nBM, and VAR mainly affect the anti-malaria activity and descriptors MSD, MAXDP, and X1sol affect the cytotoxicity of the series of ligands. PMID:26330866

  1. Artesunate–mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

    PubMed Central

    Grigg, Matthew J; William, Timothy; Menon, Jayaram; Dhanaraj, Prabakaran; Barber, Bridget E; Wilkes, Christopher S; von Seidlein, Lorenz; Rajahram, Giri S; Pasay, Cielo; McCarthy, James S; Price, Ric N

    2016-01-01

    Summary Background The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate–mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. Methods We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate–mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Findings Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate–mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76–91]) of 115 patients in the artesunate–mefloquine group versus 61 (55% [45–64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0–40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate–mefloquine than in those given chloroquine (18·0 h [range 6·0–48·0] vs 24·0 h [6·0–60·0]; p<0·0001), with faster clearance of ring stages in the artesunate–mefloquine group (mean time to 50% clearance

  2. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.

    PubMed

    Nasveld, Peter E; Edstein, Michael D; Reid, Mark; Brennan, Leonard; Harris, Ivor E; Kitchener, Scott J; Leggat, Peter A; Pickford, Philip; Kerr, Caron; Ohrt, Colin; Prescott, William

    2010-02-01

    This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis. PMID:19995933

  3. High prevalence of mefloquine-resistant falciparum malaria in eastern Thailand.

    PubMed Central

    Fontanet, A. L.; Johnston, D. B.; Walker, A. M.; Rooney, W.; Thimasarn, K.; Sturchler, D.; Macdonald, M.; Hours, M.; Wirth, D. F.

    1993-01-01

    In order to assess the risk and predictors of mefloquine resistance we monitored a cohort of 113 patients in eastern Thailand who had been treated for uncomplicated falciparum malaria with a single dose of 15 mg/kg of the drug and followed up for 42 days. The overall treatment failure rate at day 42 was 59.1% (95% confidence interval (CI) = 50%, 68%) with only 2.7% of the patients being lost to follow-up. There were 6.4% RIII, 20.9% RII, 31.8% RI, and 40.9% sensitive responses, based on a modified WHO classification. A low haemoglobin level on the day of treatment and diarrhoea during the first two days after treatment were independent predictors of treatment failure. These findings remained statistically significant in a Cox proportional hazards model, after controlling for other baseline characteristics and adverse effects. Although a history of digestive disorders prior to treatment was associated with diarrhoea on day 2 (P = 0.024), it was in itself not a predictor of treatment failure (adjusted hazard ratio = 1.16; 95% CI = 0.35, 2.14). A total of 60 patients with an R response were hospitalized for 7 days to receive supervised treatment with quinine-tetracycline. Only three had a positive thick smear for asexual forms of Plasmodium falciparum 14 days later, and quinine-tetracycline therefore remains a good alternative treatment for mefloquine-resistant falciparum malaria. PMID:8324857

  4. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso

    PubMed Central

    Valea, Innocent; Tinto, Halidou; Traore/Coulibaly, Maminata; Toe, Laeticia C.; Lindegardh, Niklas; Tarning, Joel; Van Geertruyden, Jean-Pierre; D'Alessandro, Umberto; Davies, Geraint R.; Ward, Stephen A.

    2014-01-01

    Objectives Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria. Methods Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961). Results The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P > 0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656 700 versus 542 400 h × ng/mL; P = 0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735 600 versus 1 499 000 h × ng/mL; P < 0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P = 0.039) compared with non-pregnant controls. Conclusions The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better

  5. Mefloquine in combination with hemin causes severe damage to adult Schistosoma japonicum in vitro.

    PubMed

    Xiao, Shu-hua; Qiao, Chunhua; Xue, Jian; Wang, Lili

    2014-03-01

    In order to explore the interaction of mefloquine with hemin against adult Schistosoma japonicum in vitro, the 50% and 95% lethal concentration (LC50 and LC95) of mefloquine and hemin against schistosomes, some factors, such as other iron providing agents, iron chelaters, zinc protoporphyrin-IX, and biological relevant reductants, that might impact on antischistosomal activity induced by interaction of mefloquine with hemin, and preliminary analysis of chemical interaction of both compounds were undertaken. The LC50 and LC95 of mefloquine and hemin alone against schistosomes were determined to be 6.5μg/ml and 7.8μg/ml as well as 232μg/ml and 355μg/ml, respectively. The LC50 and LC95 of mefloquine in the presence of hemin 100μg/ml was 0.24μg/ml and 0.59μg/ml, respectively. On the other hand the LC50 and LC95 of hemin in the presence of mefloquine 1μg/ml was 23.2μg/ml and 77.2μg/ml, respectively. Meanwhile, mefloquine/hemin combinations showed potential synergistic effects against adult S. japonicum, with combination index (CI) values <1. Apart from hemin, zinc protoporphyrin-IX, and other iron providing agents such as ferrous sulfate and ferriammonium sulfate combined with mefloquine exhibited no toxic effect against schistosomes. On the other hand, addition of iron chelators (deferiprone, desferrioxamine mesylate, or 2,2'-bipyridine) to the medium containing mefloquine-hemin resulted in no protective effect on the worms. Furthermore, biological reductants like glutathione, vitamine C or cysteine showed no apparent worm protection effect from toxic mefloquine-hemin even at higher concentrations (242.3-614.6μg/ml, i.e., 6.4-17.8-fold higher than the concentration of hemin). Chemical interaction of mefloquine with hemin was studied in 40% DMSO-Tris buffer solution. Both UV-Vis spectrum and mass spectrum demonstrated the strong interaction of mefloquine with hemin, which resulted in a reduction of hemin color and emergence of an adduct formed by mefloquine

  6. Artemisinin--an innovative cornerstone for anti-malaria therapy.

    PubMed

    Kuhn, Thomas; Wang, Ying

    2008-01-01

    Artemisinin-based Combination Therapies (ACT) are recommended by the World Health Organization (WHO) to treat especially multidrug resistant forms of malaria, as currently used medications have become increasingly ineffective. In this chapter, the discovery of artemisinin from Traditional Chinese Medicine and its further development to ACT are reviewed. It is highlighted how the complex supply chain to the naturally occurring endoperoxide artemisinin, required to produce ACT-based drugs, was established; thus addressing the significant therapeutic needs and high demands for the medication.

  7. Historical perspectives on malaria: the Rockefeller antimalaria strategy in the 20th century.

    PubMed

    Stapleton, Darwin H

    2009-10-01

    Malaria, a serious disease for all of human history, was not effectively handled until methods for control of its insect vector, the Anopheles mosquito, were developed at the beginning of the 20th century. The Rockefeller Foundation's antimalaria program spread vector-control strategies throughout the world, and its adoption of dichlorodiphenyltrichloroethane during World War II created an especially powerful and effective malaria control strategy. However, insect resistance to dichlorodiphenyltrichloroethane and restrictions on dichlorodiphenyltrichloroethane use due to its long-term environmental effects are factors in the persistence of malaria as a serious health problem. Mt Sinai J Med 76:468-473, 2009. (c) 2009 Mount Sinai School of Medicine.

  8. Synthesis, structures and anti-malaria activity of some gold(I) phosphine complexes containing seleno- and thiosemicarbazonato ligands.

    PubMed

    Molter, Anja; Rust, Jörg; Lehmann, Christian W; Deepa, Ganesh; Chiba, Peter; Mohr, Fabian

    2011-10-14

    A series of both mono- and dinuclear gold(I) phosphine complexes containing monoanionic seleno- and thiosemicarbazones as ligands were prepared and fully characterized by spectroscopic methods and, in some cases, by single crystal X-ray diffraction. The in vitro anti-malaria activity of some of these compounds was investigated in chloroquine sensitive strains of Plasmodium falciparum. The IC(50) results show that the sulfur containing compounds exhibit activity similar to that of chloroquine, whilst the selenium derivatives display only moderate anti-malaria activity. PMID:21879088

  9. Synthesis, structures and anti-malaria activity of some gold(I) phosphine complexes containing seleno- and thiosemicarbazonato ligands.

    PubMed

    Molter, Anja; Rust, Jörg; Lehmann, Christian W; Deepa, Ganesh; Chiba, Peter; Mohr, Fabian

    2011-10-14

    A series of both mono- and dinuclear gold(I) phosphine complexes containing monoanionic seleno- and thiosemicarbazones as ligands were prepared and fully characterized by spectroscopic methods and, in some cases, by single crystal X-ray diffraction. The in vitro anti-malaria activity of some of these compounds was investigated in chloroquine sensitive strains of Plasmodium falciparum. The IC(50) results show that the sulfur containing compounds exhibit activity similar to that of chloroquine, whilst the selenium derivatives display only moderate anti-malaria activity.

  10. Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial

    PubMed Central

    2012-01-01

    Background Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. Methods The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Results Overall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Conclusion Artesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients. PMID:23234606

  11. Influence of mefloquine administration during early pregnancy on rat embryonic development.

    PubMed

    El-Dakdoky, Mai Helmy

    2015-02-01

    Mefloquine (MQ) is a potent effective antimalarial drug against multiple drug-resistant Plasmodium falciparum. It has been proved that MQ can be given safely during the second and third trimesters. However, there is very limited information on the drug safety during the first trimester. The aim of the present work was to investigate the embryotoxicity and teratogenicity of MQ during critical periods of early development. Wistar rats were orally administered with a single dose of MQ (45 mg/kg bwt or 187 mg/kg bwt) on the 1st, 6th or 13th days of pregnancy. Cyclophosphamide (CPA) was chosen as a positive control. On the 21st day of gestation, standard parameters of reproductive performance and fetal examination were estimated. Malondialdehyde (MDA) level, glutathione reductase activity and glutathione (GSH) content were evaluated in placenta and liver homogenates of mothers and fetuses. The results indicated that MQ did not adversely affect the number of implantation, resorption, litter size and fetal body weight and length. Only groups treated with MQ on the 1st day of gestation exhibited significant decrease in fetal body weight. Examination of fetuses for external, visceral and skeletal changes showed minimal variations involving extension of lateral brain ventricles and renal pelvis and signs of delayed ossification. These variations were accompanied with significant elevation of MDA level and reduction of GSH content of fetal liver. Prenatal exposure to MQ at early pregnancy did not cause any embryolethal or teratogenic effect. It could slightly exacerbate minor variations. PMID:25406758

  12. Behavioral effects of mefloquine in tail suspension and light/dark tests.

    PubMed

    Holden, John Michael; Slivicki, Richard; Dahl, Rachel; Dong, Xia; Dwyer, Matt; Holley, Weston; Knott, Crissa

    2015-01-01

    Mefloquine hydrochloride has been used widely in the past few decades for malaria prophylaxis and treatment. However, in recent years, it has fallen out of favor due to reports of exposure being linked to numerous neuropsychiatric effects, including emotional disturbances. In this study we examined the effects of different doses (5, 25, or 100 mg/kg) of mefloquine relative to vehicle on male C57BL/6 J mice in two tests of emotional behavior, the light-dark box and the tail suspension test. It was found that mefloquine exposure reduced anxiety-linked behaviors in the light-dark box and reduced total immobility times in the tail suspension test, especially at higher doses. Our results lend support to the notion that mefloquine exposure could induce emotional disinhibition.

  13. A Systems Thinking Framework for Assessing and Addressing Malaria Locally: An Alternative to the Globalization of Anti-Malaria Policies

    ERIC Educational Resources Information Center

    Willis, Derek W.

    2010-01-01

    This dissertation analyzes a decision system that was used in the early 1900s in the Federated Malay States (FMS) by Malcolm Watson in order to make anti-malaria program recommendations to decision makers in a wide range of ecological settings. Watson's recommendations to decision makers throughout the FMS led to a dramatic suppression of malaria…

  14. In vitro response of chloroquine-resistant Plasmodium falciparum to mefloquine.

    PubMed

    López Antuñano, F J; Wernsdorfer, W H

    1979-01-01

    The present study was conducted to evaluate the application of the in vitro microtechnique system in determining the response of chloroquine-resistant Plasmodium falciparum to mefloquine.Using isolates of P. falciparum from Boa Vista, Brazil, and Villavicencio, Colombia, mefloquine was more than 7.7, 7.1, 7.1, and 6.4 times more effective than chloroquine in vitro at the ED(90), ED(95), ED(99), and ED(99.9) levels, respectively.

  15. Impact assessment of IEC campaign during anti-malaria month, June 1998 through KABP study.

    PubMed

    Sharma, S N; Saxena, N B; Phukan, P K; Anjan, J K; Pandya, A P; Lal, S

    2000-03-01

    To assess the IEC Campaign during anti malaria month (June, 98), a base line KABP study through pre-assessment and post-assessment was conducted in the State of Gujarat (four districts namely Ahmedabad, Dang, Panchmahal and Baroda). The study was carried out based on questionnaire (open and closed) developed by NAMP in the randomly selected population. A rapid assessment of the current level of KABP among a sample of population before and after the observance of anti-malaria month. The results of the KABP study revealed that there is definite impact (between 2.18 to 30%) and change in the KABP of the local people, where intensive and continuous I.E.C. activities are being undertaken. In order to achieve the desired change in knowledge, attitude, behaviour and practice of the respondents, it requires continuous I.E.C. campaign throughout the year. The attitude, behaviour and practice in the hard core areas need special efforts, where maximum efforts are required to bring a change in. It should be taken more intensively in the problematic and hardcore areas on priority basis. PMID:11129565

  16. Malaria-Infected Mice Live Until At Least Day 30 After A New Artemisinin-Derived Thioacetal Thiocarbonate Combined with Mefloquine Are Administered Together In A Single, Low, Oral Dose

    PubMed Central

    Jacobine, Alexander M.; Mazzone, Jennifer R.; Slack, Rachel D.; Tripathi, Abhai K.; Sullivan, David J.; Posner, Gary H.

    2012-01-01

    In only three steps and in 21–67% overall yields from the natural trioxane artemisinin, a series of 21 new trioxane C-10 thioacetals was prepared. Upon receiving a single oral dose of only 6 mg/kg of the monomeric trioxane 12c combined with 18 mg/kg of mefloquine hydrochloride, Plasmodium berghei-infected mice survived on average 29.8 days after infection. Two of the four mice in this group had no parasites detectable in their blood on day 30 after infection and they behaved normally and appeared healthy. One of the mice had 11% blood parasitemia on day 30, and one mouse in this group died on day 29. Of high medicinal importance, the efficacy of this ACT chemotherapy is much better than (almost double) the efficacy under the same conditions using as a positive control the popular trioxane drug artemether plus mefloquine hydrochloride (average survival time of only 16.5 days). PMID:22891714

  17. Severe neuropsychiatric reaction in a deployed military member after prophylactic mefloquine.

    PubMed

    Peterson, Alan L; Seegmiller, Robert A; Schindler, Libby S

    2011-01-01

    Recent studies of military personnel who have deployed to Iraq and Afghanistan have reported a number of combat-related psychiatric disorders such as posttraumatic stress disorder, depression, and traumatic brain injury. This case report involves a 27-year-old male active-duty US military service member who developed severe depression, psychotic hallucinations, and neuropsychological sequelae following the prophylactic use of the antimalarial medication mefloquine hydrochloride. The patient had a recent history of depression and was taking antidepressant medications at the time of his deployment to the Middle East. Psychiatrists and other health care providers should be aware of the possible neuropsychiatric side effects of mefloquine in deployed military personnel and should consider the use of other medications for malaria prophylaxis in those individuals who may be at increased risk for side effects. PMID:22937403

  18. Reversible binocular visual loss in temporal association with artesunate-amodiaquine treatment in a child on mefloquine chemoprophylaxis.

    PubMed

    Adjei, G O; Adabayeri, V M; Annobil, S H

    2012-09-01

    A case of an acute reversible visual loss in a 10-year-old child who was on mefloquine prophylaxis, and was treated with artesunate-amodiaquine for an acute febrile illness diagnosed clinically as uncomplicated malaria, is reported. On admission the patient could not perceive light and had bilateral papilloedema. She was treated with dexamethasone and recovered her sight gradually over a 21-day period. There has been no previous report to our knowledge, of an association between acute visual loss and mefloquine, amodiaquine, or artesunate in the published literature, even though mefloquine is associated with blurring of vision, and antimalarials of the quinoline class have been associated with retinopathy (during long term use). While causality is difficult to ascribe in this case, it may be prudent to avoid the use of quinoline-based antimalarials for treating acute malaria in travelers taking mefloquine prophylaxis, because information on the safety of concurrent use of artemisinin combination therapies and mefloquine, or other recommended prophylactic regimens, is limited.

  19. Flux Balance Analysis with Objective Function Defined by Proteomics Data-Metabolism of Mycobacterium tuberculosis Exposed to Mefloquine.

    PubMed

    Montezano, Daniel; Meek, Laura; Gupta, Rashmi; Bermudez, Luiz E; Bermudez, José C M

    2015-01-01

    We present a study of the metabolism of the Mycobacterium tuberculosis after exposure to antibiotics using proteomics data and flux balance analysis (FBA). The use of FBA to study prokaryotic organisms is well-established and allows insights into the metabolic pathways chosen by the organisms under different environmental conditions. To apply FBA a specific objective function must be selected that represents the metabolic goal of the organism. FBA estimates the metabolism of the cell by linear programming constrained by the stoichiometry of the reactions in an in silico metabolic model of the organism. It is assumed that the metabolism of the organism works towards the specified objective function. A common objective is the maximization of biomass. However, this goal is not suitable for situations when the bacterium is exposed to antibiotics, as the goal of organisms in these cases is survival and not necessarily optimal growth. In this paper we propose a new approach for defining the FBA objective function in studies when the bacterium is under stress. The function is defined based on protein expression data. The proposed methodology is applied to the case when the bacterium is exposed to the drug mefloquine, but can be easily extended to other organisms, conditions or drugs. We compare our method with an alternative method that uses experimental data for adjusting flux constraints. We perform comparisons in terms of essential enzymes and agreement using enzyme abundances. Results indicate that using proteomics data to define FBA objective functions yields less essential reactions with zero flux and lower error rates in prediction accuracy. With flux variability analysis we observe that overall variability due to alternate optima is reduced with the incorporation of proteomics data. We believe that incorporating proteomics data in the objective function used in FBA may help obtain metabolic flux representations that better support experimentally observed features

  20. Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

    PubMed Central

    Wurtz, Nathalie; Fall, Bécaye; Pascual, Aurélie; Fall, Mansour; Baret, Eric; Camara, Cheikhou; Nakoulima, Aminata; Diatta, Bakary; Fall, Khadidiatou Ba; Mbaye, Pape Saliou; Diémé, Yaya; Bercion, Raymond; Wade, Boubacar

    2014-01-01

    The involvement of Pfmdr1 (Plasmodium falciparum multidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms in Pfmdr1 (N86Y, Y184F, S1034C, N1042D, and D1246Y) and Pfcrt (K76T) and in vitro responses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174 Plasmodium falciparum isolates from Dakar, Senegal. The Pfmdr1 86Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. The Pfmdr1 86Y mutation was significantly associated with increased susceptibility to MDAQ (P = 0.0023), LMF (P = 0.0001), DHA (P = 0.0387), and MQ (P = 0.00002). The N86Y mutation was not associated with CQ (P = 0.214) or QN (P = 0.287) responses. The Pfmdr1 184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P = 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). The Pfmdr1 86Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P = 0.0136), LMF (P = 0.0019), and MQ (P = 0.0001). The additional Pfmdr1 86Y mutation increased significantly the in vitro susceptibility to MDAQ (P < 0.0001), LMF (P < 0.0001), MQ (P < 0.0001), and QN (P = 0.0026) in wild-type Pfcrt K76 parasites. The additional Pfmdr1 86Y mutation significantly increased the in vitro susceptibility to CQ (P = 0.0179) in Pfcrt 76T CQ-resistant parasites. PMID:25199781

  1. Factors affecting the use of anti-malaria preventive measures among Taiwan immigrants returning to malaria-endemic regions.

    PubMed

    Hung, Wen-Shin; Hu, Susan C; Hsu, Yu-Chen; Chen, Kwo-Liang; Chen, Kou-Huang; Yu, Mei-Ching; Chen, Kow-Tong

    2014-01-01

    The aim of this study was to investigate the predictors of anti-malaria preventive measures (AMPMs) among Taiwan immigrants returning to their country of origin using the Health Belief Model (HBM). Between March and May 2011, all permanent immigrants originating from malaria-endemic countries, attended by either the Taipei or Tainan Immigrant Service Center, Taiwan, and who reported a history of returning to their country of origin within the preceding year during the malarious season in their country of origin were enrolled in the study. Complete information was collected from 316 immigrants, with a response rate of 87% (316/364). The mean age of the subjects was 38.1 years (SD = 9.9). The majority (70%) of participants did not receive travel information through a pre-travel consultation; more than 40% reported that they did not use measures to prevent insect bites. Multiple regression analyses revealed that Chinese proficiency, travel consultation before travel, lower perceived susceptibility to malaria, higher perceived severity of malaria infection, higher perceived benefit for taking measures, and higher self-efficacy for taking measures significantly predicted the use of AMPMs during the return to their country of origin (R(2) = 0.20; F = 50.42; P < 0.001). A high proportion of immigrants were not using appropriate AMPMs when they returned to their country. Educational approaches should be targeted toward immigrants who return to visit their country of origin.

  2. Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

    PubMed

    Kurmann, Rebekka; Weisstanner, Christian; Kardas, Piotr; Hirsch, Hans H; Wiest, Roland; Lämmle, Bernhard; Furrer, Hansjakob; Du Pasquier, Renaud; Bassetti, Claudio L; Sturzenegger, Mathias; Krestel, Heinz

    2015-12-01

    Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy. PMID:25916731

  3. Mefloquine (Lariam)

    MedlinePlus

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  4. Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine.

    PubMed

    Alin, M H; Kihamia, C M; Bjorkman, A; Bwijo, B A; Premji, Z; Mtey, G J; Ashton, M

    1995-12-01

    The clinical efficacy of oral and intravenous (iv) artesunate was compared in an open randomized trial in 50 male adult patients with uncomplicated Plasmodium falciparum malaria in Kibaha, Tanzania. Oral artesunate treatment was started with 2 x 50 mg initially followed by 50 mg 12 hr later and then 50 mg twice a day for four days (total dose = 550 mg or 9.6 mg/kg). Intravenous artesunate administration began with 2 x 0.8 mg/kg initially followed by 0.8 mg/kg 12 hr later and then 0.8 mg/kg twice a day for four days (total dose = 8.8 mg/kg). The mean +/- SD parasite clearance times (PCTs) were nearly identical at 23.4 +/- 5.9 hr and 24.2 +/- 7.2 hr after oral and iv administration, respectively. Mean +/- SD fever subsidence times (FSTs) were also similar at 18.7 +/- 8.3 hr and 21.0 +/- 4.8 hr, respectively. All patients remained negative for P. falciparum for at least 14 days. Recrudescence/reinfection occurred between days 21 and 28 in five of 25 patients (20%) after oral treatment and in four of 25 patients (16%) after iv treatment. The mean erythrocyte count and hemoglobin concentration were slightly reduced after iv treatment but remained in the normal range. Otherwise, there was no change in blood biochemistry, hematology, and electrocardiograms monitored prior to and during the last dose. It is concluded that treatment with oral and iv artesunate was equally efficacious and well tolerated. A 24-hr in vitro susceptibility test of P. falciparum to artemisinin, chloroquine, and mefloquine was performed in samples from all patients. The three compounds exhibited 100% inhibition with the exception of three isolates, which showed chloroquine resistance. Parameter estimates of a sigmoid Emax model (drug concentration at which 50% of the growth inhibition occurs [EC50]), the sigmoidicity factor s and EC95 fitted to the growth inhibition data differed between compounds and isolates, indicating different sensitivity of P. falciparum isolates. There was no correlation

  5. Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a single dose of mefloquine.

    PubMed Central

    Fontanet, A. L.; Johnston, B. D.; Walker, A. M.; Bergqvist, Y.; Hellgren, U.; Rooney, W.

    1994-01-01

    Reported are the results of a randomized trial of a single dose of mefloquine (15 mg/kg or 25 mg/kg body weight) for the treatment of uncomplicated multidrug-resistant falciparum malaria. Of the 110 adult patients enrolled in the study 57 were randomly assigned to the 15 mg/kg group and 53 to the 25 mg/kg group. The baseline characteristics of the patients did not differ significantly in the two groups, except that those in the 15 mg/kg group had lower haemoglobin levels. Adverse effects following treatment were commoner in the 25 mg/kg group, but not significantly so. Seven patients (6%) did not complete the 42-day follow-up. The parasitological failure rates in the 15 and 25 mg/kg groups were, respectively, 50% (28/56) and 43% (25/53) on day 28, and 62% (33/53) and 56% (28/50) on day 42. Treatment failures were not correlated with the serum mefloquine concentrations on day 2, and 13 out of 19 patients with serum mefloquine concentrations > 2000 micrograms/l on day 2 showed an R response during the follow-up. The mean ratio between the concentrations of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine on day 2 was 3.37, indicating that there are differences in their pharmacokinetics. Re-treatment of patients who showed an R response with seven days of quinine (30 mg.kg-1.day-1)+tetracycline (25 mg.kg-1.day-1) was successful in 93% of the cases. PMID:8131253

  6. Central nervous system exposure of next generation quinoline methanols is reduced relative to mefloquine after intravenous dosing in mice

    PubMed Central

    2011-01-01

    Background The clinical use of mefloquine (MQ) has declined due to dose-related neurological events. Next generation quinoline methanols (NGQMs) that do not accumulate in the central nervous system (CNS) to the same extent may have utility. In this study, CNS levels of NGQMs relative to MQ were measured and an early lead chemotype was identified for further optimization. Experimental design The plasma and brain levels of MQ and twenty five, 4-position modified NGQMs were determined using LCMS/MS at 5 min, 1, 6 and 24 h after IV administration (5 mg/kg) to male FVB mice. Fraction unbound in brain tissue homogenate was assessed in vitro using equilibrium dialysis and this was then used to calculate brain-unbound concentration from the measured brain total concentration. A five-fold reduction CNS levels relative to mefloquine was considered acceptable. Additional pharmacological properties such as permeability and potency were determined. Results The maximum brain (whole/free) concentrations of MQ were 1807/4.9 ng/g. Maximum whole brain concentrations of NGQMs were 23 - 21546 ng/g. Maximum free brain concentrations were 0.5 to 267 ng/g. Seven (28%) and two (8%) compounds exhibited acceptable whole and free brain concentrations, respectively. Optimization of maximum free brain levels, IC90s (as a measure or potency) and residual plasma concentrations at 24 h (as a surrogate for half-life) in the same molecule may be feasible since they were not correlated. Diamine quinoline methanols were the most promising lead compounds. Conclusion Reduction of CNS levels of NGQMs relative to mefloquine may be feasible. Optimization of this property together with potency and long half-life may be feasible amongst diamine quinoline methanols. PMID:21645370

  7. Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon

    PubMed Central

    2013-01-01

    Background The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. Methods The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. Results As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. Conclusions The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10–20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health

  8. The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation.

    PubMed

    Senarathna, S M D K Ganga; Page-Sharp, Madhu; Crowe, Andrew

    2016-01-01

    The combination of passive drug permeability, affinity for uptake and efflux transporters as well as gastrointestinal metabolism defines net drug absorption. Efflux mechanisms are often overlooked when examining the absorption phase of drug bioavailability. Knowing the affinity of antimalarials for efflux transporters such as P-glycoprotein (P-gp) may assist in the determination of drug absorption and pharmacokinetic drug interactions during oral absorption in drug combination therapies. Concurrent administration of P-gp inhibitors and P-gp substrate drugs may also result in alterations in the bioavailability of some antimalarials. In-vitro Caco-2 cell monolayers were used here as a model for potential drug absorption related problems and P-gp mediated transport of drugs. Artemisone had the highest permeability at around 50 x 10(-6) cm/sec, followed by amodiaquine around 20 x 10(-6) cm/sec; both mefloquine and artesunate were around 10 x 10(-6) cm/sec. Methylene blue was between 2 and 6 x 10(-6) cm/sec depending on the direction of transport. This 3 fold difference was able to be halved by use of P-gp inhibition. MRP inhibition also assisted the consolidation of the methylene blue transport. Mefloquine was shown to be a P-gp inhibitor affecting our P-gp substrate, Rhodamine 123, although none of the other drugs impacted upon rhodamine123 transport rates. In conclusion, mefloquine is a P-gp inhibitor and methylene blue is a partial substrate; methylene blue may have increased absorption if co-administered with such P-gp inhibitors. An upregulation of P-gp was observed when artemisone and dihydroartemisinin were co-incubated with mefloquine and amodiaquine. PMID:27045516

  9. The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation.

    PubMed

    Senarathna, S M D K Ganga; Page-Sharp, Madhu; Crowe, Andrew

    2016-01-01

    The combination of passive drug permeability, affinity for uptake and efflux transporters as well as gastrointestinal metabolism defines net drug absorption. Efflux mechanisms are often overlooked when examining the absorption phase of drug bioavailability. Knowing the affinity of antimalarials for efflux transporters such as P-glycoprotein (P-gp) may assist in the determination of drug absorption and pharmacokinetic drug interactions during oral absorption in drug combination therapies. Concurrent administration of P-gp inhibitors and P-gp substrate drugs may also result in alterations in the bioavailability of some antimalarials. In-vitro Caco-2 cell monolayers were used here as a model for potential drug absorption related problems and P-gp mediated transport of drugs. Artemisone had the highest permeability at around 50 x 10(-6) cm/sec, followed by amodiaquine around 20 x 10(-6) cm/sec; both mefloquine and artesunate were around 10 x 10(-6) cm/sec. Methylene blue was between 2 and 6 x 10(-6) cm/sec depending on the direction of transport. This 3 fold difference was able to be halved by use of P-gp inhibition. MRP inhibition also assisted the consolidation of the methylene blue transport. Mefloquine was shown to be a P-gp inhibitor affecting our P-gp substrate, Rhodamine 123, although none of the other drugs impacted upon rhodamine123 transport rates. In conclusion, mefloquine is a P-gp inhibitor and methylene blue is a partial substrate; methylene blue may have increased absorption if co-administered with such P-gp inhibitors. An upregulation of P-gp was observed when artemisone and dihydroartemisinin were co-incubated with mefloquine and amodiaquine.

  10. The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation

    PubMed Central

    Senarathna, S M D K Ganga; Page-Sharp, Madhu; Crowe, Andrew

    2016-01-01

    The combination of passive drug permeability, affinity for uptake and efflux transporters as well as gastrointestinal metabolism defines net drug absorption. Efflux mechanisms are often overlooked when examining the absorption phase of drug bioavailability. Knowing the affinity of antimalarials for efflux transporters such as P-glycoprotein (P-gp) may assist in the determination of drug absorption and pharmacokinetic drug interactions during oral absorption in drug combination therapies. Concurrent administration of P-gp inhibitors and P-gp substrate drugs may also result in alterations in the bioavailability of some antimalarials. In-vitro Caco-2 cell monolayers were used here as a model for potential drug absorption related problems and P-gp mediated transport of drugs. Artemisone had the highest permeability at around 50 x 10−6 cm/sec, followed by amodiaquine around 20 x 10−6 cm/sec; both mefloquine and artesunate were around 10 x 10−6 cm/sec. Methylene blue was between 2 and 6 x 10−6 cm/sec depending on the direction of transport. This 3 fold difference was able to be halved by use of P-gp inhibition. MRP inhibition also assisted the consolidation of the methylene blue transport. Mefloquine was shown to be a P-gp inhibitor affecting our P-gp substrate, Rhodamine 123, although none of the other drugs impacted upon rhodamine123 transport rates. In conclusion, mefloquine is a P-gp inhibitor and methylene blue is a partial substrate; methylene blue may have increased absorption if co-administered with such P-gp inhibitors. An upregulation of P-gp was observed when artemisone and dihydroartemisinin were co-incubated with mefloquine and amodiaquine. PMID:27045516

  11. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

    PubMed Central

    Abdulla, Salim; Aponte, John J.; Bulo, Helder; Kabanywanyi, Abdunoor M.; Katana, Abraham; Maculuve, Sonia; Mayor, Alfredo; Nhacolo, Arsenio; Otieno, Kephas; Pahlavan, Golbahar; Rupérez, María; Sevene, Esperança; Slutsker, Laurence; Vala, Anifa; Williamsom, John; Menéndez, Clara

    2014-01-01

    Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). Methods and Findings A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. Conclusions An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need

  12. Progressive Multifocal Leukoencephalopathy with Balanced CD4/CD8 T-Cell Infiltration and Good Response to Mefloquine Treatment.

    PubMed

    Sanjo, Nobuo; Kina, Satoko; Shishido-Hara, Yukiko; Nose, Yurie; Ishibashi, Satoru; Fukuda, Tetsuya; Maehara, Taketoshi; Eishi, Yoshinobu; Mizusawa, Hidehiro; Yokota, Takanori

    2016-01-01

    A 53-year-old man was admitted for sub-acute progressive dementia and Gerstmann syndrome. MRI demonstrated lesions in the white matter involving the left parietal lobe, accompanied by speckled or faint linear peripheral enhancement. Brain biopsy revealed JC virus infection in oligodendrocytes and balanced infiltration of CD8+ and CD4+ T lymphocytes. We diagnosed progressive multifocal leukoencephalopathy (PML) with controlled inflammation. The finding of CD4/CD8 T cells in the infected PML brain suggested therapeutically valuable immune system involvement, which we decided to preserve by withholding corticosteroids. We treated the patient with risperidone, cytarabine and mefloquine to suppress virus replication, but not with the corticosteroid that is conventionally used in inflammatory PML cases. The patient was discharged three months after admission, and one year later, his score on the Mini-Mental State Examination had recovered to 26/30, from 5/30 on admission. PMID:27301518

  13. Inhibition of native 5-HT3 receptor-evoked contractions in guinea pig and mouse ileum by antimalarial drugs.

    PubMed

    Kelley, Stephen P; Walsh, Jacqueline; Kelly, Mark C; Muhdar, Simerjyot; Adel-Aziz, Mohammed; Barrett, Iain D; Wildman, Scott S

    2014-09-01

    Quinine, chloroquine and mefloquine are commonly used to treat malaria, however, with associated gastrointestinal (GI) side-effects. These drugs act as antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3 receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted longitudinally in organ baths. The concentration-response curves for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50 = 7.57 ± 0.33, 12) more potent (P = 0.004) than 2-Me-5-HT (pEC50 = 5.45 ± 0.58, n = 5) in mouse ileum. There was no difference in potency of 5-HT (pEC50 = 5.42 ± 0.15, n = 8) and 2-Me-5-HT (pIC50 = 5.01 ± 0.55, n = 11) in guinea pig ileum (P > 0.05). Quinine, chloroquine or mefloquine was applied for 10 min and inhibitions prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50 = 4.9 ± 0.17, n = 7; 4.76 ± 0.14, n = 5; 6.21 ± 0.2, n = 4, correspondingly) with mefloquine most potent (P < 0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT-induced contractions (pIC50 = 6.35 ± 0.11, n = 8; 4.64 ± 0.2, n = 7; 5.11 ± 0.22, n = 6, correspondingly) with quinine most potent (P < 0.05). In guinea-pig ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50 = 5.02 ± 0.15, n = 6; 4.54 ± 0.1, n = 7; 5.32 ± 0.13, n = 5) and 2-me-5-HT-induced contractions (pIC50 = 4.62 ± 0.25, n = 5; 4.56 ± 0.14, n = 6; 5.67 ± 0.12, n = 4) with chloroquine least potent against 5-HT and mefloquine most potent against 2-me-5-HT (P < 0.05). These results support previous studies identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and may also demonstrate the ability of these drugs to influence native 5-HT3 receptor-evoked contractile responses which may account for their associated GI side-effects. PMID:24886883

  14. Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus.

    PubMed

    Germi, R; Mariette, C; Alain, S; Lupo, J; Thiebaut, A; Brion, J P; Epaulard, O; Saint Raymond, C; Malvezzi, P; Morand, P

    2014-01-01

    Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.

  15. Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni▿

    PubMed Central

    Manneck, Theresia; Braissant, Olivier; Haggenmüller, Yolanda; Keiser, Jennifer

    2011-01-01

    Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current “gold standard” to assess the in vitro antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. The in vitro effects of praziquantel, oxamniquine, artesunate, and mefloquine on metabolic activity and parasite motility of Schistosoma mansoni (newly transformed schistosomula [NTS] and 49-day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results obtained for the four drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects that were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two developmental stages were noted with oxamniquine and artesunate. IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in in vitro antischistosomal drug assays. PMID:21270220

  16. Efficacy and effectiveness of mefloquine and artesunate combination therapy for uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon.

    PubMed

    de Oliveira, Alexandre Macedo; Chavez, Jorge; de Leon, Gabriel Ponce; Durand, Salomon; Arrospide, Nancy; Roberts, Jacquelin; Cabezas, Cesar; Marquiño, Wilmer

    2011-09-01

    We evaluated the efficacy and effectiveness of mefloquine (MQ) plus artesunate (AS) to treat patients with uncomplicated malaria in the Peruvian Amazon Basin in April 2005-March 2006. Patients ≥ 1 year of age with fever (axillary temperature ≥ 37.5°C) or history of fever and Plasmodium falciparum monoinfection were included. Patients received antimalarial treatment with MQ (12.5 mg/kg/day for two days) and AS (4.0 mg/kg/day for three days) either by directly observed therapy or without directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed on the basis of clinical and parasitologic outcomes. Ninety-six patients were enrolled in each study group; nine patients were lost to follow-up. All patients, except for one in the observed group, demonstrated adequate clinical and parasitologic response; none had detectable parasitemia on day 3. The efficacy of MQ + AS efficacy was 98.9% (95% confidence interval = 94.1-100.0%) and the effectiveness was 100.0% (95% confidence interval = 95.9-100.0%). Our study shows that MQ + AS is highly efficacious in the Peruvian Amazon.

  17. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  18. A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice.

    PubMed

    Moon, Deuk Kyu; Tripathi, Abhai; Sullivan, David; Siegler, Maxime A; Parkin, Sean; Posner, Gary H

    2011-05-01

    Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally. PMID:20952197

  19. Antimalarial drug resistance in Bangladesh, 1996-2012.

    PubMed

    Haque, Ubydul; Glass, Gregory E; Haque, Waziul; Islam, Nazrul; Roy, Shyamal; Karim, Jahirul; Noedl, Harald

    2013-12-01

    Malaria remains an important health problem in Bangladesh, with approximately 14 million people at risk. Antimalarial drug resistance is a major obstacle to the control of malaria in endemic countries. In 2012, Bangladesh reported an estimated 29 522 malaria episodes, of which 94% were reported as being caused by Plasmodium falciparum. In this study, we reviewed and summarized antimalarial drug resistance data from Bangladesh published until June 2013. We searched published sources for data referring to any type of P. falciparum drug resistance (in vivo, in vitro, or molecular) and found 169 articles published in peer-reviewed journals. Of these, 143 articles were excluded because they did not meet our inclusion criteria. After detailed review of the remaining 26 articles, 14 were selected for evaluation. Published studies indicate that P. falciparum shows varying levels of resistance to chloroquine, mefloquine and sulfadoxine-pyrimethamine. Combination therapy of chloroquine and primaquine has proven ineffective and combinations of sulfadoxine-pyrimethamine with either quinine or chloroquine have also shown poor efficacy. Recent studies indicate that artemisinin derivatives, such as artesunate, remain highly efficacious in treating P. falciparum malaria. Available data suggest that artemisinins, quinine, doxycyline, mefloquine-artesunate and azithromycin-artesunate combination therapy remain efficacious in the treatment of P. falciparum malaria in Bangladesh.

  20. Network-based gene prediction for Plasmodium falciparum malaria towards genetics-based drug discovery

    PubMed Central

    2015-01-01

    Background Malaria is the most deadly parasitic infectious disease. Existing drug treatments have limited efficacy in malaria elimination, and the complex pathogenesis of the disease is not fully understood. Detecting novel malaria-associated genes not only contributes in revealing the disease pathogenesis, but also facilitates discovering new targets for anti-malaria drugs. Methods In this study, we developed a network-based approach to predict malaria-associated genes. We constructed a cross-species network to integrate human-human, parasite-parasite and human-parasite protein interactions. Then we extended the random walk algorithm on this network, and used known malaria genes as the seeds to find novel candidate genes for malaria. Results We validated our algorithms using 77 known malaria genes: 14 human genes and 63 parasite genes were ranked averagely within top 2% and top 4%, respectively among human and parasite genomes. We also evaluated our method for predicting novel malaria genes using a set of 27 genes with literature supporting evidence. Our approach ranked 12 genes within top 1% and 24 genes within top 5%. In addition, we demonstrated that top-ranked candied genes were enriched for drug targets, and identified commonalities underlying top-ranked malaria genes through pathway analysis. In summary, the candidate malaria-associated genes predicted by our data-driven approach have the potential to guide genetics-based anti-malaria drug discovery. PMID:26099491

  1. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

    PubMed Central

    Abdulla, Salim; Accrombessi, Manfred; Aponte, John J.; Akerey-Diop, Daisy; Basra, Arti; Briand, Valérie; Capan, Meskure; Cot, Michel; Kabanywanyi, Abdunoor M.; Kleine, Christian; Kremsner, Peter G.; Macete, Eusebio; Mackanga, Jean-Rodolphe; Massougbodgi, Achille; Mayor, Alfredo; Nhacolo, Arsenio; Pahlavan, Golbahar; Ramharter, Michael; Rupérez, María; Sevene, Esperança; Vala, Anifa; Zoleko-Manego, Rella; Menéndez, Clara

    2014-01-01

    Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. Methods and Findings A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP

  2. Modulation of PF10_0355 (MSPDBL2) Alters Plasmodium falciparum Response to Antimalarial Drugs

    PubMed Central

    Van Tyne, Daria; Uboldi, Alessandro D.; Healer, Julie; Cowman, Alan F.

    2013-01-01

    Malaria's ability to rapidly adapt to new drugs has allowed it to remain one of the most devastating infectious diseases of humans. Understanding and tracking the genetic basis of these adaptations are critical to the success of treatment and intervention strategies. The novel antimalarial resistance locus PF10_0355 (Pfmspdbl2) was previously associated with the parasite response to halofantrine, and functional validation confirmed that overexpression of this gene lowered parasite sensitivity to both halofantrine and the structurally related antimalarials mefloquine and lumefantrine, predominantly through copy number variation. Here we further characterize the role of Pfmspdbl2 in mediating the antimalarial drug response of Plasmodium falciparum. Knockout of Pfmspdbl2 increased parasite sensitivity to halofantrine, mefloquine, and lumefantrine but not to unrelated antimalarials, further suggesting that this gene mediates the parasite response to a specific class of antimalarial drugs. A single nucleotide polymorphism encoding a C591S mutation within Pfmspdbl2 had the strongest association with halofantrine sensitivity and showed a high derived allele frequency among Senegalese parasites. Transgenic parasites expressing the ancestral Pfmspdbl2 allele were more sensitive to halofantrine and structurally related antimalarials than were parasites expressing the derived allele, revealing an allele-specific effect on drug sensitivity in the absence of copy number effects. Finally, growth competition experiments showed that under drug pressure, parasites expressing the derived allele of Pfmspdbl2 outcompeted parasites expressing the ancestral allele within a few generations. Together, these experiments demonstrate that modulation of Pfmspdbl2 affects malaria parasite responses to antimalarial drugs. PMID:23587962

  3. Highly active ozonides selected against drug resistant malaria

    PubMed Central

    Lobo, Lis; de Sousa, Bruno; Cabral, Lília; Cristiano, Maria LS; Nogueira, Fátima

    2016-01-01

    Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID:27276364

  4. Determinants of Adherence with Malaria Chemoprophylactic Drugs Used in a Traveler's Health Clinic

    PubMed Central

    Shady, Ibrahim

    2015-01-01

    Background. The WHO recommends mefloquine, atovaquone/proguanil, and doxycycline for malaria chemoprophylaxis. Adherence to a drug is determined by many factors. Objective. To detect the determinants of travelers' adherence to malaria chemoprophylaxis. Methods. A prospective comparative study was conducted from January 2012 to July 2013 that included travelers (928 travelers) to malaria endemic countries who visited the THC. They were classified into 3 groups: the 1st is the mefloquine group (396 travelers), the 2nd is the doxycycline group (370 travelers), and finally those who did not receive any drugs (162 travelers). The participants from the 1st and 2nd groups enrolled in the study. Results. Univariate and multivariate analyses were performed. The predictors for adherence in the mefloquine group were travel to an African destination [OR = 51 (6.8–2385)], higher than a secondary school education [OR = 21 (4.1–144.2)], organized travel [OR = 4 (2.1–6.5)], traveling for leisure [OR = 2.1 (1.1–0.4)], and nationality [OR = 2 (1.11–4.00)]. In the doxycycline group, the predictors included higher than a secondary education [OR = 20.1 (4.5–125.1)], organized travel [OR = 11.4 (5.5–20.9)], travel for leisure [OR = 7 (2.3–22.9)], travel to an African destination [OR = 6.1 (0.41–417)], and nationality [OR = 4.5 (2.3–9.5)]. Conclusion. Adherence with malaria chemoprophylaxis could be affected by many factors such as nationality, education, and organized travel. PMID:26379712

  5. Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study.

    PubMed

    Asghari-Khiavi, Mehdi; Vongsvivut, Jitraporn; Perepichka, Inna; Mechler, Adam; Wood, Bayden R; McNaughton, Don; Bohle, D Scott

    2011-12-01

    To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine-FP complex is not μ-oxo dimeric indicating that the hypothesis that chloroquine binds to FP μ-oxo dimer with a stoichiometry of 1 chloroquine:2 μ-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine. Raman spectroscopy data does not provide any evidence to support the formation of a similar salt bridge in the complexes of FP with quinine and mefloquine; however, it suggests that the interaction of these drugs with FP happens through coordination of the Fe(III) center of the porphyrin to the 9-hydroxy group of the drug.

  6. Toxic effects of antimalarial drugs in Paramecium: role of calcium channels.

    PubMed

    Nori, V S; Barry, S R

    1997-05-01

    The antimalarial drugs, quinacrine, quinine and mefloquine, as well as the structurally-similar compound, W-7, inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi. These drugs are also toxic to paramecia at high concentrations. Therefore, one site of toxic action of the drugs may be the calcium channel. To test this hypothesis, the toxicity of the antimalarials and W-7 was compared in paramecia with and without calcium channels. Since calcium channels are located on the cilia, calcium channels were removed from the paramecia by deciliating the cells. Deciliated cells were found to be less susceptible to the lethal effects of the antimalarials and W-7 than their ciliated counterparts. Moreover, Pawns, mutants of P. tetraurelia that possess cilia but lack functional calcium channels, were also less susceptible to the antimalarials than wild-type cells. Thus, calcium channels may be one site of toxic action of the antimalarial drugs in paramecia and perhaps in other protists.

  7. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development

    PubMed Central

    McCarthy, James S.; Marquart, Louise; Sekuloski, Silvana; Trenholme, Katharine; Elliott, Suzanne; Griffin, Paul; Rockett, Rebecca; O'Rourke, Peter; Sloots, Theo; Angulo-Barturen, Iñigo; Ferrer, Santiago; Jiménez-Díaz, María Belén; Martínez, María-Santos; Duparc, Stephan; Leroy, Didier; Wells, Timothy N. C.; Baker, Mark

    2016-01-01

    Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ−/− (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.) PMID:27044554

  8. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.

    PubMed

    McCarthy, James S; Marquart, Louise; Sekuloski, Silvana; Trenholme, Katharine; Elliott, Suzanne; Griffin, Paul; Rockett, Rebecca; O'Rourke, Peter; Sloots, Theo; Angulo-Barturen, Iñigo; Ferrer, Santiago; Jiménez-Díaz, María Belén; Martínez, María-Santos; Hooft van Huijsduijnen, Rob; Duparc, Stephan; Leroy, Didier; Wells, Timothy N C; Baker, Mark; Möhrle, Jörg J

    2016-06-01

    Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ(-/-) (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.). PMID:27044554

  9. New approaches for the identification of drug targets in protozoan parasites.

    PubMed

    Müller, Joachim; Hemphill, Andrew

    2013-01-01

    Antiparasitic chemotherapy is an important issue for drug development. Traditionally, novel compounds with antiprotozoan activities have been identified by screening of compound libraries in high-throughput systems. More recently developed approaches employ target-based drug design supported by genomics and proteomics of protozoan parasites. In this chapter, the drug targets in protozoan parasites are reviewed. The gene-expression machinery has been among the first targets for antiparasitic drugs and is still under investigation as a target for novel compounds. Other targets include cytoskeletal proteins, proteins involved in intracellular signaling, membranes, and enzymes participating in intermediary metabolism. In apicomplexan parasites, the apicoplast is a suitable target for established and novel drugs. Some drugs act on multiple subcellular targets. Drugs with nitro groups generate free radicals under anaerobic growth conditions, and drugs with peroxide groups generate radicals under aerobic growth conditions, both affecting multiple cellular pathways. Mefloquine and thiazolides are presented as examples for antiprotozoan compounds with multiple (side) effects. The classic approach of drug discovery employing high-throughput physiological screenings followed by identification of drug targets has yielded the mainstream of current antiprotozoal drugs. Target-based drug design supported by genomics and proteomics of protozoan parasites has not produced any antiparasitic drug so far. The reason for this is discussed and a synthesis of both methods is proposed.

  10. Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial

    PubMed Central

    Grigg, Matthew J.; William, Timothy; Menon, Jayaram; Barber, Bridget E.; Wilkes, Christopher S.; Rajahram, Giri S.; Edstein, Michael D.; Auburn, Sarah; Price, Ric N.; Yeo, Tsin W.; Anstey, Nicholas M.

    2016-01-01

    Background. Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown. Methods. A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan–Meier analysis. Results. From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8–75.6) after CQ and 0% (95% CI, 0–.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5–9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P = .001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5–9.3; P = .005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60–.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment. Conclusions. High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected. Clinical Trials Registration. NCT01708876. PMID:27107287

  11. Repurposing drugs for the treatment and control of helminth infections

    PubMed Central

    Panic, Gordana; Duthaler, Urs; Speich, Benjamin; Keiser, Jennifer

    2014-01-01

    Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed. PMID:25516827

  12. Targeting Plasmodium Metabolism to Improve Antimalarial Drug Design.

    PubMed

    Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Betancourt-Conde, Irene; Aguirre-Raudry, Miriam; Vázquez-Raygoza, Alejandra; Luevano-De la Cruz, Artemisa; Favela-Candia, Alejandro; Sarabia-Sanchez, Marie; Ríos-Soto, Lluvia; Méndez-Hernández, Edna; Cisneros-Martínez, Jorge; Palacio-Gastélum, Marcelo Gómez; Valdez-Solana, Mónica; Hernández-Rivera, Jessica; De Lira-Sánchez, Jaime; Campos-Almazán, Mara; Téllez-Valencia, Alfredo

    2016-01-01

    Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria. PMID:26983887

  13. Human Disease-Drug Network Based on Genomic Expression Profiles

    PubMed Central

    Hu, Guanghui; Agarwal, Pankaj

    2009-01-01

    Background Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. Methodology/Principal Findings We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the ∼24.5 million comparisons between ∼7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the ∼37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. Conclusions/Significance We have automatically generated thousands of disease and

  14. Drugs for treating urinary schistosomiasis

    PubMed Central

    Kramer, Christine V; Zhang, Fan; Sinclair, David; Olliaro, Piero L

    2014-01-01

    , another anti-malarial mefloquine has been evaluated in two small trials with inconsistent effects. Adverse events were described as mild for all evaluated drugs, but adverse event monitoring and reporting was generally of low quality. Authors' conclusions Praziquantel 40 mg/kg is the most studied drug for treating urinary schistosomiasis, and has the strongest evidence base. Potential strategies to improve future treatments for schistosomiasis include the combination of praziquantel with metrifonate, or with antimalarial drugs with antischistosomal properties such as artesunate and mefloquine. Evaluation of these combinations requires rigorous, adequately powered trials using standardized outcome measures. Plain Language summary Drugs for treating urinary schistosomiasis What is urinary schistosomiasis and how is it treated? Urinary schistosomiasis is a disease caused by infection of people with the parasitic worm Schistosoma haematobium. These worms live in blood vessels around the infected person's bladder and the worm releases eggs which are released in the person's urine. If the urine is passed into ponds or lakes, the eggs can hatch and infect people that are washing or swimming there. Infection can cause blood in the urine and if left untreated can eventually lead to anaemia, malnutrition, kidney failure, or bladder cancer. Urinary schistosomiasis is diagnosed by looking for worm eggs in the urine. The disease occurs mainly in school-aged children and young adults in sub-Saharan Africa. The drug currently recommended for treatment is praziquantel, which can be given as a single dose, but other drugs such as metrifonate, artesunate, and mefloquine have also been evaluated. After examining the research published up to 23th May 2014, we included 30 randomized controlled trials, enrolling 8165 children and adults. What does the research say? On average, the standard dose of praziquantel cures around 60% of people at one to two months after treatment (high quality

  15. Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance.

    PubMed

    Chaorattanakawee, Suwanna; Saunders, David L; Sea, Darapiseth; Chanarat, Nitima; Yingyuen, Kritsanai; Sundrakes, Siratchana; Saingam, Piyaporn; Buathong, Nillawan; Sriwichai, Sabaithip; Chann, Soklyda; Se, Youry; Yom, You; Heng, Thay Kheng; Kong, Nareth; Kuntawunginn, Worachet; Tangthongchaiwiriya, Kuntida; Jacob, Christopher; Takala-Harrison, Shannon; Plowe, Christopher; Lin, Jessica T; Chuor, Char Meng; Prom, Satharath; Tyner, Stuart D; Gosi, Panita; Teja-Isavadharm, Paktiya; Lon, Chanthap; Lanteri, Charlotte A

    2015-08-01

    Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure.

  16. Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance.

    PubMed

    Chaorattanakawee, Suwanna; Saunders, David L; Sea, Darapiseth; Chanarat, Nitima; Yingyuen, Kritsanai; Sundrakes, Siratchana; Saingam, Piyaporn; Buathong, Nillawan; Sriwichai, Sabaithip; Chann, Soklyda; Se, Youry; Yom, You; Heng, Thay Kheng; Kong, Nareth; Kuntawunginn, Worachet; Tangthongchaiwiriya, Kuntida; Jacob, Christopher; Takala-Harrison, Shannon; Plowe, Christopher; Lin, Jessica T; Chuor, Char Meng; Prom, Satharath; Tyner, Stuart D; Gosi, Panita; Teja-Isavadharm, Paktiya; Lon, Chanthap; Lanteri, Charlotte A

    2015-08-01

    Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure. PMID:26014942

  17. Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance

    PubMed Central

    Chaorattanakawee, Suwanna; Saunders, David L.; Sea, Darapiseth; Chanarat, Nitima; Yingyuen, Kritsanai; Sundrakes, Siratchana; Saingam, Piyaporn; Buathong, Nillawan; Sriwichai, Sabaithip; Chann, Soklyda; Se, Youry; Yom, You; Heng, Thay Kheng; Kong, Nareth; Kuntawunginn, Worachet; Tangthongchaiwiriya, Kuntida; Jacob, Christopher; Takala-Harrison, Shannon; Plowe, Christopher; Lin, Jessica T.; Chuor, Char Meng; Prom, Satharath; Tyner, Stuart D.; Gosi, Panita; Teja-Isavadharm, Paktiya; Lon, Chanthap

    2015-01-01

    Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure. PMID:26014942

  18. A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

    PubMed Central

    Mayxay, Mayfong; Keomany, Sommay; Khanthavong, Maniphone; Souvannasing, Phoutthalavanh; Stepniewska, Kasia; Khomthilath, Tiengthong; Keola, Siamphay; Pongvongsa, Tiengkham; Phompida, Samlane; Ubben, David; Valecha, Neena; White, Nicholas J.; Newton, Paul N.

    2010-01-01

    We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study. PMID:21118925

  19. Structural polymorphism in the promoter of pfmrp2 confers Plasmodium falciparum tolerance to quinoline drugs

    PubMed Central

    Mok, Sachel; Liong, Kek-Yee; Lim, Eng-How; Huang, Ximei; Zhu, Lei; Preiser, Peter Rainer; Bozdech, Zbynek

    2014-01-01

    Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programmes around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline-based drugs is becoming critical. So far only few resistance markers have been identified from which only two transmembrane transporters namely PfMDR1 (an ATP-binding cassette transporter) and PfCRT (a drug-metabolite transporter) have been experimentally verified. Another P. falciparum transporter, the ATP-binding cassette containing multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identified a parasite clone that is derived from the 3D7 P. falciparum strain and shows increased resistance to chloroquine, mefloquine and quinine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5′ upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription and thus increased level of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of genetic polymorphisms within these regions to underlie drug resistance. PMID:24372851

  20. Perspective for the production of antimalarial drugs in Brazil.

    PubMed

    Gilbert, B

    1992-01-01

    There appears to be no chemical manufacture of antimalarial drugs in Brazil. Technology at the laboratory process level has been developed for chloroquine, mefloquine, pyrimethamine and cycloguanil, but not perfected nor scaled-up, largely for economic reasons and market uncertainty. Development of primaquine has been contracted but it will run into the same difficulty. Manufacturing capacity for sulfadoxine was registered in the SDI by Roche. A project to produce artemisinine and its derivatives is under way at UNICAMP-CPQBA but is hampered by low content in the plant. Proguanil could be produced easily, but apparently no attempt has been made to do so. Quinine is imported on a large scale mostly for soft-drink production. Since malarial treatment falls largely within the responsibility of the Government health authorities, manufacture of drugs in Brazil will depend on an assured medium-term purchase order made to a potential local manufacturer, since competition in the world market is scarcely viable at the present moment.

  1. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  2. Anti-malarial Drugs Primaquine and Chloroquine Have Different Sensitization Effects with Anti-mitotic Drugs in Resistant Cancer Cells.

    PubMed

    Choi, Ae-Ran; Kim, Ju-Hwa; Woo, Yeon Hwa; Kim, Hyung Sik; Yoon, Sungpil

    2016-04-01

    The purpose of this study was to identify conditions that would increase the sensitivity of drug-resistant cancer cells. Previously, two anti-malarial drugs, chloroquine (CHL) and primaquine (PRI), showed different sensitization effects for vinblastine (VIB)-resistant cancer cells. Herein, we tested co-treatment of cells with CHL or PRI and other microtubule-targeting cancer drugs, namely, vinorelbine (VIO), paclitaxel (PAC), docetaxel (DOC), vincristine (VIC), or halaven (HAL). We found that PRI sensitized P-glycoprotein (P-gp)-overexpressing drug-resistant KBV20C cells to all six anti-mitotic drugs to a similar extent. CHL had a similar sensitization effect only for co-treatment with PAC, DOC, VIC, and HAL, while the sensitization effect was less marked for co-treatment with VIB or VIO. FACS analysis and western blot analysis revealed that G2arrest and apoptosis showed only a slight increase on co-treatment with VIB or VIO and CHL. We also found that phospho-histone H3 and pRb were markedly increased only by PRI-VIB co-treatment, but not by CHL-VIB co-treatment. This suggests that reduction in the expression of these proteins correlates with decreased G2arrest in CHL-VIB co-treatment. We further compared the effect of another anti-malarial drug, mefloquine (MEF), in combination with the six anti-mitotic drugs. We found that MEF and PRI had similar sensitization effects in co-treatment with these anti-mitotic drugs. PRI and MEF had generally similar sensitization effects in co-treatment with anti-mitotic drugs, suggesting that they do not have any preferred anti-mitotic drug partner in co-treatment. This indicates that only CHL shows specificity in co-treatment with anti-mitotic drugs in resistant cancer cells. Our results may contribute to the choice of anti-mitotic drugs to be used in co-treatment of resistant cancer cells with the anti-malarial drugs, CHL, PRI, and MEF. PMID:27069141

  3. Potentiation of antimalarial drug action by chlorpheniramine against multidrug-resistant Plasmodium falciparum in vitro.

    PubMed

    Nakornchai, Sunan; Konthiang, Phattanapong

    2006-09-01

    Chlorpheniramine, a histamine H1 receptor antagonist, was assayed for in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum K1 strain and chloroquine-resistant P. falciparum T9/94 clone, by measuring the 3H-hypoxanthine incorporation. Chlorphenirame inhibited P. falciparum K1 and T9/94 growth with IC50 values of 136.0+/-40.2 microM and 102.0+/-22.6 microM respectively. A combination of antimalarial drug and chlorpheniramine was tested against resistant P. falciparum in vitro. Isobologram analysis showed that chlorpheniramine exerts marked synergistic action on chloroquine against P. falciparum K1 and T9/94. Chlorpheniramine also potentiated antimalarial action of mefloquine, quinine or pyronaridine against both of the resistant strains of P. falciparum. However, chlorpheniramine antagonism with artesunate was obtained in both P. falciparum K1 and T9/94. The results in this study indicate that antihistaminic drugs may be promising candidates for potentiating antimalarial drug action against drug resistant malarial parasites.

  4. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  5. Drug Safety

    MedlinePlus

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  6. Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model.

    PubMed

    Henrich, Philipp P; O'Brien, Connor; Sáenz, Fabián E; Cremers, Serge; Kyle, Dennis E; Fidock, David A

    2014-01-01

    The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria.

  7. Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study

    PubMed Central

    Rupérez, María; González, Raquel; Mombo-Ngoma, Ghyslain; Kabanywanyi, Abdunoor M.; Sevene, Esperança; Ouédraogo, Smaïla; Kakolwa, Mwaka A.; Vala, Anifa; Accrombessi, Manfred; Briand, Valérie; Aponte, John J.; Manego Zoleko, Rella; Adegnika, Ayôla A.; Cot, Michel; Kremsner, Peter G.; Massougbodji, Achille; Abdulla, Salim; Ramharter, Michael; Macete, Eusébio; Menéndez, Clara

    2016-01-01

    Background Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes. Methods and Findings In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%). Conclusions No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared

  8. Injections, Cocktails and Diviners: Therapeutic Flexibility in the Context of Malaria Elimination and Drug Resistance in Northeast Cambodia

    PubMed Central

    Gryseels, Charlotte; Uk, Sambunny; Erhart, Annette; Gerrets, René; Sluydts, Vincent; Durnez, Lies; Muela Ribera, Joan; Hausmann Muela, Susanna; Menard, Didier; Heng, Somony; Sochantha, Tho; D’Alessandro, Umberto; Coosemans, Marc; Peeters Grietens, Koen

    2013-01-01

    Background Adherence to effective malaria medication is extremely important in the context of Cambodia’s elimination targets and drug resistance containment. Although the public sector health facilities are accessible to the local ethnic minorities of Ratanakiri province (Northeast Cambodia), their illness itineraries often lead them to private pharmacies selling “cocktails” and artemether injections, or to local diviners prescribing animal sacrifices to appease the spirits. Methods The research design consisted of a mixed methods study, combining qualitative (in-depth interviews and participant observation) and quantitative methods (household and cross-sectional survey). Results Three broad options for malaria treatment were identified: i) the public sector; ii) the private sector; iii) traditional treatment based on divination and ceremonial sacrifice. Treatment choice was influenced by the availability of treatment and provider, perceived side effects and efficacy of treatments, perceived etiology of symptoms, and patient-health provider encounters. Moreover, treatment paths proved to be highly flexible, changing mostly in relation to the perceived efficacy of a chosen treatment. Conclusions Despite good availability of anti-malarial treatment in the public health sector, attendance remained low due to both structural and human behavioral factors. The common use and under-dosage of anti-malaria monotherapy in the private sector (single-dose injections, single-day drug cocktails) represents a threat not only for individual case management, but also for the regional plan of drug resistance containment and malaria elimination. PMID:24244678

  9. Synthesis of Artemiside and Its Effects in Combination with Conventional Drugs against Severe Murine Malaria

    PubMed Central

    Guo, Jin; Guiguemde, Armand W.; Bentura-Marciano, Annael; Clark, Julie; Haynes, Richard K.; Chan, Wing-Chi; Wong, Ho-Ning; Hunt, Nicholas H.; Guy, R. Kiplin

    2012-01-01

    This research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both in Plasmodium falciparum culture and in vivo in a murine malaria model depicting cerebral malaria (CM). In vitro high-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM. PMID:22006004

  10. Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay

    PubMed Central

    2012-01-01

    Background In vitro drug susceptibility assay of Plasmodium falciparum field isolates processed “immediate ex vivo” (IEV), without culture adaption, and tested using histidine-rich protein-2 (HRP-2) detection as an assay, is an expedient way to track drug resistance. Methods From 2005 to 2010, a HRP-2 in vitro assay assessed 451 P. falciparum field isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC50) against seven anti-malarial drugs, including artesunate (AS), dihydroartemisinin (DHA), and piperaquine. Results In western Cambodia, from 2006 to 2010, geometric mean (GM) IC50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC50 values for most drugs approximated the highest western Cambodia GM IC50 values in 2009 or 2010. Conclusions Western Cambodia is associated with sustained reductions in anti-malarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continued in vitro drug IC50 monitoring of P. falciparum isolates at key locations in the region. PMID:22694953

  11. Compliance with antimalaria chemoprophylaxis in a combat zone.

    PubMed

    Brisson, Michael; Brisson, Paul

    2012-04-01

    Compliance with malaria chemoprophylaxis by military service members (MSMs) is notoriously low, ranging from 30% to 56%. Our objective was to determine the rate of compliance and reasons for non-compliance with malaria chemoprophylaxis among healthy US MSMs in Afghanistan. An eight-question, anonymous online survey was used to collect data regarding the compliance of healthy MSMs with malaria chemoprophylaxis. E-mail surveys were sent to 1,200 MSMs; 528 (44%) MSMs completed the survey. One-time daily doxycycline was the most commonly prescribed chemoprophylaxis (90%); 60% (N = 318) responded that they were compliant with their chemoprophylaxis as prescribed, whereas 40% (N = 221) indicated that they were not compliant. Compliance with daily dosing was 61% and weekly dosing was 38%. The most common reasons for non-compliance were gastrointestinal effects (39%), forgetfulness (31%), and low perception of risk (24%). Malaria chemoprophylaxis compliance by healthy MSMs in Afghanistan is poor. Side effects, forgetfulness, and lack of education are contributing factors. Commanders bear the primary responsibility for the health of their soldiers, and the individual MSM bears personal responsibility; however, additional public health interventions could possibly have a positive impact on prevention. PMID:22492140

  12. Malaria: prevention in travellers

    PubMed Central

    2007-01-01

    Introduction Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10-14 days but can be up to 18 months depending on the strain of parasite. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in adult travellers? What are the effects of drug prophylaxis in adult travellers? What are the effects of antimalaria vaccines in travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acoustic buzzers, aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), doxycycline, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vaporising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines. PMID:19450348

  13. Malaria: prevention in travellers

    PubMed Central

    2010-01-01

    Introduction Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10 to 14 days but can be up to 18 months depending on the strain of parasite. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in non-pregnant adult travellers? What are the effects of drug prophylaxis in non-pregnant adult travellers? What are the effects of antimalaria vaccines in adult and child travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 79 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone–proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), dietary supplementation, doxycycline, electronic mosquito repellents, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vapourising mats, primaquine, pyrimethamine–dapsone, pyrimethamine–sulfadoxine, smoke

  14. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  15. Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

    PubMed Central

    Adhin, Malti R.; Labadie-Bracho, Mergiory; Bretas, Gustavo

    2013-01-01

    The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname. PMID:23836573

  16. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  17. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  18. Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model

    PubMed Central

    Obaldía III, Nicanor; Dow, Geoffrey S.; Gerena, Lucia; Kyle, Dennis; Otero, William; Mantel, Pierre-Yves; Baro, Nicholas; Daniels, Rachel; Mukherjee, Angana; Childs, Lauren M.; Buckee, Caroline; Duraisingh, Manoj T.; Volkman, Sarah K.; Wirth, Dyann F.; Marti, Matthias

    2016-01-01

    Infections with Plasmodium falciparum, the most pathogenic of the Plasmodium species affecting man, have been reduced in part due to artemisinin-based combination therapies. However, artemisinin resistant parasites have recently emerged in South-East Asia. Novel intervention strategies are therefore urgently needed to maintain the current momentum for control and elimination of this disease. In the present study we characterize the phenotypic and genetic properties of the multi drug resistant (MDR) P. falciparum Thai C2A parasite strain in the non-human Aotus primate model, and across multiple passages. Aotus infections with C2A failed to clear upon oral artesunate and mefloquine treatment alone or in combination, and ex vivo drug assays demonstrated reduction in drug susceptibility profiles in later Aotus passages. Further analysis revealed mutations in the pfcrt and pfdhfr loci and increased parasite multiplication rate (PMR) across passages, despite elevated pfmdr1 copy number. Altogether our experiments suggest alterations in parasite population structure and increased fitness during Aotus adaptation. We also present data of early treatment failures with an oral artemisinin combination therapy in a pre-artemisinin resistant P. falciparum Thai isolate in this animal model. PMID:26880111

  19. Interspecies Allometric Scaling of Antimalarial Drugs and Potential Application to Pediatric Dosing

    PubMed Central

    Senarathna, S. M. D. K. Ganga

    2014-01-01

    Pharmacopeial recommendations for administration of antimalarial drugs are the same weight-based (mg/kg of body weight) doses for children and adults. However, linear calculations are known to underestimate pediatric doses; therefore, interspecies allometric scaling data may have a role in predicting doses in children. We investigated the allometric scaling relationships of antimalarial drugs using data from pharmacokinetic studies in mammalian species. Simple allometry (Y = a × Wb) was utilized and compared to maximum life span potential (MLP) correction. All drugs showed a strong correlation with clearance (CL) in healthy controls. Insufficient data from malaria-infected species other than humans were available for allometric scaling. The allometric exponents (b) for CL of artesunate, dihydroartemisinin (from intravenous artesunate), artemether, artemisinin, clindamycin, piperaquine, mefloquine, and quinine were 0.71, 0.85, 0.66, 0.83, 0.62, 0.96, 0.52, and 0.40, respectively. Clearance was significantly lower in malaria infection than in healthy (adult) humans for quinine (0.07 versus 0.17 liter/h/kg; P = 0.0002) and dihydroartemisinin (0.81 versus 1.11 liters/h/kg; P = 0.04; power = 0.6). Interpolation of simple allometry provided better estimates of CL for children than MLP correction, which generally underestimated CL values. Pediatric dose calculations based on simple allometric exponents were 10 to 70% higher than pharmacopeial (mg/kg) recommendations. Interpolation of interspecies allometric scaling could provide better estimates than linear scaling of adult to pediatric doses of antimalarial drugs; however, the use of a fixed exponent for CL was not supported in the present study. The variability in allometric exponents for antimalarial drugs also has implications for scaling of fixed-dose combinations. PMID:25092696

  20. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  1. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing.

  2. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  3. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  4. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  5. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  6. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria

    PubMed Central

    Charman, Susan A.; Arbe-Barnes, Sarah; Bathurst, Ian C.; Brun, Reto; Campbell, Michael; Charman, William N.; Chiu, Francis C. K.; Chollet, Jacques; Craft, J. Carl; Creek, Darren J.; Dong, Yuxiang; Matile, Hugues; Maurer, Melanie; Morizzi, Julia; Nguyen, Tien; Papastogiannidis, Petros; Scheurer, Christian; Shackleford, David M.; Sriraghavan, Kamaraj; Stingelin, Lukas; Tang, Yuanqing; Urwyler, Heinrich; Wang, Xiaofang; White, Karen L.; Wittlin, Sergio; Zhou, Lin; Vennerstrom, Jonathan L.

    2011-01-01

    Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC50 values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei-infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death. PMID:21300861

  7. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.

    PubMed

    Charman, Susan A; Arbe-Barnes, Sarah; Bathurst, Ian C; Brun, Reto; Campbell, Michael; Charman, William N; Chiu, Francis C K; Chollet, Jacques; Craft, J Carl; Creek, Darren J; Dong, Yuxiang; Matile, Hugues; Maurer, Melanie; Morizzi, Julia; Nguyen, Tien; Papastogiannidis, Petros; Scheurer, Christian; Shackleford, David M; Sriraghavan, Kamaraj; Stingelin, Lukas; Tang, Yuanqing; Urwyler, Heinrich; Wang, Xiaofang; White, Karen L; Wittlin, Sergio; Zhou, Lin; Vennerstrom, Jonathan L

    2011-03-15

    Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC(50) values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei-infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death. PMID:21300861

  8. Drugs for treating urinary schistosomiasis

    PubMed Central

    Kramer, Christine V; Zhang, Fan; Sinclair, David; Olliaro, Piero L

    2014-01-01

    Background Urinary schistosomiasis is caused by an intravascular infection with parasitic Schistosoma haematobium worms. The adult worms typically migrate to the venous plexus of the human bladder and excrete eggs which the infected person passes in their urine. Chronic infection can cause substantial morbidity and long-term complications as the eggs become trapped in human tissues causing inflammation and fibrosis. We summarised evidence of drugs active against the infection. This is new edition of a review first published in 1997. Objectives To evaluate the efficacy and safety of drugs for treating urinary schistosomiasis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, CENTRAL, EMBASE and LILACS and reference lists of articles up to 23 May 2014. Selection criteria Randomized controlled trials (RCTs) of antischistosomal drugs and drug combinations compared to placebo, no intervention, or each other. Data collection and analysis Two researchers independently screened the records, extracted the data and assessed risk of bias. The primary efficacy outcomes were parasitological failure (defined as the continued presence of S. haematobium eggs in the urine at time points greater than one month after treatment), and percent reduction of egg counts from baseline. We presented dichotomous data as risk ratios (RR), and continuous data as mean difference (MD), alongside their 95% confidence intervals (CIs). Where appropriate we combined trials in meta analyses or tables. We assessed the quality of evidence using the GRADE approach. Main results We included 30 RCTs enrolling 8165 participants in this review. Twenty-four trials were conducted in children in sub-Saharan Africa, and 21 trials were over 20 years old. Many studies were assessed as being at unclear risk of bias due to inadequate descriptions of study methods. Praziquantel On average, a single 40 mg/kg dose of praziquantel reduced the proportion of people still

  9. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  10. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  11. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  12. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  13. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  14. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  15. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  16. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  17. 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 ...

  18. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  19. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  20. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  1. Club Drugs

    MedlinePlus

    ... also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known ...

  2. Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

    PubMed Central

    Bin Dajem, Saad M.; Al-Farsi, Hissa M.; Al-Hashami, Zainab S.; Al-Sheikh, Adel Ali H.; Al-Qahtani, Ahmed; Babiker, Hamza A.

    2012-01-01

    Two hundred and three Plasmodium falciparum isolates from Jazan area, southwest Saudi Arabia, were typed for Pfcrt, Pfmdr1, dhps, and dhfr mutations associated with resistance to chloroquine, mefloquine, halofantrine, artemisinin, sulfadoxine-pyrimethamine, and the neutral polymorphic gene Pfg377. A large proportion (33%) of isolates harbored double mutant dhfr genotype (51I,59C,108N). However, only one isolate contained mutation dhps-437G. For Pfcrt, almost all examined isolates (163; 99%) harbored the mutant genotype (72C,73V,74I,75E,76T), whereas only 49 (31%) contained the mutant Pfmdr1 genotype (86Y,184F,1034S,1042N), 109 (66%) harbored the single mutant genotype (86N,184F,1034S,1042N), and no mutations were seen in codons 1034, 1042, and 1246. Nonetheless, three new single-nucleotide polymorphisms were detected at codons 182, 192, and 102. No differences were seen in distribution of drug resistance genes among Saudis and expatriates. There was a limited multiplicity (5%), mean number of clones (1.05), and two dominant multilocus genotypes among infected individuals in Jazan. A pattern consistent with limited cross-mating and recombination among local parasite was apparent. PMID:22556074

  3. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  4. Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions

    PubMed Central

    Woodrow, Charles J.; Wangsing, Chirapat; Sriprawat, Kanlaya; Christensen, Peter R.; Nosten, Francois; Rénia, Laurent; Russell, Bruce

    2015-01-01

    Flow cytometry is an objective method for conducting in vitro antimalarial sensitivity assays with increasing potential for application in field sites. We examined in vitro susceptibility to seven anti-malarial drugs for 40 fresh P. falciparum field isolates via a flow cytometry method (FCM), a colorimetric LDH-based ELISA (DELI), and standard microscopic slide analysis of growth. For FCM, 184/280 (66%) assays met analytical acceptance criteria, compared to 166/280 (59%) for DELI. There was good agreement between FCM and microscopy, while DELI tended to produce higher half-maximal inhibition constants (IC50s) than FCM, with an overall bias of 2.2-fold (Bland-Altman comparison). Values for artesunate and dihydroartemisinin were most affected. Paradoxical increases in signal at very high concentrations of mefloquine and related compounds were more marked with the DELI assay, suggesting that off-target effects on LDH production may be responsible. Loss of FCM signal due to reinvasion or slow growth was observed in a small number of samples. These results extend previous work on use of flow cytometry to determine antimalarial susceptibility in terms of the number of samples, range of drugs, and comparison with other methods. PMID:26269616

  5. Drug misuse.

    PubMed Central

    Waller, T.

    1992-01-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  6. Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011

    PubMed Central

    2014-01-01

    Background Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK’s Yellow Card Scheme from 1998 to 2011. Methods We obtained Yellow Card data from the Medicines and Healthcare products Regulatory Agency for the drugs with the most frequent spontaneous reports of depression and suicidal behaviour from 1964 onwards. Prescribing data were obtained from the NHS Information Centre and the Department of Health. We examined the frequency of reports for drugs and estimated rates of reporting of psychiatric ADRs using prescribing data as proxy denominators from 1998 to 2011, as prescribing data were not available prior to 1998. Results There were 110 different drugs with ≥ 20 reports of depression, 58 with ≥10 reports of non-fatal suicidal behaviour and 33 with ≥5 reports of fatal suicidal behaviour in the time period. The top five drugs with the most frequent reports of depression were the smoking cessation medicines varenicline and bupropion, followed by paroxetine (a selective serotonin reuptake inhibitor), isotretinoin (used in acne treatment) and rimonabant (a weight loss drug). Selective serotonin reuptake inhibitors, varenicline and the antipsychotic medicine clozapine were included in the top five medicines with the most frequent reports of fatal and non-fatal suicidal behaviour. Medicines with the highest reliably measured reporting rates of psychiatric ADRs per million prescriptions dispensed in the community included rimonabant, isotretinoin, mefloquine (an antimalarial), varenicline and bupropion. Robust denominators for community prescribing were not available for two drugs with five or more suicide reports, efavirenz (an antiretroviral medicine) and clozapine. Conclusions Depression and suicide-related ADRs are reported for many nervous system and non

  7. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided.

  8. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  9. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.

  10. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  11. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

  12. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  13. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.

  14. Determinants of in vitro drug susceptibility testing of Plasmodium vivax.

    PubMed

    Russell, B; Chalfein, F; Prasetyorini, B; Kenangalem, E; Piera, K; Suwanarusk, R; Brockman, A; Prayoga, P; Sugiarto, P; Cheng, Q; Tjitra, E; Anstey, N M; Price, R N

    2008-03-01

    In Papua, Indonesia, the antimalarial susceptibility of Plasmodium vivax (n = 216) and P. falciparum (n = 277) was assessed using a modified schizont maturation assay for chloroquine, amodiaquine, artesunate, lumefantrine, mefloquine, and piperaquine. The most effective antimalarial against P. vivax and P. falciparum was artesunate, with geometric mean 50% inhibitory concentrations (IC50s) (95% confidence intervals [CI]) of 1.31 nM (1.07 to 1.59) and 0.64 nM (0.53 to 0.79), respectively. In contrast, the geometric mean chloroquine IC50 for P. vivax was 295 nM (227 to 384) compared to only 47.4 nM (42.2 to 53.3) for P. falciparum. Two factors were found to significantly influence the in vitro drug response of P. vivax: the initial stage of the parasite and the duration of the assay. Isolates of P. vivax initially at the trophozoite stage had significantly higher chloroquine IC50s (478 nM [95% CI, 316 to 722]) than those initially at the ring stage (84.7 nM [95% CI, 45.7 to 157]; P < 0.001). Synchronous isolates of P. vivax and P. falciparum which reached the target of 40% schizonts in the control wells within 30 h had significantly higher geometric mean chloroquine IC50s (435 nM [95% CI, 169 to 1,118] and 55.9 nM [95% CI, 48 to 64.9], respectively) than isolates that took more than 30 h (39.9 nM [14.6 to 110.4] and 36.9 nM [31.2 to 43.7]; P < 0.005). The results demonstrate the marked stage-specific activity of chloroquine with P. vivax and suggest that susceptibility to chloroquine may be associated with variable growth rates. These findings have important implications for the phenotypic and downstream genetic characterization of P. vivax.

  15. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  16. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  17. In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity.

    PubMed

    Lucchi, Naomi W; Komino, Franklin; Okoth, Sheila Akinyi; Goldman, Ira; Onyona, Philip; Wiegand, Ryan E; Juma, Elizabeth; Shi, Ya Ping; Barnwell, John W; Udhayakumar, Venkatachalam; Kariuki, Simon

    2015-12-01

    Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.

  18. In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity

    PubMed Central

    Komino, Franklin; Okoth, Sheila Akinyi; Goldman, Ira; Onyona, Philip; Wiegand, Ryan E.; Juma, Elizabeth; Shi, Ya Ping; Barnwell, John W.; Udhayakumar, Venkatachalam; Kariuki, Simon

    2015-01-01

    Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya. PMID:26392510

  19. In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity.

    PubMed

    Lucchi, Naomi W; Komino, Franklin; Okoth, Sheila Akinyi; Goldman, Ira; Onyona, Philip; Wiegand, Ryan E; Juma, Elizabeth; Shi, Ya Ping; Barnwell, John W; Udhayakumar, Venkatachalam; Kariuki, Simon

    2015-12-01

    Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya. PMID:26392510

  20. CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs.

    PubMed

    Ng, Caroline L; Siciliano, Giulia; Lee, Marcus C S; de Almeida, Mariana J; Corey, Victoria C; Bopp, Selina E; Bertuccini, Lucia; Wittlin, Sergio; Kasdin, Rachel G; Le Bihan, Amélie; Clozel, Martine; Winzeler, Elizabeth A; Alano, Pietro; Fidock, David A

    2016-08-01

    Emerging resistance to first-line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine-containing compound ACT-451840 exhibits single-digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro-derived ACT-451840-resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane-bound ATP-binding cassette transporter known to alter P. falciparum susceptibility to multiple first-line antimalarials. CRISPR-Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT-451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9-introduced pfmdr1 mutations also acquired ACT-451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease-relieving and transmission-blocking antimalarials.

  1. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  2. Plasmodium falciparum Polymorphisms associated with ex vivo drug susceptibility and clinical effectiveness of artemisinin-based combination therapies in Benin.

    PubMed

    Dahlström, Sabina; Aubouy, Agnès; Maïga-Ascofaré, Oumou; Faucher, Jean-François; Wakpo, Abel; Ezinmègnon, Sèm; Massougbodji, Achille; Houzé, Pascal; Kendjo, Eric; Deloron, Philippe; Le Bras, Jacques; Houzé, Sandrine

    2014-01-01

    Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of Plasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine (n = 96), fixed-dose artesunate-amodiaquine (n = 96), and sulfadoxine-pyrimethamine (n = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed. pfcrt, pfmdr1, pfmrp1, pfdhfr, and pfdhps polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by Plasmodium lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC50) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC50s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the pfmdr1 N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. The importance of pfmdr1 N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC50s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of pfmdr1 loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical, ex

  3. Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia

    PubMed Central

    Mohd Abd Razak, Mohd Ridzuan; Abdullah, Noor Rain; Sastu, Umi Rubiah; Imwong, Mallika; Muniandy, Prem Kumar; Saat, Muhammad Nor Farhan; Muhammad, Amirrudin; Jelip, Jenarun; Tikuson, Moizin; Yusof, Norsalleh; Rundi, Christina; Mudin, Rose Nani; Syed Mohamed, Ami Fazlin

    2016-01-01

    Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control. PMID:27788228

  4. Drugs Approved for Neuroblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Retinoblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  6. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  8. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  9. [Drug poisoning].

    PubMed

    Gainza, I; Nogué, S; Martínez Velasco, C; Hoffman, R S; Burillo-Putze, G; Dueñas, A; Gómez, J; Pinillos, M A

    2003-01-01

    A review is made of acute poisoning by opiates and its treatment in the emergency services, bearing in mind the progressive decline in the number of cases presented with the arrival of new forms of their administration, as well as the presence of new addictive drugs that have resulted in a shift in consumption habits. Reference is also made to the way in which the different types of existing substances originated, with the aim of achieving a better understanding of their use and in order to administer the most suitable treatment when poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical picture, diagnosis and treatment. The consumption of illegal drugs in our country has undergone a notable change in recent years, with heroin being relegated and the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA), "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of cannabis and its derivates, from the history of its consumption and the preparations employed to the effects produced in the different bodily systems. A brief explanation is also given of its metabolites and its principal mechanisms of action. Finally, we comment on the effects of LSD and hallucinogenic mushrooms.

  10. Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults.

    PubMed

    Petit, Caroline; Jullien, Vincent; Samson, Adeline; Guedj, Jérémie; Kiechel, Jean-René; Zohar, Sarah; Comets, Emmanuelle

    2016-03-01

    The objectives of this study were to design a pharmacokinetic (PK) study by using information about adults and evaluate the robustness of the recommended design through a case study of mefloquine. PK data about adults and children were available from two different randomized studies of the treatment of malaria with the same artesunate-mefloquine combination regimen. A recommended design for pediatric studies of mefloquine was optimized on the basis of an extrapolated model built from adult data through the following approach. (i) An adult PK model was built, and parameters were estimated by using the stochastic approximation expectation-maximization algorithm. (ii) Pediatric PK parameters were then obtained by adding allometry and maturation to the adult model. (iii) A D-optimal design for children was obtained with PFIM by assuming the extrapolated design. Finally, the robustness of the recommended design was evaluated in terms of the relative bias and relative standard errors (RSE) of the parameters in a simulation study with four different models and was compared to the empirical design used for the pediatric study. Combining PK modeling, extrapolation, and design optimization led to a design for children with five sampling times. PK parameters were well estimated by this design with few RSE. Although the extrapolated model did not predict the observed mefloquine concentrations in children very accurately, it allowed precise and unbiased estimates across various model assumptions, contrary to the empirical design. Using information from adult studies combined with allometry and maturation can help provide robust designs for pediatric studies. PMID:26711749

  11. Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults.

    PubMed

    Petit, Caroline; Jullien, Vincent; Samson, Adeline; Guedj, Jérémie; Kiechel, Jean-René; Zohar, Sarah; Comets, Emmanuelle

    2015-12-28

    The objectives of this study were to design a pharmacokinetic (PK) study by using information about adults and evaluate the robustness of the recommended design through a case study of mefloquine. PK data about adults and children were available from two different randomized studies of the treatment of malaria with the same artesunate-mefloquine combination regimen. A recommended design for pediatric studies of mefloquine was optimized on the basis of an extrapolated model built from adult data through the following approach. (i) An adult PK model was built, and parameters were estimated by using the stochastic approximation expectation-maximization algorithm. (ii) Pediatric PK parameters were then obtained by adding allometry and maturation to the adult model. (iii) A D-optimal design for children was obtained with PFIM by assuming the extrapolated design. Finally, the robustness of the recommended design was evaluated in terms of the relative bias and relative standard errors (RSE) of the parameters in a simulation study with four different models and was compared to the empirical design used for the pediatric study. Combining PK modeling, extrapolation, and design optimization led to a design for children with five sampling times. PK parameters were well estimated by this design with few RSE. Although the extrapolated model did not predict the observed mefloquine concentrations in children very accurately, it allowed precise and unbiased estimates across various model assumptions, contrary to the empirical design. Using information from adult studies combined with allometry and maturation can help provide robust designs for pediatric studies.

  12. Drugs and the Brain.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  13. A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs

    PubMed Central

    2013-01-01

    Background Based on report of declining efficacy of chloroquine, Ghana shifted to the use of artemisinin-based combination therapy (ACT) in 2005 as the first-line anti-malarial drug. Since then, there has not been any major evaluation of the efficacy of anti-malarial drugs in Ghana in vitro. The sensitivity of Ghanaian Plasmodium falciparum isolates to anti-malarial drugs was, therefore, assessed and the data compared with that obtained prior to the change in the malaria treatment policy. Methods A SYBR Green 1 fluorescent-based in vitro drug sensitivity assay was used to assess the susceptibility of clinical isolates of P. falciparum to a panel of 12 anti-malarial drugs in three distinct eco-epidemiological zones in Ghana. The isolates were obtained from children visiting health facilities in sentinel sites located in Hohoe, Navrongo and Cape Coast municipalities. The concentration of anti-malarial drug inhibiting parasite growth by 50% (IC50) for each drug was estimated using the online program, ICEstimator. Results Pooled results from all the sentinel sites indicated geometric mean IC50 values of 1.60, 3.80, 4.00, 4.56, 5.20, 6.11, 10.12, 28.32, 31.56, 93.60, 107.20, and 8952.50 nM for atovaquone, artesunate, dihydroartemisin, artemether, lumefantrine, amodiaquine, mefloquine, piperaquine, chloroquine, tafenoquine, quinine, and doxycycline, respectively. With reference to the literature threshold value indicative of resistance, the parasites showed resistance to all the test drugs except the artemisinin derivatives, atovaquone and to a lesser extent, lumefantrine. There was nearly a two-fold decrease in the IC50 value determined for chloroquine in this study compared to that determined in 2004 (57.56 nM). This observation is important, since it suggests a significant improvement in the efficacy of chloroquine, probably as a direct consequence of reduced drug pressure after cessation of its use. Compared to that measured prior to the change in treatment policy

  14. Clinically significant drug interactions.

    PubMed

    Ament, P W; Bertolino, J G; Liszewski, J L

    2000-03-15

    A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references. PMID:10750880

  15. Personality, Drug Preference, Drug Use, and Drug Availability

    ERIC Educational Resources Information Center

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  16. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  17. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  18. Attitudes towards drug legalization among drug users.

    PubMed

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  19. Drug Use by Students of Drug Abuse

    ERIC Educational Resources Information Center

    Linder, Ronald; And Others

    1973-01-01

    The purpose of this study was to determine the significance of differences in the use of certain psychoactive drugs among students who enrolled for an elective drug abuse course and students not enrolled, or who have not previously taken a drug abuse course. (Author)

  20. Discontinued drugs in 2008: cardiovascular drugs.

    PubMed

    Zhang, Xu-Song; Xiang, Bing-Ren

    2009-07-01

    This perspective is part of an annual series of papers discussing drugs dropped from clinical development in the previous year. Specifically, this paper focuses on the 16 cardiovascular drugs discontinued in 2008. Information for this perspective was derived from a search of the Pharmaprojects database for drugs discontinued after reaching Phase I-III clinical trials. PMID:19548849

  1. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  2. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  3. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  4. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  5. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  6. Drug-induced hepatitis

    MedlinePlus

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

  7. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  8. [Drug-induced dementia].

    PubMed

    Kojima, Taro; Akishita, Masahiro

    2016-03-01

    Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function. PMID:27025096

  9. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  10. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  11. Dynamics of Malaria Drug Resistance Patterns in the Amazon Basin Region following Changes in Peruvian National Treatment Policy for Uncomplicated Malaria▿ †

    PubMed Central

    Bacon, David J.; McCollum, Andrea M.; Griffing, Sean M.; Salas, Carola; Soberon, Valeria; Santolalla, Meddly; Haley, Ryan; Tsukayama, Pablo; Lucas, Carmen; Escalante, Ananias A.; Udhayakumar, Venkatachalam

    2009-01-01

    Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, multidrug resistance gene 1 (Pfmdr-1), the chloroquine (CQ) resistance transporter gene (Pfcrt), and the Ca2+ ATPase gene (PfATP6); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr-1 loci were also determined. There was a significant decline in the highly SP resistant Pfdhfr and Pfdhps genotypes from 1999 to 2006. In contrast, a CQ-resistant Pfcrt genotype increased in frequency during the same period. Among five different Pfmdr-1 allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the PfATP6 gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pfdhfr, Pfdhps, and Pfcrt genotypes have each evolved from a single founder haplotype, while Pfmdr-1 genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America. PMID:19258269

  12. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  13. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  14. Drugs and Young People

    MedlinePlus

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  15. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  16. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  17. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  18. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  19. Do drug offences matter?

    PubMed

    Gordon, A M

    1978-07-15

    Drug offences in addicts are often thought to indicate little more than continued dependency. In a four-year follow-up study of 60 men attending a drug clinic a history of repeated convictions for drug offences was found to be strongly related to patterns of delinquency. The following variables were associated with a history of repeated drug offences: a higher conviction rate for "non-drug" offences; younger age at first conviction; conviction preceding drug use; convictions for offences of sex and violence; longer prison sentences; and regular narcotic use and continued dependency at follow-up. Receiving a clinic prescription was not associated with a lower incidence of drug offences. Repeated drug offences identified a subgroup of drug users who were characterised by extensive sociopathic behaviour. Such offences should not be dismissed as an unavoidable, unimportant part of addiction. PMID:678840

  20. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  1. Discontinued drugs in 2010: cardiovascular drugs.

    PubMed

    Zhao, Hong-ping; Zhang, Xu-song; Xiang, Bing-ren

    2011-10-01

    This perspective is a paper discussing drugs dropped from clinical development in the previous years. Specifically, this paper focuses on 16 cardiovascular drugs discontinued in 2010 after reaching Phase I - III clinical trials. Information for this perspective is mainly derived from a search of Pharmaprojects. PMID:21870899

  2. Economic Evaluation of an Alternative Drug to Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy

    PubMed Central

    Sicuri, Elisa; Fernandes, Silke; Macete, Eusebio; González, Raquel; Mombo-Ngoma, Ghyslain; Massougbodgi, Achille; Abdulla, Salim; Kuwawenaruwa, August; Katana, Abraham; Desai, Meghna; Cot, Michel; Ramharter, Michael; Kremsner, Peter; Slustker, Laurence; Aponte, John; Hanson, Kara; Menéndez, Clara

    2015-01-01

    Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy. Methods The cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women’s loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken. Results For HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet. Conclusions Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV

  3. Phenolic compounds from the stem bark Erythrina Orientalis and detection of antimalaria activity by ELISA

    NASA Astrophysics Data System (ADS)

    Tjahjadarie, Tjitjik Srie; Saputri, Ratih Dewi; Tanjung, Mulyadi

    2016-03-01

    Erythrina orientalis has local name "Dadap". This plant has known producing alkaloids, flavonoids, pterocarpans, stilbenes, and arylbenzofurans which are active compounds.Three prenylated flavonoids, 8-prenyl-daidzein (1), alpinumisoflavone (2) and 4'-O-methyl licoflavanone (3) had been isolated from the stem bark of Erythrina Orientalis. The structures were elucidated on the basis of spectroscopic data,which are IR, UV, MS, and NMR 1D (1H-NMR and 13C-NMR) and 2D (COSY, HMQC, and HMBC).

  4. Introductory paper: The orientation of immunological research in relation to the global antimalaria programme

    PubMed Central

    Wernsdorfer, W. H.

    1979-01-01

    Immunological research on malaria has produced a wealth of information on the relationship between Plasmodium and the vertebrate host, introducing new serological tools into epidemiological methodology and experimentally proving the possibility of protecting vertebrates against malaria, thus moving vaccination from the realm of pure hypothesis to the level of feasibility. The alarming malaria situation in the world is reason enough to expand immunological research further to improve diagnostic and epidemiological tools and to develop methods for the protection of man against malaria. The programme of the Scientific Working Group on the Immunology of Malaria, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, complies with these objectives. A projection of potential effects of malaria vaccines on the malaria situation shows considerable promise in areas with relatively low basic reproduction rates; in areas with high basic reproduction rates they would need to complement other malaria control measures and may ultimately add the critical momentum required to render adequate malaria control feasible in tropical Africa. PMID:317437

  5. [Malaria, anopheles, the anti-malaria campaign in French Guyana: between dogmatism and judgment].

    PubMed

    Raccurt, C P

    1997-01-01

    The recrudescence of malaria in French Guiana involves both border regions. One notes the predominance of Plasmodium falciparum along the Maroni River on the Surinam frontier and the transmission of both Plasmodium falciparum and Plasmodium vivax in amerindian settlements along the Oyapock River on the Brazilian frontier. The main mosquito vector is the endoexophile species, Anopheles darlingi. The role of man-biting forest anophelines in malaria transmission is still unclear. At the present time, malaria control is based on curative treatment of the confirmed cases (approximately 4,000 cases a year by active and passive screening). Vector control is supported by annual houses insecticides spraying and, to a lesser degree, use of insecticide-impregnated bednets. The main limiting factors for successful control have been difficulty in implementing a strategy adapted to the cultures of the amerindian and bushnegro populations living on either side of the river-frontiers and in organizing effective cross-border cooperation. The alleged role of immigration in transmission dynamics has been more speculative than real. However the growth of the population and the increase of human activities inside rain forest areas have favorized Anopheles darlingi breeding by uncontrolled deforestation. This situation need to be monitored closely. Information campaigns to improve public awareness could be useful. Following measures could improve control in sparsely populated, remote areas: to promote an integrated preventive program for a real community-wide distribution of primary health care; to discontinue insecticides spraying in houses which is poorly accepted by the bushnegro population and unsuitable to the amerindian dwellings; to support the use of personal protection; to initiate an effective anopheline larvae control; to determine the impact of the transmission during day-time activities especially among very small settlements far from the main villages where members of the Djuka tribe practise slash-and-burn cultivation. Teledetection might be highly useful for monitoring the epidemiology of malaria in French Guiana and neighbouring countries. A change in the official administrative dogma and policy is necessary to optimize malaria control within the framework of regional cooperation between Brazil and the three Guianas. PMID:9612784

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

    PubMed

    Mealey, Katrina L

    2013-09-01

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

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

    PubMed

    Mealey, Katrina L

    2013-09-01

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

  8. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  9. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  10. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  11. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  12. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  13. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  14. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  15. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  16. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  17. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...

  18. Treating Prescription Drug Addiction

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  19. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  20. Contemporary drugs of abuse.

    PubMed

    Giannini, A J; Price, W A; Giannini, M C

    1986-03-01

    The physician needs to know the signs, symptoms and recommended treatments of drug overdoses. Overdose of hallucinogens usually does not require drug therapy. Overdose of amphetamines ("uppers") may be complicated by the presence of PCP, a dissociative substance. It is important for the physician to be familiar with the street terminology for contemporary drugs of abuse and to be aware of how users obtain these drugs.

  1. Polypharmacology in a single drug: multitarget drugs.

    PubMed

    Bolognesi, M L

    2013-01-01

    Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.

  2. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  3. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  4. Other Drugs of Abuse

    MedlinePlus

    ... can make you pass out. It's called a "date rape" drug because someone can secretly put it in your ... you without your permission. Rohypnol (roofies) is a date rape pill and can ... about these drugs . Bath Salts are drugs made with chemicals like ...

  5. Strategies against Drugs.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1996-01-01

    The main private organization in Germany dedicated to combatting drug addition--the DHS and the Federal Health Information Agency (BzGA) jointly estimate the number of persons addicted to "illegal" drugs in Germany at around 200,000. Yet, people may grow up immune to drug addiction if they acquire a stable basis for self-confidence and…

  6. Keeping Youth Drug Free.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This guide is designed to help caregivers prevent children from getting involved in drugs. It details six key prevention principles, including actions caregivers can take that can help their child make healthy choices. Each section includes language to use with children, activities to do, information about drugs, statistics about youth drug use,…

  7. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  8. Drugs of Abuse.

    ERIC Educational Resources Information Center

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  9. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death.

  10. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePlus

    ... microscope by a specially trained physician (dermatopathologist). In addition, your doctor may want to perform blood work to look for signs of an allergic reaction. The best treatment for a drug rash is ...

  11. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

  12. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  13. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePlus

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  14. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  15. Drugs Approved for Wilms Tumor

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  18. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  19. COPD - quick-relief drugs

    MedlinePlus

    COPD - quick-relief drugs; Chronic obstructive pulmonary disease - control drugs; Chronic obstructive airways disease - quick-relief drugs; Chronic obstructive lung disease - quick-relief drugs; Chronic bronchitis - quick-relief ...

  20. Drugs Approved for Skin Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Drugs Approved for Vaginal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  2. DEA Multimedia Drug Library: Marijuana

    MedlinePlus

    ... OPERATIONS Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip DRUG INFO Drug Fact Sheets ... Operations Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip Drug Info Drug Fact Sheets ...

  3. Drugs Approved for Penile Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  4. Drugs Approved for Vulvar Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Liver Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  6. Drugs Approved for Bone Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Esophageal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  8. Drugs Approved for Endometrial Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. 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.

  10. Drug abuse and reproduction.

    PubMed

    Smith, C G; Asch, R H

    1987-09-01

    It is clear that a number of CNS agents, including drugs of abuse, can inhibit reproductive function. Figure 1 shows the chemical diversity of some of the drug groups that affect reproductive hormones. Their structural dissimilarity to the steroid hormones is also readily apparent in the figure. These chemically diverse drugs share an important pharmacologic property: they are highly potent neuroactive drugs, and they can disrupt hypothalamic-pituitary function. Although it is frequently difficult to distinguish between direct drug actions on the hypothalamic-pituitary axis and subsequent effects on gonadal hormones and sex accessory gland function, the distinction is an important one. Most neuroactive drugs produce only transient effects on the central nervous pathways necessary for normal gonadotropin secretion. The disruptive effects of these drugs are likely to be transient and completely reversible, and tolerance to the inhibitory drug effects may occur even with continued drug use. Under these circumstances, normal adults may experience only subtle changes in sexual function. However, individuals with compromised reproductive function may exhibit major problems. It is also likely that adolescents may be at substantial risk for reproductive damage from these neuroactive drugs since the endocrine events associated with puberty are dependent on the normal development of the hypothalamic-pituitary axis.

  11. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  12. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

  13. Opioid pharmacokinetic drug-drug interactions.

    PubMed

    Overholser, Brian R; Foster, David R

    2011-09-01

    Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.

  14. Informatics confronts drug-drug interactions.

    PubMed

    Percha, Bethany; Altman, Russ B

    2013-03-01

    Drug-drug interactions (DDIs) are an emerging threat to public health. Recent estimates indicate that DDIs cause nearly 74000 emergency room visits and 195000 hospitalizations each year in the USA. Current approaches to DDI discovery, which include Phase IV clinical trials and post-marketing surveillance, are insufficient for detecting many DDIs and do not alert the public to potentially dangerous DDIs before a drug enters the market. Recent work has applied state-of-the-art computational and statistical methods to the problem of DDIs. Here we review recent developments that encompass a range of informatics approaches in this domain, from the construction of databases for efficient searching of known DDIs to the prediction of novel DDIs based on data from electronic medical records, adverse event reports, scientific abstracts, and other sources. We also explore why DDIs are so difficult to detect and what the future holds for informatics-based approaches to DDI discovery. PMID:23414686

  15. Discontinued drugs in 2012: cardiovascular drugs.

    PubMed

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products. PMID:23992034

  16. New Antithrombotic Drugs

    PubMed Central

    Eikelboom, John W.; Samama, Meyer Michel

    2012-01-01

    This article focuses on new antithrombotic drugs that are in or are entering phase 3 clinical testing. Development of these new agents was prompted by the limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this article (1) outlines the rationale for development of new antithrombotic agents; (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs; and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents. PMID:22315258

  17. [Safety nonsteroidal antiinflammatory drugs].

    PubMed

    Oscanoa-Espinoza, Teodoro Julio

    2015-01-01

    The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drug in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity.

  18. Grapefruit and drug interactions.

    PubMed

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  19. Grapefruit and drug interactions.

    PubMed

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  20. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  1. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  2. Newer drugs for arthritis.

    PubMed

    McGillivray, D C

    1977-01-01

    The major area of new drug discoveries for the treatment of arthritis is in non-steroidal anti-inflammatory agents (NSAIA). Unfortunately, as yet no new and safe drug of major significance has appeared. Aspirin still ranks high beside the newcomers. Indomethacin, ibuprofen, naproxen, fenoprofen and tolmetin are described and their roles in therapy are discussed. A further group of older drugs receiving new application in the treatment of arthritis is presented. These include penicillamine and the immunosuppressive drugs. Gold and chloroquin are also discussed to put these agents in their proper perspective.

  3. [The importance of therapeutic drug monitoring for psychotropic drugs].

    PubMed

    Messer, Thomas; Schmauss, Max

    2006-05-15

    The goal of therapeutic drug monitoring (TDM) is the optimization of the psychiatric pharmacotherapy. Above all, TDM is absolutely indicated for the prevention of adverse drug effects or poisoning. TDM is well-established for therapies with antidepressants, antipsychotic drugs and mood stabilizers. For anti-dementia drugs, anxiolytic drugs, hypnotic drugs and medications for treating addiction, monitoring is currently applied to the interpretation of side effects, drug interactions and to forensic questions. PMID:20104722

  4. Recommunalizing Drug Offenders: The "Drug Peace" Agenda.

    ERIC Educational Resources Information Center

    Arrigo, Bruce A.

    1997-01-01

    Examines the manner in which substance-using shelter tenants, many of them ex-offenders, who lived in an urban, single- room-occupancy neighborhood, engaged in the process of recommunalization. Identifies and describes eight developmental stages of recommunalization, and links recommunalization to proposals for solving the war on drugs. (RJM)

  5. Drugs and Drug Abuse: A Bibliography.

    ERIC Educational Resources Information Center

    State Univ. of New York, Stony Brook.

    For a relatively new field of research and interest, the bibliographic control of drug literature (indexing and recording for retrieval) is remarkable. Public and private agencies have taken the initiative in compiling catalogs, bibliographies and indexes which, although often duplicatory, nonetheless ensure access to the many aspects of the drug…

  6. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  7. The Drug War.

    ERIC Educational Resources Information Center

    DeCrosta, Anthony

    1989-01-01

    The role of teachers in helping fight against drug abuse is discussed stressing the teacher's ability to see changes in the students and the potential for positive influence. A vital school role involves teaching life skills and wellness principles. Information on commonly abused drugs and their effects is presented. (SM)

  8. Drug and Substance Abuse

    MedlinePlus

    ... Latest Research Getting More Help Related Topics Anxiety COPD Delirium Depression Pain Management Prevention Related News Older Adults Who Drink Alcohol at Risk for Drug Interactions Monday, November 23, 2015 Join our e-newsletter! Aging & Health A to Z Drug and Substance Abuse ...

  9. Dimensions of Drug Information

    ERIC Educational Resources Information Center

    Sharp, Mark E.

    2011-01-01

    The high number, heterogeneity, and inadequate integration of drug information resources constitute barriers to many drug information usage scenarios. In the biomedical domain there is a rich legacy of knowledge representation in ontology-like structures that allows us to connect this problem both to the very mature field of library and…

  10. Drug effects on spermatogenesis.

    PubMed

    Amory, John K

    2007-10-01

    Many drugs can adversely affect spermatogenesis. These effects can occur either by directly inhibiting sperm or testicular function or indirectly by impairing the hypothalamic pituitary testicular axis. In this paper, we will review the drugs that are known to adversely impact spermatogenesis, and/or sperm function and detail what is known about the mechanisms through which these compounds impair fertility in men.

  11. Drugs and Personal Values.

    ERIC Educational Resources Information Center

    Blum, Richard H.

    Drug use and abuse have two major motivations: the medical or curative, and the religious or supplementary. The author discusses the expanding use of drugs for both purposes, suggesting a possible connection between increased medical use and confidence, and increased religious or pleasure use. He outlines many problems of definition and public…

  12. Enhancing Drug Court Success

    ERIC Educational Resources Information Center

    Deschenes, Elizabeth Piper; Ireland, Connie; Kleinpeter, Christine B.

    2009-01-01

    This study evaluates the impact of enhanced drug court services in a large county in Southern California. These enhanced services, including specialty counseling groups, educational/employment resources, and increased Residential Treatment (RT) beds, were designed to increase program retention and successful completion (graduation) of drug court.…

  13. Automated drug identification system

    NASA Technical Reports Server (NTRS)

    Campen, C. F., Jr.

    1974-01-01

    System speeds up analysis of blood and urine and is capable of identifying 100 commonly abused drugs. System includes computer that controls entire analytical process by ordering various steps in specific sequences. Computer processes data output and has readout of identified drugs.

  14. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2007-01-01

    In 2002, the United States Supreme Court confirmed that in the school's role of in loco parentis, drug testing of students who were involved in athletics and extracurricular activities was constitutional. In a state of the union address, George W. Bush stated that drug testing in schools had been effective and was part of "our aggressive…

  15. Drugs, Alcohol & Pregnancy.

    ERIC Educational Resources Information Center

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  16. Alternative drugs of abuse.

    PubMed

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations. PMID:23636733

  17. Interoception and Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.

    2013-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

  18. Prescription Drug Abuse

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  19. Newer antithrombotic drugs

    PubMed Central

    Sikka, Pranav; Bindra, V. K.

    2010-01-01

    Thromboembolic disorders are one of the disorders for which we are still on the look out for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows our inefficiency in searching efficacious and safe antithrombotic drugs. We have reached the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, we can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, we are using Clopidogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide). Warfarin is an old antithrombotic drug which is still being used; but due to various side effects and drug interactions, we are bound to use newer drugs. Newer antiplatelet drugs include Prasugrel, Ticagrelor and Cangrelor, whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban is also a newer entry in this category as factor Xa inhibitor. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are ongoing. PMID:21572750

  20. PRESERVATION OF DRUGS

    PubMed Central

    Rao, R. Bhima; Natarajan, R.K.; Sarma, P.S. Nataraja; Purushothaman, K.K.

    1982-01-01

    In this article the factors likely to cause spoilage of the drugs of the Indian systems of medicine are reviewed. Methods for the prevention of spoilage are discussed. The results of a limited study carried out on the stability of a few selected drug preparations representing the main dosage forms are also presented PMID:22556951

  1. Implantable Drug Dispenser

    NASA Technical Reports Server (NTRS)

    Collins, E. R. J.

    1983-01-01

    Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

  2. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  3. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2005-01-01

    The Vernonia School District v. Acton Supreme Court decision in 1995, forever changed the landscape of the legality of drug testing in schools. This decision stated that students who were involved in athletic programs could be drug tested as long as the student's privacy was not invaded. According to some in the medical profession, there are two…

  4. Alternative drugs of abuse.

    PubMed

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  5. 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.

  6. Drugs and Addictions.

    ERIC Educational Resources Information Center

    Smith, S. Mae; Miller, Eva

    The effects of drug abuse and dependence vary, depending on the type of drug, polydrug use, and characteristics of the user. The influence of genetic, neurochemical, neuropsyiological, sociocultural, and economic factors suggest that the etiology of substance abuse and dependence is multiply determined. Models explaining the causation of substance…

  7. Medicare Prescription Drug Coverage

    MedlinePlus

    ... people also have to pay an additional monthly cost. Private companies provide Medicare prescription drug coverage. You choose the drug plan you like best. Whether or not you should sign up depends on how good your current coverage is. You need to sign up as ...

  8. Ayurvedic drug discovery.

    PubMed

    Balachandran, Premalatha; Govindarajan, Rajgopal

    2007-12-01

    Ayurveda is a major traditional system of Indian medicine that is still being successfully used in many countries. Recapitulation and adaptation of the older science to modern drug discovery processes can bring renewed interest to the pharmaceutical world and offer unique therapeutic solutions for a wide range of human disorders. Eventhough time-tested evidences vouch immense therapeutic benefits for ayurvedic herbs and formulations, several important issues are required to be resolved for successful implementation of ayurvedic principles to present drug discovery methodologies. Additionally, clinical examination in the extent of efficacy, safety and drug interactions of newly developed ayurvedic drugs and formulations are required to be carefully evaluated. Ayurvedic experts suggest a reverse-pharmacology approach focusing on the potential targets for which ayurvedic herbs and herbal products could bring tremendous leads to ayurvedic drug discovery. Although several novel leads and drug molecules have already been discovered from ayurvedic medicinal herbs, further scientific explorations in this arena along with customization of present technologies to ayurvedic drug manufacturing principles would greatly facilitate a standardized ayurvedic drug discovery.

  9. Safety of obesity drugs.

    PubMed

    Greenway, Frank L; Caruso, Mary K

    2005-11-01

    The safety of obesity drugs has historically been poor. This and the stigmatisation of obesity in society ensured that a higher standard of safety for obesity drugs must be met. The authors review the safety disasters of obesity drugs that were withdrawn. The authors then review the safety of presently available drugs--benzphetamine, phendimetrazine, diethylpropion, phentermine, sibutramine and orlistat. The safety of rimonabant, a drug with a pending new drug application that has an independent effect on metabolic syndrome, is also reviewed. The authors compare the stage of obesity drug development to that of hypertension in the 1950s. As new and safer drugs with more downstream mechanisms are developed that have independent effects on the cardiovascular risks associated with obesity, third party reimbursement for obesity medicine is likely to improve. This may lead to obesity being treated like hypertension and other chronic diseases with long-term medication. With improved technological tools, the authors believe this process will be more rapid for obesity than it was for hypertension.

  10. Evaluation of enzyme inhibition kinetics in drug-drug interactions.

    PubMed

    Chen, Ang; Qin, Xuan; Tang, Yu; Liu, Mingyao; Wang, Xin

    2014-10-01

    Inhibition of CYP enzymes is thought to be the most common cause of drug-drug and/or herb-drug interactions. To characterize the inhibition of CYP enzymes activities by chemicals, enzyme inhibition kinetic experiments are usually carried out. The purpose of this letter is to call attention to evaluate the enzyme inhibition kinetics in drug-drug interactions.

  11. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  12. Potential Drug - Drug Interactions among Medications Prescribed to Hypertensive Patients

    PubMed Central

    Ganguly, Barna

    2014-01-01

    Context: Drug-drug interactions(DDIs) are significant but avoidable causes of iatrogenic morbidity and hospital admission. Aim: To detect potential drug-drug interactions among medications received by hypertensive patients. Materials and Methods: Patients of both sex and all adult age groups, who were attending medicine out -patient department (OPD) of a tertiary care teaching rural hospital since last six months and were being prescribed antihypertensive drug/s for essential hypertension, were selected for the study. Hypertensive patient with co-morbities diabetes mellitus, ischemic heart diseases, congestive heart failure, and chronic renal diseases were also included in the study. Potential drug drug interactions were checked with medscape drug interaction software. Results: With the help of medscape drug interaction software, 71.50% prescriptions were identified having atleast one drug-drug interaction. Total 918 DDIs were found in between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs were found significant type of DDIs. Drug drug interaction between atenolol & amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88) in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to cause DDIs in our study. Conclusion: We detected a significant number of drug drug interaction in hypertensive patients. These interactions were between antihypertensive agents or between hypertensive and drug for co-morbid condition. PMID:25584241

  13. Drugs Approved for Multiple Myeloma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  14. Drugs Approved for Myeloproliferative Neoplasms

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  15. Drugs Approved for Hodgkin Lymphoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  16. Off-Label Drug Use

    MedlinePlus

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  17. Is the Drug Problem Soluble?

    ERIC Educational Resources Information Center

    Jonas, Steven

    1989-01-01

    Concludes that the principle drug problems in the United States arise from the use of cigarette tobacco and alcoholic beverages. Identifies a drug culture as the persistent force in society that promotes drug use. Points out that the influence of the primary drug industries inhibit attempts to deal effectively with drug problems. (KO)

  18. Drugs, Society, and Human Behavior.

    ERIC Educational Resources Information Center

    Ray, Oakley

    The varied aspects of drugs, their source, abuse, chemical composition, and physical, personal, and social effects are explored. Seven units cover the following areas: (1) an overview on drug use, a brief history of drugs and discussion of social implications; (2) the human nervous system and the actions of drugs; (3) "nondrug drugs" such as…

  19. Drugs Approved for Cervical Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  20. Drugs Approved for Testicular Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  1. The Great Drug Debate: II. Taking Drugs Seriously.

    ERIC Educational Resources Information Center

    Kaplan, John

    1988-01-01

    Argues that legalization is not the solution to drug-related problems. Proposes increased emphasis on the small retailers of drugs, and mandatory urinalysis for heroin, cocaine, and PCP for those arrested for typical drug-related crimes. (FMW)

  2. Irreversible enzyme inhibition kinetics and drug-drug interactions.

    PubMed

    Mohutsky, Michael; Hall, Stephen D

    2014-01-01

    This chapter describes the types of irreversible inhibition of drug-metabolizing enzymes and the methods commonly employed to quantify the irreversible inhibition and subsequently predict the extent and time course of clinically important drug-drug interactions.

  3. Bioequivalence of generic drugs.

    PubMed

    Andrade, Chittaranjan

    2015-09-01

    Generic drugs are bioequivalent to the original brand; this is a prerequisite for marketing approval. It is theoretically possible that one generic drug may overestimate the pharmacokinetic (PK) parameters of the original and another generic may underestimate these PK parameters; in consequence, these 2 generics may not be bioequivalent between themselves. The result could be loss of efficacy or development of drug-related adverse effects if these generics are interchanged in stable patients. In a recent study involving 292 indirect comparisons of generic formulations of 9 different drugs, mathematical modeling showed that in most cases (87.0% for maximum concentration, 90.1% for area under the curve, and 80.5% for both) generic drugs are bioequivalent to each other. These reassuring findings notwithstanding, prudence dictates that, in stable patients, generic drugs should be interchanged only if there is a good reason for it. This is because bioequivalent brands of drugs may differ in their excipient content, and this can result in variations in safety profiles. PMID:26455677

  4. Benzylpiperazine: "A messy drug".

    PubMed

    Katz, D P; Deruiter, J; Bhattacharya, D; Ahuja, M; Bhattacharya, S; Clark, C R; Suppiramaniam, V; Dhanasekaran, M

    2016-07-01

    Designer drugs are synthetic structural analogues/congeners of controlled substances with slightly modified chemical structures intended to mimic the pharmacological effects of known drugs of abuse so as to evade drug classification. Benzylpiperazine (BZP), a piperazine derivative, elevates synaptic dopamine and serotonin levels producing stimulatory and hallucinogenic effects, respectively, similar to the well-known drug of abuse, methylenedioxymethamphetamine (MDMA). Furthermore, BZP augments the release of norepinephrine by inhibiting presynaptic autoreceptors, therefore, BZP is a "messy drug" due to its multifaceted regulation of synaptic monoamine neurotransmitters. Initially, pharmaceutical companies used BZP as a therapeutic drug for the treatment of various disease states, but due to its contraindications and abuse potential it was withdrawn from the market. BZP imparts predominately sympathomimetic effects accompanied by serious cardiovascular implications. Addictive properties of BZP include behavioral sensitization, cross sensitization, conditioned place preference and repeated self-administration. Additional testing of piperazine derived drugs is needed due to a scarcity of toxicological data and widely abuse worldwide. PMID:27207154

  5. Anticancer drugs during pregnancy.

    PubMed

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. PMID:27284093

  6. Anti-Microtubule Drugs.

    PubMed

    Florian, Stefan; Mitchison, Timothy J

    2016-01-01

    Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug-disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment. PMID:27193863

  7. Bioequivalence of generic drugs.

    PubMed

    Andrade, Chittaranjan

    2015-09-01

    Generic drugs are bioequivalent to the original brand; this is a prerequisite for marketing approval. It is theoretically possible that one generic drug may overestimate the pharmacokinetic (PK) parameters of the original and another generic may underestimate these PK parameters; in consequence, these 2 generics may not be bioequivalent between themselves. The result could be loss of efficacy or development of drug-related adverse effects if these generics are interchanged in stable patients. In a recent study involving 292 indirect comparisons of generic formulations of 9 different drugs, mathematical modeling showed that in most cases (87.0% for maximum concentration, 90.1% for area under the curve, and 80.5% for both) generic drugs are bioequivalent to each other. These reassuring findings notwithstanding, prudence dictates that, in stable patients, generic drugs should be interchanged only if there is a good reason for it. This is because bioequivalent brands of drugs may differ in their excipient content, and this can result in variations in safety profiles.

  8. Teratogenic drugs and their drug interactions with hormonal contraceptives.

    PubMed

    Ahn, M R; Li, L; Shon, J; Bashaw, E D; Kim, M-J

    2016-09-01

    The US Food and Drug Administration (FDA) Guidance for Industry-Drug Interaction Studies, recommends that a potential human teratogen needs to be studied in vivo for effects on contraceptive steroids.(1) This article highlights the need to evaluate the drug-drug interactions (DDIs) between drugs with teratogenic potential and hormonal contraceptives (HCs) during drug development. It also addresses the FDA's effort of communicating DDI findings in product labels to mitigate the risk of unintended pregnancy. PMID:27090193

  9. [Pharmacopsychoses during drug addiction].

    PubMed

    Cottereau, M J; Lôo, H; Poirier, M F; Deniker, P

    1975-01-01

    Widespread use of certain drugs (amphetamines, L.S.D., hypnotics) in France, allowed us to observe more than 200 cases of acute or chronic psychoses among addicts. Sometimes these are transitory outburst but the occurrence of a delusional psychosis with long range evolution raises a difficult diagnosis problem in relation to functional psychoses. The emphasis should be put on respective roles of the drug and of a predisposed mental state. Circumstances of beginning, apparently direct relationship between drug taking and pathological symptoms, therapy efficiency, absence of earlier pathological traits (as in many of our patients) and relapse when intoxication starts again, are in favour of a pharmacological origin of the troubles.

  10. Lipidomics in drug development.

    PubMed

    Dehairs, Jonas; Derua, Rita; Rueda-Rincon, Natalia; Swinnen, Johannes V

    2015-06-01

    Numerous human pathologies, including common conditions such as obesity, diabetes, cardiovascular disease, cancer, inflammatory disease and neurodegeneration, involve changes in lipid metabolism. Likewise, a growing number of drugs are being developed that directly or indirectly affect lipid metabolic pathways. Instead of classical and cumbrous radiochemical analyses, lipid profiling by mass spectrometry (MS)-based lipidomics holds great potential as companion diagnostic in several steps along the drug development process. In this review we describe some typical lipidomics set-ups and illustrate how these technologies can be implemented in target discovery, compound screening, in vitro and in vivo preclinical testing, toxicity testing of drugs, and prediction and monitoring of response. PMID:26190681

  11. Prescription Drugs and Cold Medicines

    MedlinePlus

    ... Abuse » Prescription Drugs & Cold Medicines Prescription Drugs & Cold Medicines Email Facebook Twitter What is Prescription Drug Abuse: ... treatment of addiction. Read more Safe Disposal of Medicines Disposal of Unused Medicines: What You Should Know ( ...

  12. Drugs Approved for Pancreatic Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  13. Drugs Approved for Bladder Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Drugs Approved for Thyroid Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) ...

  15. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  16. Drugs Approved for Breast Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Keoxifene (Raloxifene Hydrochloride) Nolvadex (Tamoxifen ...

  17. Drugs Approved for Brain Tumors

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Brain Tumors This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Brain Tumors Afinitor (Everolimus) Afinitor Disperz (Everolimus) Avastin (Bevacizumab) ...

  18. Drugs + HIV, Learn the Link

    MedlinePlus

    ... Children & Teens Search Connect with NIDA : Google Plus Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs ... HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug abuse ...

  19. Drugs Approved for Lung Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  20. Drugs Approved for Breast Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  1. Drugs Approved for Bone Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Bone Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Bone Cancer Abitrexate (Methotrexate) Cosmegen (Dactinomycin) Dactinomycin Denosumab Doxorubicin Hydrochloride ...

  2. Drugs Approved for Myeloproliferative Disorders

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Myeloproliferative Neoplasms This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Myeloproliferative Neoplasms Adriamycin PFS (Doxorubicin Hydrochloride) Adriamycin RDF (Doxorubicin Hydrochloride) ...

  3. Analysis of Street Drugs

    ERIC Educational Resources Information Center

    James, Stuart H.; Bhatt, Sudhir

    1972-01-01

    A study of the content of street drugs available to a college campus and a community is presented. Emphasis is given to the adulterants and substitutions encountered in the illicit preparations. (Author)

  4. Metalloid compounds as drugs

    PubMed Central

    Sekhon, B. S.

    2013-01-01

    The six elements commonly known as metalloids are boron, silicon, germanium, arsenic, antimony, and tellurium. Metalloid containing compounds have been used as antiprotozoal drugs. Boron-based drugs, the benzoxaboroles have been exploited as potential treatments for neglected tropical diseases. Arsenic has been used as a medicinal agent and arsphenamine was the main drug used to treat syphilis. Arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Pentavalent antimonials have been the recommended drug for visceral leishmaniasis and cutaneous leishmaniasis. Tellurium (IV) compounds may have important roles in thiol redox biological activity in the human body, and ammonium trichloro (dioxoethylene-O, O’-)tellurate (AS101) may be a promising agent for the treatment of Parkinson’s disease. Organosilicon compounds have been shown to be effective in vitro multidrug-resistance reverting agents. PMID:24019824

  5. Drug testing programs.

    PubMed

    Willette, R E

    1986-01-01

    Many Federal agencies and private companies are conducting drug tests on job applicants and employees. Although the reasons for testing and the circumstances under which testing is conducted vary considerably, the main intent of these programs is to provide a drug-free environment for other employees and a safe service to the public. The programs that have been most successful usually include a clear communication to all employees and applicants as to the nature of the drug program and the consequences of detected drug use. Also, successful programs usually afford employees some type of assistance and a second chance. Finally, it is essential for successful programs to provide a reasonable and fair approach that includes procedures for due process, that is, a line of review and appeal. PMID:3127722

  6. Information for Consumers (Drugs)

    MedlinePlus

    ... Advertising: Questions to Ask Yourself Sample Prescription Drug Advertisements Give Us Feedback Resources for You Report a ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  7. Neuropathy secondary to drugs

    MedlinePlus

    ... provider). The following drugs may be used to control pain: Over-the-counter pain relievers may be helpful ... as morphine or fentanyl, may be needed to control severe pain. Whenever possible, avoid or reduce use of medicines ...

  8. Drug-induced infertility.

    PubMed

    Buchanan, J F; Davis, L J

    1984-02-01

    Primary infertility may result from the use of various drugs. This phenomenon may be the result of an effect on the hypothalamic-pituitary-gonadal axis or a direct toxic effect on the gonads. Some of the drugs considered in this article demonstrate sex-related differences in their ability to cause infertility; there also may be age-related differences. The drugs described in this review, in regard to their association with the development of infertility, include various individual antineoplastic agents (cyclophosphamide, chlorambucil, busulphan, and methotrexate) and combinations of these chemotherapeutic drugs, glucocorticosteroids, hormonal steroids (diethylstilbestrol, medroxyprogesterone acetate, estrogen, and the constituents of oral contraceptives), antibiotics (sulfasalazine and co-trimoxazole), thyroid supplements, spironolactone, cimetidine, colchicine, marihuana, opiates, and neuroleptic agents.

  9. Calculating drug doses.

    PubMed

    2016-09-01

    Numeracy and calculation are key skills for nurses. As nurses are directly accountable for ensuring medicines are prescribed, dispensed and administered safely, they must be able to understand and calculate drug doses. PMID:27615351

  10. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  11. Teenagers and drugs

    MedlinePlus

    ... Loss of appetite (occurs with amphetamine, methamphetamine, or cocaine use) Increased appetite (with marijuana use) Unsteady gait ... drugs) Hyperactivity (as seen with uppers such as cocaine and methamphetamine) You also may notice changes in ...

  12. Drug use first aid

    MedlinePlus

    ... addiction is gradual. And some drugs (such as cocaine ) can cause addiction after only a few doses. ... Saunders; 2013:chap 150. Rao RB, Hoffman RS. Cocaine and other sympathomimetics. In: Marx JA, Hockberger RS, ...

  13. Vitiligo, drug induced (image)

    MedlinePlus

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

  14. The drug swindlers.

    PubMed

    Silverman, M; Lydecker, M; Lee, P R

    1990-01-01

    In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors."

  15. National Drug IQ Challenge

    MedlinePlus

    ... See 2016's Chat Day Transcript Drugs: SHATTER THE MYTHS Order Free Copies Now for Your NDAFW Event! ... dress are registered trademarks of HHS. SHATTER THE MYTHS is a trademark and service mark of HHS. ...

  16. The drug swindlers.

    PubMed

    Silverman, M; Lydecker, M; Lee, P R

    1990-01-01

    In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors." PMID:2265874

  17. Substance use - prescription drugs

    MedlinePlus

    ... substance use; Oxycodone - substance use; Hydrocodone - substance use; Morphine - substance use; Fentanyl - substance use ... fluff, hydros, v-itamin, vic, vike, Watson-387. Morphine. Drugs include Avinza, Duramorph, Kadian, Ormorph, Roxanol. Street ...

  18. Inexpensive portable drug detector

    NASA Technical Reports Server (NTRS)

    Dimeff, J.; Heimbuch, A. H.; Parker, J. A.

    1977-01-01

    Inexpensive, easy-to-use, self-scanning, self-calibrating, portable unit automatically graphs fluorescence spectrum of drug sample. Device also measures rate of movement through chromatographic column for forensic and medical testing.

  19. Drugs in breastfeeding.

    PubMed

    Hotham, Neil; Hotham, Elizabeth

    2015-10-01

    Most commonly used drugs are relatively safe for breastfed babies. The dose received via milk is generally small and much less than the known safe doses of the same drug given directly to neonates and infants. Drugs contraindicated during breastfeeding include anticancer drugs, lithium, oral retinoids, iodine, amiodarone and gold salts. An understanding of the principles underlying the transfer into breast milk is important, as is an awareness of the potential adverse effects on the infant. Discussion with the mother about the possibility of either negative product information or ill-informed advice from others will reduce the confusion and anxiety that may be generated. Good resources about medicines and breastfeeding are available and include state-based medicines information services. PMID:26648652

  20. Drug therapy smartens up

    NASA Astrophysics Data System (ADS)

    Martin, Christian

    2015-11-01

    The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

  1. Professional thieves and drugs.

    PubMed

    Inciardi, J A; Russe, B R

    1977-12-01

    The "professional thief" is a highly specialized predatory offender with a history that dates back to Elizabethan England. Although this type of criminal is generally associated with narcotic addiction, his drug-taking typically involved the use of heroin, morphine, and cocaine on an intermittent basis. However, trafficking in drugs was common to the "professional" underworld, and as a result this deviant fraternity had a notable impact on the impressment of a criminal model of drug use on twentieth century conceptions of the addict. The concept of "professional" theft is reviewed, the use of drugs by professional thieves is discussed, and the interaction between this underworld group and the early Federal Bureau of Narcotics is examined.

  2. Club Drug Use

    MedlinePlus

    ... MDMA ("ecstasy"), GHB ("liquid ecstasy"), flunitrazepam ("roofies") and ketamine ("special K"). They have many other slang names. ... also can become addicted if they use GHB, ketamine and flunitrazepam repeatedly. These drugs can cause severe ...

  3. Drug-induced diarrhea

    MedlinePlus

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

  4. Drugs, Alcohol and HIV

    MedlinePlus

    ... Combat Veterans & their Families Readjustment Counseling (Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning ... follow these reminders: Never reuse or "share" syringes, water, or drug preparation equipment. Use only syringes obtained ...

  5. Oral Diabetes Drugs

    MedlinePlus

    ... could save hundreds of dollars a month by switching to generic metformin, a Consumer Reports Best Buy ... drugs because they are effective, generally safe, and cost less. Work with your doctor to choose the ...

  6. Bibliography [On Drugs].

    ERIC Educational Resources Information Center

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  7. Clinical nutrition and drug interactions.

    PubMed

    Ekincioğlu, Aygin Bayraktar; Demirkan, Kutay

    2013-01-01

    A drug's plasma level, pharmacological effects or side effects, elimination, physicochemical properties or stability could be changed by interactions of drug-drug or drug-nutrition products in patients who receive enteral or parenteral nutritional support. As a result, patients might experience ineffective outcomes or unexpected effects of therapy (such as drug toxicity, embolism). Stability or incompatibility problems between parenteral nutrition admixtures and drugs might lead to alterations in expected therapeutic responses from drug and/or parenteral nutrition, occlusion in venous catheter or symptoms or mortality due to infusion of composed particles. Compatibilities between parenteral nutrition and drugs are not always guaranteed in clinical practice. Although the list of compatibility or incompatibilities of drugs are published for the use of clinicians in their practices, factors such as composition of parenteral nutrition admixture, drug concentration, contact time in catheter, temperature of the environment and exposure to light could change the status of compatibilities between drugs and nutrition admixtures. There could be substantial clinical changes occurring in the patient's nutritional status and pharmacological effects of drugs due to interactions between enteral nutrition and drugs. Drug toxicity and ineffective nutritional support might occur as a result of those predictable interactions. Although administration of drugs via feeding tube is a complex and problematic route for drug usage, it is possible to minimise the risk of tube occlusion, decreased effects of drug and drug toxicity by using an appropriate technique. Therefore, it is important to consider pharmacological dosage forms of drugs while administering drugs via a feeding tube. In conclusion, since the pharmacists are well-experienced and more knowledgeable professionals in drugs and drug usage compared to other healthcare providers, it is suggested that provision of information and

  8. Boston Collaborative Drug Surveillance Program

    Cancer.gov

    The Boston Collaborative Drug Surveillance Program started in 1966 and conducted epidemiologic research to quantify the potential adverse effects of prescription drugs, utilizing in-hospital monitoring.

  9. Drug-induced lupus erythematosus

    MedlinePlus

    ... that caused the condition. Treatment may include: Nonsteroidal anti-inflammatory drugs (NSAIDs) to treat arthritis and pleurisy Corticosteroid creams to treat skin rashes Antimalarial drugs (hydroxychloroquine) to ...

  10. New drugs of abuse.

    PubMed

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. PMID:25471045

  11. Eosinophilic Drug Allergy.

    PubMed

    Kuruvilla, Merin; Khan, David A

    2016-04-01

    While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management. PMID:26006718

  12. Safety of antiobesity drugs.

    PubMed

    Cheung, Bernard Man Yung; Cheung, Tommy Tsang; Samaranayake, Nithushi Rajitha

    2013-08-01

    Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn. Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves. Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of significant psychiatric adverse effects. Orlistat was approved in Europe and the United States for long-term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects. Phentermine and diethylpropion can only be used for less than 12 weeks because the long-term safety of these drugs is unknown. Ephedrine and caffeine are natural substances but the effects on weight reduction are modest. As a result there is a huge unmet need for effective and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long-term safety data are lacking. PMID:25114779

  13. Drug abuse in athletes

    PubMed Central

    Reardon, Claudia L; Creado, Shane

    2014-01-01

    Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. PMID:25187752

  14. [Drug use in pregnancy].

    PubMed

    von Mandach, U

    2005-01-01

    Drug use in pregnancy is associated with a number of serious complications for mother and fetus. There are safe data on destructive effects of alcohol, cocain, marijuana and tobacco on pregnancy and neonatal outcome. Of importance is the fact that for many drugs similar effects on pregnancy could be observed: vasoconstriction of the placental vessels resulting in placental abruption, preterm labour (mother), spontaneous abortion, intrauterine growth retardation, low birth weight, preterm delivery and stillbirth (fetus). Symptoms of withdrawal and neurodevelopmental disorders are the most important problems of the neonate. However, only small data exist about the effects of recently popular party drugs like ecstasy or LSD. In addition, from most drugs, with exception of alcohol, safe information about the risk of congenital malformations doesn't exist. Nevertheless they may be a useful guide in the diagnostic of potential malformations by ultrasound. Most of pregnant women using drugs are poly-drug users and are often in reduced general condition. They need therefore the intensive care of the obstetrician in cooperation with other specialists (internal medicine, psychiatry).

  15. Miami Drug Court Gives Drug Defendants a Second Chance.

    ERIC Educational Resources Information Center

    Finn, Peter; Newlyn, Andrea K.

    1993-01-01

    Describes the Diversion and Drug Treatment program, known as "Drug Court," in Miami (Florida) in which nonviolent drug offenders have prosecution of their cases deferred while they participate in a court-ordered drug-rehabilitation program. Those who successfully complete the program have their cases dismissed. Whereas typical recidivism rates for…

  16. Delayed drug hypersensitivity reactions.

    PubMed

    Pichler, Werner J

    2003-10-21

    Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of 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.

  17. Role of Hepatic Drug Transporters in Drug Development.

    PubMed

    Liu, Houfu; Sahi, Jasminder

    2016-07-01

    Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug-drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug-induced liver injury (DILI), as well as methods for predicting transporter-mediated pharmacokinetics and DDIs. PMID:27385168

  18. Recent New Drug Approvals. Part 1: Drugs with Pediatric Indications

    PubMed Central

    Shelton, Chasity M.; Chhim, Rebecca F.; Christensen, Michael L.

    2012-01-01

    This two-part review provides information about drugs that have been recently approved by the Food and Drug Administration and focuses on drugs approved with pediatric indications or approved in adults with active pediatric studies. Information was obtained from the product labeling and selected published studies. Part 1 reviews recently approved drugs with labeled pediatric indications, and Part 2 will review recent drug approvals in adults that have potential use in pediatrics and have active studies. PMID:23412997

  19. [Benefit assessment of drugs].

    PubMed

    Kaiser, Thomas; Vervölgyi, V; Wieseler, B

    2015-03-01

    In Germany, new drugs are subject to a benefit assessment at the time of their market access. This "early benefit assessment" is the method primarily used for the benefit assessment of pharmaceuticals in Germany. While for the authorization of a drug a positive risk-benefit ratio is sufficient, early benefit assessment examines whether the new drug has an added benefit compared with other therapies, and thus differs significantly from authorization. For the evaluation, the manufacturer is required to submit a dossier, which must contain all the relevant studies. Early benefit assessment is very transparent in international comparisons, because all the relevant data and the evaluation report will be published. The assessment is carried out with regard to the evidence-based standard of care (the "appropriate comparator"). If the new drug is found to have an additional benefit, the extent of this added benefit is assessed. In addition, groups of patients should be identified with the particular extent of the added benefit. Therefore, subgroup analyses have to be carried out frequently. Often, for new drugs, only registration studies are available. General requirements for such studies (e.g., placebo comparison, endpoints) and decisions regarding the approval process (e.g., dosage regimens) can affect the level of confidence of these studies in the benefit assessment. Joint scientific advice by regulatory authorities and HTA (health technology assessment) agencies are provided to solve this problem. However, this is not possible without additional expense for the pharmaceutical companies. PMID:25566842

  20. Drug hypersensitivity syndrome.

    PubMed

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  1. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

    Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

  2. Drug consumption among Polish centenarians.

    PubMed

    Rajska-Neumann, A; Mossakowska, M; Klich-Rączka, A; Życzkowska, J; Grześkowiak, E; Shieh, S; Wieczorowska-Tobis, K

    2011-01-01

    The aim of the study was to describe the quantitative and qualitative aspects of pharmacotherapy of Polish centenarians. The studied group consisted of 92 centenarians (mean age: 101.7±1.2 years, 77 females, mean age: 101.5±1.2; 15 males mean age: 102.2±1.2). Among the studied subjects, 18 individuals (19.6% of all subjects) did not use any drugs in his or her daily regimen. The mean number of drugs per person was 2.5±2.5 drugs (prescription drugs: 1.9±2.2 and non-prescription drugs: 0.5±0.8). Fifty-six centenarians (60.9% of all studied subjects) took concomitantly 0-3 drugs daily while 36 (39.1%) took more than 3 drugs daily. Within this group, 30 centenarians (32.6%) took 5 or more drugs concomitantly every day. The most commonly used groups of drugs were: gastrointestinal drugs (55 centenarians, 74.3% of all drug consumed), cardiovascular drugs (51 centenarians, 68.9%) and central nervous system drugs (N) (38 centenarians, 51.4%). In the studied group, 6 persons (8.1% of all drug consumers) were taking one potentially inappropriate drug based on the Beers criteria. To conclude, the mean number of drugs, the prevalence of polypharmacy, and the tendency for potential inappropriateness of treatment are lower among Polish centenarians comparing to the common elderly.

  3. National Drug Control Strategy. Update.

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, Washington, DC.

    President Bush's new National Drug Control Strategy for 2003 focuses on three core priorities: stopping drug use before it starts; healing America's drug users; and disrupting the market. The 2003 strategy reports progress toward meeting the President's goals of reducing drug use by 10 percent over 2 years, and 25 percent over 5 years. With regard…

  4. Overview of Selected Drug Trends.

    ERIC Educational Resources Information Center

    Adams, Edgar H.; And Others

    This document begins with a brief overview of findings from national surveys conducted by the National Institute on Drug Abuse which show increasing drug use throughout the 1970s and a decreasing trend in drug use during the 1980s. In spite of this decline, drug use in the U.S. is described as still constituting a major public health problem that…

  5. Drug Use in American History.

    ERIC Educational Resources Information Center

    McWilliams, John C.

    1991-01-01

    Discusses drug use in U.S. history. Argues that a "get-tough" approach did not work in the past and will not work in the future. Suggests that history can provide a scholarly assessment of drugs, foster understanding of drugs in contemporary society, and enable students to evaluate drug policies more objectively. (DK)

  6. 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.

  7. Drugs, the Internet and change.

    PubMed

    Walsh, Charlotte

    2011-01-01

    This article investigates the symbiotic relationship between drugs and the Internet, focusing (though not exclusively) on psychedelics. Programming on psychedelics in Silicon Valley from the 1960s to date is detailed, as are the twinned conceptualizations of drugs as a technology and technology as a drug. The correlation between drugs, the Internet, and consumerism is explored: the Internet is a medium through which "white," "grey" and "black" drug markets flourish. Thus, this article details the burgeoning online trades in pharmaceuticals, recreational, and "life-style" drugs that turn the Internet into a veritable candy store. Drug forums transmogrify into street corners, threatening the continued existence of the current system of global prohibition. However, it is arguably the use of the Web as an information source that may offer the greatest challenge to the incumbent paradigm, with experiential discourses offering alternatives to the hegemonic narrative, as the relationships between drugs, those who sell drugs and drug takers are reconfigured online. PMID:21615008

  8. 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

  9. Drug Screening in Neonates.

    PubMed

    Bell, Susan Givens

    2016-01-01

    Gestational substance exposure continues to be a significant problem. Neonates may be exposed to various substances including illicit drugs, prescription drugs, and other legal substances that are best not used during pregnancy because of their potential deleterious effects as possible teratogens or their potential to create dependence and thus withdrawal in the neonate. Screening the newborn for gestational substance exposure is important for both acute care and early intervention to promote the best possible long-term outcomes. This column provides insight into what is known about the extent of substance use by pregnant women, an overview of neonatal biologic matrices for drug testing, and a discussion of the legal implications of neonatal substance screening. PMID:27636697

  10. Drug Resistance in Leishmaniasis

    PubMed Central

    Chakravarty, Jaya; Sundar, Shyam

    2010-01-01

    The treatment options of leishmaniasis are limited and far from satisfactory. For more than 60 years, treatment of leishmaniasis has centered around pentavalent antimonials (Sbv). Widespread misuse has led to the emergence of Sbv resistance in the hyperendemic areas of North Bihar. Other antileishmanials could also face the same fate, especially in the anthroponotic cycle. The HIV/ visceral leishmaniasis (VL) coinfected patients are another potential source for the emergence of drug resistance. At present no molecular markers of resistance are available and the only reliable method for monitoring resistance of isolates is the technically demanding in vitro amastigote-macrophage model. As the armametrium of drugs for leishmaniasis is limited, it is important that effective monitoring of drug use and response should be done to prevent the spread of resistance. Regimens of simultaneous or sequential combinations should be seriously considered to limit the emergence of resistance. PMID:20606973

  11. Drug-induced pseudolupus.

    PubMed

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

    1975-07-26

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

  12. Toxins and drug discovery.

    PubMed

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process.

  13. [INFORMATION ON DRUGS].

    PubMed

    Foucher, Jean-pierre

    2015-03-01

    Drugs not being just a product like any other, prescribers, providers and patients must have access to the information relating the characteristics of such medicinal products. This information must be complete, objective and scientifically rigorous. It must be adapted to the use of the drug and be fully understandable. It should help in prescribing, expedite dispensing, and help the patient adhere to treatment. Thus, according to the recipient, the information will be different. It is the role of the pharmacist and the physician to use it for patient education. The information given must be objective. Medication guidelines published by HAS (Haute Autorité de Santé/National Health Agency) and Inserts given with the drugs should be considered the most reliable. Information can also be found in major scientific publication journals, in independent papers produced by groups of doctors and pharmacists, or in treatment guidelines. One must be very reserved about such information found on certain "Internet" sites. PMID:26606769

  14. Drugs, discrimination and disability.

    PubMed

    Gibson, Frances

    2009-12-01

    Whether addiction to prohibited drugs should be classified as a disability for the purposes of disability discrimination is a controversial question in Australia. The leading Australian case of Marsden v Human Rights Equal Opportunity Commission & Coffs Harbour & District Ex-Servicemen & Women's Memorial Club Ltd (HREOC, No H98/51, 30 August 1999); [2000] FCA 1619 concerned a disability discrimination complaint brought by Mr Marsden as a result of his treatment by the club. The case was brought as a public interest test case by the New South Wales Legal Aid Commission. Mr Marsden was on a methadone program at the time. The reasoning of the decision at the Federal Court opened the way for a finding that dependence on illegal drugs constituted a disability under disability discrimination legislation. The media reaction to the court's decision led to State and federal governments proposing legislation limiting legal protection from discrimination for people addicted to illegal drugs on the basis of their drug use. While the proposed federal legislation lapsed after objections from a coalition of medical, legal and other advocacy groups, the New South Wales legislation still provides that, in employment matters, it is not unlawful to discriminate against a person on the ground of disability if the disability relates to the person's addiction to a prohibited drug and the person is actually addicted to a prohibited drug at the time of the discrimination. The article details the sequence of events in the Marsden case, reflects on the role of public interest litigation in achieving social justice outcomes and suggests that Australia's recent ratification of the Convention on the Rights of Persons with Disabilities on 17 July 2008 should encourage legislators to review legislation which may have a discriminatory effect on people suffering from addictions. PMID:20169800

  15. Antiplatelet drug interactions.

    PubMed

    Mackenzie, I S; Coughtrie, M W H; MacDonald, T M; Wei, L

    2010-12-01

    Both laboratory studies in healthy volunteers and clinical studies have suggested adverse interactions between antiplatelet drugs and other commonly used medications. Interactions described include those between aspirin and ibuprofen, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and the thienopyridine, clopidogrel, and drugs inhibiting CYP2C19, notably the proton pump inhibitors (PPI) omeprazole and esomeprazole. Other interactions between thienopyridines and CYP3A4/5 have also been reported for statins and calcium channel blockers. The ibuprofen/aspirin interaction is thought to be caused by ibuprofen blocking the access of aspirin to platelet cyclo-oxygenase. The thienopyridine interactions are caused by inhibition of microsomal enzymes that metabolize these pro-drugs to their active metabolites. We review the evidence for these interactions, assess their clinical importance and suggest strategies of how to deal with them in clinical practice. We conclude that ibuprofen is likely to interact with aspirin and reduce its anti-platelet action particularly in those patients who take ibuprofen chronically. This interaction is of greater relevance to those patients at high cardiovascular risk. A sensible strategy is to advise users of aspirin to avoid chronic ibuprofen or to ingest aspirin at least 2 h prior to ibuprofen. Clearly the use of NSAIDs that do not interact in this way is preferred. For the clopidogrel CYP2C19 and CYP3A4/5 interactions, there is good evidence that these interactions occur. However, there is less good evidence to support the clinical importance of these interactions. Again, a reasonable strategy is to avoid the chronic use of drugs that inhibit CYP2C19, notably PPIs, in subjects taking clopidogrel and use high dose H2 antagonists instead. Finally, anti-platelet agents probably interact with other drugs that affect platelet function such as selective serotonin reuptake inhibitors, and clinicians should probably judge

  16. Drug use as consumer behavior.

    PubMed

    Foxall, Gordon Robert; Sigurdsson, Valdimar

    2011-12-01

    Seeking integration of drug consumption research by a theory of memory function and emphasizing drug consumption rather than addiction, Müller & Schumann (M&S) treat drug self-administration as part of a general pattern of consumption. This insight is located within a more comprehensive framework for understanding drug use as consumer behavior that explicates the reinforcement contingencies associated with modes of drug consumption.

  17. Smart drugs: green shuttle or real drug?

    PubMed

    Cornara, L; Borghesi, B; Canali, C; Andrenacci, M; Basso, M; Federici, S; Labra, M

    2013-11-01

    We have combined morphological, molecular, and chemical techniques in order to identify the plant and chemical composition of some last-generation smart drugs, present on the market under the following names: Jungle Mistic Incense, B-52, Blendz, and Kratom 10x. Micromorphological analyses of botanical fragments allowed identification of epidermal cells, stomata, trichomes, starch, crystals, and pollen. DNA barcoding was carried out by the plastidial gene rbcL and the spacer trnH-psbA as universal markers. The combination of morphological and molecular data revealed a mixture of plants from different families, including aromatic species, viz., Lamiaceae and Turneraceae. GC-MS and LC-MS analyses on ethanol or methanol extracts showed the presence of synthetic cannabinoids, including JWH-250 in Jungle, JWH-122 in B-52, and JWH-073 and JWH-018 in Blendz. In Kratom 10x, only the indole alkaloid mitragynine was detected. All the identified synthetic cannabinoids, apart from mitragynine, are under the restriction of law in Italy (TU 309/90). Synthetic cannabinoid crystals were also identified by scanning electron microscopy and energy dispersive X-ray spectroscopy, which also detected other foreign organic chemicals, probably preservatives or antimycotics. In Kratom only leaf fragments from Mitragyna speciosa, containing the alkaloid mitragynine, were found. In the remaining products, aromatic plant species have mainly the role of hiding synthetic cannabinoids, thus acting as a "green shuttle" rather than as real drugs. Such a multidisciplinary approach is proposed as a method for the identification of herbal blends of uncertain composition, which are widely marketed in "headshops" and on the Internet, and represent a serious hazard to public health. PMID:23842669

  18. Driving forces for drug loading in drug carriers.

    PubMed

    Li, Yang; Yang, Li

    2015-01-01

    The loading capacity of a drug carrier is determined essentially by intermolecular interactions between drugs and carrier materials. In this review, the process of drug loading is described in detail based on the differences in the driving force for drug incorporation, including hydrophobic interaction, electrostatic interaction, hydrogen bonding, Pi-Pi stacking and van der Waals force. Modifying drug-loading sites of carrier materials with interacting groups aiming at tailoring drug-carrier interactions is reviewed by highlighting its importance for improving in vitro properties such as the loading capacity, release behaviour and stability. Other factors affecting drug loading, methods employed to predict the encapsulation capacity and the techniques to verify intermolecular interactions are also discussed to inform the readers of all-sided information on drug-loading processes and theories. The drug carriers can be designed more reasonably with the better understanding of the nature and interacting mechanism of intermolecular interactions.

  19. [Mechanisms of drug metabolism--implications for drug interaction].

    PubMed

    Sitkiewicz, D

    2000-09-01

    Most drugs undergo biotransformation before excretion by renal, biliary or other routes. The main purpose of metabolism is to make the drug, which is usually lipophilic, more water soluble. Metabolic reactions, depending upon the end product formed, can be classified as functionalisation (phase I) or conjugation (Phase II) reactions. Phase I metabolic reactions include oxidation, reduction and hydrolysis; while phase II processes are glucuronidation, sulfation, methylation, acetylation and mercapture formation. Cytochrome P-450 isozymes play a central role in metabolism of great majority of xenobiotics, as well as some endogenous substances. Many drugs can inhibit, induce and alter relative amounts of different P-450 enzymes; therefore, possibilities of drug-drug interactions exist in that one drug can influence biodisposition of another with potential clinical implications. One drug can inhibit metabolism of another, leading to excessive accumulation and toxicity. Alternatively, one drug can stimulate or induce metabolism of another drug resulting in subtherapeutic plasma levels of the later.

  20. The metaphorical nature of drugs and drug taking.

    PubMed

    Montagne, M

    1988-01-01

    An inquiry into the role metaphor plays in personal and societal conceptions of drugs and drug taking reveals that drug metaphors and symbols are quite pervasive in individual thinking, social discourse, and the cultural media. They appear to influence beliefs and attitudes regarding drugs, the nature and meaning of drug experiences, and the reasons behind drug-taking behaviors. Some drug metaphors are common to different cultures and historical periods, while others are specific and exclusive to particular individuals and groups or drug-taking situations. These metaphors can carry positive as well as negative connotations. Further study is needed to delineate the metaphorical structuring of our thinking about drugs, and the process whereby these metaphors are generated and spread throughout society.

  1. Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing

    PubMed Central

    Udrescu, Lucreţia; Sbârcea, Laura; Topîrceanu, Alexandru; Iovanovici, Alexandru; Kurunczi, Ludovic; Bogdan, Paul; Udrescu, Mihai

    2016-01-01

    Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications. PMID:27599720

  2. Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing.

    PubMed

    Udrescu, Lucreţia; Sbârcea, Laura; Topîrceanu, Alexandru; Iovanovici, Alexandru; Kurunczi, Ludovic; Bogdan, Paul; Udrescu, Mihai

    2016-01-01

    Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications. PMID:27599720

  3. A statistical methodology for drug-drug interaction surveillance.

    PubMed

    Norén, G Niklas; Sundberg, Rolf; Bate, Andrew; Edwards, I Ralph

    2008-07-20

    Interaction between drug substances may yield excessive risk of adverse drug reactions (ADRs) when two drugs are taken in combination. Collections of individual case safety reports (ICSRs) related to suspected ADR incidents in clinical practice have proven to be very useful in post-marketing surveillance for pairwise drug--ADR associations, but have yet to reach their full potential for drug-drug interaction surveillance. In this paper, we implement and evaluate a shrinkage observed-to-expected ratio for exploratory analysis of suspected drug-drug interaction in ICSR data, based on comparison with an additive risk model. We argue that the limited success of previously proposed methods for drug-drug interaction detection based on ICSR data may be due to an underlying assumption that the absence of interaction is equivalent to having multiplicative risk factors. We provide empirical examples of established drug-drug interaction highlighted with our proposed approach that go undetected with logistic regression. A database wide screen for suspected drug-drug interaction in the entire WHO database is carried out to demonstrate the feasibility of the proposed approach. As always in the analysis of ICSRs, the clinical validity of hypotheses raised with the proposed method must be further reviewed and evaluated by subject matter experts. PMID:18344185

  4. The Drug Alternative.

    ERIC Educational Resources Information Center

    Winn, Mitchell

    This book was written for educators and counselors, but its concepts are applicable to anyone who works with youth. It contains five chapters, the first of which emphasizes that building self-esteem is the best way to counter serious drug misuse. In chapter two, the kinds of pressures youngsters must cope with are discussed. In this chapter…

  5. Prevention and Drug Treatment

    ERIC Educational Resources Information Center

    Testa, Mark F.; Smith, Brenda

    2009-01-01

    Evidence linking alcohol and other drug abuse with child maltreatment, particularly neglect, is strong. But does substance abuse cause maltreatment? According to Mark Testa and Brenda Smith, such co-occurring risk factors as parental depression, social isolation, homelessness, or domestic violence may be more directly responsible than substance…

  6. Drug-mineral interactions

    SciTech Connect

    Kramer, L.

    1986-03-01

    The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Ca 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.

  7. Drug Errors in Anaesthesiology

    PubMed Central

    Jain, Rajnish Kumar; Katiyar, Sarika

    2009-01-01

    Summary Medication errors are a leading cause of morbidity and mortality in hospitalized patients. The incidence of these drug errors during anaesthesia is not certain. They impose a considerable financial burden to health care systems apart from the patient losses. Common causes of these errors and their prevention is discussed. PMID:20640103

  8. "Reasonable" Drug Testing.

    ERIC Educational Resources Information Center

    Dowling-Sendor, Benjamin

    2002-01-01

    Analysis of the U.S. Supreme Court's recent decision in "Board of Education of Independent School District No. 92 of Pottawatomie County v. Earls," wherein the Court held that random drug testing of students taking part in extracurricular activities is constitutional. (PKP)

  9. Drugs Used in COPD.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on drugs used in chronic obstructive pulmonary disease (COPD) is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first.…

  10. Drug development and manufacturing

    SciTech Connect

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

    2015-10-13

    X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

  11. NARCOTIC DRUG ADDICTION.

    ERIC Educational Resources Information Center

    YAHRAES, HERBERT; AND OTHERS

    MUCH HAS BEEN LEARNED IN RECENT YEARS ABOUT THE NATURE OF DRUG ADDICTION, THE FACTORS WHICH LEAD A PERSON INTO ADDICTION, AND THE EFFECTIVE TREATMENT OF PERSONS WHO HAVE BECOME ADDICTED. THIS PAMPHLET SURVEYS THE NEW FINDINGS AND IS INTENDED PRIMARILY FOR (1) THOSE WHO IN THE COURSE OF THEIR PROFESSIONAL DUTIES COME IN CONTACT WITH ADDICTED…

  12. [Resistance to antituberculous drugs].

    PubMed

    Veziris, N; Cambau, E; Sougakoff, W; Robert, J; Jarlier, V

    2005-08-01

    Mycobacteria responsible for tuberculosis (M. tuberculosis, M. bovis, M. africanum) are susceptible to a very small number of antibiotics. As soon as these drugs were used in humans all gave rise to the selection of resistant mycobacteria. Study of the mechanisms of acquired resistance, with the help of the genetics of mycobacteria, led to a more accurate understanding of the mode of action of antituberculous drugs. The antibiotics isoniazid, pyrazinamide, ethionamide and ethambutol are mycobacteria-specific because they inhibit the synthesis of mycolic acids, which are specific constituants of the bacterial wall. Mutations responsible for resistance to these drugs affect genes coding for activator enzymes (katg for isoniazid, pncA for pyrazinamide) or genes coding for their target (inhA for isoniazid/ethionamide, embB for ethambutol). With rifamycins, aminosides and quinolones, mechanisms of action and resistance are the same for mycobacteria as for non-mycobacterial organisms. No plasmid or resistance transposon has been described in M. tuberculosis. Currently a test for the quick detection of resistance to rifampicin is widely available but in the future DNA chips may allow the simultaneous detection of multiple resistances. Monitoring of antituberculous drugs shows that in France the prevalence of multiresistance ( resistance to both isoniazid and rifampicin) is 0.5%, primary resistance (before treatment) is 9%, and secondary resistance (after treatment) is 16%.

  13. Should Drugs Be Legalized?

    ERIC Educational Resources Information Center

    Chambliss, William; Scorza, Thomas

    1989-01-01

    Presents two opposing viewpoints concerning the legalization of drugs. States that control efforts are not cost effective and suggests that legalization with efforts at education is a better course of action (W. Chambliss). The opposing argument contends that the cost in human suffering negates any savings in dollars gained through legalization…

  14. Prescription Drug Abuse

    ERIC Educational Resources Information Center

    Hamilton, Gloria J.

    2009-01-01

    This article presents current statistics on nonmedical use of both categories of prescription medications by high school and college students. The incidence of nonmedical use of prescription medications continues to increase among high school and college students. Two categories of drugs that are commonly used for reasons other than those for…

  15. Cognition-Enhancing Drugs

    PubMed Central

    Mehlman, Maxwell J

    2004-01-01

    New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality of opportunity, and that individuals are free to decide whether or not to use them. PMID:15330974

  16. Drugs in Sport

    ERIC Educational Resources Information Center

    Mottram, David

    2012-01-01

    Drugs may be used by athletes for a number of reasons, including performance enhancement. The role of the World Anti-Doping Agency (WADA) is vital to ensure a winning performance has been achieved by fair means. Substances and methods that are included on the WADA Prohibited List are described. The procedures for testing banned substances are…

  17. Obesity drug therapy.

    PubMed

    Baretić, M

    2013-09-01

    Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question. PMID:24126545

  18. Drug Education in Tune.

    ERIC Educational Resources Information Center

    Janowiak, John J.

    1995-01-01

    Discusses Vietnam-era folk musician John Prine's song "Sam Stone" as an example of heroin-related musical lyricism. Notes the potential use of this and other songs as a teaching method in drug education programs. Notes that many researchers believe heroin addiction is a disease of biological irregularity encoded in the genes fueled by abuse of the…

  19. Drug discovery today.

    PubMed

    Schwardt, Oliver; Kolb, Hartmuth; Ernst, Beat

    2003-01-01

    In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

  20. The 50 Drug Program

    ERIC Educational Resources Information Center

    Chernick, Warren S.

    1977-01-01

    The "50 Drug Program" is an attempt by the faculty of the Department of Pharmacology at Hahnemann Medical College and Hospital, in association with other clinical departments, to provide structured guidance outside the realm of formal courses in the study of pharmacology and therapeutics throughout the entire four-year curriculum. (LBH)

  1. Antimalarial drug resistance: An overview

    PubMed Central

    Antony, Hiasindh Ashmi; Parija, Subhash Chandra

    2016-01-01

    Malaria is a major public health burden throughout the world. Resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. Monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. It is important to understand the mechanism of the antimalarial drugs, as it is one of the key factors in the emergence and spread of drug resistance. This review summarizes the commonly used antimalarial drugs, their mechanism of action and the genetic markers validated so far for the detection of drug-resistant parasites. PMID:26998432

  2. Immunosuppressive drugs and fertility.

    PubMed

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. PMID:26490561

  3. Immunosuppressive drugs and fertility.

    PubMed

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.

  4. Drug approval and surveillance.

    PubMed

    Potts, M

    1980-01-01

    This article argues that current regulations governing the licensing of drugs, particularly in the U.S., need to be changed and replaced by a system of provisional or conditional licensing and increased postmarketing surveillance of drug use. In terms of research and development of new forms of contraception, this proposal would have great impact. It is believed that the U.S./Food and Drug Administration (FDA) requirements--animal experiments and Phase 1 and 2 clinical trials--not only put an unacceptable financial burden on any institution attempting to develop new contraceptives, but do not demonstrably contribute to the reduction of risks. The author questions whether even if oral contraceptives introduced prior to new U.S./FDA regulations had been subject to these current regulations that convincing evidence would have been found to alert anyone to the now-known rare adverse effects, such as risk of thromboembolism. It is pointed out that these sorts of rare risks were uncovered by continuous screening processes which are not now a part of the FDA drug regulation requirements. The author also questions the politics of "conpulsory safety," such as might be legislated for regulated car safety belt use. Citing a partnership already established between government and private industry in high-risk/low cost ventures in the aerospace industry, the author sees no reason why such a relationship could not evolve in the pharmaceutical industry. In Britain, proposals have been made to establish a fund to compensate patients adversely affected by drugs which pharmaceutical companies would reimburse if proved negligent; such a fund may work in the U.S. under new regulations which stress postmarketing surveillance.

  5. Drug Information in Space Medicine

    NASA Technical Reports Server (NTRS)

    Bayuse, Tina M.

    2009-01-01

    Published drug information is widely available for terrestrial conditions. However, information on dosing, administration, drug interactions, stability, and side effects is scant as it relates to use in Space Medicine. Multinational crews on board the International Space Station present additional challenges for drug information because medication nomenclature, information available for the drug as well as the intended use for the drug is not standard across countries. This presentation will look at unique needs for drug information and how the information is managed in Space Medicine. A review was conducted of the drug information requests submitted to the Johnson Space Center Pharmacy by Space Medicine practitioners, astronaut crewmembers and researchers. The information requested was defined and cataloged. A list of references used was maintained. The wide range of information was identified. Due to the information needs for the medications in the on-board medical kits, the Drug Monograph Project was created. A standard method for answering specific drug information questions was generated and maintained by the Johnson Space Center Pharmacy. The Drug Monograph Project will be presented. Topic-centered requests, including multinational drug information, drug-induced adverse reactions, and medication events due to the environment will be highlighted. Information management of the drug information will be explained. Future considerations for drug information needs will be outlined.

  6. 77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ... HUMAN SERVICES Food and Drug Administration Guidance on Investigational New Drug Applications for... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs)....

  7. 76 FR 13880 - Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 312 and 314 Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment AGENCY: Food and Drug Administration... amending its investigational new drug application (IND) regulations and abbreviated new drug...

  8. Drug Usage and Attitude Toward Drugs Among College Students

    ERIC Educational Resources Information Center

    Cross, Herbert J.; Keir, Richard G.

    1971-01-01

    Results of the data presented suggest that there is considerable experimentation among college students with illegal drugs, especially marijuana. Their attitudes toward other drugs still seems cautious. Marijuana, however, seems-to be accepted and generally positively evaluated. (Author)

  9. Scaffold Repurposing of Old Drugs Towards New Cancer Drug Discovery.

    PubMed

    Chen, Haijun; Wu, Jianlei; Gao, Yu; Chen, Haiying; Zhou, Jia

    2016-01-01

    As commented by the Nobelist James Black that "The most fruitful basis of the discovery of a new drug is to start with an old drug", drug repurposing represents an attractive drug discovery strategy. Despite the success of several repurposed drugs on the market, the ultimate therapeutic potential of a large number of non-cancer drugs is hindered during their repositioning due to various issues including the limited efficacy and intellectual property. With the increasing knowledge about the pharmacological properties and newly identified targets, the scaffolds of the old drugs emerge as a great treasure-trove towards new cancer drug discovery. In this review, we summarize the recent advances in the development of novel small molecules for cancer therapy by scaffold repurposing with highlighted examples. The relevant strategies, advantages, challenges and future research directions associated with this approach are also discussed.

  10. Direct comparison of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I fluorescence (MSF) drug sensitivity tests in Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia

    PubMed Central

    2013-01-01

    Background Performance of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR Green I fluorescence (MSF) drug sensitivity tests were directly compared using Plasmodium falciparum reference strains and fresh ex vivo isolates from Cambodia against a panel of standard anti-malarials. The objective was to determine which of these two common assays is more appropriate for studying drug susceptibility of “immediate ex vivo” (IEV) isolates, analysed without culture adaption, in a region of relatively low malaria transmission. Methods Using the HRP-2 and MSF methods, the 50% inhibitory concentration (IC50) values against a panel of malaria drugs were determined for P. falciparum reference clones (W2, D6, 3D7 and K1) and 41 IEV clinical isolates from an area of multidrug resistance in Cambodia. Comparison of the IC50 values from the two methods was made using Wilcoxon matched pair tests and Pearson’s correlation. The lower limit of parasitaemia detection for both methods was determined for reference clones and IEV isolates. Since human white blood cell (WBC) DNA in clinical samples is known to reduce MSF assay sensitivity, SYBR Green I fluorescence linearity of P. falciparum samples spiked with WBCs was evaluated to assess the relative degree to which MSF sensitivity is reduced in clinical samples. Results IC50 values correlated well between the HRP-2 and MSF methods when testing either P. falciparum reference clones or IEV isolates against 4-aminoquinolines (chloroquine, piperaquine and quinine) and the quinoline methanol mefloquine (Pearson r = 0.85-0.99 for reference clones and 0.56-0.84 for IEV isolates), whereas a weaker IC50 value correlation between methods was noted when testing artemisinins against reference clones and lack of correlation when testing IEV isolates. The HRP-2 ELISA produced a higher overall success rate (90% for producing IC50 best-fit sigmoidal curves), relative to only a 40% success rate for the

  11. 77 FR 65198 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, and Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-25

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee--Abbreviated New Drug Application, Prior Approval Supplement, and Drug Master File Fee Rates for Fiscal Year 2013 AGENCY: Food and Drug... the Abbreviated New Drug Application (ANDA), Prior Approval Supplement (PAS), and Drug Master...

  12. Projecting future drug expenditures: 2011.

    PubMed

    Doloresco, Fred; Fominaya, Cory; Schumock, Glen T; Vermeulen, Lee C; Matusiak, Linda; Hunkler, Robert J; Shah, Nilay D; Hoffman, James M

    2011-05-15

    PURPOSE. Drug expenditure trends in 2009 and 2010, projected drug expenditures for 2011, and factors likely to influence drug expenditures are discussed. SUMMARY. Various factors are likely to influence drug expenditures in 2011, including drugs in development, the diffusion of new drugs, generic drugs, health care reform, and biosimilars. Two distinct patterns of drug expenditures continue to exist. The dominant trend over the past several years is substantial moderation in expenditure growth for widely used drugs, primarily due to the ongoing introduction of generic medications for high-cost, frequently used medications and the influence of the economic downturn. The second pattern is substantial increases in expenditures for specialized medications, particularly in the outpatient setting. The influence of health care reform, the economy, and the emergence of biosimilars will be important trends to follow over the next several years, but they are unlikely to have substantial impact on drug expenditures in 2011. From 2008 to 2009, total U.S. drug expenditures increased by 5.2%, with total spending rising from $284.8 billion to $299.5 billion. Growth in drug expenditures in clinics grew by 5.1% from 2008 to 2009. Hospital drug expenditures increased at the moderate rate of 2.8% from 2008 to 2009; through the first nine months of 2010, hospital drug expenditures increased by only 0.8% compared with the same period in 2009. CONCLUSION. For 2011, we project a 3-5% increase in drug expenditures in outpatient settings, a 4-6% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

  13. Over-the-Counter Drugs: A Challenge for Drug Education

    ERIC Educational Resources Information Center

    Serrone, David M.

    1973-01-01

    Drug education should be a complete program including information on the all too frequently overused group of self medicaments. Misuse of these drugs by self medication may, in many circumstances, lead to serious consequences. Knowledge of their use should be an effort of every drug education program. (Author)

  14. Federal Strategy for Drug Abuse and Drug Traffic Prevention 1979.

    ERIC Educational Resources Information Center

    Strategy Council on Drug Abuse, Washington, DC.

    This represents an approach to the Nation's drug abuse problem and reflects the views of departments and agencies involved in the federal drug control and prevention effort, public interest groups and members of Congress. It describes a comprehensive strategy for federal activities relating to drug abuse prevention and control. Major topics…

  15. Federal Strategy for Drug Abuse and Drug Traffic Prevention 1974.

    ERIC Educational Resources Information Center

    Strategy Council on Drug Abuse, Washington, DC.

    The Drug Abuse Office and Treatment Act of 1972 directed the development and promulgation of a comprehensive, coordinated long-term Federal strategy for all drug abuse prevention and drug traffic control functions conducted, sponsored, or supported by the Federal Government. This second annual report of the Strategy Council builds on the…

  16. Drug models of schizophrenia.

    PubMed

    Steeds, Hannah; Carhart-Harris, Robin L; Stone, James M

    2015-02-01

    Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia. PMID:25653831

  17. Drugs and sexual behavior.

    PubMed

    Bruno, Antonio; Scimeca, Giuseppe; Marino, Antonio G; Mento, Carmela; Micò, Umberto; Romeo, Vincenzo M; Pandolfo, Gianluca; Zoccali, Rocco; Muscatello, Maria R A

    2012-01-01

    This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed. PMID:23457886

  18. [Drug therapy for cough].

    PubMed

    Koskela, Heikki; Naaranlahti, Toivo

    2016-01-01

    An efficient therapy for cough usually requires identification and treatment of the underlying disease, like asthma. However an underlying disease in cough is not found in all cases and conventional treatment of the underlying disease is ineffective against cough. Drug therapy options are available also for these situations. Honey or menthol can be tried for cough associated with respitatory infections, antihistamines for cough associated with allergic rhinitis, blockers of the leukotriene receptor or muscarinic receptor for asthma-associated cough and morphine for cough associated with a malignant disease. Menthol, blockers of the muscarinic receptor, or dextrometorphan can be tried for prolonged idiopathic cough. Codeine is not necessary in the treatment of cough. Refraining from drug treatment should always be considered. PMID:27089619

  19. Drug mechanisms in anxiety.

    PubMed

    Bourin, M; Hascoët, M

    2001-02-01

    The most common and successful therapyfor the majority of patients suffering from anxiety is treatment with benzodiazepines (BZDs). The problem of drug-induced dependency following treatment with these drugs may be avoided by developing more selective and specific BZD compounds, such as 2,3-substituted BZDs. Alternative approaches to the treatment of anxiety include the following: (i) antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), which are active in treating most anxiety disorders, including GAD; (ii) metabotropic glutamate (mGluR2) receptor agonists, which negatively modulate glutamate neurotransmission, and CRF antagonists, which have been proposed to exhibit anxiolytic properties; (iii) 5-HT1A receptor agonists which have demonstrated anxiolytic effects in clinical studies, although preclinical studies have reported weak or variable effects; (iv) 5-HT moduline antagonists, as well as 5-HT2C receptor antagonists, which may have anxiolytic properties; and, finally, (v) other approaches which are under investigation, including CCK2 antagonists.

  20. Pharmacogenetics of analgesic drugs

    PubMed Central

    Russo, Giovanna; Gubbay, Anthony; Branford, Ruth; Sato, Hiroe

    2013-01-01

    Summary points • Individual variability in pain perception and differences in the efficacy of analgesic drugs are complex phenomena and are partly genetically predetermined. • Analgesics act in various ways on the peripheral and central pain pathways and are regarded as one of the most valuable but equally dangerous groups of medications. • While pharmacokinetic properties of drugs, metabolism in particular, have been scrutinised by genotype–phenotype correlation studies, the clinical significance of inherited variants in genes governing pharmacodynamics of analgesics remains largely unexplored (apart from the µ-opioid receptor). • Lack of replication of the findings from one study to another makes meaningful personalised analgesic regime still a distant future. • This narrative review will focus on findings related to pharmacogenetics of commonly used analgesic medications and highlight authors’ views on future clinical implications of pharmacogenetics in the context of pharmacological treatment of chronic pain. PMID:26516523

  1. [Drug therapy for cough].

    PubMed

    Koskela, Heikki; Naaranlahti, Toivo

    2016-01-01

    An efficient therapy for cough usually requires identification and treatment of the underlying disease, like asthma. However an underlying disease in cough is not found in all cases and conventional treatment of the underlying disease is ineffective against cough. Drug therapy options are available also for these situations. Honey or menthol can be tried for cough associated with respitatory infections, antihistamines for cough associated with allergic rhinitis, blockers of the leukotriene receptor or muscarinic receptor for asthma-associated cough and morphine for cough associated with a malignant disease. Menthol, blockers of the muscarinic receptor, or dextrometorphan can be tried for prolonged idiopathic cough. Codeine is not necessary in the treatment of cough. Refraining from drug treatment should always be considered.

  2. Drugging Membrane Protein Interactions

    PubMed Central

    Yin, Hang; Flynn, Aaron D.

    2016-01-01

    The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind the cell to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally “undruggable” regions of membrane proteins, enabling modulation of protein–protein, protein–lipid, and protein–nucleic acid interactions. In this review, we survey the state of the art in high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets. PMID:26863923

  3. Curiosities in drug metabolism.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H; Smith, Robert L

    2014-07-01

    1. It is inevitable that during some xenobiotic biotransformation studies, a certain metabolite or degradation product arises of which the identity is uncertain, the route of formation is ambiguous, or it is just a plain mystery. 2. The following communication draws attention to three drugs reported in the literature, chlorphentermine, phenothiazine and aminopyrine, where after many years of investigation there still exists uncertainty over some of their metabolites. Noticeably, these three examples probably involve (potential) interaction of a nitrogen centre within the drug molecule. 3. It is hoped that the resurrection and assemblage of these data will offer interesting reading and that these examples may prove sufficiently intriguing to motivate further exploration and some resolution of these lingering concerns. PMID:24779638

  4. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  5. Drug models of schizophrenia

    PubMed Central

    Steeds, Hannah; Carhart-Harris, Robin L.

    2015-01-01

    Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia. PMID:25653831

  6. Pharmacophores in Drug Research.

    PubMed

    Langer, Thierry

    2010-07-12

    The pharmacophore concept in modern drug research is highlighted and the most important use examples and success stories are reviewed. These include papers from method development as well as from application areas. As indicated by the number of publications available, the pharmacophore approach has proven to be extremely useful as interface between medicinal and computational chemistry, both in virtual screening and library design for efficient hit discovery, but also in the optimization of lead compounds to clinical candidates. Recent studies focus on the usage of parallel screening using pharmacophore models for bio-activity profiling and early stage risk assessment of potential side effects and toxicity due to interaction of drug candidates with anti-targets. PMID:27463325

  7. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

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

  8. Microdosing of protein drugs.

    PubMed

    Rowland, M

    2016-02-01

    Poor pharmacokinetics (PK) can seriously limit clinical utility. Knowing early whether a new compound is likely to have the desired PK profile at therapeutic doses is therefore important. One approach, microdosing, has shown high success with small molecular weight compounds, despite early skepticism. Vlaming et al. report the first, and successful, clinical application of a microdose of a humanized recombinant protein. But what is the likely success for this class of drugs more generally?

  9. [Pollinosis: drug treatments].

    PubMed

    Harf, R

    2013-06-01

    The medical treatment of allergic rhino-conjunctivitis involves different classes of drugs administered locally or by general route. They belong to three main classes, antihistamines, steroids and mast cell stabilizers. Since it is a relatively benign and also highly common disease, treatment options are limited by possible, even mild, side effects and by cost efficacy restriction. In the more severe forms of the condition, treatment efficacy remains unsatisfactory.

  10. The Drug Alternative.

    ERIC Educational Resources Information Center

    Winn, Mitchell

    While this book is directed toward educators and counselors, its concepts are applicable to all who work with youth, including parents. What the author does is to look honestly at one fact--that a linkage exists between serious drug misuse and lack of self-esteem--and to turn this fact around to encourage the building of self-esteem from K-12 as…

  11. Drug abuse in Slovak Republic.

    PubMed

    Kresanek, Jaroslav; Plackova, Silvia; Caganova, Blazena; Klobusicka, Zora

    2005-01-01

    The drug abusing structure has dramatically changed since 1989. While in 1989 the sniffing of the fluid drugs represented 98% of the global drug abuse, the most abused drugs were: heroin, marijuana, cocaine, amphetamine and its derivatives. During last 10 years situation with drug abuse has changed. Currently the most abused drugs: cannabinoides, amphetamines. The plant drugs (Datura stramonium, hallucinogenic mushrooms Psilocybe semilanceata, nutmeg--the seed of Myristica fragrans) combined with the alcohol are popular among the young abusers. According to an analysis of the phone consultations in our Toxicological Information Centre (TIC) we found out, that the number of intoxications with the plant drugs has increased five times during the last year (comparing with the year 2000), because of their easy availability, low price and quick spreading of information.

  12. RAS - Screens & Assays - Drug Discovery

    Cancer.gov

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  13. Drugs Approved for Lung Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Lung Cancer This page lists cancer ... in lung cancer that are not listed here. Drugs Approved for Non-Small Cell Lung Cancer Abitrexate ( ...

  14. Drugs Approved for Bladder Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Bladder Cancer This page lists cancer ... in bladder cancer that are not listed here. Drugs Approved for Bladder Cancer Atezolizumab Cisplatin Doxorubicin Hydrochloride ...

  15. Drugs Approved for Hodgkin Lymphoma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Hodgkin Lymphoma This page lists cancer ... in Hodgkin lymphoma that are not listed here. Drugs Approved for Hodgkin Lymphoma Adcetris (Brentuximab Vedotin) Ambochlorin ( ...

  16. Drugs Approved for Pancreatic Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Pancreatic Cancer This page lists cancer ... in pancreatic cancer that are not listed here. Drugs Approved for Pancreatic Cancer Abraxane (Paclitaxel Albumin-stabilized ...

  17. Drugs Approved for Testicular Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Testicular Cancer This page lists cancer ... in testicular cancer that are not listed here. Drugs Approved for Testicular Cancer Blenoxane (Bleomycin) Bleomycin Cisplatin ...

  18. Drugs Approved for Malignant Mesothelioma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer ... in malignant mesothelioma that are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed ...

  19. Drugs Approved for Vulvar Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Vulvar Cancer This page lists cancer ... in vulvar cancer that are not listed here. Drugs Approved to Prevent Vulvar Cancer Gardasil (Recombinant HPV ...

  20. Drugs Approved for Cervical Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Cervical Cancer This page lists cancer ... in cervical cancer that are not listed here. Drugs Approved to Prevent Cervical Cancer Cervarix (Recombinant HPV ...

  1. Drugs Approved for Skin Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Skin Cancer This page lists cancer ... in skin cancer that are not listed here. Drugs Approved for Basal Cell Carcinoma Aldara (Imiquimod) Efudex ( ...

  2. Comparing Osteoporosis Drugs: The Bisphosphonates

    MedlinePlus

    Drugs to Treat Low Bone Density Comparing Osteoporosis Drugs: The Bisphosphonates What is osteoporosis (low bone density)? Osteoporosis is a condition in which the body does not build enough new bone. ...

  3. Drugs in the Elementary School

    ERIC Educational Resources Information Center

    Lerner, Steven E.; Linder, Ronald L.

    1974-01-01

    The purpose of this study was to determine at what grade levels and to what extent upper elementary school students used selected psychoactive drugs, reasons for use, and availability of selected drugs within the school. (Author)

  4. Understanding Drug Use and Addiction

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... Drugs Anabolic Steroids Cigarettes and Other Tobacco Products Cocaine Cough and Cold Medicine Abuse Electronic Cigarettes (e- ...

  5. Advances in ophthalmic drug delivery.

    PubMed

    Morrison, Peter W J; Khutoryanskiy, Vitaliy V

    2014-12-01

    Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime.

  6. Would decriminalising drugs improve care?

    PubMed

    Riddell, Stephen

    The decriminalisation of illegal drugs is controversial. This article examines the debate in the UK, and argues that a change in the laws would help to remove stigma and consequently change health professionals' attitudes towards drug users and improve services.

  7. Medications and Drug Allergic Reactions

    MedlinePlus

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

  8. Drugs: What You Should Know

    MedlinePlus

    ... people on the hamster wheel of chasing a high just to feel better. Commonly abused drugs include: ... — or a friend — may be addicted to drugs, talk to your doctor , school counselor , or nurse. They can help you get ...

  9. Medical Consequences of Drug Abuse

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... Public Health What Can We Do About the Heroin Overdose Epidemic? NIDA's Publication Series Brain Power DrugFacts ...

  10. Trends in Prescription Drug Abuse

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  11. Drug interactions with quinolones.

    PubMed

    Davies, B I; Maesen, F P

    1989-01-01

    Numerous drug interactions with the new 4-quinolone antimicrobial agents have now been established. Many, but not all, quinolones are extensively metabolized and can have inhibitory effects on the liver cytochrome P450 enzyme system, leading to reduced metabolism and clearance of certain other drugs that are normally thus eliminated. Examples include the highly significant interaction between enoxacin and theophylline and the interaction between ciprofloxacin and theophylline, which may also be important clinically. The quinolone-caffeine interaction does not usually cause problems. Absorption of all quinolones from the stomach and small intestine is greatly reduced by antacids containing magnesium or aluminium salts, including sucralfate, probably as a result of the formation of nonabsorbable chelates. Cimetidine can reduce the clearance of pefloxacin (but not of ciprofloxacin) through its effects on liver metabolism, although newer H2-inhibitors appear not to have these effects. Probenecid reduces the renal elimination of some quinolones by inhibiting tubular secretion. New evidence is now coming to light of interactions between certain nonsteroid antiinflammatory drugs (e.g., fenbufen), quinolones, and gamma-aminobutyric acid (GABA) receptors, producing increased cerebral excitation and, sometimes, epileptiform convulsions. PMID:2570456

  12. 21 CFR 201.105 - Veterinary drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to...

  13. 21 CFR 201.105 - Veterinary drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to...

  14. 21 CFR 201.105 - Veterinary drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to...

  15. 21 CFR 201.105 - Veterinary drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to...

  16. 21 CFR 201.105 - Veterinary drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to...

  17. Patients' perceptions of psychotropic drugs

    PubMed Central

    Helman, Cecil G.

    1981-01-01

    This pilot study examined patients' perceptions of, and attitudes towards, psychotropic drug-taking. Fifty chronic users of benzodiazepines in two Middlesex group practices were interviewed, and data were collected on their knowledge, experience and expectations of these drugs. The data suggest that psychotropic drug-taking has become an important part of many patients' self-image and of their social relationships, and that these factors should be taken into account when dealing with psychological dependence on psychotropic drugs. PMID:7265056

  18. Adverse ocular reactions to drugs.

    PubMed Central

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

    1983-01-01

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

  19. Drug Abuse in Southeast Asia.

    ERIC Educational Resources Information Center

    Scorzelli, James F.

    This report examines the incidence of drug abuse and the methods of treatment and prevention of drug abuse used in Southeast Asia. Countries studied include Malaysia, Singapore, Thailand, Indonesia, and the Philippines. Because of Malaysia's intensive effort to eliminate its drug abuse problem, emphasis is placed on this country's treatment and…

  20. Drug Testing in Public Schools.

    ERIC Educational Resources Information Center

    Bjorklun, Eugene C.; Gluckman, Ivan B., Ed.

    1995-01-01

    Public concern about use of drugs by young people in the United States remains high and efforts to counter drug abuse through education and intervention continue. While drug testing of athletes at the collegiate level is fairly common, legal restraints make testing less common at the secondary school level. After citing numerous statistics…

  1. Drug Advertising and the FDA.

    ERIC Educational Resources Information Center

    Levesque, Cynthia

    With increases in consumer focused advertising for prescription drugs, the Federal Drug Administration has renewed efforts to protect the public from false advertising. In 1982, it charged that the press kits Eli Lilly and Company distributed to reporters on its new antiarthritis drug, Oraflex, misrepresented the product. It recommended that Lilly…

  2. The Biochemistry of Psychoactive Drugs.

    ERIC Educational Resources Information Center

    Abood, Leo G.

    The effect of psychochemicals on the higher central nervous system, and recent theories regarding drug addiction are discussed. The effect of drugs upon each individual is different. Many drugs have no effect on the brain because of a blood-brain barrier. However, alterations in the rate and character of one's metabolic pattern can lead to…

  3. National Drug Control Strategy, 2006

    ERIC Educational Resources Information Center

    The White House, 2006

    2006-01-01

    This report presents a summary of the Fiscal Year 2007 Budget for the National Drug Control Strategy within the three key priority areas; education and community action, treatment and intervention, and disruption in the illegal drug market. The first chapter, "Stopping Drug Use Before It Starts," outlines the Administration's work to prevent the…

  4. National Drug Control Strategy, 2011

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, 2011

    2011-01-01

    In May of 2010, President Obama released the Administration's inaugural "National Drug Control Strategy". Based on the premise that drug use and its consequences pose a threat not just to public safety, but also to public health, the 2010 "Strategy" represented the first comprehensive rebalancing of Federal drug control policy in the nearly 40…

  5. Drug Misuse in Older People.

    ERIC Educational Resources Information Center

    Raffoul, Paul R.; And Others

    1981-01-01

    Drug misuse of prescription and OTC drugs was studied among 67 older subjects to determine the frequency of misuse and relationship to various psychosocial, medical and pharmacological factors. Drug misuse was found among 43 percent of subjects with number of prescribing physicians and number of pharmacies directly related to misuse. (Author)

  6. Club Drugs. The DAWN Report.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Office of Applied Studies.

    This report was prepared in response to requests from the media, law enforcement, and community leaders for information about club drugs. By being able to utilize statistics from hospital emergency departments and by compiling statistics on drug-related deaths, the Drug Abuse Warning Network (DAWN) is able to alert parents, educators, and others…

  7. Drug Education: Is Ignorance Bliss?

    ERIC Educational Resources Information Center

    Zazzaro, Joanne

    1973-01-01

    Explains that drug education in schools has failed to work the way schoolmen expected, and may have cause more harm than good. Contends that just knowing about overdoses and chromosome damage hasn't convinced students to steer clear of drugs. Describes Boulder Valley Public Schools program for integrating drug information into broader mental…

  8. Aptamers as Both Drugs and Drug-Carriers

    PubMed Central

    Ashrafuzzaman, Md.

    2014-01-01

    Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer's disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery. PMID:25295268

  9. Glutamatergic transmission in drug reward: implications for drug addiction

    PubMed Central

    D'Souza, Manoranjan S.

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse. PMID:26594139

  10. Drug-drug plasma protein binding interactions of ivacaftor.

    PubMed

    Schneider, Elena K; Huang, Johnny X; Carbone, Vincenzo; Baker, Mark; Azad, Mohammad A K; Cooper, Matthew A; Li, Jian; Velkov, Tony

    2015-06-01

    Ivacaftor is a novel cystic fibrosis (CF) transmembrane conductance regulator (CFTR) potentiator that improves the pulmonary function for patients with CF bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs may compete for the same plasma protein binding sites and impact the free drug concentration. This, in turn, could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This biochemical study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1 -acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site-selective probes. Because of their ability to strongly compete for the ivacaftor binding sites on HSA and AGP, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole, and loratadine. The significance of these plasma protein drug-drug interactions is also interpreted in terms of molecular docking simulations. This in vitro study provides valuable insights into the plasma protein drug-drug interactions of ivacaftor with co-administered CF drugs. The data may prove useful in future clinical trials for a staggered treatment that aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor. PMID:25707701

  11. Drug abuse and illicit drug use in Puerto Rico.

    PubMed Central

    Canino, G; Anthony, J C; Freeman, D H; Shrout, P; Rubio-Stipec, M

    1993-01-01

    OBJECTIVES. Based on an epidemiologic field survey of community households in Puerto Rico, this study estimates the frequency of illicit drug use and clinically defined drug abuse and/or dependence syndromes. Results are compared with those from surveys on the United States mainland. Suspected risk factors are studied as well, with a special focus on childhood misbehavior. METHODS. Trained lay interviewers administered a Spanish Diagnostic Interview Schedule to 912 respondents aged 17 to 68 years who were selected by multistage probability sampling of island households. RESULTS. An estimated 8.2% of the population had a history of illicit drug use and 1.2% qualified for a standardized lifetime diagnosis of drug abuse, dependence, or both. An estimated 18.4% of the male drug users and 7.7% of the female drug users met criteria for drug abuse and/or dependence. A history of drug use was related to the diagnoses of alcohol abuse and/or dependence and antisocial personality, but few persons who had used illicit drugs at least once in their lifetime reported a history of receiving treatment for alcohol, drug, or mental health problems. CONCLUSIONS. The data were consistent with a suspected association between level of childhood misbehavior and occurrence of illicit drug use, even after statistical control for potentially confounding variables. PMID:8427322

  12. Glutamatergic transmission in drug reward: implications for drug addiction.

    PubMed

    D'Souza, Manoranjan S

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse. PMID:26594139

  13. Glutamatergic transmission in drug reward: implications for drug addiction.

    PubMed

    D'Souza, Manoranjan S

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

  14. [Customizing dosage drugs what contribution in therapeutic drug monitoring?].

    PubMed

    Abdessadek, Mohammed; Magoul, Rabia; Amarti, Afaf; El Ouezzani, Seloua; Khabbal, Youssef

    2014-01-01

    Drug response is often variable from an individual to another: the same dose of drug administered to different patients could cause variable pharmacological effects in nature and intensity. Those effects are often the result of variability in drugs pharmacokinetics (absorption, distribution, metabolism and elimination) which alter their bioavailability. In fact, two factors should be taken into account: the disease(s) from which the patient suffers, and the associated drugs, because many drug interactions may alter their pharmacokinetics causing consequently quite enough of different therapeutic effects. The choice of the assay of the drug subject in monitoring is crucial, it allows quantifying the in vivo dose of the drug and the quality of compliance thereof, the pharmacokinetic characteristics allows the clinician to adjust the dosage by different approaches so that plasma concentrations are included in the therapeutic range. Therapeutic monitoring aims to increase clinical efficacy and to minimize toxicity.

  15. Preventing and Recognizing Prescription Drug Abuse

    MedlinePlus

    ... Abuse » Preventing and recognizing prescription drug abuse Prescription Drug Abuse Email Facebook Twitter Preventing and recognizing prescription drug abuse To ensure proper medical care, patients should discuss ...

  16. 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. PMID:27280198

  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. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  19. [New aspects of drug hepatotoxicity].

    PubMed

    Denjean, P; Nouel, O; N'Guyen, J M; Beneton, C; Allain, H

    1990-12-01

    This article sets out to report the new hepatotoxic drugs identified during the course of 1989 and to describe the state of the art about drugs suspected of hepatotoxicity, such as amoxicillin-a clavulinic or, to a lesser extent, octreotide. In contrast, Exifone, a recently introduced drug, was withdrawn from the market within a year. One is surprised to find drugs such as Buprenorphine and Trimebutine listed, which have never induced clinical cases of hepatitis despite widespread use. The article also reviews the drugs with recognized hepatotoxicity and tries to present the most up-to-date information about them. PMID:2082807

  20. Drug addiction and periodontal diseases.

    PubMed

    Saini, Gurpreet Kaur; Gupta, N D; Prabhat, K C

    2013-09-01

    The prevalence of drug addiction is increasing globally. Drug abuse damages many parts of the body such as oral cavity, lungs, liver, brain, heart etc., Addicts suffer from physical, psychological, emotional and behavioral problems. Their nutrition is also compromised. There is certainly an impact of all these factors on the health of periodontium. Dentists should be aware of the effects of drugs while treating the drug addicts. This article correlates the studies done on the impact of abused drugs such as alcohol, tobacco, opiates, cannabis, amphetamines etc., on general and periodontal health. PMID:24174750

  1. Drug-Induced Metabolic Acidosis.

    PubMed

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

    2015-01-01

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

  2. In vitro sensitivity of Plasmodium falciparum to artesunate in Thailand.

    PubMed Central

    Wongsrichanalai, C.; Wimonwattrawatee, T.; Sookto, P.; Laoboonchai, A.; Heppner, D. G.; Kyle, D. E.; Wernsdorfer, W. H.

    1999-01-01

    Reported are the in vitro susceptibilities of Plasmodium falciparum to artesunate, mefloquine, quinine and chloroquine of 86 isolates and to dihydroartemisinin of 45 isolates collected from areas of high resistance to mefloquine within Thailand near the borders with Myanmar and Cambodia, and from southern Thailand where P. falciparum is generally still sensitive to mefloquine. All the isolates were highly sensitive to artesunate, but the geometric mean IC50S were higher in isolates from the Thai-Myanmar and Thai-Cambodian borders than in those from southern Thailand. The IC50S for mefloquine and artesunate were strongly correlated (Pearson r = 0.605; n = 86; P < 0.00001). As expected, the in vitro sensitivities to dihydroartemisinin and artesunate were similar and strongly correlated (at IC50, Pearson r = 0.695; n = 45; P < 0.00002). The correlation between the activity of mefloquine and artesunate requires further investigation in order to determine the potential for development of cross-resistance in nature. Our results suggest that combination with mefloquine is not the ideal way of protecting the usefulness of artemisinin and its derivatives. A search for more suitable partner drugs to these compounds and careful regulation of their use are necessary in the interest of ensuring their long therapeutic life span. PMID:10361756

  3. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  4. Supramolecular approaches for drug development.

    PubMed

    Kawakami, K; Ebara, M; Izawa, H; Sanchez-Ballester, N M; Hill, J P; Ariga, K

    2012-01-01

    Various supramolecular systems can be used as drug carriers to alter physicochemical and pharmacokinetic characteristics of drugs. Representative supramolecular systems that can be used for this purpose include surfactant/polymer micelles, (micro)emulsions, liposomes, layer-by-layer assemblies, and various molecular conjugates. Notably, liposomes are established supramolecular drug carriers, which have already been marketed in formulations including AmBisome(®) (for treatment of fungal infection), Doxil(®) (for Kaposi's sarcoma), and Visudyne(®) (for age-related macular degeneration and choroidal neovascularization). Microemulsions have been used oral drug delivery of poorly soluble drugs due to improvements in bioavailability and predictable of absorption behavior. Neoral(®), an immunosuppressant used after transplant operations, is one of the most famous microemulsion-based drugs. Polymer micelles are being increasingly investigated as novel drug carriers and some formulations have already been tested in clinical trials. Supramolecular systems can be functionalized by designing the constituent molecules to achieve efficient delivery of drugs to desired sites in the body. In this review, representative supramolecular drug delivery systems, that may improve usability of candidate drugs or add value to existing drugs, are introduced. PMID:22455591

  5. Drug-induced cutaneous vasculitides.

    PubMed

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Quintarelli, L; Volpi, W; Fabbri, P; Caproni, M

    2015-04-01

    Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

  6. Emerging Frontiers in Drug Delivery.

    PubMed

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  7. Epidemiology of Injection Drug Use

    PubMed Central

    Arruda, Nelson; Bruneau, Julie; Jutras-Aswad, Didier

    2016-01-01

    After more than 30 years of research, numerous studies have shown that injection drug use is associated with a wide range of adverse health outcomes such as drug overdoses, drug-related suicidal behaviours, comorbid psychiatric disorders, bloodborne pathogens and other infectious diseases, and traumas. This review explores new trends and prominent issues associated with injection drug use. The dynamic nature of injection drug use is underlined by examining its recent trends and changing patterns in Canada and other “high-income countries.” Three research topics that could further contribute to the development of comprehensive prevention and intervention strategies aimed at people who inject drugs are also discussed: risk behaviours associated with the injection of prescription opioids, binge injection drug use, and mental health problems as determinants of injection risk behaviours. PMID:27254088

  8. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  9. Antiarrhythmic drugs and epilepsy.

    PubMed

    Borowicz, Kinga K; Banach, Monika

    2014-08-01

    For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDEP) has most likely a cardiac mechanism. Common elements of pathogenesis create a basis for the assumption that antiarrhythmic drugs (AADs) may affect seizure phenomena and interact with antiepileptic drugs (AEDs). Numerous studies have demonstrated anticonvulsant effects of AADs. Among class I AADs (sodium channel blockers), phenytoin is an established antiepileptic drug. Propafenone exerted low anti-electroshock activity in rats. Lidocaine and mexiletine showed the anticonvulsant activity not only in animal models, but also in patients with partial seizures. Among beta-blockers (class II AADs), propranolol was anticonvulsant in models for generalized tonic-clonic and complex partial seizures, but not for myoclonic convulsions. Metoprolol and pindolol antagonized tonic-clonic seizures in DBA/2 mice. Timolol reversed the epileptiform activity of pentylenetetrazol (PTZ) in the brain. Furthermore, amiodarone, the representative of class III AADs, inhibited PTZ- and caffeine-induced convulsions in mice. In the group of class IV AADs, verapamil protected mice against PTZ-induced seizures and inhibited epileptogenesis in amygdala-kindled rats. Verapamil and diltiazem showed moderate anticonvulsant activity in genetically epilepsy prone rats. Additionally, numerous AADs potentiated the anticonvulsant action of AEDs in both experimental and clinical conditions. It should be mentioned, however, that many AADs showed proconvulsant effects in overdose. Moreover, intravenous esmolol and intra-arterial verapamil induced seizures even at therapeutic dose ranges. PMID:24948053

  10. National drug policy: implications of the 'tough on drugs' ideology.

    PubMed

    Norman, R

    2001-10-01

    Australia has emerged over the last decade as a world leader in drug policy. According to Single and Rohl (1997 pvii) Australia's National Drug Strategy 'has been characterised by a unique combination of features which have brought it international attention and acclaim'. The strength of Australia's policy has been its emphasis on both licit and illicit drugs, and also its clear articulation of harm minimisation as a guiding principle in all areas of action. The key policy goals recognised the harm associated with all substances and sought results in key areas of alcohol-related problems, tobacco-related problems, under-age consumption, prescription medication problems and illicit drug use. However, Australia has a new drug policy document for the new millennium, The National Drug Strategic Framework 1998 - 2002. As a result of a conservative influence in national politics, this framework has moved from the harm minimisation philosophy to a moralistic 'tough on drugs' philosophy that stresses zero tolerance, law enforcement and abstinence. There is a risk that Australia will experience an increase in adverse health, social and economic consequences as a result of this new policy direction. Nurses need to think critically about the 'tough on drugs' ideology. There is a risk that significant adverse affects may occur for their drug-using patients as a result of this policy change. In their practice, nurses need to challenge the validity of a punitive response, and to commit themselves to improving the health and safety of the illicit drug-using community.

  11. Unapproved drugs--the drug information pharmacists' perspective.

    PubMed

    Giouroukakis, Mary; Dryer, Megan

    2013-04-01

    Pharmacists in all areas of practice frequently dispense or recommend drugs without realizing that some commonly used medications have never received Food and Drug Administration (FDA) approval. Most of these medications have been available for many years and are usually misconceived as generic drugs, when in fact they never went through the required quality, safety, and efficacy testing required by FDA. As a result, unapproved drugs can pose serious safety risks to patients and create uncertainty in the market. FDA established the "Unapproved Drugs Initiative" to protect public health by decreasing the number of available unapproved drugs with minimal disruptions to the market. Unapproved drugs remain in the market for various historical reasons. It is important for health care providers, particularly pharmacists, to be knowledgeable about unapproved products and consider switching patients to FDA-approved alternatives if possible when selecting drug therapy. Several resources are available on the FDA Website to determine approval status. Although FDA is working to remove unapproved drugs from the market, there will be circumstances when the use of unapproved drugs is medically necessary and appropriate. In these cases, pharmacists can monitor for and report adverse events and stay informed regarding any changes in approval status. PMID:23459285

  12. Antiepileptic drugs and memory.

    PubMed

    Thompson, P J

    1992-01-01

    Assessing the effects of medication on cognitive functions including memory is fraught with methodological problems. This article illustrates the range of approaches that have been employed. Medication effects have been more readily demonstrated in patients with intractable epilepsy, in whom drug dosages are higher and the risk of polytherapy is greater. Newly diagnosed cases and individuals treated with monotherapy show fewer effects. Evaluation of memory functions in most studies has been very limited, and where effects have been recorded these may well be secondary to changes in attentional level or mental processing speed.

  13. Antibiotic drug discovery.

    PubMed

    Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. PMID:27470984

  14. [Importance of drug interactions with smoking in modern drug research].

    PubMed

    Laki, Szilvia; Kalapos-Kovács, Bernadett; Antal, István; Klebovich, Imre

    2013-01-01

    Drug interaction is a process during which a drug's fate in the body or its pharmacological properties are altered by an influencing factor. The extent of the drug interaction's effect can vary. The interaction could result from the modulation by another drug, food, alcohol, caffeine, narcotics, a drug influencing absorption or smoking. Moreover, transporter interactions with smoking could also have a major impact on many drug's efficacy. Clinically relevant drug interactions with smoking were classified in terms of their effect: pharmacokinetic, pharmacodynamic and transporter interactions. Policyclic aromatic carbohydrates, found in cigarette smoke, have enzyme inducing properties. The interaction affects mainly the hepatic isoenzyme CYP1A2. Interactions caused by smoking have an effect on all drugs being substrates of and therefore metabolised by CYP1A2. Pharmacokinetic alteration can also occur during the absorption, distribution and elimination process. The pharmacodynamic interactions are mainly caused by the effects of nicotine, a cigarette smoke component. Through interactions, smoking could also modify the activity of transporter proteins, altering this way the ADME properties of many drugs. Since smoking is one of the deadliest artefact in the history of human civilisation, identifying drug interactions with smoking is the physician's and pharmacist's major responsibility and task. Moreover, it is necessary to identify the patient's smoking habits during a medical treatment. This review aims to investigate the main types of drug interactions (PK/PD), identify factors influencing the activity of CYP enzymes and transporters, and also summarize the mechanisms of the most important drug interactions with smoking and their clinically relevant consequences (Table II-VI.). Drugs, with effects somehow altered by smoking-interactions, have been studied. PMID:24575657

  15. Drug-Induced Itch Management.

    PubMed

    Ebata, Toshiya

    2016-01-01

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

  16. 21 CFR 310.502 - Certain drugs accorded new drug status through rulemaking procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Certain drugs accorded new drug status through... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS Requirements for Specific New Drugs or Devices § 310.502 Certain drugs accorded new drug status through rulemaking procedures. (a)...

  17. 21 CFR 310.502 - Certain drugs accorded new drug status through rulemaking procedures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Certain drugs accorded new drug status through... HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS Requirements for Specific New Drugs or Devices § 310.502 Certain drugs accorded new drug status through rulemaking procedures. (a)...

  18. 21 CFR 201.2 - Drugs and devices; National Drug Code numbers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs and devices; National Drug Code numbers. 201.2 Section 201.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.2 Drugs and devices; National Drug...

  19. 21 CFR 201.2 - Drugs and devices; National Drug Code numbers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Drugs and devices; National Drug Code numbers. 201.2 Section 201.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.2 Drugs and devices; National Drug...

  20. 21 CFR 201.2 - Drugs and devices; National Drug Code numbers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Drugs and devices; National Drug Code numbers. 201.2 Section 201.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.2 Drugs and devices; National Drug...