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Sample records for antimalaria drug mefloquine

  1. Anti-Malaria Drug Mefloquine Induces Motor Learning Deficits in Humans

    PubMed Central

    van Essen, Thomas A.; van der Giessen, Ruben S.; Koekkoek, Sebastiaan K. E.; VanderWerf, Frans; Zeeuw, Chris I. De; van Genderen, Perry J. J.; Overbosch, David; de Jeu, Marcel T. G.

    2010-01-01

    Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans. The main aim of this study was to investigate the effect of mefloquine on olivary-related motor performance and motor learning tasks in humans. We subjected nine participants to voluntary motor timing (dart throwing task), perceptual timing (rhythm perceptual task) and reflex timing tasks (eye-blink task) before and 24 h after the intake of mefloquine. The influence of mefloquine on motor learning was assessed by subjecting participants with and without mefloquine intake (controls: n = 11 vs mefloquine: n = 8) to an eye-blink conditioning task. Voluntary motor performance, perceptual timing, and reflex blinking were not affected by mefloquine use. However, the influence of mefloquine on motor learning was substantial; both learning speed as well as learning capacity was impaired by mefloquine use. Our data suggest that mefloquine disturbs motor learning skills. This adverse effect can have clinical as well as social clinical implications for mefloquine users. Therefore, this side-effect of mefloquine should be further investigated and recognized by clinicians. PMID:21151372

  2. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  3. Determining the absolute configuration of (+)-mefloquine HCl, the side-effect-reducing enantiomer of the antimalaria drug Lariam.

    PubMed

    Schmidt, Manuel; Sun, Han; Rogne, Per; Scriba, Gerhard K E; Griesinger, Christian; Kuhn, Lars T; Reinscheid, Uwe M

    2012-02-15

    Even though the important antimalaria drug rac-erythro-mefloquine HCl has been on the market as Lariam for decades, the absolute configurations of its enantiomers have not been determined conclusively. This is needed, since the (-) enantiomer is believed to cause adverse side effects in malaria treatment resulting from binding to the adenosine receptor in the human brain. Since there are conflicting assignments based on enantioselective synthesis and anomalous X-ray diffraction, we determined the absolute configuration using a combination of NMR, optical rotatory dispersion (ORD), and circular dichroism (CD) spectroscopy together with density functional theory calculations. First, structural models of erythro-mefloquine HCl compatible with NMR-derived (3)J(HH) scalar couplings, (15)N chemical shifts, rotational Overhauser effects, and residual dipolar couplings were constructed. Second, we calculated ORD and CD spectra of the structural models and compared the calculated data with the experimental values. The experimental results for (-)-erythro-mefloquine HCl matched our calculated chiroptical data for the 11R,12S model. Accordingly, we conclude that the assignment of 11R,12S to (-)-erythro-mefloquine HCl is correct.

  4. Mefloquine, an anti-malaria agent, causes reactive oxygen species-dependent cell death in mast cells via a secretory granule-mediated pathway

    PubMed Central

    Paivandy, Aida; Calounova, Gabriela; Zarnegar, Behdad; Öhrvik, Helena; Melo, Fabio R; Pejler, Gunnar

    2014-01-01

    Mast cells are known to have a detrimental impact on a variety of pathological conditions. There is therefore an urgent need of developing strategies that limit their harmful effects. The aim of this study was to accomplish this by developing a means of inducing mast cell apoptosis. The strategy was to identify novel compounds that induce mast cell apoptosis by permeabilization of their secretory lysosomes (granules). As a candidate, we assessed mefloquine, an anti-malarial drug that has been proposed to have lysosome-permeabilizing activity. Mefloquine was added to mast cells and administered in vivo, followed by assessment of the extent and mechanisms of mast cell death. Mefloquine was cytotoxic to murine and human mast cells. Mefloquine induced apoptotic cell death of wild-type mast cells whereas cells lacking the granule compounds serglycin proteoglycan or tryptase were shown to undergo necrotic cell death, the latter finding indicating a role of the mast cell granules in mefloquine-induced cell death. In support of this, mefloquine was shown to cause compromised granule integrity and to induce leakage of granule components into the cytosol. Mefloquine-induced cell death was refractory to caspase inhibitors but was completely abrogated by reactive oxygen species inhibition. These findings identify mefloquine as a novel anti-mast cell agent, which induces mast cell death through a granule-mediated pathway. Mefloquine may thus become useful in therapy aiming at limiting harmful effects of mast cells. PMID:25505612

  5. Development of mefloquine as an antimalarial drug*

    PubMed Central

    1983-01-01

    The spread of multiresistant strains of Plasmodium falciparum in south-east Asia and South America and the appearance of chloroquine resistance in Africa indicates the urgent need for alternative drugs against these parasites. Mefloquine, a 4-quinoline methanol, is the only new drug that is currently at an advanced stage of development. Studies in animal models and in the clinic have shown that it is highly active as a blood schizontocide against strains that are resistant to many established antimalarials, e.g., chloroquine and pyrimethamine. It is not, however, effective as a causal prophylactic agent. Preclinical toxicological, teratological, and carcinogenicity studies do not indicate any major contraindications to its use. Intensive clinical studies have been carried out in Africa, North and South America, south-east Asia, and Europe. These studies have indicated that the compound is generally well tolerated, safe, and effective in the treatment of malaria, particularly infections with chloroquine-resistant parasites. In order to protect this new and promising drug against the development of resistance to it in endemic areas, it is important that its introduction should be accomplished in a rational and deliberate manner. Appropriate precautionary measures include the development of mefloquine combinations (a combination of mefloquine with pyrimethamine—sulfadoxine is presently under investigation), its use with primaquine as a gametocytocidal drug to prevent transmission, and its deployment primarily for treatment, being used for prophylaxis only in special risk groups. PMID:6407767

  6. Study on the developmental toxicity of combined artesunate and mefloquine antimalarial drugs on rats.

    PubMed

    Boareto, Ana Cláudia; Müller, Juliane Centeno; de Araujo, Samanta Luiza; Lourenço, Ana Carolina; Lourenço, Emerson Luiz Botelho; Gomes, Caroline; Minatovicz, Bruna; Lombardi, Natália; Paumgartten, Francisco Roma; Dalsenter, Paulo Roberto

    2012-12-01

    Antimalarial drug combinations containing artemisinins (ACTs) have become first choice therapies for Plasmodium falciparum malaria. Data on safety of ACTs in pregnancy are limited and no previous study has been conducted on the developmental toxicity of artesunate-mefloquine combinations on the first trimester of gestation. To evaluate the developmental toxicity of an artesunate/mefloquine combination, pregnant rats were treated orally with artesunate (15 and 40 mg/kg bwt/day), mefloquine (30 and 80 mg/kg bwt/day) and artesunate/mefloquine (15/30 and 40/80 mg/kg bwt/day) on gestation days 9-11. Dams were C-sectioned on day 20, and their uteri and fetuses removed and examined for soft tissue and skeleton abnormalities. Artesunate increased embryolethality and the incidence of limb long bone malformations on the absence of overt maternal toxicity. Mefloquine (80 mg/kg bwt/day) was maternally toxic and enhanced fetal variations. Combination of artesunate and mefloquine did not enhance their toxicity compared to the toxicity observed after its separate administration. Embryotoxicity of artesunate was apparently attenuated when it is co-administered with mefloquine.

  7. 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.

  8. 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.

  9. 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

  10. The antimalarial drug mefloquine inhibits cardiac inward rectifier K+ channels: evidence for interference in PIP2-channel interaction.

    PubMed

    López-Izquierdo, Angélica; Ponce-Balbuena, Daniela; Moreno-Galindo, Eloy G; Aréchiga-Figueroa, Iván A; Rodríguez-Martínez, Martín; Ferrer, Tania; Rodríguez-Menchaca, Aldo A; Sánchez-Chapula, José A

    2011-04-01

    The antimalarial drug mefloquine was found to inhibit the KATP channel by an unknown mechanism. Because mefloquine is a Cationic amphiphilic drug and is known to insert into lipid bilayers, we postulate that mefloquine interferes with the interaction between PIP2 and Kir channels resulting in channel inhibition. We studied the inhibitory effects of mefloquine on Kir2.1, Kir2.3, Kir2.3(I213L), and Kir6.2/SUR2A channels expressed in HEK-293 cells, and on IK1 and IKATP from feline cardiac myocytes. The order of mefloquine inhibition was Kir6.2/SUR2A ≈ Kir2.3 (IC50 ≈ 2 μM) > Kir2.1 (IC50 > 30 μM). Similar results were obtained in cardiac myocytes. The Kir2.3(I213L) mutant, which enhances the strength of interaction with PIP2 (compared to WT), was significantly less sensitive (IC50 = 9 μM). In inside-out patches, continuous application of PIP2 strikingly prevented the mefloquine inhibition. Our results support the idea that mefloquine interferes with PIP2-Kir channels interactions.

  11. 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

  12. 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.

  13. Trapped in misbelief for almost 40 years: selective synthesis of the four stereoisomers of mefloquine.

    PubMed

    Schützenmeister, Nina; Müller, Michael; Reinscheid, Uwe M; Griesinger, Christian; Leonov, Andrei

    2013-12-16

    Here we report the synthesis of all four stereoisomers of mefloquine. Mefloquine (Lariam) is an important anti-malaria drug that is applied as a racemate of the erythro form. However, the (-)-isomer induces psychosis, while the (+)-enantiomer does not have this undesired side effect. There are six syntheses of which five lead to the wrong enantiomer without the authors of these syntheses noting that they had synthesized the wrong compound. At the same time physical chemistry investigations had assigned the absolute configuration correctly and the last enantioselective synthesis that took these results into account delivered the correct absolute configuration. Since various synthetic approaches failed to provide the correct stereoisomers in previous syntheses, we submit here a synthetic approach with a domino Sonogashira-6π-electrocyclisation as key step that confirmed synthetically the correct absolute configuration of all four isomers.

  14. Mefloquine (Lariam)

    MedlinePlus

    ... in Somalia, Iraq, and Afghanistan, for protection against malaria. Malaria is an infectious disease transmitted by mosquitoes. Mefloquine, ... is also used for travelers visiting areas where malaria is found, based on recommendations from the Centers ...

  15. Effect of an anti-malaria drug on behavioural performance on a problem-solving task: an experiment in wild great tits.

    PubMed

    Cauchard, Laure; Angers, Bernard; Boogert, Neeltje J; Doligez, Blandine

    2016-10-29

    Malaria parasites have been shown to decrease host fitness in several species in the wild and their detrimental effects on host cognitive ability are well established in humans. However, experimental demonstrations of detrimental effects on non-human host behaviour are currently limited. In this study, we experimentally tested whether injections of an anti-malaria drug affected short-term behavioural responses to a problem-solving task during breeding in a wild population of great tits (Parus major) naturally infected with malaria. Adult females treated against malaria were more active than control females, even though they were not more likely to solve the task or learn how to do so, suggesting that energetic constraints could shape differences in some behaviours while changes in cognitive performances might require more time for the neural system to recover or may depend mainly on infection at the developmental stage. Alternatively, parasite load might be a consequence, rather than a cause, of inter-individual variation in cognitive performance. These results also suggest that inter-individual as well as inter-population differences in some behavioural traits may be linked to blood parasite load.

  16. 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

  17. Carboxymefloquine, the major metabolite of the antimalarial drug mefloquine, induces drug-metabolizing enzyme and transporter expression by activation of pregnane X receptor.

    PubMed

    Piedade, Rita; Traub, Stefanie; Bitter, Andreas; Nüssler, Andreas K; Gil, José P; Schwab, Matthias; Burk, Oliver

    2015-01-01

    Malaria patients are frequently coinfected with HIV and mycobacteria causing tuberculosis, which increases the use of coadministered drugs and thereby enhances the risk of pharmacokinetic drug-drug interactions. Activation of the pregnane X receptor (PXR) by xenobiotics, which include many drugs, induces drug metabolism and transport, thereby resulting in possible attenuation or loss of the therapeutic responses to the drugs being coadministered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on nonartemisinin-type antimalarials are still missing. Therefore, this study aimed to elucidate the potential of nonartemisinin antimalarial drugs and drug metabolites to activate PXR. We screened 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR using the two-hybrid PXR ligand binding domain assembly assay; this identified carboxymefloquine, the major and pharmacologically inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. Two-hybrid PXR-coactivator and -corepressor interaction assays and PXR-dependent promoter reporter gene assays confirmed carboxymefloquine to be a novel PXR agonist which specifically activated the human receptor. In the PXR-expressing intestinal LS174T cells and in primary human hepatocytes, carboxymefloquine induced the expression of drug-metabolizing enzymes and transporters on the mRNA and protein levels. The crucial role of PXR for the carboxymefloquine-dependent induction of gene expression was confirmed by small interfering RNA (siRNA)-mediated knockdown of the receptor. Thus, the clinical use of mefloquine may result in pharmacokinetic drug-drug interactions by means of its metabolite carboxymefloquine. Whether these in vitro findings are of in vivo relevance has to be addressed in future clinical drug-drug interaction studies.

  18. 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

    2012-05-02

    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.

  19. Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos.

    PubMed

    Boareto, A C; Müller, J C; Lourenço, E L B; Lombardi, N; Lourenço, A C; Rabitto, I; de Morais, R N; Rios, F S; Dalsenter, P R

    2013-09-01

    Artemisinins combination therapy (ACT) is the first choice therapy for falciparum malaria. Data on the safety of ACTs in pregnancy are limited and controversial and the use is not recommended on the first trimester. To evaluate the effects of isolated and combined artesunate (AS)/mefloquine (MQ) on embryo rats, pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9-11 post coitum (pc). The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated. Embryolethality and histopathological anomalies were significant when AS was given alone or combined with MQ. Combination of AS and MQ did not enhance their toxicity compared to their separate administrations; on the other side, there was a reduction in the toxic effects of the AS when combined with MQ. Isolated MQ did not induce developmental toxicity.

  20. A randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, and pharmacokinetics of single enantiomer (+)-mefloquine compared with racemic mefloquine in healthy persons.

    PubMed

    Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

    2010-12-01

    Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (-) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (-)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted.

  1. Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition.

    PubMed

    Kim, Ju-Hwa; Choi, Ae-Ran; Kim, Yong Kee; Yoon, Sungpil

    2013-11-22

    The purpose of this study was to identify conditions that will increase the sensitivity of resistant cancer cells to anti-mitotic drugs. Currently, atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF), artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant KBV20C cancer cells. None of the six tested anti-malarial drugs was found to better sensitize the drug-resistant cells compared to the sensitive KB cells. With an exception of DOY, all other anti-malarial drugs tested could sensitize both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs could be used for sensitive as well as resistant cancer cells. Furthermore, we examined the effects of anti-malarial drugs in combination with an antimitotic drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst staining, we identified that two anti-malarial drugs, PRI and MEF, highly sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced sensitisation was not observed in VIN-treated sensitive KB parent cells, suggesting that the observed effect is specific to resistant cancer cells. We demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the inhibition of p-glycoprotein (P-gp). Our findings may contribute to the development of anti-malarial drug-based combination therapies for patients resistant to anti-mitotic drugs.

  2. Failure of malaria chemoprophylaxis with mefloquine in an oversize traveller to Mozambique.

    PubMed

    Gobbi, Federico; Rossanese, Andrea; Buonfrate, Dora; Angheben, Andrea; Lunardi, Gianluigi; Bisoffi, Zeno

    2013-12-18

    A case of failure of mefloquine prophylaxis in an oversize traveller, who correctly took the drug. This case seems to be attributed to mefloquine resistance, however it is suggested that mefloquine dosage should be modulated by body weight, as is already indicated by some authorities.

  3. 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

  4. Mefloquine damage vestibular hair cells in organotypic cultures.

    PubMed

    Yu, Dongzhen; Ding, Dalian; Jiang, Haiyan; Stolzberg, Daniel; Salvi, Richard

    2011-07-01

    Mefloquine is an effective and widely used anti-malarial drug; however, some clinical reports suggest that it can cause dizziness, balance, and vestibular disturbances. To determine if mefloquine might be toxic to the vestibular system, we applied mefloquine to organotypic cultures of the macula of the utricle from postnatal day 3 rats. The macula of the utricle was micro-dissected out as a flat surface preparation and cultured with 10, 50, 100, or 200 μM mefloquine for 24 h. Specimens were stained with TRITC-conjugated phalloidin to label the actin in hair cell stereocilia and TO-PRO-3 to visualize cell nuclei. Some utricles were also labeled with fluorogenic caspase-3, -8, or -9 indicators to evaluate the mechanism of programmed cell death. Mefloquine treatment caused a dose-dependent loss of utricular hair cells. Treatment with 10 μM caused a slight reduction, 50 μM caused a significant reduction, and 200 μM destroyed nearly all the hair cells. Hair cell nuclei in mefloquine-treated utricles were condensed and fragmented, morphological features of apoptosis. Mefloquine-treated utricles were positive for the extrinsic initiator caspase-8 and intrinsic initiator caspase-9 and downstream executioner caspase-3. These results indicate that mefloquine can induce significant hair cell degeneration in the postnatal rat utricle and that mefloquine-induced hair cell death is initiated by both caspase-8 and caspase-9.

  5. Mefloquine neurotoxicity is mediated by non-receptor tyrosine kinase.

    PubMed

    Milatovic, Dejan; Jenkins, Jerry W; Hood, Jonathan E; Yu, Yingchun; Rongzhu, Lu; Aschner, Michael

    2011-10-01

    Among several available antimalarial drugs, mefloquine has proven to be effective against drug-resistant Plasmodium falciparum and remains the drug of choice for both therapy and chemoprophylaxis. However, mefloquine is known to cause adverse neurological and/or psychiatric symptoms, which offset its therapeutic advantage. The exact mechanisms leading to the adverse neurological effects of mefloquine are poorly defined. Alterations in neurotransmitter release and calcium homeostasis, the inhibition of cholinesterases and the interaction with adenosine A(2A) receptors have been hypothesized to play prominent roles in mediating the deleterious effects of this drug. Our recent data have established that mefloquine can also trigger oxidative damage and subsequent neurodegeneration in rat cortical primary neurons. Furthermore, we have utilized a system biology-centered approach and have constructed a pathway model of cellular responses to mefloquine, identifying non-receptor tyrosine kinase 2 (Pyk2) as a critical target in mediating mefloquine neurotoxicity. In this study, we sought to establish an experimental validation of Pyk2 using gene-silencing techniques (siRNA). We have examined whether the downregulation of Pyk2 in primary rat cortical neurons alters mefloquine neurotoxicity by evaluating cell viability, apoptosis and oxidative stress. Results from our study have confirmed that mefloquine neurotoxicity is associated with apoptotic response and oxidative injury, and we have demonstrated that mefloquine affects primary rat cortical neurons, at least in part, via Pyk2. The implication of these findings may prove beneficial in suppressing the neurological side effects of mefloquine and developing effective therapeutic modalities to offset its adverse effects.

  6. 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.

  7. Antischistosomal activities of mefloquine-related arylmethanols.

    PubMed

    Ingram, Katrin; Ellis, William; Keiser, Jennifer

    2012-06-01

    Interesting antischistosomal properties have been documented for the antimalarial mefloquine, a 4-quinolinemethanol. We evaluated the antischistosomal activities of nine mefloquine-related compounds belonging to the 4-pyridinemethanols, 9-phenanthrenmethanols, and 4-quinolinemethanols. Eight compounds revealed high activities against Schistosoma mansoni in vitro, with two drugs (the 4-quinolinemethanols WR7573 and WR7930) characterized by significantly lower half-maximal inhibitory concentrations (IC(50)s) (2.7 and 3.5 μM, respectively) compared to mefloquine (11.4 μM). Mefloquine and WR7930 showed significantly decreased IC(50)s when incubated in the presence of hemoglobin. High worm burden reductions (WBR) were obtained with enpiroline (WBR, 82.7%; dosage, 200 mg/kg of body weight) and its threo isomers (+)-threo (WBR, 100%) and (-)-threo (WBR, 89%) and with WR7930 (WBR, 87%; dosage, 100 mg/kg) against adult S. mansoni in mice. Furthermore, excellent in vitro and in vivo antischistosomal activity was observed for two WR7930-related structures (WR29252 and WR7524). In addition, mefloquine (WBR, 81%), enpiroline (WBR, 77%), and WR7930 (WBR, 100%) showed high activities against S. haematobium harbored in mice following single oral doses of 200 mg/kg. These results provide a deeper insight into the structural features of the arylmethanols that rule antischistosomal activity. Further studies should be launched with enpiroline and WR7930.

  8. 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

  9. Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase.

    PubMed

    Manneck, Theresia; Keiser, Jennifer; Müller, Joachim

    2012-04-01

    The antimalarial drug mefloquine has promising antischistosomal properties killing haematophagous adult schistosomes as well as schistosomula. The mode of action and involved drug targets of mefloquine in Schistosoma mansoni schistosomula are unknown. In order to identify mefloquine-binding proteins and thus potential drug targets, mefloquine affinity chromatography with S. mansoni schistosomula crude extracts was performed. We found one specific mefloquine-binding protein that was identified by mass spectrometry as the glycolytic enzyme enolase (Q27877). Enolase activity assays were performed on schistosomula crude extracts and on the recombinant enolase Q27877 expressed in Escherichia coli. In schistosomula crude extracts enolase activity was inhibited by mefloquine and by the enolase inhibitor sodium fluoride, while activity of the recombinant enolase was not affected. In contrast to enolase from crude extracts, recombinant Q27877 did not bind to mefloquine-agarose. Using isothermal microcalorimetry, we next investigated the metabolic inhibition of mefloquine and 3 known glycolytic inhibitors in Schistosoma spp., namely sodium fluoride, 3-bromopyruvate and menadione on schistosomula in the presence or absence of glucose. We found that in the presence of glucose, schistosomula were less affected by mefloquine, sodium fluoride and 3-bromopyruvate, whereas glucose had no protective effect when schistosomula had been exposed to menadione. These results suggest a potential role of mefloquine as an inhibitor of glycolysis, at least in stages where other targets like haem degradation are not relevant.

  10. Mefloquine use, psychosis, and violence: A retinoid toxicity hypothesis

    PubMed Central

    Mawson, Anthony R.

    2013-01-01

    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. PMID:23852388

  11. 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.

  12. Mefloquine gap junction blockade and risk of pregnancy loss.

    PubMed

    Nevin, Remington Lee

    2012-09-01

    Obstetric use of the antimalarial drug mefloquine has historically been discouraged during the first trimester and immediately before conception owing to concerns of potential fetal harm. With the rise of resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP), mefloquine is now being considered as a replacement for SP for universal antenatal administration to women from malaria-endemic regions. Recent recommendations have also suggested that mefloquine may be used cautiously among pregnant travelers who cannot otherwise avoid visiting these areas. Mefloquine has been demonstrated to cause blockade of gap junction protein alpha 1 (GJA1) gap junction intercellular communication (GJIC), and recent evidence suggests that GJA1 GJIC is critical to successful embryonic implantation and early placental development. During routine use, mefloquine accumulates in organ and peripheral tissue, crosses the blood-placental barrier, and may plausibly accumulate in developing decidua and trophoblast at concentrations sufficient to interfere with GJA1 GJIC and, thus, cause deleterious effects on fetal outcomes. This conclusion is supported by epidemiological evidence that demonstrates use of the drug during early development is associated with an increased risk of miscarriage and stillbirth. Confirmatory studies are pending, but the available experimental and epidemiological evidence support renewed adherence, where feasible, to existing mefloquine package insert guidance that women avoid the drug during the periconceptional period.

  13. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26471420

  15. Investigation of the in vitro gender-specific partitioning of mefloquine in malarial infected red blood cells and plasma.

    PubMed

    Seethorn, Nongluk; Wernsdorfer, Walther H; Noedl, Harald; Karbwang, Juntra; Na-Bangchang, Kesara

    2013-10-01

    The investigation of gender-specific partitioning of the antimalarial drug mefloquine to cellular and fluid blood compartments was performed using blood collected from a female and male healthy subject that were infected with Plasmodium falciparum PCM2 clone and spiked with mefloquine (0.25, 1, and 5 μM). Mefloquine concentrations in red cells of both female and male subjects were significantly higher than plasma, which suggests an intensive uptake by red cells. This was supported by a high ratio of mefloquine concentrations in the parasitized and non-parasitized red cells of about 4-fold. Gender-specific partitioning of mefloquine in parasitized blood was seen only in plasma where significantly higher concentrations were observed in female compared with male plasma. Down-adjusting the therapeutic dose of mefloquine in female patients with malaria is not advisable because mefloquine concentrations in the target cellular compartment are similar in both genders.

  16. Peripheral Polyneuropathy and Mefloquine Prophylaxis

    PubMed Central

    Chester, Alexander C.; Sandroni, Paola

    2011-01-01

    We describe a case of a woman who developed a peripheral polyneuropathy shortly after completing 4 weekly doses of mefloquine hydrochloride (250 mg) malaria prophylaxis. Although mefloquine-related central nervous system neuropathy is well described in the literature, peripheral polyneuropathy similar to this case has been documented only once before, to our knowledge. PMID:22144435

  17. 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.

  18. 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

  19. Effects of mefloquine use on Plasmodium vivax multidrug resistance.

    PubMed

    Khim, Nimol; Andrianaranjaka, Voahangy; Popovici, Jean; Kim, Saorin; Ratsimbasoa, Arsene; Benedet, Christophe; Barnadas, Celine; Durand, Remy; Thellier, Marc; Legrand, Eric; Musset, Lise; Menegon, Michela; Severini, Carlo; Nour, Bakri Y M; Tichit, Magali; Bouchier, Christiane; Mercereau-Puijalon, Odile; Ménard, Didier

    2014-10-01

    Numerous studies have indicated a strong association between amplification of the multidrug resistance-1 gene and in vivo and in vitro mefloquine resistance of Plasmodium falciparum. Although falciparum infection usually is not treated with mefloquine, incorrect diagnosis, high frequency of undetected mixed infections, or relapses of P. vivax infection triggered by P. falciparum infections expose non-P. falciparum parasites to mefloquine. To assess the consequences of such unintentional treatments on P. vivax, we studied variations in number of Pvmdr-1 (PlasmoDB accession no. PVX_080100, NCBI reference sequence NC_009915.1) copies worldwide in 607 samples collected in areas with different histories of mefloquine use from residents and from travelers returning to France. Number of Pvmdr-1 copies correlated with drug use history. Treatment against P. falciparum exerts substantial collateral pressure against sympatric P. vivax, jeopardizing future use of mefloquine against P. vivax. A drug policy is needed that takes into consideration all co-endemic species of malaria parasites.

  20. 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

  1. Ultrasensitive fiber enhanced UV resonance Raman sensing of drugs.

    PubMed

    Frosch, Torsten; Yan, Di; Popp, Jürgen

    2013-07-02

    Fiber enhanced UV resonance Raman spectroscopy is introduced for chemical selective and ultrasensitive analysis of drugs in aqueous media. The application of hollow-core optical fibers provides a miniaturized sample container for analyte flow and efficient light-guiding, thus leading to strong light-analyte interactions and highly improved analytical sensitivity with the lowest sample demand. The Raman signals of the important antimalaria drugs chloroquine and mefloquine were strongly enhanced utilizing deep UV and electronic resonant excitation augmented by fiber enhancement. An experimental design was developed and realized for reproducible and quantitative Raman fiber sensing, thus the enhanced Raman signals of the pharmaceuticals show excellent linear relationship with sample concentration. A thorough model accounts for the different effects on signal performance in resonance Raman fiber sensing, and conclusions are drawn how to improve fiber enhanced Raman spectroscopy (FERS) for chemical selective analysis with picomolar sensitivity.

  2. The position of mefloquine as a 21st century malaria chemoprophylaxis

    PubMed Central

    2010-01-01

    Background Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. Methods A literature search to update the status of mefloquine as a malaria chemoprophylaxis. Results Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerability of mefloquine and the use of this medication by groups at high risk of malaria. Discussion Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. Conclusion The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine

  3. Mefloquine and Psychotomimetics Share Neurotransmitter Receptor and Transporter Interactions In Vitro

    PubMed Central

    Janowsky, Aaron; Eshleman, Amy J.; Johnson, Robert A.; Wolfrum, Katherine M.; Hinrichs, David J.; Yang, Jongtae; Zabriskie, T. Mark; Smilkstein, Martin J.; Riscoe, Michael K.

    2014-01-01

    Rationale Mefloquine is used for the prevention and treatment of chloroquine-resistant malaria, but its use is associated with nightmares, hallucinations, and exacerbation of symptoms of post-traumatic stress disorder. We hypothesized that potential mechanisms of action for the adverse psychotropic effects of mefloquine resemble those of other known psychotomimetics. Objectives Using in vitro radioligand binding and functional assays, we examined the interaction of (+)- and (−)-mefloquine enantiomers, the non-psychotomimetic anti-malarial agent, chloroquine, and several hallucinogens and psychostimulants with recombinant human neurotransmitter receptors and transporters. Results Hallucinogens and mefloquine bound stereoselectively and with relatively high affinity (Ki = 0.71–341 nM) to serotonin (5-HT) 2A but not 5-HT1A or 5-HT2C receptors. Mefloquine but not chloroquine was a partial 5-HT2A agonist and a full 5-HT2C agonist, stimulating inositol phosphate accumulation, with similar potency and efficacy as the hallucinogen dimethyltryptamine (DMT). 5-HT receptor antagonists blocked mefloquine’s effects. Mefloquine had low or no affinity for dopamine D1, D2, D3, and D4.4 receptors, or dopamine and norepinephrine transporters. However, mefloquine was a very low potency antagonist at the D3 receptor and mefloquine but not chloroquine or hallucinogens blocked [3H]5-HT uptake by the 5-HT transporter. Conclusions Mefloquine but not chloroquine shares an in vitro receptor interaction profile with some hallucinogens and this neurochemistry may be relevant to the adverse neuropsychiatric effects associated with mefloquine use by a small percentage of patients. Additionally, evaluating interactions with this panel of receptors and transporters may be useful for characterizing effects of other psychotropic drugs and for avoiding psychotomimetic effects for new pharmacotherapies, including antimalarial quinolines. PMID:24488404

  4. 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 ...

  5. Mefloquine effectively targets gastric cancer cells through phosphatase-dependent inhibition of PI3K/Akt/mTOR signaling pathway.

    PubMed

    Liu, Yanwei; Chen, Sen; Xue, Rui; Zhao, Juan; Di, Maojun

    2016-02-05

    Deregulation of PI3K/Akt/mTOR pathway has been recently identified to play a crucial role in the progress of human gastric cancer. In this study, we show that mefloquine, a FDA-approved anti-malarial drug, effectively targets human gastric cancer cells. Mefloquine potently inhibits proliferation and induces apoptosis of a panel of human gastric cancer cell lines, with EC50 ∼ 0.5-0.7 μM. In two independent gastric cancer xenograft mouse models, mefloquine significantly inhibits growth of both tumors. The combination of mefloquine with paclitaxel enhances the activity of either drug alone in in vitro and in vivo. In addition, mefloquine potently decreased phosphorylation of PI3K, Akt, mTOR and rS6. Overexpression of constitutively active Akt significantly restored mefloquine-mediated inhibition of mTOR phosphorylation and growth, and induction of apoptosis, suggesting that mefloquine acts on gastric cancer cells via suppressing PI3K/Akt/mTOR pathway. We further show that mefloquine-mediated inhibition of Akt/mTOR singaling is phosphatase-dependent as pretreatment with calyculin A does-dependently reversed mefloquine-mediated inhibition of Akt/mTOR phosphorylation. Since mefloquine is already available for clinic use, these results suggest that it is a useful addition to the treatment armamentarium for gastric cancer.

  6. Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis.

    PubMed

    Wong, Wilson; Bai, Xiao-Chen; Sleebs, Brad E; Triglia, Tony; Brown, Alan; Thompson, Jennifer K; Jackson, Katherine E; Hanssen, Eric; Marapana, Danushka S; Fernandez, Israel S; Ralph, Stuart A; Cowman, Alan F; Scheres, Sjors H W; Baum, Jake

    2017-03-13

    Malaria control is heavily dependent on chemotherapeutic agents for disease prevention and drug treatment. Defining the mechanism of action for licensed drugs, for which no target is characterized, is critical to the development of their second-generation derivatives to improve drug potency towards inhibition of their molecular targets. Mefloquine is a widely used antimalarial without a known mode of action. Here, we demonstrate that mefloquine is a protein synthesis inhibitor. We solved a 3.2 Å cryo-electron microscopy structure of the Plasmodium falciparum 80S ribosome with the (+)-mefloquine enantiomer bound to the ribosome GTPase-associated centre. Mutagenesis of mefloquine-binding residues generates parasites with increased resistance, confirming the parasite-killing mechanism. Furthermore, structure-guided derivatives with an altered piperidine group, predicted to improve binding, show enhanced parasiticidal effect. These data reveal one possible mode of action for mefloquine and demonstrate the vast potential of cryo-electron microscopy to guide the development of mefloquine derivatives to inhibit parasite protein synthesis.

  7. In Vitro and In Vivo Efficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis▿

    PubMed Central

    Küster, Tatiana; Stadelmann, Britta; Hermann, Corina; Scholl, Sabrina; Keiser, Jennifer; Hemphill, Andrew

    2011-01-01

    Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies. PMID:21135182

  8. In vitro and in vivo efficacies of mefloquine-based treatment against alveolar echinococcosis.

    PubMed

    Küster, Tatiana; Stadelmann, Britta; Hermann, Corina; Scholl, Sabrina; Keiser, Jennifer; Hemphill, Andrew

    2011-02-01

    Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies.

  9. 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

  10. Mefloquine--its 20 years in the Thai Malaria Control Program.

    PubMed

    Wongsrichanalai, Chansuda; Prajakwong, Somsak; Meshnick, Steven R; Shanks, G Dennis; Thimasarn, Krongthong

    2004-06-01

    Due to the deteriorating efficacy of sulfadoxine-pyrimethamine (SP or Fansidar), from the mid-1970s the Thai Malaria Control Program was actively involved in testing potential replacement drugs to be used as the primary therapy for falciparum malaria in Thailand. In 1983, a large-scale field trial of mefloquine, a long-acting antimalarial drug known for its efficacy against chloroquine- and SP-resistant Plasmodium falciparum, was initiated on the Thai-Cambodian border. The study enrolled over 60,000 patients and eventually led to the formal establishment of mefloquine as the first line drug for the treatment of uncomplicated falciparum malaria in the country. Mefloquine has played a significant role in the control of malaria in Thailand for the past two decades, initially in combination with SP, then by itself, and currently in selected areas as a partner drug in the combination therapy with artesunate. Thailand is the country with the most experience in the use of this drug in a malaria control program. We present here a review of mefloquine's pharmacology and usage in Thailand.

  11. Mefloquine inhibits voltage dependent Nav1.4 channel by overlapping the local anaesthetic binding site.

    PubMed

    Paiz-Candia, Bertin; Islas, Angel A; Sánchez-Solano, Alfredo; Mancilla-Simbro, Claudia; Scior, Thomas; Millan-PerezPeña, Lourdes; Salinas-Stefanon, Eduardo M

    2017-02-05

    Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na(+) channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na(+) channel, and a combined in silico approach using Molecular Dynamics and docking protocols. We found that mefloquine: i) inhibited Nav1.4 currents (IC50 =60μM), ii) significantly delayed fast inactivation but did not affect recovery from inactivation, iii) markedly the shifted steady-state inactivation curve to more hyperpolarized potentials. The presence of the β1 subunit significantly reduced mefloquine potency, but the drug induced a significant frequency-independent rundown upon repetitive depolarisations. Computational and experimental results indicate that mefloquine overlaps the local anaesthetic binding site by docking at a hydrophobic cavity between domains DIII and DIV that communicates the local anaesthetic binding site with the selectivity filter. This is supported by the fact that mefloquine potency significantly decreased on mutant Nav1.4 channel F1579A and significantly increased on K1237S channels. In silico this compound docked above F1579 forming stable π-π interactions with this residue. We provide structure-activity insights into how cationic amphiphilic compounds may exert inhibitory effects by docking between the local anaesthetic binding site and the selectivity filter of a mammalian Na(+) channel. Our proposed synergistic cycle of experimental and computational studies may be useful for elucidating binding sites of other drugs, thereby saving in vitro and in silico resources.

  12. Disposition of Mefloquine and Enpiroline Is Highly Influenced by a Chronic Schistosoma mansoni Infection

    PubMed Central

    Ingram, Katrin; Duthaler, Urs; Vargas, Mireille; Ellis, William

    2013-01-01

    Chronic Schistosoma mansoni infections lead to severe tissue destruction of the gut wall and liver and can influence drug disposition. This study aimed to investigate the impact of a chronic S. mansoni infection on the pharmacokinetic (PK) parameters of two promising antischistosomal lead candidates (mefloquine and enpiroline) in mice. Studies were conducted in two different mouse cohorts (S. mansoni-infected and uninfected mice) for both drugs. Plasma samples were collected at various time points after oral treatment (200 mg/kg of body weight) with study drugs. A high-performance liquid chromatography (HPLC) method was validated to analyze enpiroline and mefloquine in plasma. Livers and intestines were collected from infected animals to determine the onset of action, hepatic shift, and worm burden reduction. Following mefloquine administration, hepatic shifting and significant worm burden reductions (79.2%) were observed after 72 h. At 1 week posttreatment with enpiroline, the majority of worms had migrated to the liver and significant worm burden reductions were observed (93.1%). The HPLC method was selective, accurate (87.8 to 111.4%), and precise (<10%) for the analysis of both drugs in plasma samples. The PK profiles revealed increased values for half-life (t1/2) and area under the concentration-time curve (AUC) for both drugs in infected animals compared to the t1/2 and AUC values in uninfected animals. Considerable changes were observed for mefloquine, with a 5-fold increase of t1/2 (182.7 h versus 33.6 h) and 2-fold increase of AUC (1,116,517.8 ng · h/ml versus 522,409.1 ng · h/ml). S. mansoni infections in mice influence the PK profiles of enpiroline and mefloquine, leading to delayed clearance. Our data confirm that drug disposition should be carefully studied in schistosomiasis patients. PMID:23836173

  13. Disposition of mefloquine and enpiroline is highly influenced by a chronic Schistosoma mansoni infection.

    PubMed

    Ingram, Katrin; Duthaler, Urs; Vargas, Mireille; Ellis, William; Keiser, Jennifer

    2013-09-01

    Chronic Schistosoma mansoni infections lead to severe tissue destruction of the gut wall and liver and can influence drug disposition. This study aimed to investigate the impact of a chronic S. mansoni infection on the pharmacokinetic (PK) parameters of two promising antischistosomal lead candidates (mefloquine and enpiroline) in mice. Studies were conducted in two different mouse cohorts (S. mansoni-infected and uninfected mice) for both drugs. Plasma samples were collected at various time points after oral treatment (200 mg/kg of body weight) with study drugs. A high-performance liquid chromatography (HPLC) method was validated to analyze enpiroline and mefloquine in plasma. Livers and intestines were collected from infected animals to determine the onset of action, hepatic shift, and worm burden reduction. Following mefloquine administration, hepatic shifting and significant worm burden reductions (79.2%) were observed after 72 h. At 1 week posttreatment with enpiroline, the majority of worms had migrated to the liver and significant worm burden reductions were observed (93.1%). The HPLC method was selective, accurate (87.8 to 111.4%), and precise (<10%) for the analysis of both drugs in plasma samples. The PK profiles revealed increased values for half-life (t1/2) and area under the concentration-time curve (AUC) for both drugs in infected animals compared to the t1/2 and AUC values in uninfected animals. Considerable changes were observed for mefloquine, with a 5-fold increase of t1/2 (182.7 h versus 33.6 h) and 2-fold increase of AUC (1,116,517.8 ng · h/ml versus 522,409.1 ng · h/ml). S. mansoni infections in mice influence the PK profiles of enpiroline and mefloquine, leading to delayed clearance. Our data confirm that drug disposition should be carefully studied in schistosomiasis patients.

  14. The in vitro antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with mefloquine/artesunate.

    PubMed

    Chaijaroenkul, Wanna; Na-Bangchang, Kesara

    2014-03-01

    Multidrug resistance Plasmodium falciparum is the major health problem in Thailand. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate the antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with the standard antimalarial drugs mefloquine and artesunate in chloroquine sensitive (3D7) and chloroquine resistant (K1) P. falciparum clones in vitro. Median (range) IC50 (drug concentration which produces 50% parasite growth inhibition) values of the 9-hydroxycalabaxanthone, α-mangostin, artesunate and mefloquine for 3D7 vs K1 clones were 1.5 (0.9-2.1) vs 1.2 (1.1-1.6) μM, 17.9 (15.7.0-20.0) vs 9.7 (6.0-14.0) μM, 1.0 (0.4-3.0) vs 1.7 (1.0-2.5) nM, and 13.3 (11.1-13.3) vs 7.1 (6.7-12.2) nM, respectively. Analysis of isobologram and combination index (CI) of 9-hydroxycalabaxanthone with artesunate or mefloquine showed synergistic and indifference antimalarial interaction, respectively. α-mangostin-artesunate combination exhibited a slight antagonistic effect of antimalarial interaction, whereas α-mangostin and mefloquine combination showed indifference interaction in both clones. The combination of 9-hydroxycalabaxanthone with α-mangostin showed the synergistic antimalarial interaction in both clones.

  15. Mefloquine

    MedlinePlus

    ... you have or have ever had depression, anxiety, psychosis (difficulty thinking clearly, understanding reality, and communicating and behaving appropriately), schizophrenia (an illness that causes disturbed or unusual thinking, loss of interest in ...

  16. Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis- infected Swiss mice.

    PubMed

    Tripathi, Renu; Pandey, Swaroop Kumar; Rizvi, Amber

    2011-08-01

    During the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P450 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a useful

  17. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.

    PubMed

    Barbosa-Lima, Giselle; Moraes, Adriana M; Araújo, Adriele da S; da Silva, Emerson T; de Freitas, Caroline S; Vieira, Yasmine R; Marttorelli, Andressa; Neto, José Cerbino; Bozza, Patrícia T; de Souza, Marcus V N; Souza, Thiago Moreno L

    2017-02-15

    Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC50 values of 0.8 μM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs.

  18. Biowaiver monographs for immediate release solid oral dosage forms: mefloquine hydrochloride.

    PubMed

    Strauch, S; Jantratid, E; Dressman, J B; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2011-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing mefloquine hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. The solubility and permeability data of mefloquine hydrochloride as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability studies were taken into consideration. Mefloquine hydrochloride is not a highly soluble API. Since no data on permeability are available, it cannot be classified according to the Biopharmaceutics Classification System with certainty. Additionally, several studies in the literature failed to demonstrate BE of existing products. For these reasons, the biowaiver cannot be justified for the approval of new multisource drug products containing mefloquine hydrochloride. However, scale-up and postapproval changes (HHS-FDA SUPAC) levels 1 and 2 and most EU type I variations may be approvable without in vivo BE, using the dissolution tests described in these regulatory documents.

  19. Drug Resistance in Malaria: Investigation of Mechanisms and Patterns of Drug Resistance and Cross Resistance in Malaria.

    DTIC Science & Technology

    1987-10-19

    sites of drugs (fefloquine, etc.) in erythrocytes and/or parasites, 2) investigation of bindihg of drugs ( mefloquine in particular) in malaria strains...resistant and suscePible to other drugs (chloroquine in particu- lar), 3) investigation of the echanism of action of drugs ( mefloquine in particular...binds to phospholipids (13). This observation is of particular interest because mefloquine binds with high affinity to phospholipids (14). It is

  20. 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

  1. 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.

  2. Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane Plus Mefloquine

    PubMed Central

    Woodard, Lauren E.; Mott, Bryan T.; Singhal, Vandana; Kumar, Nirbhay; Shapiro, Theresa A.; Posner, Gary H.

    2009-01-01

    Three thermally and hydrolytically stable silylamide trioxanes have been prepared from the natural trioxane artemisinin in only five simple chemical steps and in at least 56% overall yield. Two of these new chemical entities completely cured malaria-infected mice at a single oral dose of only 8 mg/kg combined with 24 mg/kg of mefloquine hydrochloride. The high efficacy of this ACT chemotherapy is considerably better than the efficacy using the popular trioxane drug artemether plus mefloquine hydrochloride. PMID:27713236

  3. Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus westermani in dogs.

    PubMed

    Xiao, Shu-hua; Xue, Jian; Li-li, Xu; Zhang, Yong-nian; Qiang, Hui-qing

    2010-11-01

    The aim of the study is to explore the effect of mefloquine against Clonorchis sinensis and Paragonimus westermani. For anti-C. sinensis study, a total of 71 rats were divided into four batches for oral infection of each rat with 50 C. sinensis metacercariae. Five to 7 weeks post-infection, groups of rats were treated orally with mefloquine at single doses or multiple daily doses while infected, but untreated rats served as control. All treated rats were euthanized 2 weeks post-treatment for assessment of efficacy. For anti-P. westermani study, two batches of eight and ten dogs were each infected intraperitoneally with 100 P. westermani metacercariae. Eighty-five to 96 days post-infection, groups of two or three dogs were treated orally with mefloquine and groups of two dogs were treated with praziquantel at a single dose or multiple doses. In each batch of test, three untreated but infected dogs served as control. All treated dogs were euthanized 26-30 days post-treatment for evaluation of efficacy. In rats infected with C. sinensis and treated orally with mefloquine at a single dose of 75 and 150 mg/kg, no effect against C. sinensis was observed. When the dose of mefloquine was increased to 250 mg/kg, one third (five out of 15) rats died 3-5 days post-treatment. Although the mean worm burden was lower than that of the control, the difference between the treated and control groups was not statistically significant (P>0.05) with worm burden reduction of 22.4%. Whereas, the group of infected rats received mefloquine at a daily dose of 100 mg/kg for 3 days, one out of five rats died after the last administration. The mean worm burden was significantly lower than that of the control with worm burden reduction of 67.6% (P<0.01). In the first test of mefloquine against P. westermani, three infected dogs received two oral doses of the drug, 50 mg/kg, given at a 4-h interval, the mean worm burden were similar to that of the control. While other two dogs were treated with

  4. Signal detection to identify serious adverse events (neuropsychiatric events) in travelers taking mefloquine for chemoprophylaxis of malaria

    PubMed Central

    Naing, Cho; Aung, Kyan; Ahmed, Syed Imran; Mak, Joon Wah

    2012-01-01

    Background For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies. Materials and methods We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2. Results Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review) were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2. Conclusion Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were not detected for mefloquine. Further studies are needed to substantiate this. PMID:22936859

  5. Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine against Mycobacterium avium infection in mice.

    PubMed

    Bermudez, Luiz E; Inderlied, Clark B; Kolonoski, Peter; Chee, Christopher B; Aralar, Priscilla; Petrofsky, Mary; Parman, Toufan; Green, Carol E; Lewin, Anita H; Ellis, William Y; Young, Lowell S

    2012-08-01

    Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+)-erythro-, (-)-erythro-, (+)-threo-, and (-)-threo-mefloquine were 32 μg/ml, 32 μg/ml, 64 μg/ml, and 64 μg/ml, respectively. The postantibiotic effect for (+)-erythro-mefloquine was 36 h (MIC) and 41 h for a concentration of 4× MIC. The mefloquine postantibiotic effect was 25 h (MIC and 4× MIC). After baseline infection was established (7 days), the (+)- and (-)-isomers of the diastereomeric threo- and erythro-α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol were individually used to orally treat C57BL/6 bg(+)/bg(+) beige mice that were infected intravenously with M. avium. Mice were also treated with commercial mefloquine and diluent as controls. After 4 weeks of treatment, the mice were harvested, and the number of bacteria in spleen and liver was determined. Mice receiving (+)- or (-)-threo-mefloquine or (-)-erythro-mefloquine had numbers of bacterial load in tissues similar to those of untreated control mice at 4 weeks. Commercial mefloquine had a bactericidal effect. However, mice given the (+)-erythro-enantiomer for 4 weeks had a significantly greater reduction of bacterial load than those given mefloquine. Thus, (+)-erythro-mefloquine is the active enantiomer of mefloquine against M. avium and perhaps other mycobacteria.

  6. Note on the stability of mefloquine hydrochloride in aqueous solution

    PubMed Central

    Reber-Liske, Rosemaria

    1983-01-01

    Using Desjardins' technique for the testing of antimalarials against Plasmodium falciparum in vitro, a 4-year-old solution of mefloquine in water (10-3 mol/litre) was compared with a freshly prepared solution. The results showed that the two solutions had almost identical activity. There was no evidence for any instability of mefloquine in aqueous solution. PMID:6349842

  7. Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

    PubMed Central

    Nevin, Remington L

    2009-01-01

    Background Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear. Presentation of the hypothesis Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis. Testing and implications of the hypothesis Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented. PMID:19656408

  8. Asymmetric Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride.

    PubMed

    Rastelli, Ettore J; Coltart, Don M

    2016-10-21

    The asymmetric (er > 99:1) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The Sharpless asymmetric dihydroxylation is the key asymmetric transformation used in the synthesis of this intermediate. It is carried out on an olefin that is accessed in three steps from commercially available materials, making the overall synthetic sequence very concise. The common diol intermediate derived from the Sharpless asymmetric dihydroxylation is converted into either a trans- or cis-epoxide, and these are subsequently converted to (+)-anti- and (-)-syn-mefloquine, respectively. X-ray crystallographic analysis of derivatives of (+)-anti- and (-)-syn-mefloquine is used to lay to rest a 40 year argument regarding the absolute stereochemistry of the mefloquines. A formal asymmetric (er > 99:1) synthesis of (+)-anti-mefloquine hydrochloride is also presented that uses a Sharpless asymmetric epoxidation as a key step.

  9. Conformation stability and organization of mefloquine molecules in different environments.

    PubMed

    Skórska, Agnieszka; Sliwiński, Jan; Oleksyn, Barbara J

    2006-02-15

    The crystal structures of mefloquine base, [C17H16F6N2O], and two salts of mefloquine: hydrochloride [(C17H17F6N2O)+]3[Cl-]3.3H2O and hydrochloride tetrachlorocobaltate [(C17H17F6N2O)+]3Cl-[CoCl4]2-.C2H6O.H2O, were determined by X-ray diffraction measurements. A comparison of the crystal structures of mefloquine in three different crystalline environments shows that their conformations are stable regardless of mefloquine being a base or a salt. In addition, the conformation of mefloquine is similar to those of crystalline Cinchona alkaloids. The CF3 substituents in the quinoline moiety affect the packing of molecules.

  10. 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.

  11. Effect of mefloquine administered orally at single, multiple, or combined with artemether, artesunate, or praziquantel in treatment of mice infected with Schistosoma japonicum.

    PubMed

    Xiao, Shu-hua; Mei, Jing-yan; Jiao, Pei-ying

    2011-02-01

    The purpose of the study is to explore the efficacy of mefloquine administered orally at single, multiple doses, or in combination with artesuante, artemether, or praziquantel in mouse--Schistosoma japonicum model. A total of 205 mice were divided into 4 batches and each batch of mice was infected percutaneously with 40 S. japonicum cercariae for 35 days. The infected mice were treated orally with mefloquine at single doses, multiple daily doses, or combined with artesunate, artemether, or praziquantel, while infected but untreated mice served as control. All treated animals were killed 4 weeks post-treatment for assessment of effect. When infected mice were treated orally with mefloquine at single or multiple daily doses under the same total dose levels, the tendency to decrease the efficacy was seen. Particularly, when a lower single dose of 100 mg/kg was divided equally into five daily doses of 20 mg/kg, the efficacy decreased statistically significant (P<0.05), i.e., the total worm and female worm reductions of 67.9% and 73.4% decreased to 31.3% and 30.3%, respectively. In infected mice treated with mefloquine or artesuante at a single dose of 100 mg/kg, a moderate effect against schistosomes was observed. No further significant reduction of total and female worm burdens was seen, when the two drugs combined together at the same dose level. On the other hand, administration of mefloquine combined with artesunate at single dose of 50 mg/kg, which exhibited no effect against schistosomes, resulted in significant reduction of total and female worm burdens in comparison with the groups treated with mefloquine and artesunate alone at the same dose level. Similar results were observed in treatment of infected mice with mefloquine in combination with artemether at the smaller dose of 50 mg/kg. The total worm burden was significantly lower than that of control and the female worm burden was also significant lower than that of groups treated with mefloquine and

  12. An open, randomized, phase III clinical trial of mefloquine and of quinine plus sulfadoxine—pyrimethamine in the treatment of symptomatic falciparum malaria in Brazil

    PubMed Central

    de Souza, J. M.; Sheth, U. K.; de Oliveira, R. M. G.; Roulet, H.; de Souza, S. D.

    1985-01-01

    The clinical and parasitological response of adult male patients to mefloquine and to a combination of quinine and sulfadoxine—pyrimethamine during the treatment of falciparum malaria was compared. These patients were from an area in Brazil where Plasmodium falciparum is showing increasing resistance to quinine and to sulfadoxine—pyrimethamine. The drugs were administered to 100 patients (50 in each group), based on a randomized study design. The rates of clearance of parasitaemia and fever were similar in both groups. However, the parasitological cure rate (“S” response) was 100% for mefloquine but only 92% for quinine plus sulfadoxine—pyrimethamine. Tolerance was good in both groups. The main side-effects (nausea, vomiting, abdominal pain, and dizziness) were mild, transient and required no specific treatment. Nausea and vomiting were more frequent in patients who received quinine plus sulfadoxine—pyrimethamine, while abdominal pain and loose stools or mild diarrhoea were more frequent in the mefloquine group. Tinnitus and hearing difficulty were observed following the administration of quinine plus sulfadoxine—pyrimethamine, but not after mefloquine treatment. Laboratory tests of various haematological and biochemical parameters were not adversely affected in either group after drug administration. It can be concluded that mefloquine, given in a single oral dose of 1000 mg, is highly effective, well tolerated, and safe for the treatment of falciparum malaria in adult males in Brazil. PMID:3899397

  13. 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

  14. Mefloquine blockade of Pannexin1 currents: Resolution of a conflict

    PubMed Central

    Iglesias, Rodolfo; Spray, David C.; Scemes, Eliana

    2010-01-01

    Our laboratory has reported potent block of Pannexin1 (Panx1) currents by the antimalarial quinine derivative mefloquine. However, other laboratories have found little or no mefloquine sensitivity of Panx1 currents or processes attributable to these channels. In order to resolve this issue, we have performed extensive dose-response studies on Panx1 transfected neuroblastoma (Neuro2A) and rat insulinoma (Rin) cells comparing mefloquine obtained from three suppliers and also comparing the sensitivity to diastereomers. Results indicate a twenty-fold difference in sensitivity to the (−)-threo-(11R/2R) diastereomer compared to the erythro enatiomers and much lower potency of (±)-erythro-(R*/S*)-mefloquine obtained from one of the commercial sources. This markedly lower efficacy presumably accounts for the disparity in results from different laboratories who have applied it in Panx1 studies. PMID:20218915

  15. Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113.

    PubMed

    Gonçalves, Raoni S B; Kaiser, Carlos R; Lourenço, Maria C S; Bezerra, Flavio A F M; de Souza, Marcus V N; Wardell, James L; Wardell, Solange M S V; Henriques, Maria das Graças M de O; Costa, Thadeu

    2012-01-01

    Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl=substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl=5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl=3-ethoxyphenyl), 1g (Ar=3,4,5-(MeO)(3)-C(6)H(2)) and 2c were slightly more active than mefloquine (MIC=33μM) with MICs=24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl=3,4-(MeO)(2)-C(6)H(3)) and 2a (MICs=11.9 and 12.1μM, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC=15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values.

  16. A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand*

    PubMed Central

    Chongsuphajaisiddhi, T.; Sabchareon, A.; Chantavanich, P.; Singhasivanon, V.; Attanath, P.; Wernsdorfer, W. H.; Sheth, U. K.

    1987-01-01

    Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria. PMID:3301042

  17. 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.

  18. The history of the Greek Anti-Malaria League and the influence of the Italian School of Malariology.

    PubMed

    Tsiamis, Costas; Piperaki, Evangelia Theophano; Tsakris, Athanassios

    2013-03-01

    In 1905, a group of eminent Greek physicians led by Professor of Hygiene and Microbiology Constantinos Savvas and the pediatrician Dr. Ioannis Kardamatis founded the Greek Anti-Malaria League. The League assumed a role that the State would not, and for the next 25 years organized the country's anti-malaria campaign. During its first steps, the Greek Anti-Malaria League adopted the principles of Professor Angelo Celli's Italian Anti-Malaria League. The League's accomplishments include a decrease in malarial prevalence, due to mass treatment with quinine, new legislation ensuring the provision of quinine, State monopoly and the collection of epidemiologic data. However, defeat in the Greek-Turkish War (1922) and the massive influx of one million Greek refugees that ensued, led to a change in malarial epidemiology. In 1928, following a visit to Italy, the Greek League adopted the organization and knowledge of the Italian Malaria Schools in Rome and in Nettuno, and this experience served as the basis of their proposal to the State for the development of the anti-malaria services infrastructure. The State adopted many of Professor Savvas' proposals and modified his plan according to Greek needs. The League's experience, accumulated during its 25 years of struggle against malaria, was its legacy to the campaigns that eventually accomplished the eradication of malaria from Greece after World War II.

  19. An analytical method with a single extraction procedure and two separate high performance liquid chromatographic systems for the determination of artesunate, dihydroartemisinin and mefloquine in human plasma for application in clinical pharmacological studies of the drug combination.

    PubMed

    Lai, Choon-Sheen; Nair, N K; Mansor, S M; Olliaro, P L; Navaratnam, V

    2007-10-01

    The combination of two sensitive, selective and reproducible reversed phase liquid chromatographic (RP-HPLC) methods was developed for the determination of artesunate (AS), its active metabolite dihydroartemisinin (DHA) and mefloquine (MQ) in human plasma. Solid phase extraction (SPE) of the plasma samples was carried out on Supelclean LC-18 extraction cartridges. Chromatographic separation of AS, DHA and the internal standard, artemisinin (QHS) was obtained on a Hypersil C4 column with mobile phase consisting of acetonitrile-0.05 M acetic acid adjusted to pH 5.2 with 1.0M NaOH (42:58, v/v) at the flow rate of 1.50 ml/min. The analytes were detected using an electrochemical detector operating in the reductive mode. Chromatography of MQ and the internal standard, chlorpromazine hydrochloride (CPM) was carried out on an Inertsil C8-3 column using methanol-acetonitrile-0.05 M potassium dihydrogen phosphate adjusted to pH 3.9 with 0.5% orthophosphoric acid (50:8:42, v/v/v) at a flow rate of 1.00 ml/min with ultraviolet detection at 284 nm. The mean recoveries of AS and DHA over a concentration range of 30-750 ng/0.5 ml plasma and MQ over a concentration of 75-1500 ng/0.5 ml plasma were above 80% and the accuracy ranged from 91.1 to 103.5%. The within-day coefficients of variation were 1.0-1.4% for AS, 0.4-3.4% for DHA and 0.7-1.5% for MQ. The day-to-day coefficients of variation were 1.3-7.6%, 1.8-7.8% and 2.0-3.4%, respectively. Both the lower limit of quantifications for AS and DHA were at 10 ng/0.5 ml and the lower limit of quantification for MQ was at 25 ng/0.5 ml. The limit of detections were 4 ng/0.5 ml for AS and DHA and 15 ng/0.5 ml for MQ. The method was found to be suitable for use in clinical pharmacological studies.

  20. Mefloquine-oxazolidine derivatives: a new class of anticancer agents.

    PubMed

    Rodrigues, Felipe A R; Bomfim, Igor da S; Cavalcanti, Bruno C; Pessoa, Claudia; Goncalves, Raoni S B; Wardell, James L; Wardell, Solange M S V; de Souza, Marcus V N

    2014-01-01

    A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines, derived from (R*, S*)-(±)-mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 μg/mL. In general compounds with aryl groups having strong electron-releasing substituents, such as HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are active. However, other factors such as steric effects may play a role. As both the active and non-active conformations of the mefloquine-oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.

  1. In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers against Echinococcus multilocularis Metacestodes▿

    PubMed Central

    Stadelmann, Britta; Küster, Tatiana; Scholl, Sabrina; Barna, Fabienne; Kropf, Christian; Keiser, Jennifer; Boykin, David W.; Stephens, Chad E.; Hemphill, Andrew

    2011-01-01

    The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new and more efficient treatment options are urgently needed. By employing a recently validated assay based on the release of functional phosphoglucose isomerase (PGI) from dying parasites, the activities of 26 dicationic compounds and of the (+)- and (−)-erythro-enantiomers of mefloquine were investigated. Initial screening of compounds was performed at 40 μM, and those compounds exhibiting considerable antiparasitic activities were also assessed at lower concentrations. Of the dicationic drugs, DB1127 (a diguanidino compound) with activities comparable to nitazoxanide was further studied. The activity of DB1127 was dose dependent and led to severe structural alterations, as visualized by electron microscopy. The (+)- and (−)-erythro-enantiomers of mefloquine showed similar dose-dependent effects, although higher concentrations of these compounds than of DB1127 were required for metacestode damage. In conclusion, of the drugs investigated here, the diguanidino compound DB1127 represents the most promising compound for further study in appropriate in vivo models for Echinococcus multilocularis infection. PMID:21768518

  2. Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria

    PubMed Central

    Agomo, Philip U; Meremikwu, Martin M; Watila, Ismaila M; Omalu, Innocent J; Odey, Friday A; Oguche, Stephen; Ezeiru, Valentine I; Aina, Olugbenga O

    2008-01-01

    Background The combination of artesunate and mefloquine has been reported to be effective against multi-drug resistant Plasmodium falciparum malaria, which has been reported in Nigeria. The objective of this multi-centre study was to evaluate the efficacy, safety and tolerability of the co-packaged formulation of artesunate and mefloquine in the treatment of uncomplicated malaria in two weight groups: those between 15 – 29 kg and ≥ 30 kg respectively. Methods The trial was conducted in rural communities in the north-east, north-central, south-west and south-eastern parts of Nigeria. The WHO protocol for testing antimalarial drugs was followed. Outpatients having amongst other criteria, parasite density of ≥1,000 μl were enrolled. The co-packaged drugs were administered for 3 days at a dosage of artesunate, 4 mg/kg body wt/day and mefloquine, 25 mg/kg/body wt total) on days 0, 1 and 2. Patients were followed up for 28 days with the assessment of the parasitological parameters on days 1, 2, 3, 7, and 28. Results Four hundred and forty-six (446) patients were enrolled and 431 completed the study. Cure rates in both treatment groups was >90% at day 28. The mean parasite clearance times in treatment groups I and II were 40.1 and 42.4 hours respectively. The combination of artesunate and mefloquine showed good gametocidal activity, (gametocyte clearance time of 42.0 & 45.6 hours in treatment groups I and II respectively). There were no serious adverse events. Other adverse events observed were headache, dizziness, vomiting and abdominal discomfort. There was no significant derangement in the haematological and biochemical parameters. Conclusion This co-packaged formulation of artesunate + mefloquine (Artequin™) is highly efficacious, safe and well-tolerated. It is recommended for the treatment of uncomplicated P. falciparum malaria in Nigeria. PMID:18782445

  3. 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…

  4. Sporozoite Immunization of Human Volunteers under Mefloquine Prophylaxis Is Safe, Immunogenic and Protective: A Double-Blind Randomized Controlled Clinical Trial

    PubMed Central

    Obiero, Joshua M.; Behet, Marije C.; van Gemert, Geert-Jan; van de Vegte-Bolmer, Marga; Graumans, Wouter; van Lieshout, Lisette; Bastiaens, Guido J. H.; Teelen, Karina; Hermsen, Cornelus C.; Scholzen, Anja; Visser, Leo G.; Sauerwein, Robert W.

    2014-01-01

    Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection. Trial Registration ClinicalTrials.gov NCT01422954 PMID:25396417

  5. Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double-blind randomized controlled clinical trial.

    PubMed

    Bijker, Else M; Schats, Remko; Obiero, Joshua M; Behet, Marije C; van Gemert, Geert-Jan; van de Vegte-Bolmer, Marga; Graumans, Wouter; van Lieshout, Lisette; Bastiaens, Guido J H; Teelen, Karina; Hermsen, Cornelus C; Scholzen, Anja; Visser, Leo G; Sauerwein, Robert W

    2014-01-01

    Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection. Trial registration: ClinicalTrials.gov NCT01422954.

  6. 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

  7. Antiviral effect of mefloquine on feline calicivirus in vitro.

    PubMed

    McDonagh, Phillip; Sheehy, Paul A; Fawcett, Anne; Norris, Jacqueline M

    2015-04-17

    Feline calicivirus (FCV) is an important viral pathogen of domestic cats causing clinical signs ranging from mild to severe oral ulceration or upper respiratory tract disease through to a severe fatal systemic disease. Current therapeutic options are limited, with no direct acting antivirals available for treatment. This study screened a panel of 19 compounds for potential antiviral activity against FCV strain F9 and recent field isolates in vitro. Using a resazurin-based cytopathic effect (CPE) inhibition assay, mefloquine demonstrated a marked inhibitory effect on FCV induced CPE, albeit with a relatively low selectivity index. Orthogonal assays confirmed inhibition of CPE was associated with a significant reduction in viral replication. Mefloquine exhibited a strong inhibitory effect against a panel of seven recent FCV isolates from Australia, with calculated IC50 values for the field isolates approximately 50% lower than against the reference strain FCV F9. In vitro combination therapy with recombinant feline interferon-ω, a biological response modifier currently registered for the treatment of FCV, demonstrated additive effects with a concurrent reduction in the IC50 of mefloquine. These results are the first report of antiviral effects of mefloquine against a calicivirus and support further in vitro and in vivo evaluation of this compound as an antiviral therapeutic for FCV.

  8. A Concise and Highly Enantioselective Total Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines.

    PubMed

    Rastelli, Ettore J; Coltart, Don M

    2015-11-16

    A concise asymmetric (>99:1 e.r.) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless-derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)-anti- and (-)-syn-mefloquine, respectively. The synthetic (+)-anti- and (-)-syn-mefloquine samples were derivatized with (S)-(+)-mandelic acid tert-butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X-ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)-anti- as well as (-)-syn-mefloquine.

  9. Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members.

    PubMed

    Eick-Cost, Angelia A; Hu, Zheng; Rohrbeck, Patricia; Clark, Leslie L

    2017-01-11

    Mefloquine was widely prescribed to U.S. military service members until 2009 when use was limited to personnel with contraindications to doxycycline and no contraindications to mefloquine. The need to estimate the occurrence of neuropsychiatric outcomes (NPOs) in service members prescribed mefloquine warranted a comprehensive evaluation of this issue. Active component service members filling a prescription for mefloquine, doxycycline, or atovaquone/proguanil (A/P) between January 1, 2008 and June 30, 2013, were included in the analysis. The risk of developing incident NPOs and the risk of subsequent NPOs among subjects with a history of the condition were assessed. A total of 367,840 individuals were evaluated (36,538 received mefloquine, 318,421 received doxycycline, and 12,881 received A/P). Among deployed individuals prescribed mefloquine, an increased risk of incident anxiety was seen when compared with doxycycline recipients (incidence rate ratio [IRR] = 1.12 [1.01-1.24]). Among nondeployed mefloquine recipients, an increased risk of posttraumatic stress disorder (PTSD) was seen when compared with A/P recipients (IRR = 1.83 [1.07-3.14]). An increased risk of tinnitus was seen for both deployed and nondeployed mefloquine recipients compared with A/P recipients (IRR = 1.81 [1.18-2.79]), 1.51 (1.13-2.03), respectively). Six percent of the mefloquine cohort had an NPO in the year before receiving mefloquine. When comparing individuals with a prior neuropsychiatric history to those without, the ratio of relative risks for adjustment disorder, anxiety, insomnia, and PTSD were higher (not statistically significant) for mefloquine compared with doxycycline. These findings emphasize the continued need for physicians prescribing mefloquine to conduct contraindication screening.

  10. Studies of the disposition and metabolism of mefloquine HCl (WR 142,490), a quinolinemethanol antimalarial, in the rat. Limited studies with an analog, WR 30,090.

    PubMed

    Mu, J Y; Israili, Z H; Dayton, P G

    1975-01-01

    The overall fate of the quinolinemethanol antimalarial, mefloquine-HCl [WR 142,490, erythro-DL-alpha-(2-piperidyl)-2,9-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins, high tissue/plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine (and its metabolites) and extensive biliary and gastric secretion, followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats, dogs, and one human subject with another quinolinemethanol, WR 30,090-14C [DL-6,8-dichloro-2-(3',4'-dichlorophenyl)-alpha-(di-n-butylaminomethyl)-4-quinolinemethanol hydrochloride]. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine.

  11. 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

  12. Interactions of mefloquine with ABC proteins, MRP1 (ABCC1) and MRP4 (ABCC4), that are present in human red cell membranes

    PubMed Central

    Wu, Chung-Pu; Klokouzas, Antonios; Hladky, Stephen B.; Ambudkar, Suresh V.; Barrand, Margery A.

    2005-01-01

    Human erythrocyte membranes express the multidrug resistance-associated proteins, MRP1, MRP4 and MRP5, that collectively can efflux oxidised glutathione, glutathione conjugates and cyclic nucleotides. It is already known that the quinoline derivative, MK-571, is a potent inhibitor of MRP-mediated transport. We here examine whether the quinoline-based antimalarial drugs, amodiaquine, chloroquine, mefloquine, primaquine, quinidine and quinine, also interact with erythrocyte MRPs with consequences for their access to the intracellular parasites or for efflux of oxidised glutathione from infected cells. Using inside-out vesicles prepared from human erythrocytes we have shown that mefloquine and MK-571 inhibit transport of 3 μM [3H]DNP-SG known to be mediated by MRP1 (IC50 127 μM and 1.1 μM respectively) and of 3.3 μM [3H]cGMP thought but not proven to be mediated primarily by MRP4 (IC50 21 μM and 0.41 μM). They also inhibited transport in membrane vesicles prepared from tumour cells expressing MRP1 or MRP4 and blocked calcein efflux from MRP1 overexpressing cells and BCECF efflux from MRP4 overexpressing cells. Both stimulated ATPase activity in membranes prepared from MRP1 and MRP4 overexpressing cells and inhibited activity stimulated by quercetin or PGE1 respectively. Neither inhibited [α-32P]8-azidoATP binding confirming that the interactions are not at the ATP binding site. These results demonstrate that mefloquine and MK-571 both inhibit transport of other substrates and stimulate ATPase activity and thus may themselves be substrates for transport. But at concentrations achieved clinically mefloquine is unlikely to affect the MRP1-mediated transport of GSSG across the erythrocyte membrane. PMID:16004972

  13. Mefloquine inhibits chondrocytic proliferation by arresting cell cycle in G2/M phase.

    PubMed

    Li, Qiong; Chen, Zeng-Gan; Xia, Qing; Lin, Jian-Ping; Yan, Zuo-Qin; Yao, Zheng-Jun; Dong, Jian

    2015-01-01

    Mefloquine (MQ), an analog of chloroquine, exhibits a promising cytotoxic activity against carcinoma cell lines and for the treatment of glioblastoma patients. The present study demonstrates the effect of mefloquine on proliferation and cell cycle in chondrocytes. MTT assay and propidium iodide staining were used for the analysis of proliferation and cell cycle distribution, respectively. Western blot analysis was used to examine the expression levels of cyclin B1/cdc2, cdc25c, p21WAF1/CIP1 and p53. The results revealed that mefloquine inhibited the proliferation of chondrocytes and caused cell cycle arrests in the G2/M phase. The proliferation of chondrocytes was reduced to 27% at 40 μM concentration of mefloquine after 48 h. The population of chondrocytes in G2/M phase was found to be 15.7 and 48.4%, respectively at 10 and 40 μM concentration of mefloquine at 48 h following treatment. The expression of the cell cycle regulatory proteins including, cyclin B1/cdc2 and cdc25c was inhibited. On the other hand, mefloquine treatment promoted the expression of p21WAF1/CIP1 and p53 at 40 μM concentration after 48 h. Therefore, mefloquine inhibits proliferation and induces cell cycle arrest in chondrocytes.

  14. Adverse reaction to mefloquine associated with ethanol ingestion.

    PubMed Central

    Wittes, R C; Saginur, R

    1995-01-01

    A 40-year-old man with no history of neuropsychiatric illness was taking one 250-mg tablet of mefloquine (MFQ) weekly for malaria prophylaxis while in Tanzania. He experienced no adverse reaction in association with his first two doses. Concurrently with both his third and his fourth dose he consumed about half a litre of whisky. On both occasions he experienced hallucinations, paranoid delusions and suicidal ideation. Thereafter he continued taking the MFQ, abstained completely from ethanol ingestion and had no recurrence of psychiatric symptoms. It is hypothesized that the combination of MFQ and ethanol caused the two episodes of severe psychiatric disturbance. PMID:7859199

  15. 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.

  16. Cerebral uptake of mefloquine enantiomers with and without the P-gp inhibitor elacridar (GF1210918) in mice

    PubMed Central

    de Lagerie, Sylvie Barraud; Comets, Emmanuelle; Gautrand, Céline; Fernandez, Christine; Auchere, Daniel; Singlas, Eric; Mentre, France; Gimenez, François

    2004-01-01

    Mefloquine is a chiral neurotoxic antimalarial agent showing stereoselective brain uptake in humans and rats. It is a substrate and an inhibitor of the efflux protein P-glycoprotein. We investigated the stereoselective uptake and efflux of mefloquine in mice, and the consequences of the combination with an efflux protein inhibitor, elacridar (GF120918) on its brain transport. Racemic mefloquine (25 mg kg−1) was administered intraperitoneally with or without elacridar (10 mg kg−1). Six to seven mice were killed at each of 11 time-points between 30 min and 168 h after administration. Blood and brain concentrations of mefloquine enantiomers were determined using liquid chromatography. A three-compartment model with zero-order absorption from the injection site was found to best represent the pharmacokinetics of both enantiomers in blood and brain. (−)Mefloquine had a lower blood and brain apparent volume of distribution and a lower efflux clearance from the brain, resulting in a larger brain/blood ratio compared to (+)mefloquine. Elacridar did not modify blood concentrations or the elimination rate from blood for either enantiomers. However, cerebral AUCinf of both enantiomers were increased, with a stronger effect on (+)mefloquine. The efflux clearance from the brain decreased for both enantiomers, with a larger decrease for (+)mefloquine. After administration of racemic mefloquine in mice, blood and brain pharmacokinetics are stereoselective, (+)mefloquine being excreted from brain more rapidly than its antipode, showing that mefloquine is a substrate of efflux proteins and that mefloquine enantiomers undergo efflux in a stereoselective manner. Moreover, pretreatment with elacridar reduced the brain efflux clearances with a more pronounced effect on (+)mefloquine. PMID:15023856

  17. Anti-malaria antibody-producing B cell frequencies in adults after a Plasmodium falciparum outbreak in Madagascar.

    PubMed Central

    Migot, F; Chougnet, C; Henzel, D; Dubois, B; Jambou, R; Fievet, N; Deloron, P

    1995-01-01

    The central highlands of Madagascar offer a unique opportunity to explore the malaria immune memory, as the last murderous epidemic in the study area occurred 8 years ago. Quantification of the circulating memory B lymphocytes reacting to Plasmodium falciparum was assessed among 14 Madagascans by using a limiting dilution assay, applied to the EL4 culture system, which leads to activation, proliferation and differentiation into antibody-secreting cells (ASC) of most peripheral B cells. This system allowed us to observe, without any malaria-specific restimulation, a geometric mean frequency of one anti-P. falciparum ASC among 2992 circulating B cells, except for one Madagascan who did not have any detectable ASC. A geometric mean frequency of one anti-P. falciparum ASC among 1403 was obtained for six malaria hyperimmune Cameroonians, but conversely, no anti-malaria ASC was detected in the blood of six malaria non-immune French control subjects. Anti-P. falciparum ASC frequencies and serum specific antibodies were strongly related. Our results indicate that anti-malaria ASC are still present in peripheral blood of Madagascan subjects, who have not been exposed to P. falciparum for several years. These responder B cells reflect the malaria B cell memory acquired during the last epidemic. PMID:8536368

  18. 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.

  19. Crystal structure and molecular structure of mefloquine methylsulfonate monohydrate: implications for a malaria receptor.

    PubMed Central

    Karle, J M; Karle, I L

    1991-01-01

    The crystal structure of (+/-)-mefloquine methylsulfonate monohydrate was determined by X-ray diffraction and was compared with the crystal structures of mefloquine hydrochloride and mefloquine free base. The conformation of mefloquine was essentially the same in all three crystalline environments and was not dependent on whether mefloquine was a salt or a free base. In mefloquine methylsulfonate monohydrate, the angle between the average plane of the quinoline ring and the average plane of the piperidine ring was 76.9 degrees. The intramolecular aliphatic N-13...O-1 distance was 2.730 +/- 0.008 A (1 A = 0.1 nm), which is close to the aliphatic N...O distance found in the antimalarial cinchona alkaloids. The hydroxyl group formed a hydrogen bond with the water molecule, and the amine group formed hydrogen bonds with two different methylsulfonate ions. The crystallographic parameters for (+/-)-mefloquine methylsulfonate monohydrate were as follows: C17H17F6N2O(+).CH3SO3(-).H2O; Mr = 492.4; symmetry of unit cell, monoclinic; space group, P2(1)/a; parameters of unit cell, a was 8.678 +/- 0.001 A, b was 28.330 +/- 0.003 A, c was 8.804 +/- 0.001 A, beta was 97.50 +/- 0.01 degrees; the volume of the unit cell was 2145.9 A3; the number of molecules per unit cell was 4; the calculated density was 1.52 g cm(-3); the source of radiation was Cu K alpha (lambda = 1.54178 A); mu (absorption coefficient) was 20.46 cm(-1); F(000) (sum of atomic scattering factors at zero scattering angle) was 1,016; room temperature was used; and the final R (residual index) was 6.58% for 1,740 reflections with magnitude of Fo greater than 3 sigma (F). Since the mechanism of antimalarial action and the mechanism of mefloquine resistance may involve hydrogen bond formation between mefloquine and a cellular effector or transport proteins, the common conformation of mefloquine found in each crystalline environment may define the orientation in which mefloquine forms these potentially critical

  20. Genomic approach to identifying the putative target of and mechanisms of resistance to mefloquine in mycobacteria.

    PubMed

    Danelishvili, Lia; Wu, Martin; Young, Lowell S; Bermudez, Luiz E

    2005-09-01

    The emergence of mycobacterial resistance to multiple antimicrobials emphasizes the need for new compounds. The antimycobacterial activity of mefloquine has been recently described. Mycobacterium avium, Mycobacterium smegmatis, and Mycobacterium tuberculosis are susceptible to mefloquine in vitro, and activity was evidenced in vivo against M. avium. Attempts to obtain resistant mutants by both in vitro and in vivo selection have failed. To identify mycobacterial genes regulated in response to mefloquine, we employed DNA microarray and green fluorescent protein (GFP) promoter library techniques. Following mefloquine treatment, RNA was harvested from M. tuberculosis H37Rv, labeled with 32P, and hybridized against a DNA array. Exposure to 4x MIC resulted in a significant stress response, while exposure to a subinhibitory concentration of mefloquine triggered the expression of genes coding for enzymes involved in fatty acid synthesis, the metabolic pathway, and transport across the membrane and other proteins of unknown function. Evaluation of gene expression using an M. avium GFP promoter library exposed to subinhibitory concentrations of mefloquine revealed more than threefold upregulation of 24 genes. To complement the microarray results, we constructed an M. avium genomic library under the control of a strong sigma-70 (G13) promoter in M. smegmatis. Resistant clones were selected in 32 microg/ml of mefloquine (wild-type M. avium, M. tuberculosis, and M. smegmatis are inhibited by 8 microg/ml), and the M. avium genes associated with M. smegmatis resistant to mefloquine were sequenced. Two groups of genes were identified: one affecting membrane transport and one gene that apparently is involved in regulation of cellular replication.

  1. A Robust, Recyclable Resin for Decagram Scale Resolution of (±)-Mefloquine and Other Chiral N-Heterocycles.

    PubMed

    Kreituss, Imants; Chen, Kuang-Yen; Eitel, Simon H; Adam, Jean-Michel; Wuitschik, Georg; Fettes, Alec; Bode, Jeffrey W

    2016-01-22

    Decagram quantities of enantiopure (+)-mefloquine have been produced via kinetic resolution of racemic mefloquine using a ROMP-gel supported chiral acyl hydroxamic acid resolving agent. The requisite monomer was prepared in a few synthetic steps without chromatography and polymerization was safely performed on a >30 gram scale under ambient conditions. The reagent was readily regenerated and reused multiple times for the resolution of 150 grams of (±)-mefloquine and other chiral N-heterocylces.

  2. The interaction of mefloquine hydrochloride with cell membrane models at the air-water interface is modulated by the monolayer lipid composition.

    PubMed

    Goto, Thiago Eichi; Caseli, Luciano

    2014-10-01

    The antiparasitic properties of antiparasitic drugs are believed to be associated with their interactions with the protozoan membrane, encouraging research on the identification of membrane sites capable of drug binding. In this study, we investigated the interaction of mefloquine hydrochloride, known to be effective against malaria, with cell membrane models represented by Langmuir monolayers of selected lipids. It is shown that even small amounts of the drug affect the surface pressure-area isotherms as well as surface vibrational spectra of some lipid monolayers, which points to a significant interaction. The effects on the latter depend on the electrical charge of the monolayer-forming molecules, with the drug activity being particularly distinctive for negatively charged lipids. Therefore, the lipid composition of the monolayer modulates the interaction with the lipophilic drug, which may have important implications in understanding how the drug acts on specific sites of the protozoan membrane.

  3. Mefloquine improved progressive multifocal leukoencephalopathy in a patient with immunoglobulin A nephropathy.

    PubMed

    Shin, Jung-Won; Jung, Keun-Hwa; Lee, Soon-Tae; Moon, Jangsup; Lim, Jung-Ah; Byun, Jung-Ick; Park, Kyung-Il; Lee, Sang Kun; Chu, Kon

    2014-10-01

    We describe a patient with immunoglobulin A nephropathy who was diagnosed with progressive multifocal leukoencephalopathy (PML) and successfully treated with mefloquine, an antimalarial medication. A 67-year-old man with immunoglobulin A nephropathy presented to the hospital emergency room with fever and generalized tonic-clonic seizure. Cerebrospinal fluid (CSF) nested polymerase chain reaction (PCR) was positive for John Cunningham virus and brain MRI displayed high signal intensity in the white matter in the right parietal lobe without gadolinium enhancement. Tapering of prednisone did not arrest the disease progression and a new lesion was detected on the cerebellum. Administration of mefloquine stopped lesion progression and resulted in dramatic clinical improvement. The CSF nested PCR for the John Cunningham virus also became negative. In reviewing the literature, mefloquine has had a heterogeneous effect in PML patients, and P-glycoprotein polymorphism and proper dosage could contribute to the various effects seen. Mefloquine may be a favorable treatment option in some patients with PML, and P-glycoprotein polymorphism may play an important role in its efficacy. More large studies in other ethnic groups including polymorphism studies for the gene encoding P-glycoprotein (ABCB1/MDR1) and taking into account various underlying conditions with secondary immunosuppression should be carried out to investigate whether mefloquine is effective for treating PML.

  4. Suicide by skull stab wounds: a case of drug-induced psychosis.

    PubMed

    Jousset, Nathalie; Rougé-Maillart, Clotilde; Turcant, Alain; Guilleux, Michel; Le Bouil, Anne; Tracqui, Antoine

    2010-12-01

    Suicide by stabbing to the head and/or driving sharp objects into the skull is of extreme rarity. This article reports the case of a 27-year-old man, who committed suicide by multiple knife stabs and cuts to the head, the torso, one shoulder and the forearms. Autopsy showed a perforating wound of the skull and the 10-cm long broken blade of the knife being still embedded in the right temporal lobe of the brain. The deceased had no history of psychiatric illness but was currently treated by mefloquine, a quinine derivative associated with a high rate of psychiatric adverse effects. Toxicological examination confirmed a recent intake of mefloquine together with chloroquine, another antimalarial drug. To our knowledge, this is the first report of a completed suicide with very strong evidence of mefloquine implication. Discussion focuses upon mefloquine-induced psychiatric disorders and highlights the importance of performing toxicological investigations in cases of unusual suicides.

  5. Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.

    PubMed

    Kobayashi, Zen; Akaza, Miho; Numasawa, Yoshiyuki; Ishihara, Shoichiro; Tomimitsu, Hiroyuki; Nakamichi, Kazuo; Saijo, Masayuki; Morio, Tomohiro; Shimizu, Norio; Sanjo, Nobuo; Shintani, Shuzo; Mizusawa, Hidehiro

    2013-01-15

    Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenström macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4(+) lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5 months and 2 months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4 months and 2 months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

  6. 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.

  7. Severe Neuropsychiatric Reaction in a Deployed Military Member after Prophylactic Mefloquine

    DTIC Science & Technology

    2011-01-01

    been reported in case studies and have included depression [8, 13, 18, 23] and psychosis [8, 12, 15–19, 25]. There have also been reports of neuropsy ...suggested that it may be related to primary liver damage with secondary thyroid damage [31]. Severe mefloquine-induced neuropsy - chiatric side effects

  8. [Recurrent psychiatric manifestations during malaria prevention with mefloquine. A case report].

    PubMed

    Rodor, F; Bianchi, G; Grignon, S; Samuelian, J C; Jouglard, J

    1990-01-01

    The authors report the case of a 22 years old woman without psychiatric antecedent who started a prophylaxis with mefloquine for a journey in a chloroquino resistant area. The first tablet induced an acute psychiatric syndrome which lasted five days; the second tablet induced the recidive of the psychiatric data and a suicide attempt by drowning.

  9. Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan

    PubMed Central

    Nevin, Remington L; Pietrusiak, Paul P; Caci, Jennifer B

    2008-01-01

    Background Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but its prescribing requires careful attention to rule out contraindications to its use, including a history of certain psychiatric and neurological disorders. The prevalence of these disorders has not been defined in cohorts of U.S. military personnel deployed to areas where long-term malaria chemoprophylaxis is indicated. Methods Military medical surveillance and pharmacosurveillance databases were utilized to identify contraindications to mefloquine use among a cohort of 11,725 active duty U.S. military personnel recently deployed to Afghanistan. Results A total of 9.6% of the cohort had evidence of a contraindication. Females were more than twice as likely as males to have a contraindication (OR = 2.48, P < 0.001). Conclusion These findings underscore the importance of proper systematic screening prior to prescribing and dispensing mefloquine, and the need to provide alternatives to mefloquine suitable for long-term administration among deployed U.S. military personnel. PMID:18267019

  10. Inhibitory effects of pepstatin A and mefloquine on the growth of Babesia parasites.

    PubMed

    Munkhjargal, Tserendorj; AbouLaila, Mahmoud; Terkawi, Mohamad Alaa; Sivakumar, Thillaiampalam; Ichikawa, Madoka; Davaasuren, Batdorj; Nyamjargal, Tserendorj; Yokoyama, Naoaki; Igarashi, Ikuo

    2012-10-01

    We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.

  11. A computer-aided drug discovery system for chemistry teaching.

    PubMed

    Gledhill, Robert; Kent, Sarah; Hudson, Brian; Richards, W Graham; Essex, Jonathan W; Frey, Jeremy G

    2006-01-01

    The Schools Malaria Project (http://emalaria.soton.ac.uk/) brings together school students with university researchers in the hunt for a new antimalaria drug. The design challenge being offered to students is to use a distributed drug search and selection system to design potential antimalaria drugs. The system is accessed via a Web interface. This e-science project displays the results of the trials in an accessible manner, giving students an opportunity for discussion and debate both with peers and with the university contacts. The project has been implemented by using distributed computing techniques, spreading computer load over a network of machines that cross institutional boundaries, forming a grid. This provides access to greater computing power and allows a much more complex and detailed formulation of the drug design problem to be tackled for research, teaching, and learning.

  12. Drug Evaluation in the Plasmodium Falciparum - Aotus Model.

    DTIC Science & Technology

    1992-03-23

    AOTUS MODEL PRINCIPAL INVESTIGATOR: Richard N. Rossan, Ph.D. CONTRACTING ORGANIZATION: PROMED TRADING, S.A. P.O. Box 025426, PTY-051 Miami, Florida...91 - 2/28/92) 4. TITLE AND SUBTITLE S. FUNDING NUMBERS DRUG EVALUATION IN THE PLASMODIUM FALCIPARUM - Contract No. AOTUS MODEL DAMD17-91-C-1072 6C...words) Tne Panamanian Autus - PLasmodium falciparum model was used to evaluate potential antimalaria drugs. Neither protriptylene nor tetrandrine, each

  13. Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling

    PubMed Central

    YAN, KUN-HUANG; YAO, CHIH-JUNG; HSIAO, CHI-HAO; LIN, KE-HSUN; LIN, YUNG-WEI; WEN, YU-CHING; LIU, CHUNG-CHI; YAN, MING-DE; CHUANG, SHUANG-EN; LAI, GI-MING; LEE, LIANG-MING

    2013-01-01

    Mefloquine (MQ) is a prophylactic anti-malarial drug. Previous studies have shown that MQ induces oxidative stress in vitro. Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells. This study investigated whether MQ also inhibits prostate cancer (PCa) cell growth. We used sulforhodamine B (SRB) staining to determine cell viability. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. The antitumor effect was most significant when examined using a colony formation assay. MQ also induces hyperpolarization of the mitochondrial membrane potential (MMP), as well as ROS generation. The blockade of MQ-induced anticancer effects by N-acetyl cysteine (NAC) pre-treatment confirmed the role of ROS. This indicates that the MQ-induced anticancer effects are caused primarily by increased ROS generation. Moreover, we observed that MQ-mediated ROS simultaneously downregulated Akt phosphorylation and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and adenosine monophosphate-activated protein kinase (AMPK) signaling in PC3 cells. These findings provide insights for further anticancer therapeutic options. PMID:23760395

  14. Severe Neuropsychiatric Reaction in a Deployed Military Member after Prophylactic Mefloquine

    PubMed Central

    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

  15. Mirtazapine and mefloquine therapy for non-AIDS-related progressive multifocal leukoencephalopathy.

    PubMed

    Epperla, Narendranath; Medina-Flores, Rafael; Mazza, Joseph J; Yale, Steven H

    2014-12-01

    Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the human nervous system caused by the JC virus. We report what is, to the best of our knowledge, the second reported case using a combination of mefloquine and mirtazapine in a patient with non-AIDS-related PML with a good clinical outcome. Conversely, the recent trial of mefloquine in 21 patients with AIDS and 3 without AIDS failed to show a reduction of JC viral DNA levels in the cerebral spinal fluid. However, the positive clinical response seen in our patient after the initiation of this combination therapy suggests that further studies in the form of randomized controlled trials for the treatment of non-AIDS-related PML are warranted.

  16. Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro.

    PubMed

    Behrens, C J; Ul Haq, R; Liotta, A; Anderson, M L; Heinemann, U

    2011-09-29

    It has been suggested that gap junctions are involved in the synchronization during high frequency oscillations as observed during sharp wave-ripple complexes (SPW-Rs) and during recurrent epileptiform discharges (REDs). Ripple oscillations during SPW-Rs, possibly involved in memory replay and memory consolidation, reach frequencies of up to 200 Hz while ripple oscillations during REDs display frequencies up to 500 Hz. These fast oscillations may be synchronized by intercellular interactions through gap junctions. In area CA3, connexin 36 (Cx36) proteins are present and potentially sensitive to mefloquine. Here, we used hippocampal slices of adult rats to investigate the effects of mefloquine, which blocks Cx36, Cx43 and Cx50 gap junctions on both SPW-Rs and REDs. SPW-Rs were induced by high frequency stimulation in the CA3 region while REDs were recorded in the presence of the GABA(A) receptor blocker bicuculline (5 μM). Both, SPW-Rs and REDs were blocked by the gap junction blocker carbenoxolone. Mefloquine (50 μM), which did not affect stimulus-induced responses in area CA3, neither changed SPW-Rs nor superimposed ripple oscillations. During REDs, 25 and 50 μM mefloquine exerted only minor effects on the expression of REDs but significantly reduced the amplitude of superimposed ripples by ∼17 and ∼54%, respectively. Intracellular recordings of CA3 pyramidal cells revealed that mefloquine did not change their resting membrane potential and input resistance but significantly increased the afterhyperpolarization following evoked action potentials (APs) resulting in reduced probability of AP firing during depolarizing current injection. Similarly, mefloquine caused a reduction in AP generation during REDs. Together, our data suggest that mefloquine depressed RED-related ripple oscillations by reducing high frequency discharges and not necessarily by blocking electrical coupling.

  17. Rituximab-associated progressive multifocal leukoencephalopathy derived from non-Hodgkin lymphoma: neuropathological findings and results of mefloquine treatment.

    PubMed

    Sano, Yasuteru; Nakano, Yuta; Omoto, Masatoshi; Takao, Masaki; Ikeda, Eiji; Oga, Atsunori; Nakamichi, Kazuo; Saijo, Masayuki; Maoka, Takashi; Sano, Hironori; Kawai, Motoharu; Kanda, Takashi

    2015-01-01

    A 66-year-old man with non-Hodgkin lymphoma (NHL) developed progressive multifocal leukoencephalopathy (PML) after undergoing chemotherapy including rituximab. Although the administration of mefloquine at a dose of 500 mg weekly temporarily led to a dramatic decrease in the copy number of JC Virus DNA in the cerebrospinal fluid, the patient's symptoms gradually worsened. The CD4(+) T count remained continuously low, at least until approximately five months after the last cycle of chemotherapy. A postmortem examination performed 10 months after the onset of PML disclosed a severe condition associated with rituximab-treated PML originating from NHL and a high mefloquine concentration in the brain. The accumulation of further data regarding mefloquine treatment in PML cases may help to elucidate the optimal dosage and time window for effectively treating PML.

  18. Synthesis of novel triazole-linked mefloquine derivatives: biological evaluation against Plasmodium falciparum.

    PubMed

    Hamann, Anton R; de Kock, Carmen; Smith, Peter J; van Otterlo, Willem A L; Blackie, Margaret A L

    2014-12-01

    Using 2,8-bis(trifluoromethyl)quinoline, the pharmacophore of mefloquine, as scaffold, eleven novel triazole-linked compounds have been synthesised by the application of CuAAC chemistry. The in vitro biological activity of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds all showed IC50s in the lower μM range with (1R,3S,5R)-N-{[1-(2,8-bis(trifluoromethyl)quinoline-4-yl)-1H-1,2,3-triazol-4-yl]methyl}adamantan-2-amine (29) exhibiting the best activity of 1.00 μM.

  19. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes.

    PubMed

    Clifford, David B; Nath, Avindra; Cinque, Paola; Brew, Bruce J; Zivadinov, Robert; Gorelik, Leonid; Zhao, Zhenming; Duda, Petra

    2013-08-01

    Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.

  20. [Curative treatment of malaria Plasmodium falciparum, P. vivax and P. ovale malaria with mefloquine].

    PubMed

    Danis, M; Felix, H; Brucker, G; Druilhe, P; Datry, A; Richard-Lenoble, D; Gentilini, M

    1982-01-01

    Mefloquine (WR 142-490, RO 21.5998), and antimalarial 4-quinoleine-methanol, active on multiresistant strains of P. falciparum is a resourceful product because of its pharmacocinetics and the possibility it opens of a single day curative therapy. Its mean half-live is 15 days, with important individual variations from 8 to 23 days as well as racial one within North-American, Asiatic or African patients. A 1,25 to 1,50 g dose divided in 2 or 3 intakes during 16 hours has proved to be effective in 34 P. falciparum cases. Lower doses, near 1 g seem sufficient for P. vivax (6 cases) and P. ovale fits (4 cases). Clinical and biological acceptance are good, according to this limited study. The use of mefloquine might nowadays be reserved for geographical areas where resistance to P. falciparum is significantly high. Its diffusion in Africa, south of the Sahara, though conceivable, might be discarded for the time beeing.

  1. Analysis of Investigational Drugs in Biological Fluids. Method Development and Routine Assay. Appendix B.

    DTIC Science & Technology

    2007-11-02

    metabolites), and 11-a multiple drug interaction study in dog plasma for WR 238,605, mefloquine, chloroguine, quinine ; doxycycline, and halofantrine...reproducibility of the analytical method, describing the extent of recovery for the method, and reporting on the stability of compounds of interest in specimens

  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.

  3. Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia

    PubMed Central

    2013-01-01

    Background Cambodia stopped using co-blistered, non-fixed, artesunate-mefloquine (ASMQ) in 2008 when treatment failure rates approximated 20%. Fixed dose combination (FDC) ASMQ is efficacious against acute uncomplicated, drug resistant Plasmodium falciparum malaria in Southeast Asia but has not been tested in Cambodia. Methods A 42-day WHO therapeutic efficacy study (TES) was conducted in 2010 in Oral, Kampong Speu province, south-west Cambodia, in patients with acute uncomplicated P. falciparum. Daily administered FDC ASMQ for three days was dosed by age. Genotyping of isolates at day 0 and day of recrudescence by polymerase chain reaction (PCR) classified post-treatment recurrent falciparum parasitaemia. Ex vivo drug sensitivity testing ([3H] hypoxanthine method) was performed on baseline parasites and reported as the drug concentration inhibiting 50% parasite growth vs no drug (IC50). Results Recruited patients numbered 45; five aged <15 years. On day 3, five of 45 [11.1 (3.7-24.05)] % patients were still parasite-positive; one of whom later failed treatment on day 21. There were 5/45 (11.1%) late treatment failures on day 21, 28 and 35; all were PCR diagnosed recrudescent infections. The day 0 MQ IC50s ranged from 11.5-238.9 (median 58.6) nM. Conclusions This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC50s. Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns. PMID:24060207

  4. Development of Microcomputer Methods for Analysis and Simulation of Clinical Pharmacokinetic Data Relevant to New Drug Development.

    DTIC Science & Technology

    1985-08-02

    interpretation, and simulation of pharmacokinetic data, dose - response kinetic data, and other data relevant to new drug development, for use with the Tektronix...Statistical Programs for Clinical Pharmacological Problems; Keywords: Clinical Pharmacokinetics, Dose - Response Relations, Pharmakinetic Simulation, Non-Parametric Statistics, Mefloquine, Microcomputer Graphics, Tektronix 4052.

  5. Questionnaire-based analysis of atovaquone-proguanil compared with mefloquine in the chemoprophylaxis of malaria in non-immune Japanese travelers.

    PubMed

    Kato, Tetsuro; Okuda, Joji; Ide, Daisuke; Amano, Katsushi; Takei, Yutaka; Yamaguchi, Yuko

    2013-02-01

    Malaria is one of the most common and serious infectious diseases in the tropics and subtropics. For high-risk travelers to endemic regions, malaria chemoprophylaxis is recommended. Internationally, atovaquone-proguanil (A/P), mefloquine (MEF), or doxycycline (DOX) are the prescribed malaria chemoprophylactic drugs. However, A/P and DOX are not approved in Japan. Therefore, the data on A/P for malaria chemoprophylaxis in Japanese travelers are not clear. We analyzed questionnaire survey data obtained in Hibiya Clinic to assess the safety and tolerability of A/P and compare them with those of MEF for non-immune Japanese travelers. A/P was given to 278 travelers and MEF to 38 travelers. The mean duration of each prophylaxis is for 20.0 ± 9.6 and 59.0 ± 15.9 days, respectively. Nine travelers discontinued prophylaxis: 5 in the A/P prescribed group (A/P group) and 4 in the MEF prescribed group (MEF group), and the rate of discontinuation was significantly less in the A/P group. The frequency of adverse events was significantly less in the A/P group than in the MEF group [52 cases (18.8 %) vs. 14 cases (36.8 %), respectively]. In particular, the frequency of psychoneurotic adverse events was significantly less in the A/P group. These results suggest that A/P is better tolerated and has fewer adverse events than MEF in non-immune Japanese travelers.

  6. Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients

    PubMed Central

    Lee, Sue J.; ter Kuile, Feiko O.; Luxemburger, Christine

    2017-01-01

    Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24–25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4–285) vs. 7.8 (3–15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days. PMID:28192434

  7. 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

  8. 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

  9. Mefloquine (Lariam)

    MedlinePlus

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research ( ... have been reported. If you are thinking about suicide, seek appropriate care immediately. Contact the Veterans Crisis ...

  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. Role of US military research programs in the development of US Food and Drug Administration--approved antimalarial drugs.

    PubMed

    Kitchen, Lynn W; Vaughn, David W; Skillman, Donald R

    2006-07-01

    US military physicians and researchers helped identify the optimum treatment dose of the naturally occurring compound quinine and collaborated with the pharmaceutical industry in the development and eventual US Food and Drug Administration approval of the synthetic antimalarial drugs chloroquine, primaquine, chloroquine-primaquine, sulfadoxine-pyrimethamine, mefloquine, doxycycline, halofantrine, and atovaquone-proguanil. Because malaria parasites develop drug resistance, the US military must continue to support the creation and testing of new drugs to prevent and treat malaria until an effective malaria vaccine is developed. New antimalarial drugs also benefit civilians residing in and traveling to malarious areas.

  12. A mitochondria-targeting artemisinin derivative with sharply increased antitumor but depressed anti-yeast and anti-malaria activities

    PubMed Central

    Sun, Chen; Cao, Yu; Zhu, Pan; Zhou, Bing

    2017-01-01

    The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins’ activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa). ARTa-TPP displays far more potent anti-tumorigenic activity than its parent compound. In contrast, ARTa-TPP is much less active against yeast respiration growth and malarial parasites. Notably, ARTa-TPP is also associated with increased toxicity to other kinds of control mammalian cells. These results suggest divergent action modes for artemisinins against cancer cells and malaria or yeast cells. We conclude that mitochondrial targeting could substantially elevate the anticancer potency of artemisinins, but the accompanied increased toxicity to normal cells raises an alert. The mechanism regarding the opposing effects of TPP conjugation to ARTa on its anticancer and anti-malarial/anti-yeast potencies is discussed based on our current understandings of artemisinins’ action. PMID:28368011

  13. A mitochondria-targeting artemisinin derivative with sharply increased antitumor but depressed anti-yeast and anti-malaria activities.

    PubMed

    Sun, Chen; Cao, Yu; Zhu, Pan; Zhou, Bing

    2017-04-03

    The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins' activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa). ARTa-TPP displays far more potent anti-tumorigenic activity than its parent compound. In contrast, ARTa-TPP is much less active against yeast respiration growth and malarial parasites. Notably, ARTa-TPP is also associated with increased toxicity to other kinds of control mammalian cells. These results suggest divergent action modes for artemisinins against cancer cells and malaria or yeast cells. We conclude that mitochondrial targeting could substantially elevate the anticancer potency of artemisinins, but the accompanied increased toxicity to normal cells raises an alert. The mechanism regarding the opposing effects of TPP conjugation to ARTa on its anticancer and anti-malarial/anti-yeast potencies is discussed based on our current understandings of artemisinins' action.

  14. Interaction of a biguanide compound with membrane model interface systems: probing the properties of antimalaria and antidiabetic compounds.

    PubMed

    Samart, Nuttaporn; Beuning, Cheryle N; Haller, Kenneth J; Rithner, Chris D; Crans, Debbie C

    2014-07-29

    Since membrane penetration is important for drug efficacy, how antimalarial precursor material 1-phenylbiguanide (PBG) interacts with an interface was characterized using a reverse micelle (RM) model system. (1)H NMR studies show that PBG partitions across the membrane interface. Specifically, the (1)H NMR studies showed that the 1-phenylbiguanide compound in an aqueous environment changed when placed near an interface. PBG is known to affect hydrogen bonding in water, and as the size of the RMs changes, the water organization in the water pool is changed. The NOESY spectrum of PBG in AOT RM contains cross-peak signals between the PBG protons and AOT protons, which is consistent with the penetration of the PBG into the interface. At the same time, there is a cross peak between the biguanide moiety and the HOD signal. This shows that these NH protons are near the HOD protons, placing the biguanide functional group in the water pool. Preliminary differential FTIR spectroscopic studies confirmed this location. In summary, we found that PBG interacts with different regions of the interface, with the phenyl group penetrating the hydrophobic interface while the biguanide remains in the water pool.

  15. 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

    DTIC Science & Technology

    2012-06-13

    hydrochlor- ide (MQ), quinine sulfate hydrate (QN) artesunate (AS), dihydroartemisinin (DHA), lumefantrine (LUM) and piperaquine (PPQ). CQ, MQ, QN and PPQ...within previ- ously validated criteria were cleared to be sent to the field. Out of range lots were destroyed. Drug plating consistency and stability ...the assessment of the response of Plasmodium falciparum to chloroquine, mefloquine, quinine , amodiaquine, sulfadoxine/pyrimethamine, and artemisinin

  16. Analysis of Investigational Drugs in Biological Fluids. Method Development and Routine Assay. Appendix A.

    DTIC Science & Technology

    2007-11-02

    chloroquine (and its metabolites), and 11-a multiple drug interaction study in dog plasma for WR 238,605, mefloquine, chloroquine, quinine ,, doxycycline...and reproducibility of the analytical method, describing the extent of recovery for the method, and reporting on the stability of compounds of...solvent with drug and internal standard. J. GENERATION OF STABILITY SAMPLES System stability samples were generated in the same way as precision

  17. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine

    PubMed Central

    van Riemsdijk, M M; Sturkenboom, M C J M; Ditters, J M; Tulen, J H M; Ligthelm, R J; Overbosch, D; Stricker, B H

    2004-01-01

    Aims We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. Methods We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine prophylaxis during the period between 1 May 1999 and 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after starting weekly intake of 250 mg mefloquine. We compared the intraindividual change in scores between baseline and follow-up visit on the Dutch shortened Profile of Mood States, and on the Continuous Performance Test (CPT) which measures sustained attention. Results The final cohort consisted of 151 subjects with a mean age of 38 years. In this population, a significant impairment of mood state was observed in those with a body mass index (BMI) ≤20 kg m−2. Stratification for gender showed that the total mood disturbance in females in the lowest BMI category significantly increased by 8.42 points [95% confidence interval (CI) 3.33, 13.50], whereas BMI did not affect the risk in males. Stratification for history of use of mefloquine showed that the risks were highest in first-time users. Analyses of the CPT showed that reaction time in women with a BMI ≤20 kg m−2 increased significantly by 22.5 ms (95% CI 7.80, 37.20), whereas reaction time in men showed a slight and nonsignificant decrease. Conclusion Risk factors for mefloquine-associated neuropsychiatric adverse events and concentration impairment are female gender, low BMI, and first-time use. The frequency of neuropsychiatric effects is highest in women with a BMI ≤20 kg m−2. PMID:15025750

  18. In vitro evaluation of drug susceptibilities of Babesia divergens isolates.

    PubMed

    Brasseur, P; Lecoublet, S; Kapel, N; Favennec, L; Ballet, J J

    1998-04-01

    The susceptibilities of three bovine and two human Babesia divergens isolates to antimicrobial agents were evaluated in vitro by a tritiated hypoxanthine incorporation assay. The MICs at which 50% of isolates are inhibited (MIC50s) for mefloquine (chlorhydrate), chloroquine (sulfate), quinine (chlorhydrate), clindamycin (phosphate), pentamidine (isethionate), phenamidine (isethionate) plus oxomemazine (chlorhydrate), lincomycin (chlorhydrate monohydrate), and imidocarb (dipropionate) were determined. Except for imidocarb, the MIC50s observed for the different isolates were close. Imidocarb and the combination of phenamidine plus oxomemazine exhibited the highest in vitro activity, while antimalarial agents such as mefloquine, choroquine, and quinine were inactive. Other drugs had intermediate activities. The data support further in vitro evaluation of antimicrobial agents active against B. divergens for the improvement of therapeutic strategies.

  19. In Vitro Evaluation of Drug Susceptibilities of Babesia divergens Isolates

    PubMed Central

    Brasseur, Philippe; Lecoublet, Sophie; Kapel, Nathalie; Favennec, Loic; Ballet, Jean J.

    1998-01-01

    The susceptibilities of three bovine and two human Babesia divergens isolates to antimicrobial agents were evaluated in vitro by a tritiated hypoxanthine incorporation assay. The MICs at which 50% of isolates are inhibited (MIC50s) for mefloquine (chlorhydrate), chloroquine (sulfate), quinine (chlorhydrate), clindamycin (phosphate), pentamidine (isethionate), phenamidine (isethionate) plus oxomemazine (chlorhydrate), lincomycin (chlorhydrate monohydrate), and imidocarb (dipropionate) were determined. Except for imidocarb, the MIC50s observed for the different isolates were close. Imidocarb and the combination of phenamidine plus oxomemazine exhibited the highest in vitro activity, while antimalarial agents such as mefloquine, choroquine, and quinine were inactive. Other drugs had intermediate activities. The data support further in vitro evaluation of antimicrobial agents active against B. divergens for the improvement of therapeutic strategies. PMID:9559789

  20. 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.…

  1. Food-drug interactions.

    PubMed

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril). In addition, the physiological response to food intake, in particular gastric acid secretion, may reduce the bioavailability of certain drugs (ampicillin, azithromycin capsules, didanosine, erythromycin stearate or enteric coated, and isoniazid). For other drugs, concomitant food intake may result in an increase in drug bioavailability either because of a food-induced increase in drug solubility (albendazole, atovaquone, griseofulvin, isotretinoin, lovastatin, mefloquine, saquinavir and tacrolimus) or because of the secretion of

  2. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

    PubMed Central

    Koo, Jinmi; Choe, Han Kyoung; Kim, Hee-Dae; Chun, Sung Kook; Son, Gi Hoon

    2015-01-01

    Background In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. Methods We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. Results Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. Conclusion These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock. PMID:25491783

  3. 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

  4. Clinical status and implications of antimalarial drug resistance.

    PubMed

    Winstanley, Peter A; Ward, Steven A; Snow, Robert W

    2002-02-01

    Africa carries the greatest burden of disease caused by Plasmodium falciparum, and we can expect this burden to rise in the near future, mainly because of drug resistance. Although effective drugs are available (such as artemether-lumefantrine, mefloquine, atovaquone-proguanil and halofantrine) they are uniformly too expensive for routine use. Affordable options include chloroquine plus sulfadoxine-pyrimethamine (SP), amodiaquine (alone or in combination with SP) and chlorproguanil-dapsone. Artemisinin combination therapy may offer considerable advantages over alternative therapies, but its introduction faces considerable logistic difficulty.

  5. Preliminary investigation of the contribution of CYP2A6, CYP2B6, and UGT1A9 polymorphisms on artesunate-mefloquine treatment response in Burmese patients with Plasmodium falciparum malaria.

    PubMed

    Phompradit, Papichaya; Muhamad, Poonuch; Cheoymang, Anurak; Na-Bangchang, Kesara

    2014-08-01

    CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response. In one patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma concentration of artesunate at one hour appeared to be higher, and the concentration of dihydroartemisinin was lower than for those carrying other genotypes (415 versus 320 ng/mL). The proportion of patients with adequate clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant genotype) was significantly lower compared with those with late parasitologic failure (14.0% versus 19.0%). Confirmation through a larger study in various malaria-endemic areas is required before a definite conclusion on the role of genetic polymorphisms of these drug-metabolizing enzymes on treatment response after artesunate-based combination therapy can be made.

  6. 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

  7. Synergistic drug combination effectively blocks Ebola virus infection.

    PubMed

    Sun, Wei; He, Shihua; Martínez-Romero, Carles; Kouznetsova, Jennifer; Tawa, Gregory; Xu, Miao; Shinn, Paul; Fisher, Ethan G; Long, Yan; Motabar, Omid; Yang, Shu; Sanderson, Philip E; Williamson, Peter R; García-Sastre, Adolfo; Qiu, Xiangguo; Zheng, Wei

    2017-01-01

    Although a group of FDA-approved drugs were previously identified with activity against Ebola virus (EBOV), most of them are not clinically useful because their human blood concentrations are not high enough to inhibit EBOV infection. We screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of three-drug combinations, toremifene-mefloquine-posaconazole and toremifene-clarithromycin-posaconazole, were identified that effectively blocked EBOV entry and were further validated for inhibition of live EBOV infection. The individual drug concentrations in the combinations were reduced to clinically relevant levels. We identified mechanisms of action of these drugs: functional inhibitions of Niemann-Pick C1, acid sphingomyelinase, and lysosomal calcium release. Our findings identify the drug combinations with potential to treat EBOV infection.

  8. Confocal laser scanning microscopic observation on adult Schistosoma japonicum harbored in mice following treatment with single-dose mefloquine.

    PubMed

    Xiao, Shu-Hua; Sun, Jun; Xue, Jian

    2012-06-01

    The aim of the present study is to assess the mefloquine-induced alteration of adult Schistosoma japonicum using confocal laser scanning microscopy (CLSM). Eight out of ten mice infected with 60-80 S. japonicum cercariae for 35 days were treated orally with mefloquine at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h and 3, 7, and 14 days post-treatment, and schistosomes were collected by perfusion from the liver and mesenteric veins, fixed in 70% alcohol, stained with acid carmine, and examined by CLSM. Worms obtained from untreated mice served as controls. Twenty-four hours post-treatment, focal tegument of adult male and female worms, which composed of fine and short villus-like materials, became thicker and longer, or disorder arrangement, while the musculatures beneath the tegument revealed in focal and irregular swelling with various degrees. In the gut of male and female schistosomes, severe dilatation accompanied by swelling, collapse, and peeling of gut mucosa was universal. In the reproductive organs, no apparent alteration in the testis structure of male worms was seen, while in female worms, slight damage to the ovary included loose arrangement of mature ovary cells accompanied by some of them degenerated and collapsed. As to vitelline glands, severe damage, such as swelling, indistinction, fusion or collapse of vitelline cells, and apparent swelling of parenchymal tissues in vitelline gland lobules, was seen. Meanwhile, abnormal ova emerged in the uterus at this time point. Three to 7 days post-treatment, the damage to the worms aggravated either in extent or in severity along with time. In some focally swollen worm body, the parenchymal tissues revealed in severe swelling. In addition, a large piece of degenerated and necrotic parenchymal tissues emerged closed to the severe destructed oral or ventral sucker. In the gut of male and female worms, the major alterations manifested by focal collapse or peeling of mucosa, and

  9. Sensitivity in vitro of Plasmodium falciparum to three currently used antimalarial drugs on the western border of Thailand.

    PubMed

    Fèvre, E M; Barnish, G; Yamokgul, P; Rooney, W

    1999-01-01

    The sensitivity in vitro of Plasmodium falciparum to mefloquine, quinine and artemisinin was assessed in an area of multi-drug resistance on the Thai-Myanmar border, using the World Health Organization's microtest, based on schizont maturation inhibition. Participating individuals were exclusively those who had contracted their infections within Myanmar. A total of 34 successful tests were carried out for mefloquine and quinine, showing a marked decrease in sensitivity compared to previously published results. Ten artemisinin tests were successful, with many failures due to the poor storage stability of the test plates. The implications of the shelf-life of the artemisinin plates is discussed. These results contribute to setting a base line of sensitivity to artemisinin in vitro.

  10. New Fixed-Dose Artesunate-Mefloquine Formulation against Multidrug-Resistant Plasmodium falciparum in Adults: a Comparative Phase IIb Safety and Pharmacokinetic Study with Standard-Dose Nonfixed Artesunate plus Mefloquine▿

    PubMed Central

    Krudsood, S.; Looareesuwan, S.; Tangpukdee, N.; Wilairatana, P.; Phumratanaprapin, W.; Leowattana, W.; Chalermrut, K.; Ramanathan, S.; Navaratnam, V.; Olliaro, P.; Vaillant, M.; Kiechel, J. R.; Taylor, W. R. J.

    2010-01-01

    A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs of malaria-induced hypotension occurring in the AS-MQ arm necessitated rescue treatment. There were no significant changes in hematology, biochemistry, or PR and QRS intervals. For all patients, mean Fridericia-corrected QT intervals were significantly (P ≤ 0.0027) prolonged on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with significant (P ≤ 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly similar to those of nonfixed AS plus MQ, and is a suitable replacement. PMID:20547795

  11. [The proper use of antimalarial drugs currently available].

    PubMed

    Bourgeade, A; Delmont, J

    1998-01-01

    French medical practitioners have at their disposal several antimalarial drugs for giving chemoprophylaxis to people travelling to a malaria endemic country or treating an imported malaria case in a patient. The choice depends on the contre-indications and indications of each drug, essentially subordinated to the presence and level of Plasmodium falciparum chemosensitivity in the visited area. For prevention, chloroquine alone can be taken in the areas where P. falciparum is absent or not chloroquine resistant; elsewhere, the choice between chloroquine/proguanil or mefloquine depends on knowing the prevalence and level of falciparum chloroquine resistance in these areas. For treatment, the only indications of chloroquine are imported malaria cases either due to P. vivax, P. ovale or P. malariae, or caused by P. falciparum contracted in one of the rare countries where the species is still sensitive to chloroquine. For uncomplicated falciparum malaria cases acquired in a chemoresistance area, mefloquine, halofantrine, sulfadoxine-pyrimethamine or oral quinine is selected, depending on the observed chemoprophylaxis, the contra-indications and the suspicion of chemoresistance type. Whatever the provenance area, P. falciparum in a patient with one or several serious symptoms or possibly profuse vomiting is treated by intravenous quinine, associated with tetracycline if the patient comes from an area known for a low quinine sensitivity of this species. The spectrum of falciparum malaria treatment has recently broadened to include new drugs such as artemisinin, artemether or atovaquone/proguanil, the latter being as yet unauthorized in France.

  12. 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

  13. Highly active ozonides selected against drug resistant malaria.

    PubMed

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

    2016-06-07

    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.

  14. [The evolution over time of the in-vitro resistance of Plasmodium falciparum to antimalarial drugs in 2 areas of the Brazilian Amazonia with distinct socioeconomic and geographic characteristics].

    PubMed

    Couto, A A; Calvosa, V S; Santos, M A; de Souza, J M

    1995-01-01

    We evaluated the temporal progression of in vitro P. falciparum resistance to chloroquine, amodiaquine, quinine and mefloquine in two areas with distinct socioeconomical and geographical characteristics: Lourenço, in Amapá state and Paragominas, in Pará state. The former region is essentially an "open" gold mining camp, whereas the latter is one currently undergoing a colonization settlement process, in addition to expanding economical activities which mainly include cattle raising and wood exploitation. Our results show high resistance rates to chloroquine in the two study areas: 79.8% and 68.4% in Lourenço and Paragominas, respectively. Variations in the response of P. falciparum to both amodiaquine and quinine were recorded throughout the study period. On the other hand, no mefloquine P. falciparum resistant strains could be identified, despite the tact we had noted a decrease in sensitivity to this antimalarial drug throughout the study period.

  15. Chemotherapy of drug-resistant malaria

    PubMed Central

    Kain, Kevin C

    1996-01-01

    OBJECTIVE: To review the impact of drug-resistant malaria on current management of plasmodial infections. DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts. DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistant Plasmodium vivax is unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious. CONCLUSIONS: The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease. PMID:22514413

  16. 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

  17. 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

  18. Effect of membrane filtration of antimalarial drug solutions on in vitro activity against Plasmodium falciparum*

    PubMed Central

    Baird, J. K.; Lambros, C.

    1984-01-01

    Antimalarial activities of chloroquine, mefloquine, amodiaquine, and quinine in vitro against Plasmodium falciparum were diminished as a consequence of membrane filtration. Filtered drug solutions gave ID50 values up to 25-fold greater than those of non-filtered (ethanol-sterilized) drug solutions. Loss of activity by filtration was overcome by increasing the drug concentration prior to filtration. Water solutions filtered through Millex-GS filter units consistently showed an absorbance maximum at 277 nm, accompanied by a lesser peak at 225 nm. Water filtrates from Nucleopore and Millex-GV filters showed no absorbance at 277 nm and only slight absorbance was evident for the Gelman filter unit. Activity losses were attributed to extractable contaminating moieties in the membrane filters and/or drug binding to the membrane filters. PMID:6380786

  19. 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

  20. 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.

  1. 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.

  2. Parallel inhibition of amino acid efflux and growth of erythrocytic Plasmodium falciparum by mefloquine and non-piperidine analogs: Implication for the mechanism of antimalarial action.

    PubMed

    Ghavami, Maryam; Dapper, Christie H; Dalal, Seema; Holzschneider, Kristina; Klemba, Michael; Carlier, Paul R

    2016-10-01

    Despite the troubling psychiatric side-effects it causes in some patients, mefloquine (MQ) has been used for malaria prophylaxis and therapy, due to its activity against all Plasmodium species, its ease of dosing, and its relative safety in children and pregnant women. Yet at present there is no consensus on the mechanism of antimalarial action of MQ. Two leading hypotheses for the mechanism of MQ are inhibition of heme crystallization and inhibition of host cell hemoglobin endocytosis. In this report we show that MQ is a potent and rapid inhibitor of amino acid efflux from intact parasitized erythrocytes, which is a measure of the in vivo rate of host hemoglobin endocytosis and catabolism. To further explore the mechanism of action of MQ, we have compared the effects of MQ and 18 non-piperidine analogs on amino acid efflux and parasite growth. Among these closely related compounds, an excellent correlation over nearly 4 log units is seen for 50% inhibition concentration (IC50) values for parasite growth and leucine efflux. These data and other observations are consistent with the hypothesis that the antimalarial action of these compounds derives from inhibition of hemoglobin endocytosis.

  3. 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

  4. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    PubMed Central

    Bai, Jane P. F.; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G.

    2017-01-01

    Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection. PMID:28287432

  5. 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

  6. Comparative efficacy and safety of chloroquine and alternative antimalarial drugs: a meta-analysis from six African countries.

    PubMed

    Mengesha, T; Makonnen, E

    1999-06-01

    A meta-analysis study evaluating the efficacy and safety of chloroquine and alternative antimalarial drugs used in six African countries including Ethiopia, Kenya, Uganda, Cote D'Ivoire, Gambia and Nigeria is presented. Findings from the six countries showed a higher efficacy of amodiaquine and quinine (over 90%) in malaria treatment compared to chloroquine, which was found to be 70% or more effective. The efficacy of amodiaquine can also be compared to other antimalarial drugs such as mefloquine and halofantrine. Data showed that fever clearance time of these drugs was less than 2 days, but parasite clearance time ranged from 2.5 days to 1 week. Recrudescence rate also varied among the different drugs. This is a very important indicator in determining which drug can be used for prophylactic or suppressive treatment of malaria. Pharmacokinetic profile demonstrates that all these drugs have similar therapeutic effects, but differ in their adverse reactions, contraindications, and half-life. A significant difference was also noted in the cost of these antimalarial drugs; chloroquine was the cheapest, while halofantrine was the most expensive among the drugs. Based on these results, the study recommends that different aspects of antimalarial drugs have to be considered before deciding which drug is the best alternative treatment.

  7. Molecular epidemiology of malaria in Cameroon. XXIV. Trends of in vitro antimalarial drug responses in Yaounde, Cameroon.

    PubMed

    Basco, Leonardo K; Ringwald, Pascal

    2007-01-01

    In vitro response to chloroquine, monodesethylamodiaquine, mefloquine, lumefantrine, and dihydroartemisinin was assessed by the radioisotopic microtest in Yaoundé, Cameroon, during 2000-2004 and compared with our previous data obtained during 1996-1999. Based on the cut-off value of 100 nmol/L, 36.3% of isolates were chloroquine-susceptible (N = 175; geometric mean IC(50), 40.3 nmol/L) and 63.7% were chloroquine-resistant (N = 307; geometric mean IC(50), 211 nmol/L). There was no significant difference (P > 0.05) in the mean IC(50)s from 1996 to 2004, but a significant linear trend (P < 0.05) toward an increased proportion of chloroquine-resistant isolates was observed from 1996 (49%) to 2004 (69%). All chloroquine-susceptible isolates and most chloroquine-resistant isolates were susceptible to monodesethylamodiaquine (i.e., IC(50) < 60 nmol/L). Despite the positive correlation between chloroquine and monodesethylamodiaquine (r = 0.739, P < 0.05), the IC(50)s for monodesethylamodiaquine remained stable during 1997-2004, with no increase in the proportion of monodesethylamodiaquine-resistant isolates. Mefloquine, lumefantrine, and dihydroartemisinin were equally active against the chloroquine-susceptible and chloroquine-resistant parasites. The responses to these three drugs were positively correlated, and a significant decrease (P < 0.05) in the mean IC(50)s was observed during the study period compared with our earlier data in 1997-1999, probably because of their inverse relationship with chloroquine response. The in vitro results were in general agreement with the in vivo response to chloroquine and amodiaquine. In vitro drug susceptibility assay is a useful, complementary laboratory tool for determining the trend of response to drugs for which there is still no established molecular marker and may serve as an early warning system for emerging drug resistance.

  8. Strengthening of national capacity in implementation of antimalarial drug quality assurance in Thailand.

    PubMed

    Vijaykadga, Saowanit; Cholpol, Sawat; Sitthimongkol, Saipin; Pawaphutanan, Anusorn; Pinyoratanachot, Arunya; Rojanawatsirivet, Chaiporn; Kovithvattanapong, Rojana; Thimasarn, Krongthong

    2006-01-01

    Substandard and counterfeit pharmaceutical products, including antimalarial drugs, appear to be widespread internationally and affect both the developing and developed countries. The aim of the study was to investigate the quality of antimalarial drugs, ie, artesunate (ART), chloroquine (CHL), mefloquine (MEF), quinine (QUI), sulfadoxine/pyrimethamine (S/P) and tetracycline (TT) obtained from the government sector and private pharmacies in 4 Thai provinces: Mae Hong Son, Kanchanaburi, Ranong, and Chanthaburi. Three hundred sixty-nine samples of 6 antimalarial drugs from 27 government hospitals, 27 malaria clinics, and 53 drugstores, were collected. Drug quality was assessed by simple disintegration test and semi-quantitative thin-layer chromatography in each province; 10% passed, 100% failed and doubtful samples were sent to be verified by high performance liquid chromatography (HPLC) at the Thai National Drug Analysis Laboratory, (NL). Fifteen point four percent of ART, 11.1% of CHL and 29.4% of QUI were substandard. Based on the finding, drug regulatory authorities in the country took appropriate action against violators to ensure that antimalarial drugs consumed by malaria patients are of good quality.

  9. Multiple drug resistance genes in malaria -- from epistasis to epidemiology.

    PubMed

    Duraisingh, Manoj T; Refour, Philippe

    2005-08-01

    A decline in our ability to successfully treat patients with malaria infections of the parasitic protozoan Plasmodium falciparum with cheap quinoline drugs has led to a huge escalation in morbidity and mortality in recent years. Many approaches have been taken, including classical genetics, reverse genetics and molecular epidemiology, to identify the molecular determinants underlying this resistance. The contribution of the P. falciparum multidrug resistance gene, pfmdr1, to antimalarial resistance has been a source of controversy for over a decade since it was first identified. In the current issue of Molecular Microbiology, Sidhu and colleagues use powerful reverse genetics to demonstrate the importance of commonly occurring alleles of pfmdr1 in conferring resistance to the second-line drugs quinine and sensitivity to the new alternatives mefloquine and artemisinin. They also elegantly highlight the importance of genetic background and epistasis between pfmdr1 and other potential modulators of drug resistance. Such molecular knowledge will facilitate surveillance/monitoring and aid the development of strategies for the reversal of resistance.

  10. 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

  11. 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 ...

  12. 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 ...

  13. 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.

  14. Drugs, drugs--who has the drugs?

    PubMed

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims.

  15. 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

  16. 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

  17. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  18. Predicting drugs and proteins in parasite infections with topological indices of complex networks: theoretical backgrounds, applications, and legal issues.

    PubMed

    González-Díaz, Humberto; Romaris, Fernanda; Duardo-Sanchez, Aliuska; Pérez-Montoto, Lázaro G; Prado-Prado, Francisco; Patlewicz, Grace; Ubeira, Florencio M

    2010-01-01

    Quantitative Structure-Activity Relationship (QSAR) models have been used in Pharmaceutical design and Medicinal Chemistry for the discovery of anti-parasite drugs. QSAR models predict biological activity using as input different types of structural parameters of molecules. Topological Indices (TIs) are a very interesting class of these parameters. We can derive TIs from graph representations based on only nodes (atoms) and edges (chemical bonds). TIs are not time-consuming in terms of computational resources because they depend only on atom-atom connectivity information. This information expressed in the molecular graphs can be tabulated in the form of adjacency matrices easy to manipulate with computers. Consequently, TIs allow the rapid collection, annotation, retrieval, comparison and mining of molecular structures within large databases. The interest in TIs has exploded because we can use them to describe also macromolecular and macroscopic systems represented by complex networks of interactions (links) between the different parts of a system (nodes) such as: drug-target, protein-protein, metabolic, host-parasite, brain cortex, parasite disease spreading, Internet, or social networks. In this work, we review and comment on the following topics related to the use of TIs in anti-parasite drugs and target discovery. The first topic reviewed was: Topological Indices and QSAR for antiparasitic drugs. This topic included: Theoretical Background, QSAR for anti-malaria drugs, QSAR for anti-Toxoplasma drugs. The second topic was: TOMO-COMD approach to QSAR of antiparasitic drugs. We included in this topic: TOMO-COMD theoretical background and TOMO-COMD models for antihelmintic activity, Trichomonas, anti-malarials, anti-trypanosome compounds. The third section was inserted to discuss Topological Indices in the context of Complex Networks. The last section is devoted to the MARCH-INSIDE approach to QSAR of antiparasitic drugs and targets. This begins with a theoretical

  19. Generic Drugs

    MedlinePlus

    Generic Drugs: The Same Medicine for Less Money What is a generic drug? A generic is a copy of a brand-name drug. A brand- name drug has a patent. When ... benefit to your health, and you will save money. 7KH IHGHUDO )RRG DQG 'UXJ $GPLQLVWUDWLRQ )'$ UHJXODWHV ERWK ...

  20. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

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

  1. Molecular surveillance as monitoring tool for drug-resistant Plasmodium falciparum in Suriname.

    PubMed

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

    2013-08-01

    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.

  2. Drug Allergy

    MedlinePlus

    ... of other allergies, such as food allergy or hay fever Allergic reaction to another drug A family history ... so, what drug was it? Do you have hay fever, food allergy or other allergies? Is there a ...

  3. Drugged Driving

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... in the past year. Middle Figure: Driving after marijuana use is more common than driving after alcohol ...

  4. Drugs (image)

    MedlinePlus

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  5. Drug Abuse

    MedlinePlus

    ... abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a ...

  6. 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)

  7. 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.

  8. Effects of quinoline-containing antimalarials on the erythrocyte membrane and their significance to drug action on Plasmodium falciparum.

    PubMed

    Ginsburg, H; Krugliak, M

    1988-05-15

    Quinoline-containing antimalarials are cationic amphiphiles which accumulate to high levels in lysosomes and are known to interact with membrane phospholipids. It was therefore hypothesized that they could exert their antimalarial effect by compromising the integrity of the parasite's acidic organelles. To test this hypothesis, the effects of chloroquine (CQ), quinine (Q) and mefloquine (MQ) on the osmotic stability of human red blood cells exposed to hypotonic solutions have been investigated. With CQ and Q stabilization was observed at pH 7.8 and destabilization at pH 5, indicating that destabilization is caused by the protonated forms of the drugs. With MQ the pH dependence was reversed, i.e. it destabilized at pH 7.8 and stabilized at pH 5, suggesting that destabilization is caused by the unprotonated drug. MQ caused cell lysis at the tenth millimolar range by a detergent effect. The possible destabilizing effect of drugs on the membranes of Plasmodium falciparum acidic organelles was investigated in metabolically-labelled parasites. We expected an increase in degradation of parasite proteins if drugs did indeed cause the release of acid hydrolases from destabilized organelles to the cytoplasm. No effect of drugs on parasite protein degradation could be observed, but protein synthesis was inhibited at therapeutic drug concentrations. These results imply that quinoline-containing antimalarials do not compromise the integrity of parasite acidic organelles, and that inhibition of protein synthesis results from a limited supply of essential amino acid(s) due to the demonstrable drug-mediated suppression of parasite digestion of host cell cytosol.

  9. Alkalinization of the food vacuole of malaria parasites by quinoline drugs and alkylamines is not correlated with their antimalarial activity.

    PubMed

    Ginsburg, H; Nissani, E; Krugliak, M

    1989-08-15

    Quinoline-containing antimalarial drugs accumulate inside the acid food vacuole of the parasite where they inhibit the digestion of ingested host cell cytosol, and consequently, parasite growth. In order to verify whether this inhibition is caused by drug-induced alkalinization of the food vacuole, we investigated the accumulation of acridine orange (AO) as a vacuolar pH probe in intact Plasmodium falciparum-infected human erythrocytes as affected by the drugs chloroquine (CQ), 7H-quinoleine (7HQ), quinine (Q) and mefloquine (MQ). It was established by various criteria that AO accumulates primarily in the acid compartment(s) of the parasite as a function of the pH difference between it and the extracellular medium. This pH gradient was dissipated by the drugs in the rank order MQ greater than CQ greater than Q greater than 7HQ. The kinetics of vacuolar alkalinization and the concentration ranges at which it was observed imply that the monoprotic drugs MQ and Q exerted their effect mostly by translocating protons across the vacuolar membrane, i.e. they could cross the membrane as a protonated species, while the diprotic drugs CQ and 7HQ raised the vacuolar pH mostly by proton trapping. Similarly, hydrophobic alkylamines raised the vacuolar pH by proton translocation, while their relatively more polar congeners and ammonia did so by proton titration. However, the alkalinizing effect of each drug was observed at a concentration which was 1-2 orders of magnitude larger than the IC50 of its antimalarial effect. These results mean that vacuolar alkalinization is not the primary effect of antiparasitic action of quinoline antimalarials.

  10. 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; ...

  11. 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.

  12. 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

  13. Drug Addiction

    MedlinePlus

    ... mental health disorders, several factors may contribute to development of drug addiction and dependence. The main factors are: Environment. Environmental factors, including your family's beliefs and attitudes ...

  14. Drugged Driving

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  15. Club Drugs

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  16. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  17. Effects of Artesunate on some biochemical parameters in pregnant albino Wistar rats challenged with lethal strain Plasmodium berghei NK65: Appreciating the activities of artemisinin drugs on key pregnancy hormone balance.

    PubMed

    Nwaehujor, Chinaka O; Asuzu, Onyeka V; Nwibo, Daniel D; Nwobi, Obichukwu C; Ezeigbo, Ihechiluru I

    2017-03-20

    In humans, malaria in pregnancy can cause serious maternal and foetal morbidity and in extreme untreated cases, foetal mortality occurs. The therapeutic approach to curbing this malaise is the administration of an effective and/or combinations of anti-malaria medicaments. Acute or chronic administration of some of these drugs, however, gives rise to some adverse medical conditions including reproductive dysfunction, especially in pregnancy. Studies aimed at the hormonal interplays following administration of these drugs in pregnancy have been limited due to too few appropriate animal models. In this experiment, pregnant albino rats were infected with rodent parasite, Plasmodium berghei on the 5th day of gestation, following which biochemical changes, specific for pregnancy maintenance were monitored in the blood of test rats. We observed that infecting the pregnant rats with P. berghei negatively impacted the measured biological parameters (hormones) compared to unchallenged controls. The observed effect was however retreated following oral administration of 3mg/kg body weight, qDay of Artesunate until the 17th day of gestation. Findings, therefore, suggest that Artesunate is an effective therapeutic agent in pregnancy, demonstrated by the restoration of the hormonal changes occasioned by the parasitic infection.

  18. Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

    PubMed Central

    2011-01-01

    Background The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour 3H-hypoxanthine uptake inhibition method using the Genbag CO2® system and compared to controlled incubator conditions (5% CO2 and 10% O2). Results The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O2) were significantly higher than those of Genbag® conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine. To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag® conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM). Conclusions The atmospheric

  19. 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…

  20. 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).

  1. Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model.

    PubMed

    Müller, Joachim; Aguado-Martínez, Adriana; Manser, Vera; Wong, Ho Ning; Haynes, Richard K; Hemphill, Andrew

    2016-02-17

    The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebral infection comprising Balb/c mice experimentally infected with the virulent isolate Nc-Spain7, the three anti-malarial compounds failed to exhibit any activity, since treatment did not reduce the parasite burden in brains and lungs compared to untreated controls. Thus, these compounds were not further evaluated in pregnant mice. On the other hand, buparvaquone, shown earlier to be effective in reducing the parasite load in the lungs in an acute neosporosis disease model, was further assessed in the pregnant mouse model. Buparvaquone efficiently inhibited vertical transmission in Balb/c mice experimentally infected at day 7 of pregnancy, reduced clinical signs in the pups, but had no effect on cerebral infection in the dams. This demonstrates proof-of-concept that drug repurposing may lead to the discovery of an effective compound against neosporosis that can protect offspring from vertical transmission and disease.

  2. [Club drugs].

    PubMed

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  3. Drug dependence

    MedlinePlus

    ... starts using drugs to try to self-treat mental illness. Support Groups Many support groups are available in ... American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. ...

  4. Drug Facts

    MedlinePlus Videos and Cool Tools

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  5. Drug abuse

    MedlinePlus

    ... 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman L, ... Hospice and Palliative Medicine, Atlanta, GA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  6. Study Drugs

    MedlinePlus

    ... may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The ... some proven ways to boost concentration and beat stress: Meditation . Even a few minutes of meditation each ...

  7. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    PubMed

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  8. Optimization of a New Cell-Based Fluorescence Assay for U.S. Army Global Malaria Surveillance Efforts in Support of the Warfighter

    DTIC Science & Technology

    2006-11-01

    hemisulfate salt, and mefloquine hydrochloride were purchased from Sigma Chemical Co., Saint Louis, Missouri. P. falciparum strains D6 (CDC...screening laboratory. The drugs tested included chloroquine, quinine, and mefloquine . Their respective IC50s were determined using the MSF assay... Mefloquine . RFU = relative fluorescence units. CONCLUSIONS The drug resistance profile of D6 and W2 has been well established by our group and

  9. 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.

  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. Club Drugs

    MedlinePlus

    ... 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 as Roofies Methamphetamine, also known as Speed, Ice, Chalk, Meth, Crystal, Crank, and Glass Lysergic Acid Diethylamide (LSD), also ...

  12. Transporter-mediated drug-drug interactions.

    PubMed

    Müller, Fabian; Fromm, Martin F

    2011-07-01

    Drug-drug interactions are a serious clinical issue. An important mechanism underlying drug-drug interactions is induction or inhibition of drug transporters that mediate the cellular uptake and efflux of xenobiotics. Especially drug transporters of the small intestine, liver and kidney are major determinants of the pharmacokinetic profile of drugs. Transporter-mediated drug-drug interactions in these three organs can considerably influence the pharmacokinetics and clinical effects of drugs. In this article, we focus on probe drugs lacking significant metabolism to highlight mechanisms of interactions of selected intestinal, hepatic and renal drug transporters (e.g., organic anion transporting polypeptide [OATP] 1A2, OATP2B1, OATP1B1, OATP1B3, P-gp, organic anion transporter [OAT] 1, OAT3, breast cancer resistance protein [BCRP], organic cation transporter [OCT] 2 and multidrug and toxin extrusion protein [MATE] 1). Genotype-dependent drug-drug interactions are also discussed.

  13. A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities.

    PubMed

    Mirza, Haris; Teo, Joshua D W; Upcroft, Jacqui; Tan, Kevin S W

    2011-02-01

    Blastocystis is an emerging protistan parasite of controversial pathogenesis. Although metronidazole (Mz) is standard therapy for Blastocystis infections, there have been accumulating reports of treatment failure, suggesting the existence of drug-resistant isolates. Furthermore, very little is known about Blastocystis susceptibility to standard antimicrobials. In the present study, we established resazurin and XTT viability microassays for Blastocystis spp. belonging to subtypes 4 and 7, both of which have been suggested to represent pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while subtype 4 parasites were sensitive. Some cross-resistance was observed to tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs were effective against both subtypes, as were ornidazole, nitazoxanide, furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim-sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the first study to report extensive variations in drug sensitivities among two clinically important subtypes. Our study highlights the need to reevaluate established treatment regimens for Blastocystis infections and offers clear new treatment options for Mz treatment failures.

  14. 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

  15. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... by Month Approvals, tentative approvals, and supplements Original New Drug Approvals (NDAs and BLAs) by Month All applications ... FDA. Does not include tentative approvals. Original Abbreviated New Drug Approvals (ANDAs) by Month Generic Drug Approvals. Does ...

  16. Analysis of Investigational Drugs in Biological Fluids - Method Development and Routine Assay

    DTIC Science & Technology

    1994-08-14

    Liquid Pyridostigmine Plasma 1.4 ng/ml Chromatography ( HPLC ) of Pyridostigmine in Plasma 04 8/23/85 Ion-Paired Liquid Chromato- halofantrine Plasma... HPLC ) of Pyridostigmine in Plasma Using Silica Gel Column and an Aqueous Mobile Phase 06 1/8/88 High Pressure Liquid Mefloquine Plasma 10.0 ng/ml...Chromatography ( HPLC ) of Mefloquine in Plasma 07 1/12/88 High Pressure Liquid Pyridostigmine Urine 13.7 ng/ml Chromatography ( HPLC ) of Pyridostigmine in

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Club Drug Use

    MedlinePlus

    ... different from other illicit drugs?What are the dangers of taking club drugs?What can I do ... Drug Use | Gamma-Hydroxybutyrate (GHB)Learn about the dangers of taking gamma-hydroxybutyrate (GHB), an illegal drug ...

  2. Effects of Drug Use

    MedlinePlus

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... and the brain , sometimes forever. Learn more about: how drug use and mental health problems often happen together the link between drug use ...

  3. Urine drug screen

    MedlinePlus

    Drug screen -- urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence indicates that you recently used these drugs. Some drugs may remain in your system for ...

  4. 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…

  5. DrugCentral: online drug compendium

    PubMed Central

    Ursu, Oleg; Holmes, Jayme; Knockel, Jeffrey; Bologa, Cristian G.; Yang, Jeremy J.; Mathias, Stephen L.; Nelson, Stuart J.; Oprea, Tudor I.

    2017-01-01

    DrugCentral (http://drugcentral.org) is an open-access online drug compendium. DrugCentral integrates structure, bioactivity, regulatory, pharmacologic actions and indications for active pharmaceutical ingredients approved by FDA and other regulatory agencies. Monitoring of regulatory agencies for new drugs approvals ensures the resource is up-to-date. DrugCentral integrates content for active ingredients with pharmaceutical formulations, indexing drugs and drug label annotations, complementing similar resources available online. Its complementarity with other online resources is facilitated by cross referencing to external resources. At the molecular level, DrugCentral bridges drug-target interactions with pharmacological action and indications. The integration with FDA drug labels enables text mining applications for drug adverse events and clinical trial information. Chemical structure overlap between DrugCentral and five online drug resources, and the overlap between DrugCentral FDA-approved drugs and their presence in four different chemical collections, are discussed. DrugCentral can be accessed via the web application or downloaded in relational database format. PMID:27789690

  6. Drug Preferences of Multiple Drug Abusers.

    ERIC Educational Resources Information Center

    Harford, Robert J.

    1978-01-01

    Examined drug preferences of a group of active multiple drug abusers referred for treatment. Nearly half the respondents preferred drugs other than type they most frequently used. Preferences were related to method of administration. Results suggest preference is one among several determinants of drug use. (Author/BEF)

  7. 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)…

  8. 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

  9. Drug combination therapy increases successful drug repositioning.

    PubMed

    Sun, Wei; Sanderson, Philip E; Zheng, Wei

    2016-07-01

    Repositioning of approved drugs has recently gained new momentum for rapid identification and development of new therapeutics for diseases that lack effective drug treatment. Reported repurposing screens have increased dramatically in number in the past five years. However, many newly identified compounds have low potency; this limits their immediate clinical applications because the known, tolerated plasma drug concentrations are lower than the required therapeutic drug concentrations. Drug combinations of two or more compounds with different mechanisms of action are an alternative approach to increase the success rate of drug repositioning.

  10. Personality, drug preference, drug use, and drug availability.

    PubMed

    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) theories. Drug preference was measured by the method of paired-comparison and personality was measured with the Zuckerman-Kuhlman Personality Questionnaire-50 CC. Contrary to expectations, high compared with low scorers on Sociability and Impulsive-Sensation Seeking preferred depressants. Surprisingly, low compared with high scorers on neuroticism did not differ in preference for alcohol. As in the previous study, drug preference, use, and availability were highly correlated, although ease of availability was slightly more predictive of drug use than drug preference. Clinical and theoretical implications are discussed.

  11. 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…

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

    PubMed Central

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

    2015-01-01

    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

  13. 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.

  14. 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.

  15. Antimicrobial (Drug) Resistance Prevention

    MedlinePlus

    ... Visitor Information Contact Us Research > NIAID's Role in Research > Antimicrobial (Drug) Resistance > Understanding share with facebook share with twitter ... Prevention, Antimicrobial (Drug) Resistance Antimicrobial (Drug) Resistance Antimicrobial ... To prevent antimicrobial resistance, you and your healthcare ...

  16. Drug Plan Coverage Rules

    MedlinePlus

    ... Medication Therapy Management programs Drug plan coverage rules , current page Using your drug plan for the first time Filling a prescription without your new plan card Costs for Medicare drug coverage Joining a health or ...

  17. Drugs Approved for Melanoma

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  18. 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.

  19. 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 ...

  20. National Drug IQ Challenge

    MedlinePlus

    ... National Drug IQ Challenge 2016 National Drug & Alcohol IQ Challenge Print Get Started! Correct/Total Questions: Score: ... accessible version of the 2016 National Drug & Alcohol IQ Challenge , [PDF, 637KB]. Download an accessible version of ...

  1. Prescription Drug Abuse

    MedlinePlus

    ... Whether they're using street drugs or medications, drug abusers often have trouble at school, at home, with ... a short period of time may make a drug abuser aggressive or paranoid. Although stimulant abuse might not ...

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

    PubMed

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

    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

  3. 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

  4. Text mining for drug-drug interaction.

    PubMed

    Wu, Heng-Yi; Chiang, Chien-Wei; Li, Lang

    2014-01-01

    In order to understand the mechanisms of drug-drug interaction (DDI), the study of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) data are significant. In recent years, drug PK parameters, drug interaction parameters, and PG data have been unevenly collected in different databases and published extensively in literature. Also the lack of an appropriate PK ontology and a well-annotated PK corpus, which provide the background knowledge and the criteria of determining DDI, respectively, lead to the difficulty of developing DDI text mining tools for PK data collection from the literature and data integration from multiple databases.To conquer the issues, we constructed a comprehensive pharmacokinetics ontology. It includes all aspects of in vitro pharmacokinetics experiments, in vivo pharmacokinetics studies, as well as drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three-level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK corpus was demonstrated by a drug interaction extraction text mining analysis.The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions.

  5. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  6. 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

  7. 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)…

  8. Utah Drug Use Questionnaire.

    ERIC Educational Resources Information Center

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  9. 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…

  10. 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 ...

  11. Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment

    PubMed Central

    Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul

    2014-01-01

    Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We

  12. New drug update: 2010.

    PubMed

    Hussar, Daniel A

    2010-10-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  13. 2016 New Drug Update.

    PubMed

    Hussar, Daniel A

    2016-04-01

    Six new drugs marketed within the last year, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. The drugs include a hypnotic, an anticoagulant, two drugs for heart failure, and two drugs to reduce low-density lipoprotein cholesterol.

  14. New drug update: 2011.

    PubMed

    Hussar, Daniel A

    2012-04-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  15. Drug hypersensitivity syndrome.

    PubMed

    Bonnetblanc, J M

    1993-01-01

    Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program.

  16. New drug update: 2012.

    PubMed

    Hussar, Daniel A

    2013-04-01

    Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  17. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    PubMed

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  18. Drugs and drug resistance in African trypanosomiasis.

    PubMed

    Delespaux, Vincent; de Koning, Harry P

    2007-01-01

    Despite the many decades of use of most of the current trypanocides, we know little of their mode of action. This may in part be because most of these will act on multiple targets once inside the cell, and they derive their selective action on the parasite from selective accumulation by the pathogen. Loss of this capacity for drug uptake by the trypanosome would thus be a major cause for drug resistance. We here discuss the use of current drugs against human and veterinary African trypanosomiasis, the prevalence, causes and mechanisms of drug resistance and new developments in trypanosomiasis therapy such as the introduction of nifurtimox and DB289.

  19. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  20. 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).

  1. Endophytic Colletrotrichum spp. from Cinchona calisaya wedd. and it's potential quinine production as antibacterial and antimalaria

    NASA Astrophysics Data System (ADS)

    Radiastuti, Nani; Mutea, Dalli; Sumarlin, La Ode

    2017-02-01

    An endophytic fungus is microorganisms that live inside plant tissues without harming its host and is capable of producing the same secondary metabolites as its host plant. The endophytic fungus is very diverse and important group of microorganisms. The objectives of the study are to identify endophyte Colletotrichum spp. using ITS rDNA analyze, alkaloid cinchona and antibacterial characteristics. Phylogenetic analysis of ITS rDNA regions and morphology are used to identify the species. The Chloroform extracts of filtrate were analyzed using the High Pressure Liquid Chromatography (HPLC) to determine the production of quinine. There were 13 isolates of Colletotrichum spp as endophytes with associated with Cinchona calisaya Wedd. from fruit (6 isolates), leaf (5 isolates), twig (1 isolate) and root (1 isolate). This is the first report as endophytes are associated with C. calisaya. Based on ITS phylogenetic analysis are introduced of 7 strains Colletotrichum sp, 1 strain closely with C. aegnigma, 2 strains closely C. cordylinicola, 1 strains C arxii, 2 strains nested C. karstii. The Colletotrichum sp. M1 (leaf), M3 (bark), M8 (fruit) and C. karstii M5 (fruit) are potential alkaloid quinine. Five strains of Colletotrichum spp. have antibacterial activity are selected against Staphylococcus aureus and nine Colletotrichum spp. against Escherichia coli. The endophyte identification of Colletotrichum species needs another gene other than ITS rDNA.

  2. 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

  3. [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.

  4. Food-drug interactions.

    PubMed

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

    2011-03-01

    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.

  5. Understanding Drug Use and Addiction

    MedlinePlus

    ... Publications » DrugFacts » Understanding Drug Use and Addiction Understanding Drug Use and Addiction Email Facebook Twitter Revised August ... drug addiction and lead productive lives. What Is drug addiction? Addiction is a chronic disease characterized by ...

  6. [Bullous drug reactions].

    PubMed

    Hertl-Yazdi, M S; Hertl, M

    2005-01-01

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

  7. 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."

  8. Drugs in breast milk.

    PubMed

    1974-03-15

    Data on the pharmacology of drugs in breast milk are incomplete. The concentration in milk of drugs present in maternal blood depends on the lipid solubility of the drug and its degree of ionization. The immature renal and hepatic functions in the nursing infant can delay excretion of drugs. There has been no documented harm to nursing infants due to maternal use of oral contraceptives although long-term studies are unavailalbe. Breast feeding is contraindicated if the mother uses therapeutic doses of radioactive iodine, is a severe chronic alcoholic, or takes corticosteroids, phenobarbitone, and anticancer drugs. During lactation, drugs should be avoided as much as possible.

  9. The drug cocktail network

    PubMed Central

    2012-01-01

    Background Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations. Results In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (Drug Combination Predictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach. Conclusions The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations. PMID:23046711

  10. Drug use first aid

    MedlinePlus

    ... gait ( ataxia ) Sweating or extremely dry, hot skin Violent or aggressive behavior Death Drug withdrawal symptoms also ... own safety in danger. Some drugs can cause violent and unpredictable behavior. Call for medical help. Do ...

  11. 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.

  12. 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.

  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. Prescription Drug Abuse

    MedlinePlus

    ... from what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that was prescribed for someone else Taking a ... at higher doses or when taken with other medicines. NIH: National Institute on Drug Abuse

  15. Drugs: Shatter the Myths

    MedlinePlus

    ... Enter Search Term(s): National Drug and Alcohol Facts Week® Print NEW 2018 DATE! You Host an NDAFW ... could not have done National Drug & Alcohol Facts Week ® without you! 2,174 events were registered for ...

  16. Stereoselectivity in drug metabolism.

    PubMed

    Lu, Hong

    2007-04-01

    Many chiral drugs are used as their racemic mixtures in clinical practice. Two enantiomers of a chiral drug generally differ in pharmacodynamic and/or pharmacokinetic properties as a consequence of the stereoselective interaction with optically active biological macromolecules. Thus, a stereospecific assay to discriminate between enantiomers is required in order to relate plasma concentrations to pharmacological effect of a chiral drug. Stereoselective metabolism of drugs is most commonly the major contributing factor to stereoselectivity in pharmacokinetics. Metabolizing enzymes often display a preference for one enantiomer of a chiral drug over the other, resulting in enantioselectivity. The structural characteristics of enzymes dictate the enantiomeric discrimination associated with the metabolism of chiral drugs. The stereoselectivity can, therefore, be viewed as the physical property characteristic that phenotypes the enzyme. This review provides a comprehensive appraisal of stereochemical aspects of drug metabolism (i.e., enantioselective metabolism and first-pass effect, enzyme-selective inhibition or induction and drug interaction, species differences and polymorphic metabolism).

  17. Drug-induced mania.

    PubMed

    Peet, M; Peters, S

    1995-02-01

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

  18. 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 ...

  19. 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)

  20. Animal Drug Safety FAQs

    MedlinePlus

    ... Animal & Veterinary Safety & Health Frequently Asked Questions Animal Drug Safety Frequently Asked Questions Share Tweet Linkedin Pin ... issues? Additional Information I gave my dog a drug and he got sick. How do I report ...

  1. Street Drugs and Pregnancy

    MedlinePlus

    ... premature birth Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... Is it safe? > Street drugs and pregnancy Street drugs and pregnancy E-mail to a friend Please ...

  2. Drug Facts: Anabolic Steroids

    MedlinePlus

    ... can avoid unwanted side effects or maximize the drugs' effects by taking them in ways that include: cycling— ... despite physical problems, high costs to buy the drugs, and negative effects on their relationships. These behaviors reflect steroids' addictive ...

  3. Access to Investigational Drugs

    MedlinePlus

    ... access to investigational drugs being developed by pharmaceutical companies? Are there specific criteria used to determine whether ... laboratory. If the results are promising, the drug company or sponsor must apply for FDA approval to ...

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. Drug Education Guidelines.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing.

    In order to supply drug education guidelines for its schools, the Michigan State Board of Education created an advisory council of professionals from the fields of drugs and education, parents, and high school and college students. The council developed the present set of guidelines designed to define the role of the school in drug education and…

  9. 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,…

  10. Drugs and Learning.

    ERIC Educational Resources Information Center

    Werry, John S.

    1981-01-01

    Reviews literature pertinent to studying the effects of drugs upon children's learning and cognitive function. The author concludes such research is in its infancy. He recommends further research focus upon whether drugs enhance the acquisition of new academic skills and upon assessment of the benefits versus side effects of such drug use.…

  11. Drugs, Alcohol and HIV

    MedlinePlus

    ... and drugs can do to your overall health. Drugs and Alcohol: Effects on your immune system Drinking too much alcohol ... getting help and finding the treatment you need. Drugs and Alcohol: ... on short- and long-term effects of drinking, with specific information on people who ...

  12. 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…

  13. 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…

  14. 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

  15. Drug-induced nephropathies.

    PubMed

    Paueksakon, Paisit; Fogo, Agnes B

    2017-01-01

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

  16. The global drug gap.

    PubMed

    Reich, M R

    2000-03-17

    Global inequities in access to pharmaceutical products exist between rich and poor countries because of market and government failures as well as huge income differences. Multiple policies are required to address this global drug gap for three categories of pharmaceutical products: essential drugs, new drugs, and yet-to-be-developed drugs. Policies should combine "push" approaches of subsidies to support targeted drug development, "pull" approaches of financial incentives such as market guarantees, and "process" approaches aimed at improved institutional capacity. Constructive solutions are needed that can both protect the incentives for research and development and reduce the inequities of access.

  17. 2015 new drug update.

    PubMed

    Hussar, Daniel A

    2015-04-01

    Six new drugs approved within the last two years, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating system developed by the author. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. The drugs include two antidiabetic agents, one bronchodilator, one antidepressant, one for erectile dysfunction, and one for menopause-associated conditions.

  18. 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

  19. 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… ...

  20. Rational drug design.

    PubMed

    Mandal, Soma; Moudgil, Mee'nal; Mandal, Sanat K

    2009-12-25

    In this article, current knowledge of drug design is reviewed and an approach of rational drug design is presented. The process of drug development is challenging, expensive, and time consuming, although this process has been accelerated due to the development of computational tools and methodologies. The current target based drug design approach is incomplete because most of the drugs developed by structure guided approaches have been shown to have serious toxic side effects. Otherwise these drugs would have been an ideal choice for the treatment of diseases. Hence, rational drug design would require a multidisciplinary approach. In this regard, incorporation of gene expression technology and bioinformatics tools would be indispensable in the structure based drug design. Global gene expression data and analysis of such data using bioinformatics tools will have numerous benefits such as efficiency, cost effectiveness, time saving, and will provide strategies for combination therapy in addition to overcoming toxic side effects. As a result of incorporation of gene expression data, partial benefit of the structure based drug design is slowly emerging and rapidly changing the approach of the drug development process. To achieve the full benefit of developing a successful drug, multidisciplinary approaches (approaches such as computational chemistry and gene expression analysis, as discussed in this article) would be necessary. In the future, there is adequate room for the development of more sophisticated methodologies.

  1. Abuse of prescription drugs.

    PubMed Central

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

  2. Drug Retention Times

    SciTech Connect

    None, None

    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. Based on anecdotal evidence, most people “party” during extended time away from the work environment. Therefore, the following scenarios were envisioned: (1) a person uses an illicit drug at a party on Saturday night (infrequent user); (2) a person uses a drug one time on Friday night and once again on Saturday night (infrequent user); and (3) a person uses a drug on Friday night, uses a drug twice on Saturday night, and once again on Sunday (frequent user).

  3. Food and Drug Interactions.

    PubMed

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  4. Drug abuse and stroke.

    PubMed

    Fonseca, Ana Catarina; Ferro, José M

    2013-02-01

    Cerebrovascular disorders contribute to the morbidity and disability associated with illicit drug use. Drug abusers have an increased risk of both hemorrhagic and ischemic stroke. In geographic areas with a high prevalence of illicit drug use, drug abuse is a frequent cause of stroke in the young adult. The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis. Toxicology screening for illicit drugs should be done in young patients with stroke with no obvious cause, or if suggested by history or examination. Although in some patients the mechanism of stroke is identified using neuroimaging and other modern diagnostic tools, in a sizeable fraction of cases the mechanism of stroke remains unclear. Further studies are needed to elucidate the role of hemodynamic and immunologic mechanisms in these cases.

  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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. National Institute on Drug Abuse

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... HIV/AIDS research New resources available for criminal justice and drug treatment counselors Medication plus ongoing care ...

  18. Health Consequences of Drug Misuse

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... in education level, employment, housing, relationships, and criminal justice involvement. For more information on how various drugs ...

  19. Drugs + HIV, Learn the Link

    MedlinePlus Videos and Cool Tools

    ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction ...

  20. [Drug-drug interactions: interactions between xenobiotics].

    PubMed

    Haen, E

    2014-04-01

    Drug-drug interactions (DDI) are a major topic in programs for continuous medical education (CME). Many physicians are afraid of being trapped into charges of malpractice; however, DDI cannot be avoided in many cases. They belong to routine medical practice and it is often impossible to avoid them. Moreover, they do not just occur between drugs but between any kind of foreign substance (xenobiotica), such as food (e.g. grapefruit juice, broccoli, barbecue) as well as legal (e.g. tobacco smoke, caffeine and alcohol) and illegal drugs. Therefore, the medical challenge is not just to avoid any interaction. Instead the physician faces the question of how to proceed with drug treatment in the presence of such interactions. Based on the medical education a physician has to judge first of all whether there is a risk for interactions in the prescription being planned for an individual patient. The classification of interactions proposed in this article (PD1-PD4, PK1-PK3) might help as a sort of check list. For more detailed information the physician can then consult one of the many databases available on the internet, such as PSIAConline (http://www.psiac.de) and MediQ (http://www.mediq.ch). Pharmacokinetic interactions can be easily assessed, monitored and controlled by therapeutic drug monitoring (TDM). Besides these tools it is important to keep in mind that nobody knows everything; even physicians do not know everything. So take pride in asking someone who might help and for this purpose AGATE offers a drug information service AID (http://www.amuep-agate.de). Just good for nothing, without being based on any kind of medical approach are computer programs that judge prescriptions without taking into account a patient's individual peculiarities. In case these types of programs produce red exclamation marks or traffic lights to underline their judgment, they might even work in a contrapuntal way by just eliciting insecurity and fear.

  1. 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.

  2. Drug availability in Jamaica.

    PubMed

    Lee, M G; Henry, G L

    1989-06-01

    The availability of drugs and the supply system in Jamaica were examined. The Jamaica Commodity Trading Company imports all drugs through an international tendering system for the public health sector, and vital drugs for private distributors. For the 18-month period from January 1988, 652 awards were made, consisting of 426 (65%) brand and 226 (35%) generic drugs. There were several strengths and formulations for many drugs, including 19 preparations of 2 antibiotics. The University Hospital of the West Indies (UHWI) has been experiencing recurrent delays in the supply of several important drugs. In contrast, the private hospitals and pharmacies surveyed were adequately supplied. Many brands of several classes of drugs were available, including 51 antibiotics and 18 different anti-inflammatory analgesic and anti-hypertensive agents. However, several drugs used in special situations were only available at the UHWI. There is a need for the supply of drugs to be a priority in the public health sector and for the use of several drugs to be rationalized.

  3. Recreational drugs of abuse.

    PubMed

    Albertson, Timothy E

    2014-02-01

    The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

  4. Drug-induced hypokalaemia.

    PubMed

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

    2009-01-01

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

  5. 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.

  6. New Drugs for CML

    DTIC Science & Technology

    2007-02-01

    AD_________________ Award Number: W81XWH-06-1-0232 TITLE: New Drugs for CML PRINCIPAL...TYPE Final 3. DATES COVERED 1 Feb 2006– 31 Jan 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for CML 5b. GRANT NUMBER W81XWH...Deisseroth A. Use of combinatorial structural variation of top design new drugs for CML. Mol Cancer Ther, 6: 655-666, 2007. Novel compounds with

  7. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  8. 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

  9. [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.

  10. Drug-induced diarrhoea.

    PubMed

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

    2000-01-01

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

  11. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

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

  12. Sublingual drug delivery.

    PubMed

    Goswami, Tarun; Jasti, Bhaskara; Li, Xiaoling

    2008-01-01

    The sublingual route is one of the early modes of administration for systemic drug delivery. This route avoids first-pass metabolism and affords quick drug entry into the systemic circulation. Attempts have been made to deliver various pharmacologically active agents, such as cardiovascular drugs, analgesics, and peptides, across the sublingual mucosa. In this review, the anatomical structure, blood supply, biochemical composition, transport pathways, permeation enhancement strategies, in vitro/in vivo models, and clinical investigations for the sublingual route of drug delivery is discussed.

  13. Drug dangers and reactions.

    PubMed

    WEILERSTEIN, R W

    1961-01-01

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

  14. DRUG DANGERS AND REACTIONS

    PubMed Central

    Weilerstein, Ralph W.

    1961-01-01

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

  15. Street drugs: everyone's business.

    PubMed

    Su'a, F

    1989-11-01

    In the profession of law enforcement, we see drug abuse as our most serious crime problem. We also realize that simply making arrests, by itself, won't solve the problem. The drug business might be the filthiest business on earth, but it's not a business that forces customers to buy dope. Dope dealers may be ruthless and may even kill, but no one forces anyone to buy drugs at gunpoint. The truth is that drug dealers would go nowhere, were it not for the customers.

  16. Drug-induced exanthems.

    PubMed

    Yawalkar, Nikhil

    2005-04-15

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

  17. The relationship between rational drug design and drug side effects.

    PubMed

    Wang, Juan; Li, Zhi-xin; Qiu, Cheng-xiang; Wang, Dong; Cui, Qing-hua

    2012-05-01

    Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.

  18. Drug-nutrient interactions.

    PubMed

    Chan, Lingtak-Neander

    2013-07-01

    Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

  19. 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)

  20. 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.

  1. Asthma - control drugs

    MedlinePlus

    ... About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Asthma - control drugs URL of this page: //medlineplus.gov/ency/patientinstructions/000005.htm Asthma - control ...

  2. 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

  3. 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 ...

  4. Drug Education, A Misnomer

    ERIC Educational Resources Information Center

    Edwards, Gerald; Holloway, Janet

    1975-01-01

    Recognizing that behavior is a result of the integration of affective and cognitive factors, drug education must focus on the motivations of students. Article focused on the responsibility for development of drug abuse programs that must be shared by schools as well as students and teachers. (Author/RK)

  5. 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…

  6. Drugs in sport.

    PubMed

    McGrath, J C; Cowan, D A

    2008-06-01

    This themed issue of the British Journal of Pharmacology has been compiled and edited by Ian McGrath, Regius Professor of Physiology at University of Glasgow and David Cowan, Director of the Drug Control Centre at King's College London. It contains 11 articles covering the mechanisms of action of the major groups of drugs used illicitly in sport. The articles, written by experts in how drugs work, set out where drugs can or cannot affect sporting performance, how this relates to their legitimate medicinal use, their other detrimental effects and how they can be detected. Publication coincides with Olympic year, when sport is highlighted in the public mind and much speculation is made concerning the use of drugs. The articles provide a framework of expert, accurate knowledge to inform and facilitate these debates and to help to overcome the ill-informed and dangerous anecdotal information by which sports men and women are persuaded to misuse drugs in the mistaken belief that this will improve their performance without present or future ill effects. A unique article is included by the Spedding brothers, Mike with a long career in drug discovery and Charlie, the 1984 Los Angeles Olympic Marathon Bronze Medallist and still the English National Marathon record holder. From their unique experience, they describe the insidious and unfair way that drug-assisted performance undermines the ethos of sport and endangers the vital place of sport in maintaining the health of the population.

  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. 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.…

  9. Drug Education. PREP-36.

    ERIC Educational Resources Information Center

    Chow, Stanley; And Others

    What schools can do and are doing to prevent the abuse of drugs by their students is the focus of this report. The first section of the report "An Overview of Current Efforts" presents the findings of a one-year study of drug education in the United States, with a subjective analysis of the various approaches in the field. In the second…

  10. Linear drug eruption.

    PubMed

    Alfonso, R; Belinchon, I

    2001-01-01

    Linear eruptions are sometimes associated with systemic diseases and they may also be induced by various drugs. Paradoxically, such acquired inflammatory skin diseases tend to follow the system of Blaschko's lines. We describe a case of unilateral linear drug eruption caused by ibuprofen, which later became bilateral and generalized.

  11. Drug Education Program.

    ERIC Educational Resources Information Center

    Department of Defense, Washington, DC.

    Although designed specifically for schools on overseas military bases, this brief guide for the development of drug education programs for elementary and secondary school students can be used as an outline for any school-related drug education program. The materials in the handbook address the following areas of concern: (1) suggestions of topics…

  12. 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…

  13. 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…

  14. 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…

  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. Interoception and drug addiction.

    PubMed

    Paulus, Martin P; Stewart, Jennifer L

    2014-01-01

    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. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  17. 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.

  18. 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.

  19. Antipsychotic drugs and seizures.

    PubMed

    Remick, R A; Fine, S H

    1979-02-01

    The authors examine the clinical problem of which antipsychotic drug to use when antipsychotics are indicated in patients with a seizuire disorder or who are susceptible to seizures. While definitive answers to this problem are still unknown, guidelines are offered for antipsychotic drug use in this situation, based on the author's understanding of psychotropics and epilepsy.

  20. [Immunotherapies for drug addictions].

    PubMed

    Montoya, Ivan

    2008-01-01

    Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders.

  1. 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.

  2. Drug Impact Index.

    ERIC Educational Resources Information Center

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  3. 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

  4. Computational drug discovery

    PubMed Central

    Ou-Yang, Si-sheng; Lu, Jun-yan; Kong, Xiang-qian; Liang, Zhong-jie; Luo, Cheng; Jiang, Hualiang

    2012-01-01

    Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field. PMID:22922346

  5. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  6. 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

  7. Targeting drugs to mitochondria.

    PubMed

    Heller, Anne; Brockhoff, Gero; Goepferich, Achim

    2012-09-01

    Mitochondria are of an increasing interest in pharmaceutical and medical research since it has been reported that dysfunction of these organelles contributes to several diseases with a great diversity of clinical appearance. By the fact that mitochondria are located inside the cell and, in turn, origins of mitochondrial diseases or targets of drugs are located inside mitochondria, a drug molecule has to cross several barriers. This is a severe drawback for the selective accumulation of drug molecules in mitochondria. Therefore, targeting strategies such as direct drug modification or encapsulation into nanocarriers have to be applied to achieve an accumulation of drug molecules in these organelles. In this review, it will be demonstrated how properties and dysfunctions of mitochondria are generating a need for the development of mitochondria specific therapies. Furthermore, intracellular targets of mitochondrial diseases, strategies to utilize mitochondrial specificities and targeting approaches will be discussed. Finally, techniques to investigate mitochondrial characteristics and functionality are reviewed.

  8. Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine☆

    PubMed Central

    Nevin, Remington L.

    2014-01-01

    Mefloquine is a quinoline derivative antimalarial which demonstrates promise for the treatment of schistosomiasis. Traditionally employed in prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria, recent changes to the approved European and U.S. product labeling for mefloquine now warn of a risk of permanent and irreversible neurological sequelae including vertigo, loss of balance and symptoms of polyneuropathy. The newly described permanent nature of certain of these neurological effects challenges the conventional belief that they are due merely to the long half-life of mefloquine and its continued presence in the body, and raises new considerations for the rational use of the drug against parasitic disease. In this opinion, it is proposed that many of the reported lasting adverse neurological effects of mefloquine are consistent with the chronic sequelae of a well characterized but idiosyncratic central nervous system (CNS) toxicity syndrome (or toxidrome) common to certain historical antimalarial and antiparasitic quinolines and associated with a risk of permanent neuronal degeneration within specific CNS regions including the brainstem. Issues in the development and licensing of mefloquine are then considered in the context of historical awareness of the idiosyncratic CNS toxicity of related quinoline drugs. It is anticipated that the information presented in this opinion will aid in the future clinical recognition of the mefloquine toxidrome and its chronic sequelae, and in informing improved regulatory evaluation of mefloquine and related quinoline drugs as they are explored for expanded antiparasitic use and for other indications. PMID:25057461

  9. Ethics and drug resistance.

    PubMed

    Selgelid, Michael J

    2007-05-01

    This paper reviews the dynamics behind, and ethical issues associated with, the phenomenon of drug resistance. Drug resistance is an important ethical issue partly because of the severe consequences likely to result from the increase in drug resistant pathogens if more is not done to control them. Drug resistance is also an ethical issue because, rather than being a mere quirk of nature, the problem is largely a product of drug distribution. Drug resistance results from the over-consumption of antibiotics by the wealthy; and it, ironically, results from the under-consumption of antibiotics, usually by the poor or otherwise marginalized. In both kinds of cases the phenomenon of drug resistance illustrates why health (care)--at least in the context of infectious disease--should be treated as a (global) public good. The point is that drug resistance involves 'externalities' affecting third parties. When one patient develops a resistant strain of disease because of her over- or under-consumption of medication, this more dangerous malady poses increased risk to others. The propriety of free-market distribution of goods subject to externalities is famously dubious--given that the 'efficiency' rationale behind markets assumes an absence of externalities. Market failure in the context of drug resistance is partly revealed by the fact that no new classes of antibiotics have been developed since 1970. I conclude by arguing that the case of drug resistance reveals additional reasons--to those traditionally appealed to by bioethicists--for treating health care as something special when making policy decisions about its distribution.

  10. 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

  11. 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)

  12. 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.

  13. 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.

  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 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.

  16. 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.

  17. 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…

  18. 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.

  19. 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.

  20. Food and Drug Interactions

    PubMed Central

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions. PMID:28261555

  1. Herb-drug interactions.

    PubMed

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  2. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

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

  3. Nanomaterials for Drugs Delivery

    DOE PAGES

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction ofmore » the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to

  4. Nanomaterials for Drugs Delivery

    SciTech Connect

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction of the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to solve many

  5. Opioids and designer drugs.

    PubMed

    Ford, M; Hoffman, R S; Goldfrank, L R

    1990-08-01

    Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

  6. Vaccines against drug abuse.

    PubMed

    Shen, X Y; Orson, F M; Kosten, T R

    2012-01-01

    The currently available medications for the treatment of drug abuse have had only limited success. Anti-addiction vaccines, aimed at eliciting antibodies that block the pharmacological effects of drugs, have great potential for treating drug abuse. We review the status of two vaccines that are undergoing clinical trials (for cocaine and nicotine addiction) and two that are still in preclinical development (for methamphetamine and heroin addiction). We also outline the challenges and ethical concerns associated with the development of anti-addiction vaccines and their use as future therapeutics.

  7. Drug-induced gynecomastia.

    PubMed

    Eckman, Ari; Dobs, Adrian

    2008-11-01

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

  8. Neonatal drug withdrawal.

    PubMed

    Hudak, Mark L; Tan, Rosemarie C

    2012-02-01

    Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

  9. A modified Plasmodium falciparum growth inhibition assay (GIA) to assess activity of plasma from malaria endemic areas.

    PubMed

    Mlambo, Godfree; Kumar, Nirbhay

    2007-02-01

    Plasma samples from patients undergoing treatment in malaria endemic countries often contain anti-malaria drugs, that may overstate effects of specific antibodies in growth inhibition assays (GIA). We describe a modified assay that uses drug resistant P. falciparum parasites (W2) that circumvents the requirement for dialyzing samples that may likely contain drugs such as chloroquine and sulfadoxine/pyrimethamine (SP).

  10. 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) ...

  11. Prescription Drugs and Cold Medicines

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... and over-the-counter (OTC) drugs are, after marijuana (and alcohol), the most commonly abused substances by ...

  12. 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 ...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Drugs Approved for Thyroid Cancer

    MedlinePlus

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

  18. List of Confused Drug Names

    MedlinePlus

    ... vaccine Inspra Intuniv INV anz Invega iodine Isordil ISO tretinoin Jantoven Jantoven Janumet Janumet Janumet Januvia Januvia ... Drug Names Drug Name Confused Drug Name tretinoin ISO tretinoin Tricor Tracleer tromethamine Trophamine Trophamine tromethamine tuberculin ...

  19. Commonly Abused Drugs Charts

    MedlinePlus

    ... with long, slender stems topped by caps with dark gills Swallowed (eaten, brewed as tea, or added ... NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home Site Map Accessibility Privacy ...

  20. DrugFacts: Heroin

    MedlinePlus

    ... Badge NIDA TV Spotlight: Heroin in the Twin Cities YouTube embedded video: http://www.youtube-nocookie.com/ ... a highlight on heroin use in the Twin Cities from her June 2013 Report on "Drug Abuse ...

  1. Drug-induced tremor

    MedlinePlus

    ... valproate (Depakene) Asthma medicines such as theophylline and albuterol Immune suppressing medicines such as cyclosporine and tacrolimus Mood stabilizers such as lithium carbonate Stimulants such as caffeine and amphetamines Antidepressant drugs such as selective serotonin reuptake inhibitors ( ...

  2. Cholesterol - drug treatment

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  3. Drug Education for Administrators

    ERIC Educational Resources Information Center

    Hackett, Peter; McKeon, Thomas L.

    1976-01-01

    The formulation of a drug policy and the implementation of that policy in a firm but fair manner are the responsibility of the school administrator. Authors give serious consideration to this responsibility. (Editor/RK)

  4. Food and Drug Administration

    MedlinePlus

    ... blog post. April 11, 2017 ‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science More FDA Voice Blog ... FEAR Act Site Map Nondiscrimination Website Policies U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver ...

  5. 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

  6. Oral Diabetes Drugs

    MedlinePlus

    ... nausea, and swelling in the legs and ankles (edema). Older drugs have been around longer, so the ... to 10 pounds •Risk of fluid build-up (edema) and low blood iron (anemia) •Rise in bad ( ...

  7. Drugs: Shatter the Myths

    MedlinePlus

    ... July 2013, March 2015 Table of Contents 4 Marijuana 8 Peer Pressure 12 Alcohol 14 Medical Consequences ... 22 Drugs & Your Brain 26 Treatment 3 TOPIC Marijuana Is marijuana Yes. The chances of becoming addicted ...

  8. Food and Drug Administration

    MedlinePlus

    ... Reportable Food Registry Report an Emergency Report Suspected Criminal Activity For Industry: Drugs and Therapeutic Biologics News & ... FDA Organization FDA Basics Advisory Committees International Programs Criminal Investigations Emergency Preparedness & Response Working at FDA Training/ ...

  9. Combatting Drugs at Work.

    ERIC Educational Resources Information Center

    Schreier, James W.

    1988-01-01

    Discusses research that looked at the actions, policies, and responses of organizations concerning training issues and substance abuse. Found that without training, an organization cannot successfully wage the war against alcohol and drug abuse at work. (JOW)

  10. Drug-induced catatonia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-09-01

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

  11. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... NIAID invests in basic research to understand the biology of microbes, their behavior, and how drug resistance ... Nucleotide Polymorphism Phylogenetics & Ontology Proteomics & Protein Analysis Systems Biology Data Portals Software Applications BCBB Mobyle Interface Designer ( ...

  12. 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

  13. [Drug facilitated sexual assault].

    PubMed

    Alempijević, Djordje; Savić, Slobodan; Stojanović, Jovan; Spasić, Andjelka

    2007-01-01

    In line with the fact that there is little information regarding drug facilitated sexual assault in national medical literature, the authors aimed to prepare a review of the phenomenon based on available international references. Therefore we offered a definition of the concept of sexual assault, and rape in particular. Consent and ability for valid consent for sexual intercourse were defined as well. A review contains discussion about the basic elements of a concept of drug-facilitated sexual assault. There is also available information in regard to pharmacology of common data rape drugs, i.e. flunitrazepam, gamma-hydroxybutyrate (GHB), and ketamine. We indicate the utmost importance of prompt collecting of biological samples for toxicological screening in patients who are suspected victims of drug facilitated sexual assault.

  14. Metrology for drug delivery.

    PubMed

    Lucas, Peter; Klein, Stephan

    2015-08-01

    In various recently published studies, it is argued that there are underestimated risks with infusion technology, i.e., adverse incidents believed to be caused by inadequate administration of the drugs. This is particularly the case for applications involving very low-flow rates, i.e., <1 ml/h and applications involving drug delivery by means of multiple pumps. The risks in infusing are caused by a lack of awareness, incompletely understood properties of the complete drug delivery system and a lack of a proper metrological infrastructure for low-flow rates. Technical challenges such as these were the reason a European research project "Metrology for Drug Delivery" was started in 2011. In this special issue of Biomedical Engineering, the results of that project are discussed.

  15. [Lifestyle drugs in medicine].

    PubMed

    Harth, Wolfgang; Seikowski, Kurt; Hermes, Barbara; Gieler, Uwe

    2008-01-01

    Lifestyle drugs have become an important new group of medications, which are taken by healthy people to increase the individual well-being and quality of life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the main groups. The wish for eternal youth, beauty and potency is central, and lifestyle medications are also requested to influence cosmetic findings, which are usually simply a result of the natural aging process. Lifestyle drugs seem to be harmless, but the physician must pay attention to possible abuse, side effects, risks and complications. Additionally, however, lifestyle drugs are also frequently used by patients suffering from emotional disorders such as somatoform disorders. Medicalization of physiological life is then expected to solve psychosocial problems, but without success. The use of lifestyle medications in somatoform disorders is contraindicated and psychotherapy or psychopharmacological treatment come first. With this overview article, we would like to make an update of new lifestyle drugs.

  16. Prescription Drug Assistance Programs

    MedlinePlus

    ... Treatment & Support Finding and Paying for Treatment Understanding Health Insurance If You Have Trouble Paying a Bill Prescription ... income and no drug coverage If you have health insurance If your income is low: Look into Medicaid ...

  17. [Designer drug induced psychosis].

    PubMed

    Fullajtar, Mate; Ferencz, Csaba

    2012-06-01

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

  18. 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 ...

  19. Drug Dosing Toolkit

    MedlinePlus

    ... Diet and Nutrition Discrimination Drugs and Alcohol Exercise Mental Health Sex and Sexuality Smoking FAQs Tips and Tools Community For Health Care Providers Provider Home Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses ( ...

  20. Chicanoizing Drug Abuse Programs

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focus is on the community of La Colonia in Oxnard, California because it has (1) a high concentration of Mexican Americans, (2) a high incidence of drug addiction, and (3) reliable statistical data available. (NQ)

  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. 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.

  3. Thromobocytopenia - drug-induced

    MedlinePlus

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

  4. 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 ...

  5. Vitiligo, drug induced (image)

    MedlinePlus

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

  6. 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.

  7. 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)

  8. Therapeutic drug levels

    MedlinePlus

    ... Principles of drug therapy. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ... Ford MD. Acute poisoning. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  9. [Occurrence of drug reactions].

    PubMed

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

    1986-01-01

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

  10. 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

  11. 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.

  12. Safety of antiobesity drugs

    PubMed Central

    Cheung, Tommy Tsang; Samaranayake, Nithushi Rajitha

    2013-01-01

    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. Emerging drugs of abuse.

    PubMed

    Nelson, Michael E; Bryant, Sean M; Aks, Steven E

    2014-02-01

    Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse.

  14. Drug treatment of haemorrhoids.

    PubMed

    Misra, Mahesh C; Imlitemsu

    2005-01-01

    Drug treatment for various anorectal conditions has been known since ancient times. Today, modern as well as traditional drugs are being increasingly used in all grades of symptomatic haemorrhoids. These drugs (oral and local) are used as a part of conservative management or as an adjuvant to invasive outpatient procedures. Flavonoids, in the new formulation of micronised purified flavonoid fraction (MPFF) or as part of the ancient traditional medicine derivative of the Ginkgo tree, are used for relief of acute symptoms (for control of bleeding and re-bleeding in all grades of haemorrhoids). MPFF has been recommended for control of acute bleeding in patients waiting for a definitive outpatient treatment. Similarly, better known drugs such as calcium dobisilate (used in diabetic retinopathy and chronic venous insufficiency), nitrates and nifedipine have also been effective and well tolerated in the medical treatment of haemorrhoids. However, drug treatment is not aimed at curing haemorrhoids. The prime objective of drug therapy is to control the acute phase (bleeding) so that definitive therapy (banding, injection sclerotherapy, infrared photocoagulation, cryotherapy or surgery) can be scheduled at a convenient time.

  15. [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).

  16. 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.

  17. Clinical nutrition and drug interactions

    PubMed Central

    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

  18. Drugs affecting the eye.

    PubMed

    Taylor, F

    1985-08-01

    This discussion reviews drugs that affect the eye, including antihyperglycemic agents; corticosteroids; antirheumatic drugs (quinolines, indomethacin, and allopurinol); psychiatric drugs (phenothiazine, thioridazine, and chlorpromazine); drugs used in cardiology (practolol, amiodarone, and digitalis gylcosides); drugs implicated in optic neuritis and atrophy, drugs with an anticholinergic action; oral contraceptives (OCs); and topical drugs and systemic effects. Refractive changes, either myopic or hypermetropic, can occur as a result of hyperglycemia, and variation in vision is sometimes a presenting symptom in diabetes mellitus. If it causes a change in the refraction, treatment of hyperglycemia almost always produces a temporary hypermetropia. A return to the original refractive state often takes weeks, sometimes months. There is some evidence that patients adequately treated with insulin improve more rapidly than those taking oral medication. Such patients always should be referred for opthalmological evaluation as other factors might be responsible, but it might not be possible to order the appropriate spectacle correction for some time. The most important ocular side effect of the systemic adiministration of corticosteroids is the formation of a posterior subcapsular cataract. Glaucoma also can result from corticosteroids, most often when they are applied topically. Corticosteroids have been implicated in the production of benign intracranial hypertension, which is paradoxical because they also are used in its treatment. The most important side effect of drugs such as chloroquine and hydroxychloroquine is an almost always irreversible maculopathy with resultant loss of central vision. Corneal and retinal changes similar to those caused by the quinolines have been reported with indomethacin, but there is some question about a cause and effect relationship. The National Registry of Drug Induced Ocular Side Effects in the US published 30 case histories of

  19. Sleep and hypnotic drugs.

    PubMed

    Johns, M W

    1975-01-01

    In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past.

  20. Systems pharmacology to predict drug safety in drug development.

    PubMed

    Trame, Mirjam N; Biliouris, Konstantinos; Lesko, Lawrence J; Mettetal, Jerome T

    2016-10-30

    Ensuring that drugs are safe and effective is a very high priority for drug development and the US Food and Drug Administration review process. This is especially true today because of faster approval times and smaller clinical trials, especially in oncology and rare diseases. In light of these trends, systems pharmacology is seen as an essential strategy to understand and predict adverse drug events during drug development by analyzing interactions between drugs and multiple targets rather than the traditional "one-drug-one-target" approach. This commentary offers an overview of the current trends and challenges of using systems pharmacology to reduce the risks of unintended adverse events.

  1. New Drugs and Drug Resistance in Malaria: Molecular Genetic Analysis.

    DTIC Science & Technology

    1996-06-26

    heterologous expressions system in yeast for potential drug target enzymes. The yeast expression system should allow rapid screening of new drugs , greatly...medication yet the world faces a crisis-drug resistance is emerging and spreading faster than drugs are being developed and the flow in the pipeline of new ... drugs has all but stopped. This represents a particular threat to the US Military. In a short time there may be parts of the world where no effective

  2. New Drugs and Drug Resistance in Malaria: Molecular Genetic Analysis.

    DTIC Science & Technology

    1995-06-20

    heterologous expressions system in yeast for potential drug target enzymes. The yeast expression system should allow rapid screening of new drugs , greatly...medication yet the world faces a crisis-drug resistance is emerging and spreading faster than drugs are being developed and the flow in the pipeline of new ... drugs has all but stopped. This represents a particular threat to the US Military. In a short time there may be parts of the world where no effective

  3. 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

  4. Molecular Characterization of Mefloquine Resistance in Plasmodium Falciparum

    DTIC Science & Technology

    1990-03-22

    prophylaxis of multidrug-resistant malaria and has recently received FDA approval for use in the U.S. In nature, it is clear from previous studies...calmodazolium and chlorpromazine ref. 9). Each of these agents was able to restore the Imefloquine sensitivity to the resistant clone MEF-2.4 but less so to

  5. Building Nanostructures with Drugs

    PubMed Central

    Ma, Wang; Cheetham, Andrew G.

    2016-01-01

    The convergence of nanoscience and drug delivery has prompted the formation of the field of nanomedicine, one that exploits the novel physicochemical and biological properties of nanostructures for improved medical treatments and reduced side effects. Until recently, this nanostructure-mediated strategy considered the drug to be solely a biologically active compound to be delivered, and its potential as a molecular building unit remained largely unexplored. A growing trend within nanomedicine has been the use of drug molecules to build well-defined nanostructures of various sizes and shapes. This strategy allows for the creation of self-delivering supramolecular nanomedicines containing a high and fixed drug content. Through rational design of the number and type of the drug incorporated, the resulting nanostructures can be tailored to assume various morphologies (e.g. nanospheres, rods, nanofibers, or nanotubes) for a particular mode of administration such as systemic, topical, and local delivery. This review covers the recent advances in this rapidly developing field, with the aim of providing an in-depth evaluation of the exciting opportunities that this new field could create to improve the current clinical practice of nanomedicine. PMID:27066106

  6. 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.

  7. 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.

  8. 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.

  9. Generic Drugs: Questions and Answers

    MedlinePlus

    ... approve it. Creating a drug costs lots of money. Since generic drug makers do not develop a drug from scratch, ... versions. The ANDA process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms already approved for ...

  10. Principles for School Drug Education

    ERIC Educational Resources Information Center

    Meyer, Lois

    2004-01-01

    This document presents a revised set of principles for school drug education. The principles for drug education in schools comprise an evolving framework that has proved useful over a number of decades in guiding the development of effective drug education. The first edition of "Principles for Drug Education in Schools" (Ballard et al.…

  11. Drugs and the Handicapped Child.

    ERIC Educational Resources Information Center

    Weiner, Ken, Ed.

    Reported are proceedings of a conference on drugs and the handicapped child. Provided is the transcript of discussions which centered on the use of legal (prescribed for medical and educational reasons) as well as illegal drugs. Considered are the following major topics: an overview of drug problems in the United States and of drug education in…

  12. 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…

  13. 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…

  14. 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)

  15. Antimicrobial drug resistance.

    PubMed

    Martinez, Marilyn; Silley, Peter

    2010-01-01

    This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed.

  16. Drug allergy in mastocytosis.

    PubMed

    Bonadonna, Patrizia; Lombardo, Carla

    2014-05-01

    Drugs are known triggers of anaphylaxis in patients with mastocytosis even to the association between drug anaphylaxis and mastocytosis does not appear frequently appear. Nevertheless, mast cell disorders might be ruled out in cases of severe systemic reactions. Careful examination of the skin should accompany measurement of basal serum tryptase levels. The data published about drug anaphylaxis in patients with mast cell disorders are scarce, and it is not currently possible to provide clear recommendations. Most papers report cases of anaphylaxis during surgical procedures or radiocontrast media exposure. There are no specific recommendations to prevent severe reactions during such procedures, although some specialists suggest performing premedication with antihistamines and corticosteroids before anesthesia or radiocontrast media administration.

  17. [Chirality and drugs].

    PubMed

    Testa, B; Reist, M; Carrupt, P A

    2000-07-01

    The two enantiomers of a chiral drug may have vastly different pharmacodynamic and pharmacokinetic properties. As a result, the research and development of chiral drugs raises specific problems some of which are discussed here. Thus, various pharmacokinetic interactions may involve two enantiomers, as seen for example when one enantiomer inhibits the metabolism of the other and modifies its effects. A different situation occurs when a third compound stereoselectively inhibits the metabolism of one of the two enantiomers. Another problem examined here results from the lack of configurational stability of some chiral drugs, a little known phenomenon whose consequences can be of pharmacological or pharmaceutical significance depending on the rate of the reaction of racemization or epimerisation. In-depth investigations are needed before choosing between a eutomer or a racemate.

  18. Genomics and drug discovery.

    PubMed

    Haseltine, W A

    2001-09-01

    Genomics, the systematic study of all the genes of an organism, offers a new and much-needed source of systematic productivity for the pharmaceutical industry. The isolation of the majority of human genes in their most useful form is leading to the creation of new drugs based on human proteins, antibodies, peptides, and genes. Human Genome Sciences, Inc, was the first company to use the systematic, genomics approach to discovering drugs, and we have placed 4 of these in clinical trials. Two are described: repifermin (keratinocyte growth factor-2, KGF-2) for wound healing and treatment of mucositis caused by cancer therapy, and B lymphocyte stimulator (BLyS) for stimulation of the immune system. An anti-BLyS antibody drug is in advanced preclinical development for treatment of autoimmune diseases.

  19. 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.

  20. 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.

  1. 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

  2. Chronicles in drug discovery.

    PubMed

    Khurdayan, V; Bozzo, J; Sorbera, L

    2005-06-01

    Chronicles in Drug Discovery is a series of brief reports on timely topics in the field of drug R&D. This month's chronicles contain the following reports: Targeting DNA repair enzymes instead of viral proteins provides a great advantage in preventing the emergence of resistant mutants. A striking increase in therapeutic approaches for the treatment of IBD has been fueled by an improved understanding of the mechanisms that underlie its pathophysiology. Peptide deformylase inhibitors are under active investigation for bacterial infections and cancer treatment. Dopamine D3 receptors present an attractive target for alcoholism therapy since they are involved in the mechanisms of alcohol dependency and abuse.

  3. Drug therapy in headache.

    PubMed

    Weatherall, Mark W

    2015-06-01

    All physicians will encounter patients with headaches. Primary headache disorders are common, and often disabling. This paper reviews the principles of drug therapy in headache in adults, focusing on the three commonest disorders presenting in both primary and secondary care: tension-type headache, migraine and cluster headache. The clinical evidence on the basis of which choices can be made between the currently available drug therapies for acute and preventive treatment of these disorders is presented, and information given on the options available for the emergency parenteral treatment of refractory migraine attacks and cluster headache.

  4. 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.

  5. Ingestion of drugs by "parachuting": a unique drug delivery technique.

    PubMed

    Kenerson, Katherine L; Lear-Kaul, Kelly C

    2012-06-01

    "Parachuting" is a technique of drug delivery where medications or illicit drugs are ingested by wrapping the drug of choice in a covering, which then will dissolve or unravel in the gastrointestinal tract, thereby releasing the drug for absorption. Parachuting of drugs can entail crushing of a pill prior to packaging to theoretically increase the surface area for absorption or may involve the packaging of a higher than usual dose of a drug in attempts to attain a sustained-release effect as the "parachute" dissolves or unravels. A case is presented in which a prescription drug abuser known to parachute his medications dies from obstruction of his airway by the inhaled packet. Risks of parachuting any drug would include overdose and fatal toxic effect from the drug itself and adverse effects from the packaging including bowel obstruction or perforation, or airway obstruction.

  6. 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

  7. Real Research in Drug Education. Real Research in Drug Education; Drug Information: The Irrelevant Variable.

    ERIC Educational Resources Information Center

    Swisher, John D.; Hoffman, Alan M.

    These 2 articles argue that the presentation of drug information in drug education has no relevance. Hoffman reviews the various approaches to drug education, most of which are based upon the idea that giving people information will act as a deterrent to their use of drugs. A scale was administered to a large and varied population of students to…

  8. Clinically relevant drug interactions with anti-Alzheimer's drugs.

    PubMed

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo

    2017-03-03

    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. In conclusion, the concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice.

  9. Drug and Substance Abuse

    MedlinePlus

    ... Adults Making Your Wishes Known Home & Community Home › Aging & Health A to Z › Drug and Substance Abuse Font size A A A Print Share Glossary Basic Facts & Information Causes & Symptoms Diagnosis & Tests Care & Treatment Lifestyle & Management Other Resources Caregiving How ...

  10. 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…

  11. Handbook On Drug Abuse.

    ERIC Educational Resources Information Center

    Dupont, Robert I.; And Others

    A decade of professional research on drug abuse has produced both an abundance of materials and a vocabulary that is not shared by planners, clinicians, and policy makers. This handbook compiles the major developments of the period and their treatment and research implications in a style intended to be understood by all three types of…

  12. Drugs and the retina.

    PubMed

    Constable, Simon; Pirmohamed, Munir

    2004-05-01

    The retina is relatively protected from systemic drug administration because of the blood-retinal barrier, a highly selective mechanism adapted to providing a regulated homeostatic environment for this highly specialised tissue. However, a number of drugs have been associated with retinal toxicity. Vigabatrin, as an adjunctive therapy for the management of partial epilepsy, is associated with visual field defects in approximately 40% of patients. Hydroxychloroquine, used in the treatment of rheumatoid arthritis and systemic lupus erythematosus, is also associated with a retinopathy. In view of this, ophthalmological screening and monitoring is recommended during prescription of both of these drugs. In these cases, the retina is the site for an adverse drug reaction and the dose of therapy may be important in determining the likelihood of retinal toxicity. However, in the case of cytomegalovirus retinitis, the retina is the intended site for pharmacological action. The treatment of this condition with the antiviral agents ganciclovir, valganciclovir, foscarnet and cidofovir, can also be associated with significant systemic toxicity.

  13. Drug Development Process

    MedlinePlus

    ... approve it. More Information Step 5 FDA Post-Market Safety Monitoring FDA Post-Market Safety Monitoring FDA monitors all drug and device ... Step 4: FDA Review Step 5: FDA Post-Market Safety Monitoring Page Last Updated: 06/24/2015 ...

  14. 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

  15. 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…

  16. To Market a Drug.

    ERIC Educational Resources Information Center

    Hay, J. E.; And Others

    This unit is one of a group of units written to fit the Certificate of Sixth Year Studies (CSYS) chemistry course, but it could be used in most Sixth Form courses. It includes: (1) teacher notes on contents, methods, and preparation; (2) two sets of data booklets and decision sheets for two new drugs (one data booklet based on 1960 information and…

  17. Drug-induced uveitis

    PubMed Central

    2013-01-01

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

  18. 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)

  19. Women, drugs and HIV

    PubMed Central

    Azim, Tasnim; Bontell, Irene; Strathdee, Steffanie A.

    2014-01-01

    Women who inject drugs are among the most vulnerable to HIV through both unsafe injections and unprotected sex. They are also among the most hidden affected populations, as they are more stigmatized than their male counterparts. Many sell sex to finance their own and their partner’s drug habit and often their partner exerts a significant amount of control over their sex work, condom use and injection practices. Women who use drugs all over the world face many different barriers to HIV service access including police harassment, judgmental health personnel and a fear of losing their children. In order to enable these women to access life-saving services including needle-syringe and condom programs, opioid substitution therapy and HIV testing and treatment, it is essential to create a conducive environment and provide tailor-made services that are adapted to their specific needs. In this commentary, we explore the risks and vulnerabilities of women who use drugs as well as the interventions that have been shown to reduce their susceptibility to HIV infection. PMID:25277726

  20. Drug development and manufacturing

    DOEpatents

    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.

  1. 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…

  2. Drugs and Air Operations

    DTIC Science & Technology

    2001-06-01

    schedules. Sleep 1998;21:79-90. 21. Bishop C, Roehrs T, Rosenthal L, Roth T. Alerting effects of methylphenidate under basal 12. Newhouse PA, Penetar DM...drug effects on performance and behaviour after prolonged sleep deprivation: A 22. Roehrs T, Papineau K, Rosenthal L, Roth T. comparison of amphetamine

  3. 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…

  4. 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…

  5. Chronicles in drug discovery.

    PubMed

    Khurdayan, V K; Bozzo, J; Prous, J R

    2005-10-01

    New brief reports this month include: Strategies for Duchenne Muscular Dystrophy: Various approaches are being explored to abate the dystrophic process including cellular therapies (transplanting stem cells or myogenic precursors into muscles), molecular approaches (delivering a functional or correcting the mutant dystrophin gene), such as MyoDys, Biostrophin(R) and antisense technology, and pharmacotherapeutics, which include calcium channel blockers, calpain inhibitors, phosphodiesterase inhibitors and monoclonal antibodies; Immunotherapy for Multiple Myeloma: Increasing numbers of antibodies and immunoconjugates with anticancer drugs are entering clinical development; Acute respiratory distress syndrome is among the most frequent reasons for intensive care. Current medications include antibiotics, diuretics, drugs to counteract low blood pressure caused by shock, anxiolytics and antiinflammatories, while there are eight potential drugs in active development; Pulmonary Hypertension: Drugs intervening at four signaling pathways (endothelin, prostacyclin, nitric oxide and platelet-derived growth factor), which are implicated in pulmonary hypertension, include readily available bosentan, sildenafil citrate and sitaxsentan sodium and investigational aviptadil and TBC-3711, among others.

  6. 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…

  7. Beyond Drug Education

    ERIC Educational Resources Information Center

    Robinson, Paul E.

    1975-01-01

    Rather than teach people about drugs, this author maintains that we should stress education of the self. Our goal should be to help people to think intelligently and rationally, to control their destructive impulses, to make wise decisions, to resist peer pressure and to understand their values, needs and desires. (Author)

  8. 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.

  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. International Drug Control Policy

    DTIC Science & Technology

    2009-02-09

    Certification Process ..................................................................... 7 Methamphetamine Precursor Chemicals...LSD,3 amphetamine, and methamphetamine . Examples of other related substances include precursor chemicals used to make narcotic drugs and psychotropic...substances—such as ephedrine and pseudoephedrine—which are used to make methamphetamine , and potassium permanganate, which is used to make cocaine

  11. International Drug Control Policy

    DTIC Science & Technology

    2008-06-23

    Certification Process . . . . . . . . . . . . . . . . . . . . 7 Methamphetamine Precursor Chemicals . . . . . . . . . . . . . . . . . . . . . . . . 8 Crop...Psychotropic substances include ecstasy,1 LSD,2 amphetamine, and methamphetamine . Examples of other related substances include precursor chemicals used to...make narcotic drugs and psychotropic substances — such as ephedrine and pseudoephedrine — which are used to make methamphetamine , and potassium

  12. International Drug Control Policy

    DTIC Science & Technology

    2009-08-24

    9 Methamphetamine Precursor Chemicals........................................................................ 11 Other Drug-Related...cannabis resin, coca leaf, cocaine, heroin, and opium. Psychotropic substances include ecstasy,2 LSD,3 amphetamine, and methamphetamine . Examples of other...are used to make methamphetamine , and potassium permanganate, which is used to make cocaine. With few exceptions, production and sale of controlled

  13. 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.

  14. Drugs and related topics.

    PubMed

    Cereijo, Ines

    2006-01-01

    Drugs is a topic that was certainly an issue of discussion at this year's annual meeting. This Committee had the responsibility of organizing a half day symposium on "Pharmaceutical Authenticity and Safety" that took place September 12, 2005. This symposium aims at improving the critical points in the analytical pharmaceutical field related to traceability assessment, use of certified reference materials (CRMs), and proficiency testing implementation to get the highest quality of the obtained results. Recognized experts presented these topics. Also, other complementary subjects, such as the application of advanced analytical technologies to reach the authenticity and safety of the pharmaceutical drugs and drug products, their microbiological quality assessment, without disregarding an important topic such as sampling, was presented and discussed. The talks that were presented are the following: "Proficiency Testing as a Need in the Pharmaceutical Field," Arlene Fox (AOAC INTERNATIONAL, Gaithersburg, MD); "Implementation of Traceability in the Pharmaceutical Laboratory," Thomas Layloff, (Management Sciences for Health, Arlington, VA); "Harmonized Characteristics of Certified Reference Materials According to ISO Guides-Attractive also for Pharmaceutical Analysis," Hendrik Emons (Reference Materials, Unit Institute for Reference Materials and Measurements (IRMM), Joint Research Centre European Commission, (Geel, Belgium); "Importance of LC/MS/MS for the Fingerprinting of Pharmaceutical Drugs," Paul A. Steinberg, (Thermo Electron Corp., Woodstock, GA); "Process Analytical Technology (PAT) as a Way for Better Manufacturing and Quality Assurance," John F. Kauffman (Division of Pharmaceutical Analysis, U.S. Food and Drug Administration (St. Louis, MO); "Stability Testing for the Safety Assessment of Pharmaceuticals," Marta Vidal (Boeringher Ingelheim Argentina, Buenos Aires, Argentina); "Validation of Microbiological Methods for Sterile and Nonsterile Pharmaceutical

  15. Drug-drug, drug-dietary supplement, and drug-citrus fruit and other food interactions: what have we learned?

    PubMed

    Huang, Shiew-Mei; Lesko, Lawrence J

    2004-06-01

    Serious drug-drug interactions have contributed to recent U.S. market withdrawals and also recent nonapprovals of a few new molecular entities. Many of these interactions involved the inhibition or induction of metabolizing enzymes and efflux transporters, resulting in altered systemic exposure and adverse drug reactions or loss of efficacy. In addition to drug-drug interactions, drug-dietary supplement and drug-citrus fruit interactions, among others, could also cause adverse drug reactions or loss of efficacy and are important issues to consider in the evaluation of new drug candidates. This commentary reviews (1). the current understanding of the mechanistic basis of these interactions, (2). issues to consider in the interpretation of study results, and (3). recent labeling examples to illustrate the translation of study results to information useful for patients and health care providers.

  16. Epigenetic Drugs for Multiple Sclerosis.

    PubMed

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

  17. 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.

  18. Drug Rechallenge Following Drug-Induced Liver Injury.

    PubMed

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

    2017-03-13

    Drug induced hepatocellular injury is identified internationally by ALT 5x upper limits normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decreases by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT 3-5xULN or greater. Nearly 50 drugs are associated with positive rechallenge after drug-induced liver injury (DILI): antimicrobials, central nervous system, cardiovascular and oncology therapeutics. Drugs associated with high rates of positive rechallenge exhibit multiple risk factors: daily dose >50 mg, an increased incidence of ALT elevations in clinical trials, immunoallergic clinical injury, and mitochondrial impairment in vitro. These drug factors interact with personal genetic, immune, and metabolic factors to influence positive rechallenge rates and outcomes. Drug rechallenge following drug-induced liver injury is associated with up to 13% mortality in prospective series of all prescribed drugs. In recent oncology trials, standardized systems enable safer drug rechallenge with weekly liver chemistry monitoring during the high risk period and exclusion of patients with hypersensitivity. Yet, high positive rechallenge rates with other innovative therapeutics suggest caution with rechallenge of high risk drugs.

  19. Fixed drug eruption to sitagliptin.

    PubMed

    Gupta, Mrinal; Gupta, Anish

    2015-01-01

    Fixed drug eruption is a common adverse effect seen with various drugs notably antibiotics, antiepileptics and non-steroidal anti-inflammatory drugs. Herein we report a case of Sitagliptin induced fixed drug eruption in a 46 year old female who developed circumscribed, erythematous macules all over the body within one week of initiation of Sitagliptin. The lesions resolved with residual hyperpigmentation on cessation of the drug. The diagnosis was confirmed by an oral provocation test which led to a reactivation of the lesions. To the best of our knowledge, this is the first case of fixed drug eruption to Sitagliptin reported in the literature.

  20. 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.