Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antimalarials”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2005

The quality of antimalarials available in Yemen.

BACKGROUND: Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine) available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. METHODS: Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only) in comparison to standard specifications for these products in the relevant pharmacopoeia. RESULTS: The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. CONCLUSION: There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This appears to be due to non-compliance with Good Manufacturing Practice guidelines by manufacturers in the production of the antimalarials.

Antimalarials↗
PubMed2005

Brands, costs and registration status of antimalarial drugs in the Kenyan retail sector.

BACKGROUND: Although an important source of treatment for fevers, little is known about the structure of the retail sector in Africa with regard to antimalarial drugs. This study aimed to assess the range, costs, sources and registration of antimalarial drugs in the Kenyan retail sector. METHODS: In 2002, antimalarial drug registration and trade prices were established by triangulating national registration lists, government gazettes and trade price indices. Data on registration status and trade prices were compared with similar data generated through a retail audit undertaken among 880 randomly sampled retailers in four districts of Kenya. RESULTS: Two hundred and eighteen antimalarial drugs were in circulation in Kenya in 2002. These included 65 "sulfur"-pyrimethamine (sulfadoxine-pyrimethamine and sulfalene-pyrimethamine (SP), the first-line recommended drug in 2002) and 33 amodiaquine (AQ, the second-line recommended drug) preparations. Only half of SP and AQ products were registered with the Pharmacy and Poisons Board. Of SP and AQ brands at district level, 40% and 44% were officially within legal registration requirements. 29% of retailers at district level stocked SP and 95% stocked AQ. The retail price of adult doses of SP and AQ were on average 0.38 and 0.76 US dollars, 100% and 347% higher than trade prices from manufacturers and importers. Artemether-lumefantrine, the newly announced first-line recommended antimalarial drug in 2004, was found in less than 1% of all retail outlets at a median cost of 7.6 US dollars. CONCLUSION: There is a need to ensure that all antimalarial drugs are registered with the Pharmacy and Poisons Board to facilitate a more stringent post-marketing surveillance system to ensure drugs are safe and of good quality post-registration.

Antimalarials↗
PubMed2006

Decreased availability of antimalarials in the private sector following the policy change from chloroquine to sulphadoxine-pyrimethamine in the Kilombero Valley, Tanzania.

BACKGROUND: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. METHODS: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. RESULTS: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment. CONCLUSION: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population.

Analgesics, Non-Narcotic↗
PubMed2004

Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake.

The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

Animals↗
PubMed2003

Stereoselectivity in the pharmacodynamics and pharmacokinetics of the chiral antimalarial drugs.

Several of the antimalarial drugs are chiral and administered as the racemate. These drugs include chloroquine, hydroxychloroquine, quinacrine, primaquine, mefloquine, halofantrine, lumefantrine and tafenoquine. Quinine and quinidine are also stereoisomers, although they are given separately rather than in combination. From the perspective of antimalarial activity, most of these agents demonstrate little stereoselectivity in their effects in vitro. Mefloquine, on the other hand, displays in vitro stereoselectivity against some strains of P. falciparum, with a eudismic ratio of almost 2 : 1 in favour of the (+)-enantiomer. Additionally, for some of these agents (e.g. halofantrine, primaquine, chloroquine), stereoselectivity has been noted in the ability of the enantiomers to cause certain adverse effects. In recent years, stereospecific analytical methods capable of measuring the individual enantiomers after the administration of racemic drugs have been reported for a number of chiral antimalarial drugs. These assays have revealed that almost all the studied antimalarial drugs display stereoselectivity in their pharmacokinetics, leading to enantioselectivity in their plasma concentrations. Whereas the oral absorption of these agents appears to be non-stereoselective, stereoselectivity is often seen in their volume of distribution and/or clearance. With regard to distribution, plasma protein binding of some chiral antimalarial drugs exhibits a significant degree of stereoselectivity, leading to stereoselective distribution to blood cells and other tissues. Because of their low hepatic extraction ratios, stereoselective plasma protein binding also contributes to the stereoselectivity in the metabolism of these drugs. Chiral metabolites are formed from some parent antimalarial drugs, although stereoselective aspects of the pharmacokinetics of the metabolites are not well understood. It is concluded that knowledge of the stereoselective aspects of these agents may be helpful in better understanding their mechanisms of action and possibly optimising their clinical safety and/or effectiveness.

Animals↗
PubMed1999

Discontinuation of antimalarial drugs in systemic lupus erythematosus.

OBJECTIVE: To assess the reasons for and timing of discontinuation of antimalarial drugs, principally hydroxychloroquine (HCQ), in systemic lupus erythematosus (SLE). METHODS: A lupus database was reviewed to identify antimalarial use from inception to April 1996. Reasons for drug discontinuation were assessed by medical record review. RESULTS: Of 224 patients with SLE, 156 (70%) had received antimalarials. The 156 users received 203 courses of antimalarials, of which 197 (97%) were for HCQ. The average duration of use was 6.9 years/patient. Antimalarials were discontinued at least once in 62 patients. When only the first course of use was considered, 67, 50, and 38% of patients continued to receive antimalarials at 5, 10, and 15 years, respectively (for all courses, the rates were 82, 66, and 52%, respectively). Reasons for discontinuation were disease remission in 26 (42%), side effects in 18 (29%), noncompliance in 9 (15%), lack of efficacy in 5 (8%), and miscellaneous causes such as pregnancy/surgery in 4 (6%). When all courses were considered, 20 subjects were withdrawn for side effects, including gastrointestinal in 11; headache and dizziness, and nonretinal eye problem in 2 each; and hearing loss and rash in one each. Two developed HCQ myopathy (1.9 cases/1000 patient-years of HCQ therapy; 95% CI 0.2, 7.0). One developed HCQ retinopathy after 6 years at a dose of 6.5 mg/kg/day (0.95 cases/1000 patient-years of HCQ; 95% CI 0.0, 5.5). Among patients who had received HCQ for at least 6 years, 1.3% developed retinopathy (95% CI 0.03, 7.0%). CONCLUSION: HCQ is well tolerated in SLE. However, ophthalmologic testing remains essential, as retinopathy does occur, albeit rarely.

Adult↗
PubMed2000

Decreased progression to rheumatoid arthritis or other connective tissue diseases in patients with palindromic rheumatism treated with antimalarials.

OBJECTIVE: To determine whether the use of antimalarials is associated with a reduction in the risk of developing rheumatoid arthritis (RA) or other connective tissue diseases in patients with palindromic rheumatism. METHODS: We conducted a retrospective cohort study based on a review of medical records to evaluate the outcome of patients with palindromic rheumatism referred to an academic center from 1986 to 1996: 113 patients complied with the selection criteria, including diagnostic criteria for palindromic rheumatism and onset of disease since 1980. After adjusting for potential confounders, Kaplan-Meier methods and Cox regression models were used to estimate the risk of developing RA or other connective tissue disease in patients who had received antimalarials compared to those who had not. RESULTS: Age of disease onset was 40+/-12 yrs, and mean disease duration 4.8+/-4 yrs; two-thirds of the patients were female. Sixty-two (55%) patients received antimalarials, for a mean duration of therapy of 28 mo. Thirty-three (29%) patients developed RA, 3 developed systemic lupus, and 4 developed other connective tissue diseases. Twenty (32%) patients in the antimalarial group developed a secondary disease, compared to 20 (39%) who did not receive therapy. Statistically significant differences were observed comparing time to event in both groups. The estimated median time to development of a chronic disease was 162 months in treated and 56 months in untreated patients. After adjusting for other variables in the Cox regression models, significant risk reduction in the development of a secondary disease was observed for antimalarial use (hazard ratio = 0.24; 95% CI 0.09-0.61). For RA, the risk reduction was 0.19 (95% CI 0.07-0.57). We conducted a sensitivity analysis around our censoring estimates. The risk reduction remained statistically significant, with 0.36 for RA and 0.41 for RA or other connective tissue disease. CONCLUSION: Use of antimalarials in patients with palindromic rheumatism is associated with a reduction in the risk of developing subsequent RA or other connective tissue disease.

Adult↗
PubMed2000

Patients with cutaneous lupus erythematosus who smoke are less responsive to antimalarial treatment.

BACKGROUND: Reports suggest that cigarette smoking might interfere with the effectiveness of antimalarial therapy as first-line treatment for cutaneous lupus erythematosus. Patients refractory to this treatment often must be treated with potentially more toxic regimens. OBJECTIVE: Our purpose was to examine the effects of cigarette smoking on the therapeutic response to antimalarial agents in patients with discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). METHODS: A total of 61 patients (47 DLE, 14 SCLE) were selected on the basis of the following criteria: (1) skin biopsy was consistent with cutaneous LE, (2) a smoking history was available, and (3) an adequate trial of antimalarial therapy was completed. Patients were classified as antimalarial responders or nonresponders on the basis of descriptions in their medical records. Two-by-two table analysis was performed comparing response rates in smokers versus nonsmokers. RESULTS: A significant difference (P<.0002) in the antimalarial response rate was observed for smokers (40%) versus nonsmokers (90%). CONCLUSION: These results indicate that patients with cutaneous LE who smoke are significantly less likely to respond to antimalarial therapy.

Adult↗
PubMed2001

Effects of hydroxypyridinone iron chelators in combination with antimalarial drugs on the in vitro growth of Plasmodium falciparum.

Using standard in vitro drug susceptibility methods, we assessed the antimalarial activity of 3 orally administered iron chelators (hydroxypyridinones) alone and in combination with conventional antimalarials drugs (quinine, mefloquine, artesunate, tetracycline, atovaquone) against a chloroquine-resistant Plasmodium falciparum isolate. When tested alone, all iron chelators and antimalarial compounds inhibited the growth of the parasites. IC50 values for iron chelators were 60-70 microM, whereas the IC50 values for antimalarial drugs were in nM ranges, with artesunate being the most potent. The derived isobolograms for the interaction of hydroxypyridinones and antimalarial drugs showed addition or mild antagonism, similar to desferroxamine (Sum of Fractional Inhibitory Concentration, sigma FIC < 0.5 or > 4.0). Despite the absence of synergy with conventional drugs, intrinsic antimalarial activity of hydroxypyridinones supports the continued assessment of these iron chelators as treatment adjuncts.

Animals↗
PubMed2003

Adherence to ophthalmologic monitoring for antimalarial toxicity in a lupus cohort.

OBJECTIVE: Antimalarial agents (hydroxychloroquine and chloroquine) are important in the treatment of various rheumatic diseases, including systemic lupus erythematosus (SLE). Although these agents may lead to ocular complications, little is known about adherence to policies for ophthalmologic monitoring. We investigated adherence to the 1996 American College of Rheumatology (ACR) guidelines (recommending yearly ophthalmologic assessments) at our clinic, and determined the factors associated with nonadherence. METHODS: Chart review of the Montreal General Hospital lupus clinic cohort. RESULTS: Of 195 subjects with at least one full year of antimalarial exposure during 1996-2001, 5 refused participation and data on ophthalmology monitoring was incomplete for 42. Of the remaining 148 patients, 47 (32%) had missed at least one annual ophthalmology assessment (were nonadherent) during the interval; almost half of these had missed </= 2 assessments. Nonadherence was present in 50% of the 52 patients who had been taking an antimalarial agent for </= 5 years. In adjusted logistic regression models, cumulative damage (measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index) and antimalarial exposure </= 5 years were predictive of nonadherence. Adjusted estimates indicated a 1.2-fold increase (95% CI 1.0, 1.5) in the odds of nonadherence for every point increase in the total Damage Index score. The adjusted OR for individuals exposed to an antimalarial for </= 5 years was 5.2 (95% CI 2.1, 13.8). CONCLUSION: Our results indicate incomplete adherence to ACR guidelines at our center. Because patients with higher Damage Index scores were more likely to have missed ophthalmology appointments, even after adjusting for pertinent covariates, it suggests that sicker patients may be more at risk of nonadherence. The association of nonadherence with duration of antimalarial exposure, while not surprising, is still an important reminder that adherence to ophthalmologic monitoring may decrease as risk for retinal toxicity is increasing.

Adult↗
PubMed2005

Self-medication with antibiotics and antimalarials in the community of Khartoum State, Sudan.

PURPOSE: To estimate the prevalence of self medication with antibiotics and antimalarials in Khartoum State, Sudan and evaluate factors associated with self medication. METHODS: A pre-tested questionnaire was used to collect data from a sample of 600 households, (1750 adult persons), selected from three cities in Khartoum State, Sudan, using a multistage stratified clustered sampling. RESULTS: One thousand two hundred and ninety three (73.9%) of the study population had used antibiotics or antimalarials without a prescription within one month prior to the study. Eight hundred and forty one (48.1%) of the respondents agreed that they have used antibiotics, 43.4% used antimalarials, while 17.5% used both. Self medication with either antibiotics/ antimalarials was found to be significantly associated with age, income, gender and level of education. Overall, self medication with any antibiotics or antimalarials was least common among the > or = 60 years compared to youngest age group (OR: 0.07; 0.04 -0.11) and most common among the female gender (OR: 1.8; 1.4 -2.4), the middle income group (OR: 3.7; 2.6-5.3) and the university graduates. Self medication with antibiotic was found to be significantly higher among females (OR: 1.5; 1.16-1.87), middle aged respondents aged 40-59 (OR: 2.1; 1.5-3.0) compared to younger respondents. Lower income and higher level of education was also found to be significantly associated with the increase risk of self medicating with antibiotic. Increase risk for self medication with antimalarials were, however, found to be significantly associated with male gender and younger age group of < 40 years and middle income earners and less educated respondents. The main reason that was indicated for the self-medication was financial constraints. The main source of medicines was the private pharmacies, which were regarded as a cheaper alternative to other primary healthcare sources. CONCLUSION: The prevalence of self-medication with antibiotics/antimalarials in Khartoum State, Sudan is alarmingly high. Self medication behaviour varies significantly with a number of socio-economic characteristics. Given the growing global resistance for antibiotic and documented health issues related to inappropriate use of such drugs, our findings has major public health policy implications for countries like Sudan.

Adult↗
PubMed1995

[Role of modulators in Plasmodium falciparum resistance to antimalarials].

Modulating agents that circumvent the Plasmodium falciparum resistance to antimalarials are components without any intrinsic antimalarial activity but able, in association with a standard antimalarial drug, to restore the sensitivity of Plasmodium falciparum to this drug. Two hypotheses are forwarded about their possible mechanisms of action : the mechanisms involving the inhibition of the drug efflux and the mechanisms involving the inhibition of antimalarial drug metabolic degradation. None of these mechanisms is able to alone explain the effect of all modulating agents. The future use prospects of these compounds are limited by their in vivo toxicity. That relevant to the calcium channels blockers seems to be circumvented by the use of dextro-enantiomers. A toxicity relevant to a possible accumulation of the antimalarial in healthy, non target cells must be also suspected. Moreover the use of these agents evidences a socio-economic problem : a complete new development of the association (antimalaria plus modulatin drugs) is needed and that, in developing countries. Nevertheless, the agents modulating the Plasmodium falciparum resistance are a new approach for the treatment of resistant malaria which might give a recrudescence of activity to the old antimalarials as chloroquine.

Animals↗
PubMed1996

The use of antimalarials in combination with other disease modifying agents in RA--the British experience.

Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination therapy due to their efficacy, mechanisms of action and toxicity profile. In this review, the evidence for the use of antimalarials in combination in RA is examined. No advantage has been shown in combining antimalarials with gold, penicillamine or sulphasalazine compared with monotherapeutic regimens. There is some evidence to suggest a beneficial combination of antimalarials with methotrexate, but this is as yet inconclusive. Open non-randomised uncontrolled studies have shown that antimalarials combined with cytotoxic agents are effective but highly toxic. The authors conclude that there is little good evidence to support the introduction of combination second-line drug therapy for RA into widespread therapeutic use.

Antimalarials↗
PubMed1985

Paired-ion liquid chromatographic method for the analysis of a phenanthrenemethanol antimalarial in whole blood.

A sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of the candidate antimalarial (+/-)-(1,3-dichloro-6-trifluoromethyl-9-phenanthryl)-3-di-(n-butyl )aminopropanol hydrochloride in whole blood. A reversed-phase, paired-ion (lauryl sulfate) system achieved separation of the antimalarial and internal standard from interfering constituents with a sensitivity limit of 10 ng/mL by UV detection (254 nm). Chromatographic variables (counterion concentration, pH, and column temperature) were examined to determine their effect on assay characteristics (retention, efficiency, and relative response) in clinical analysis. The antimalarial was isolated from 2.0 mL of whole blood using overnight extraction with 30% ethyl acetate in hexane followed by an acid/base partition sequence to remove major interferences. Overall recovery for the antimalarial was 84% with a CV of 5.0%, and the recovery of the internal standard was 81% (CV = 3.6%). The assay was validated by analysis of both intra- and interlaboratory samples. The assay was applied to the analysis of whole blood samples taken from a 30-year-old healthy human male who had received a single 14.1-mg/kg oral dose. The stability of the antimalarial in whole blood for up to 4 months and in sample extracts for up to 34 d at -17 degrees C was also demonstrated.

Animals↗
PubMed1993

Abnormal circulatory control in falciparum malaria: the effects of antimalarial drugs.

We have studied blood pressure and heart rate responses to standing in 29 previously ambulant adult Thai patients with acute uncomplicated falciparum malaria before and after treatment with quinine or mefloquine. There was significant, symptomatic, and usually profound orthostatic hypotension in 12 patients (41%) before antimalarial treatment. The median maximum fall in systolic pressure was 24 mm Hg, significantly greater than the maximum fall in diastolic pressure 16 mm Hg. Blood pressure fell in two phases: an initial transient and usually asymptomatic fall immediately on standing, and a progressive, usually symptomatic fall, worsening over several minutes without a rise in pulse rate. Orthostatic hypotension was associated with core temperature (r = 0.37, P = 0.05). Antimalarial treatment accentuated the delayed orthostatic hypotension during malaria, despite (in the case of quinine) a significant reduction in fever. Both antimalarial drugs attenuated the cardioacceleratory response to symptomatic postural hypotension; the mean reduction in heart rate at the time of lowest blood pressure was 22 beats.min-1. The electrocardiograph ratio of RR intervals at the 30th and 15th beats was reduced significantly in acute malaria, but was not affected further by the drugs. When restudied in convalescence all the patients had normal postural cardiovascular responses. Acute falciparum malaria is associated with impaired circulatory control and the tendency to postural hypotension is worsened significantly by antimalarial treatment with the quinoline antimalarials quinine and mefloquine.

Acute Disease↗
PubMed1994

Progress in the research of artemisinin-related antimalarials: an update.

Artemisinin, a sesquiterpene lactone endoperoxide isolated from Artemisia annua L., and a number of its semisynthetic derivatives have shown to possess antimalarial properties. They are all effective against Plasmodium parasites that are resistant to the newest and commonly used antimalarial drugs. This article gives a survey of the literature dealing with artemisinin-related antimalarial issues that have appeared from the end of 1989 up to the beginning of 1994. A broad range of medical and pharmaceutical disciplines is covered, including phytochemical aspects like the selection of high-producing plants, analytical procedures, and plant biotechnology. Furthermore, the organic synthesis of artemisinin derivatives is discussed, as well as their mechanism of action and antimalarial activity, metabolism and pharmacokinetics, clinical studies, side-effects and toxicology, and biological activities other than antimalarial activity.

Animals↗
PubMed1997

Neuro-psychiatric effects of antimalarials.

OBJECTIVE: To study the neuro-psychiatric adverse effects of antimalarial drugs. SETTING: Persons who visited a Travel Clinic in Rotterdam over a period of 3 months. DESIGN: Prospective cohort study on 394 persons taking mefloquine, 493 persons taking proguanil and 340 persons not taking antimalarial drugs who visited Africa, South America, Asia, or the Middle East. METHODS: All persons received a structured questionnaire within 14 days of their return to the Netherlands. The questionnaire consisted of questions regarding use of alcohol, smoking, general health, medical history, tropical diseases during the trip, and other medicines, and contained an extensive list of general complaints regarding all body systems at four levels of severity. A modified and validated version of the Profile of Mood States was included. RESULTS: In the study period, 2541 persons visited the Travel Clinic, of whom 1791 (70%) were both eligible and willing to co-operate. Of these 1791, data were obtained from 1501 (84%). Insomnia was most frequently encountered in users of mefloquine and mouth ulcers in proguanil users. After adjustment for gender, age, destination, and alcohol use, the relative risk for insomnia to mefloquine versus non-users of antimalarials was 1.6, and the excess risk was 6 per 100 users over an average period of 2 months. There were no significant differences between groups in depression, anxiety, agitation, and confusion. Stratification by gender demonstrated that insomnia was more common in women on mefloquine, but not in men. Also, women more frequently mentioned palpitations as an adverse event. After adjustment for age, destination, and alcohol use in women, the relative risks for insomnia and palpitations to mefloquine versus non-use of antimalarials were 2.4, and 22.5, respectively. When travellers were specifically asked for the adverse reactions they had experienced, anxiety, vertigo, agitation, and nightmares were significantly more frequently mentioned by mefloquine users. CONCLUSION: Insomnia was more commonly encountered during use of mefloquine than proguanil or during non-use of antimalarials.

Adult↗
PubMed1997

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

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

Animals↗