Antimalarial drugs mefloquine

Speich R, Haller A. Central anticholinergic syndrome with the antimalarial drug mefloquine. N Engl J Med 1994 331(l) 57-8. 

Kang J, Chen XL, Wang L, et al. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQTl/minK and HERG. / Pharmacol Ex The. 2001 299(l) 290-296. 

Miscellaneous compounds of pharmacological interest have been shown to inhibit aromatase in vitro, including the antimalarial drug mefloquine, [138], the oral hypoglycaemic agent, tolbutamide [139], and nicotine, its metabolite cotinine, and anabasine, all of which are found in tobacco [140]. These effects probably have little clinical relevance, although the latter three compounds may account for the reduced urinary [141] and plasma [142] oestrogen concentrations found in smokers [140],... 

Adovelande J, Boulard Y, Berry J-P, Galle P, Slodzian G, Schrevel J. Detection and cartography of the fluorinated antimalarial drug mefloquine in normal and Plasmodium falciparum infected red blood cells by scanning ion microscopy and mass spectrometry. Biol Cell 1994 81 185-192. 

Knight J, Sauer S, Coltart D (2011) Asymmetric total synthesis of the antimalarial drug (+)-mefloquine hydrochloride via chiral N-amino cyclic carbamate hydrazones. Oig Lett 13 3118-3121... 

The E-state indices may define chemical spaces that are relevant in similarity/ diversity search in chemical databases. This similarity search is based on atom-type E-state indices computed for the query molecule [55]. Each E-state index is converted to a z score, Z =(% -p )/0 , where is the ith E-state atomic index, p is its mean and O is its standard deviation in the entire database. The similarity was computed with the EucHdean distance and with the cosine index and the database used was the Pomona MedChem database, which contains 21000 chemicals. Tests performed for the antiinflamatory drug prednisone and the antimalarial dmg mefloquine as query molecules demonstrated that the chemicals space defined by E-state indices is efficient in identifying similar compounds from drug and drug-tike databases. 

Antimalarial drugs are designed to prevent or treat malaria. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

There is very limited evidence available on the effectiveness of the drugs in pregnant women. A possible increase in risk of stillbirth with the use of mefloquine in pregnancy has been reported. Standard adult dose of antimalarial drugs recommended for 2nd and 3rd trimester pregnancy did not cause harm or congenital abnormalities. Evidence on the safety of all recommended antimalarial drugs in the 1st trimester is still unclear. 

Clinical Use. Mefloquine (Lariam) has emerged as one of the most important antimalarial agents.61 This drug is especially important in the prevention and treatment of malaria that is resistant to traditional antimalarial drugs such as chloroquine and quinine.50 Mefloquine is often the drug of choice for antimalarial prophylaxis, especially in areas of the world where chloroquine-resistant strains of malaria are common.23 Mefloquine can be used alone, but combining this... 

A postal survey of the incidence of psychiatric disturbances in 2500 returning Israeli travellers (505) showed that travellers with this class of adverse effects were more likely to have taken mefloquine than other antimalarial drugs. Of 117 travellers with psychiatric adverse effects, 115 had taken mefloquine compared with 948/1340 for the entire cohort. This was a retrospective postal study with a response rate of 54% (1340 out of 2500), and of those who responded 71% had taken mefloquine, 5% had taken chloroquine, and 24% had taken no prophylaxis. In this study 11% (117) of the respondents reported psychiatric disturbances, mainly sleep disturbance, fatigue, vivid dreams, or lack of mood. Only 16 of the respondents had symptoms lasting 2 months or more. Those who had had a psychiatric disturbance were also more likely to have been female and to have taken recreational drug use. 

In another major review the risk of depression, psychosis, a panic attack, or a suicide attempt during current or previous use of mefloquine was compared with the risk during the use of proguanil and/or chloroquine or doxy-cycline (513). The study population (n = 35 370) was aged 17-79 years (45% men). There was no evidence that the risk of depression was increased during or after the use of mefloquine, but psychoses and panic attacks were more frequent in current users of mefloquine than in those using other antimalarial drugs. 

ANTI EPILEPTICS 1. ANTIMALARIALS -chloroquine, mefloquine 2. ANTIDEPRESSANTS-MAOIs, SSRIs, TCAs 3. ANTIPSYCHOTICS t risk of seizures These drugs lower seizure threshold Care with co-administration. Watch for t fit frequency warn patient of this risk when starting these drugs and take suitable precautions. Consider increasing dose of antiepileptic... 

BUPROPION 1. ANTIBIOTICS - fluoroquinolones 2. ANTICANCER AND IMMUNO-MODULATING DRUGS-corticosteroids, interferons 3. ANTIDEPRESSANTS-TCAs 4. ANTIMALARIALS - chloroquine, mefloquine 5. ANTIPSYCHOTICS 6. BRONCHODILATORS -theophylline 7. CNS STIMULANTS 8. PARASYMPATHOMIMETICS T risk of seizures. This risk is marked in elderly people, in patients with a history of seizures, with addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin Bupropion is associated with a dose-related risk of seizures. These drugs, which lower seizure threshold, are individually epileptogenic. Additive effects occur when combined Extreme caution. The dose of bupropion should not exceed 4S0 mg/day (or 150 mg/day in patients with severe hepatic cirrhosis)... 

Unfortunately, many persons experience extreme side effects from antimalarial medications. Further, chloroquine-resistant strains of falciparum malaria are on the increase worldwide. For this resistant parasite, the drug mefloquine is the preferred method of prophylaxis and treatment, although resistance to this drug may emerge rapidly, and resistant strains have been found in areas where the drug has never been used. 

The adverse effects of mefloquine have been extensively reviewed both for prophylaxis (when rare neuropsychiatric adverse effects make its use controversial) and in treatment doses, when it has been linked to an increased incidence of the postmalaria neurological syndrome. A retrospective review of 5120 Itahan soldiers showed an overall chemoprophylaxis curtailment rate of less than 1%, which was not significantly different from the combination of chloroquine and proguanil (11). A semi-systematic review also suggested no significant difference in tolerabihty compared with other antimalarial drugs (12). 

It has tentatively been suggested that mefloquine can exacerbate psoriasis (as can other antimalarial drugs, such as quinidine, chloroquine, and proguanil) (38). 

A review of the use of mefloquine in pregnancy (47) did not suggest that mefloquine has a worse effect in pregnancy than other antimalarial drugs, such as chloroquine and pyrimethamine + sulfadoxine. 

However, a further study of 208 pregnant women on the Thai-Burmese border showed a significantly increased incidence of still-births compared with 1565 women treated with other antimalarial drugs (51). Other adverse effects were no more common than with other antimalarial drugs. The study was performed during a period of emerging mefloquine-resistant malaria, and the findings may also reflect the effect of suboptimal malaria treatment. 

UNDPAVorld BankAVHO update. Development of mefloquine as an antimalarial drug. Bull World Health Organ 1983 61(2) 169-78. 

Nguyen-Cong, V. and Rode, B.M. (1996a). Quantum Pharmacological Analysis of Structure-Activity Relationships for Mefloquine Antimalarial Drugs Using Optimal Tlransformations. J.Chem.lnf.Comput.Sci., 36,114-117. 

In the course of 20th century, especially during World War II, a series of effective synthetic antimalarial drugs have been developed. Among them, chloroquine (2), mefloquine (3), and pyrimethamine (4), Fig. (1), became the drugs of choice in several programs and contributed to the almost complete eradication of malaria from Europe and North America. 

Fig. (1) First-line antimalarial drugs quinine (1) chloroquine (2) mefloquine (3) pyrimetamine (4).

ANTIMALARIAL ACTIONS Mefloquine is a highly effective blood schizontocide but has no activity against early hepatic stages and mature gametocytes of P. falciparum or latent tissue forms of P. vivax. The drug may have some sporontoddal activity but is not used clinically for this purpose. 

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