It is a drug developed to deal with the problem of chloroquine resistant P. falciparum, and has emerged from reinvestigation of quinoline methanols that were originally tested during World War II.
MEFLOQUINE
It is a drug developed
to deal with the problem of chloroquine resistant P. falciparum, and has emerged from reinvestigation of quinoline
methanols that were originally tested during World War II. Mefloquine is a
relatively fastacting erythrocytic schizontocide, slower than chloroquine or quinine;
effective against chloroquine-sensitive as well as resistant plasmodia. In
field trials, single dose (15 mg/kg, max 1 g) has rapidly controlled fever and
eliminated circulating parasites in infections caused by P. falciparum or P. vivax in
partially immune as well as nonimmune individuals. However, like chloroquine,
relapses occur subsequently in vivax malaria. It is also an efficacious suppressive
prophylactic for multiresistant P.
falciparum and other types of malaria. Mefloquine-resistance among P. falciparum
has become common in Thailand, Cambodia
and Myanmar, but is sporadic in Africa, South America and Middle east. Since it
has not been extensively used in India, mefloquine-resistance is not a problem
yet, but due to its long t½ chances of selection of resistant strains are high;
mefloquine-resistant P. falciparum
isolates have been reported from Gujarat and Andhra Pradesh. Resistance to
mefloquine confers cross resistance to quinine and halofantrine.
The mechanism of
action of mefloquine is not known, but the morphological changes produced in
the intraerythrocytic parasite resemble quinine. It is actively taken up even
by chloroquine-resistant P. falciparum
and, like chloroquine raises intravesicular pH. It appears to bind to haeme and
the complex damages membranes of the parasite. Resistant organisms accumulate
less mefloquine.
Pharmacokinetics
Oral absorption of
mefloquine is good but quite slow. It is highly plasma protein bound and
concentrated in many organs including liver, lung and intestines. Extensive metabolism
occurs in liver and it is primarily secreted in bile. Considerable
enterohepatic circulation of mefloquine and its tissue binding accounts for the
long t½ which is 2–3 weeks.
Adverse Effects
Mefloquine is bitter
in taste; common reaction is
dizziness, nausea, vomiting, diarrhoea, abdominal pain and sinus bradycardia.
These are usually mild and largely dose related, but may be severe in some.
Major concern has been a variety of neuropsychiatric reactions (disturbed sense
of balance, ataxia, errors in operating machinery, strange dreams, anxiety,
hallucinations, rarely convulsions) occurring in some recipients. These are
dose related and subside in 1–3 weeks. Rare events are haematological, hepatic
and cutaneous toxicity. Mefloquine appears to be safe during pregnancy, but
should be avoided in 1st trimester unless absolutely essential.
Interactions
Halofantrine or quinidine/quinine given to patients who
have received mefloquine cause QTc lengthening—cardiac arrests are reported.
Exaggerated bradycardia or arrhythmias were apprehended when mefloquine is
given to patients on β blockers, Ca2+ channel blockers, digitalis
and antidepressants, but no such reactions have occurred and comedication with
these drugs is no longer contraindicated (WHO 1996).
Use
Mefloquine is an effective drug for multiresistant P. falciparum. Because of its potential
toxicity, cost and long t½, its use is being restricted to areas where such
strains are prevalent. To check the spread of mefloquine-resistance, current
recommendation is to use it only along with the rapidly acting drug artesunate,
as ACT for uncomplicated chloroquine as well as S/P resistant falciparum
malaria. For vivax malaria, it should be used only in the rare case of the
parasite being both chloroquine and quinine + doxycycline resistant. Mefloquine
cannot be given parenterally and is not used in complicated/ cerebral malaria.
For prophylaxis of malaria among travellers to areas with
multidrug resistance; 5 mg/kg (adults 250 mg) per week is started preferably
2–3 weeks before travel to assess side effects in the individual. Not recommended
for prophylaxis in residents of the endemic area.
MEFLOTAS, MEFLIAM, CONFAL, FACITAL 250 mg tab; to be taken with
plenty of water after meals.
Mepacrine (Quinacrine, Atabrine)
It is an acridine derivative
erythrocytic schizontocide, more toxic and less effective than chloroquine. It
is obsolete as an antimalarial, but is also active against giardia and
tapeworms.
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