Other Antimalarial Drugs
It is an antimalarial agent which is
a blood schizontocide. It is a 4-quinolone-methanol developed in the 1960s to
combat drug-resistant strains of Plasmodium
falciparum. It is admin-istered orally, and plama levels rise in a biphasic
manner to reach their peak in about 15 to 17 hours. Mefloquine is widely
distributed and highly protein-bound (98%). Excretion is mainly by faecal
route.
Therapeutic doses are usually well
tolerated, but may occa-sionally cause abdominal pain, vomiting, diarrhoea, and
vertigo. Higher doses result in ataxia, headache, bradycardia, prolonga-tion of
the QTc interval, hypoglycaemia, psychosis, anxiety, depression, agitation,
nightmares, hallucinations, paranoia and audiovisual disturbances. Women may be
more susceptible to mefloquine-induced neuropsychiatric effects. Other effects
reported include skin rashes, pruritus and urticaria, hair loss, muscle
weakness, myalgia, liver function disturbances, and occasionally
thrombocytopenia and leucopenia. Rare compli-cations include encephalopathy and
seizures. Concomitant administration of quinine or chloroquine enhances the
risk of convulsions as well as cardiotoxicity. Since mefloquine has a long
elimination half-life (13 to 24 days), adverse effects may persist for several
weeks after drug cessation. A post-malaria neurological syndrome has been
reported, consisting of confu-sion, psychosis, seizures, or tremor developing
after treatment for malaria.
Treatment of acute toxicity is on
general lines with special attention directed towards control of seizures. All
patients with mefloquine overdose should be admitted and observed with
continuous cardiac monitoring, along with neurologic and psychiatric
assessment, for at least 24 hours. Activated charcoal can be administered or
stomach wash done, if decontamination is applicable in a given case. Atropine,
dobutamine, or pacing can control bradycardia. Phenytoin, lignocaine, or
amiodarone may be required for ventricular arrhythmias. Methods of
extra-corporeal elimination are unlikely to be of benefit because of the large
volume of distribution and extensive protein binding of mefloquine.
Spontaneous abortions and an
increased number of stillbirths were seen in women who received mefloquine for
malaria prophylaxis early in pregnancy. Animal experiments suggest that
mefloquine is teratogenic.
It is a phenanthrene methanol which
is sometimes used as an alternative to quinine and mefloquine for the treatment
of drug-resistant falciparum malaria. It is a blood schizontocide with no
apparent activity against the sporocyte, gametocyte, or hepatic stages of the infection.
Side effects include vomiting,
diarrhoea, and abdominal pain. Syncope, dizziness, pruritus, and convulsions
may also occur. High doses induce cardiotoxicity (QTc interval prolon-gation
and ventricular arrhythmias). Halofantrine should be taken on an empty stomach.
Food, especially food high in fat content, increases the absorption of
halofantrine, which may increase its toxicity.
Although not reported, overdose of
halofantrine might also be expected to cause cardiotoxicity (ECG abnormalities
and ventricular arrhythmias) and gastrointestinal toxicity (nausea, vomiting,
diarrhoea, and abdominal pain).
Treatment of halofantrine overdose
is mainly symptomatic and supportive. Activated charcoal and/or gastric lavage
may be of help in the initial stages. Monitor fluid and electrolytes in cases
of severe vomiting and diarrhoea, and ECG for ventricular arrhythmias.
Antiarrhythmic agents (lignocaine, phenytoin, amiodarone, etc.) may be
required. Convulsions can be controlled with benzodiazepines. Liver function
tests should be monitored in symptomatic patients.
They
are recent entrants in the field of antimalarial therapy, and are represented
mainly by qinghaosu (a sesquiterpene
lactone discovered in China), and its derivatives artemether and artesunate.
They are used in the treatment of drug-resistant falciparum malaria. They are
generally well tolerated, but can occasionally cause gastrointestinal distress
and cardiotoxicity.
It
is a dihydrofolate reductase inhibitor, and is used in combination with sulfadoxine (a long -acting
sulfonamide), or trimethoprim, for
the treatment of chloroquine-resistantfalciparum malaria. This drug combination
is also recom-mended for the therapy of toxoplasmosis. Adverse reactions
include severe cutaneous eruptions, DIC, blood dyscrasias, anaphylactoid
reactions, peripheral neuritis, ataxia, vertigo, and renal/hepatic damage. Use
of trimethoprim at high doses and/or for extended periods of time may cause
bone marrow depression manifested as thrombocytopenia, leukopenia, and/ or
megaloblastic anaemia.
Most
serious cases of pyrimethamine overdose have been reported in children under
three years old. Symptoms include vomiting, rashes, CNS depression,
convulsions, hyperpyrexia, tachycardia, respiratory rate changes, and jaundice.
Signs of acute overdosage with trimethoprim may appear following ingestion of 1
gram or more and include nausea, vomiting, dizziness, headaches, mental
depression, confusion, and bone marrow depression.
Treatment
of overdose with either agent is supportive in nature. Haemodialysis is
moderately effective in eliminating trimethoprim. Due to higher protein
binding, it is not likely that haemodialysis will be very effective for the
elimination of pyrimethamine.
It
is an acridine derivative which was formerly used widely as an antimalarial
drug, but is unpopular today owing to severe side effects including vertigo,
headache, ataxia, vomiting, yellowish discolouration of skin and urine,
bluish-black discol-ouration of palate and nails, psychosis, convulsions,
ocular toxicity, exfoliative dermatitis, liver damage, and aplastic anaemia. It
is incompatible with alcohol and can produce a disulfiram-like reaction.
Mepacrine has been banned in the USA and most other Western countries since the
early 1990s. That it is still available in India is a sad reflection of
govern-mental apathy towards the sale of dangerous and obsolete drugs.
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