Antimalarial Drug Pharmacology
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Direct answer
Antimalarial drugs act on different stages of the Plasmodium life cycle, and their mechanisms explain both their uses and their toxicities. Chloroquine inhibits haem polymerisation in the food vacuole of erythrocytic parasites, artemisinins generate free radicals that damage parasite proteins, and primaquine targets the dormant liver hypnozoites of Plasmodium vivax and Plasmodium ovale. Radical cure, not symptom control alone, is the key principle for relapsing species.
What you must remember
- Chloroquine: Blood-stage schizonticide now limited by resistance in Plasmodium falciparum; long-term use causes retinopathy, and pruritus is common in darker-skinned patients.
- Artemisinins: Give rapid parasite clearance and are used only as artemisinin-based combination therapy, never as monotherapy, to prevent recrudescence and resistance.
- Primaquine: Gives radical cure for vivax and ovale, causes oxidative haemolysis in G6PD-deficient patients, and needs a G6PD test before prescribing.
- Mefloquine: Causes neuropsychiatric effects including vivid dreams, anxiety and psychosis, is avoided in people with psychiatric illness, and also prolongs the QT interval.
- Quinine: Causes cinchonism with tinnitus, headache and visual disturbance, carries a hypoglycaemia risk, and intravenous quinine is the alternative in severe malaria when artesunate is unavailable.
- Sulfadoxine-pyrimethamine: Its main concern is serious skin reactions, including Stevens-Johnson syndrome.
A graded pathway: radical cure of vivax malaria
Consider a 24-year-old returning from a forest area with Plasmodium vivax infection. The smear confirms vivax, and blood-stage infection is treated with chloroquine where it remains effective. Radical cure needs primaquine to eliminate the liver hypnozoites that would otherwise cause relapse. Before primaquine is prescribed, a G6PD test is done wherever it is available, because oxidative haemolysis can be severe in deficient patients. If the test shows deficiency, primaquine is withheld and the case is discussed with a specialist, since alternatives carry their own restrictions. Haemoglobin, reticulocytes and urine colour are monitored during treatment, and the patient is told to report dark urine at once. Had the same patient presented with falciparum malaria, the pathway would change to an artemisinin-based combination, with intravenous artesunate reserved for severe disease. Once radical cure is complete, the team arranges follow-up and advises the patient on mosquito avoidance, since vivax can recur months after the first episode. The G6PD result is recorded in the notes so that future prescribers avoid oxidant drugs without checking first. Haemolysis is looked for by checking haemoglobin and urine colour during the first days of therapy.
Where the exam tries to catch you
The exam often tests whether candidates separate blood-stage activity from radical cure. Primaquine is not a rapid blood schizonticide and is given to prevent relapse of vivax and ovale, so a stem describing relapse should lead to primaquine rather than a fresh chloroquine course. Artemisinin monotherapy is a recurring trap, since recrudescence and resistance follow when it is given alone. Mefloquine's neuropsychiatric effects are the classic reason it is avoided in some patients, and quinine's cinchonism is sometimes confused with allergy. G6PD deficiency is a repeated theme: the same test that guards against primaquine haemolysis matters for other oxidant drugs such as sulfonamides, dapsone and nitrofurantoin.
Frequently asked questions
Why must G6PD status be checked before primaquine?
Primaquine causes oxidative haemolysis in people with G6PD deficiency, because their red cells cannot regenerate the reduced glutathione needed to resist oxidant stress. A G6PD assay is therefore done before the first dose where facilities exist, and the result determines whether primaquine can be prescribed; where testing is unavailable, national programmes weigh the risk and counsel the patient to stop and report dark urine.
What is the first-line treatment for severe falciparum malaria in India?
Intravenous artesunate is the first-line treatment for severe falciparum malaria, and intravenous quinine is the alternative when artesunate is unavailable. Supportive management of hypoglycaemia, acidosis and fluid balance is also part of care, as advised in national guidelines.
Why is an artemisinin never given alone for malaria?
Artemisinins clear parasites rapidly but have short half-lives, so given alone they leave residual parasites that cause recrudescence and promote resistance. They are therefore always combined with a longer-acting partner drug in artemisinin-based combination therapy.
What adverse effects are typical of mefloquine?
Mefloquine causes neuropsychiatric effects such as vivid dreams, anxiety, depression and, rarely, psychosis. It can also cause vestibular symptoms and QT prolongation, and it is avoided in people with psychiatric illness.