Miscellaneous antimalarials such as Pyrimethamine, Artesunate, Artemether and Atovoquone (Atovaquone) are essential for B. Pharm students studying antimalarial pharmacotherapy. This concise introduction highlights mechanisms of action, pharmacokinetics, clinical indications, adverse effects, resistance mechanisms and key drug interactions for pyrimethamine–sulfonamide regimens, artemisinin derivatives and atovaquone-containing therapies. Emphasis is placed on dosing principles, combination strategies (to prevent recrudescence and resistance), monitoring for toxicity and pregnancy-related considerations. MCQs focus on clinical decision-making, mechanism-based adverse effects, dosing calculations and interpretation of lab monitoring. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which enzyme is primarily inhibited by pyrimethamine in Plasmodium?
- Dihydrofolate reductase
- Dihydropteroate synthase
- Cytochrome bc1 complex
- Heme polymerase
Correct Answer: Dihydrofolate reductase
Q2. The major mechanism of action of atovaquone against Plasmodium is:
- Inhibition of dihydrofolate reductase
- Disruption of mitochondrial electron transport at cytochrome bc1
- Interference with heme detoxification in the digestive vacuole
- Alkylation of parasite DNA
Correct Answer: Disruption of mitochondrial electron transport at cytochrome bc1
Q3. Artemisinin derivatives (artesunate, artemether) exert rapid antimalarial action primarily by:
- Blocking folate synthesis
- Generating free radicals via an endoperoxide bridge that damage parasite proteins
- Inhibiting parasite protein synthesis at ribosomes
- Inhibiting mitochondrial DNA replication
Correct Answer: Generating free radicals via an endoperoxide bridge that damage parasite proteins
Q4. Which combination is classically used as intermittent preventive therapy or treatment in some regions and involves pyrimethamine?
- Pyrimethamine–sulfadoxine
- Pyrimethamine–atovaquone
- Pyrimethamine–artesunate
- Pyrimethamine–chloroquine
Correct Answer: Pyrimethamine–sulfadoxine
Q5. Which adverse effect is most directly associated with pyrimethamine monotherapy due to folate antagonism?
- Delayed hemolysis
- Megaloblastic anemia and bone marrow suppression
- Severe neurotoxicity with gait disturbances
- Renal tubular acidosis
Correct Answer: Megaloblastic anemia and bone marrow suppression
Q6. The clinical role of IV artesunate in severe falciparum malaria is best described as:
- Not recommended due to toxicity
- First-line treatment for severe malaria due to rapid parasite clearance
- Only used in combination with chloroquine
- Only effective for prophylaxis
Correct Answer: First-line treatment for severe malaria due to rapid parasite clearance
Q7. A major pharmacokinetic property of atovaquone affecting its oral absorption is:
- High water solubility leading to rapid absorption
- Improved bioavailability with fatty meals due to high lipophilicity
- Renal excretion requiring dose adjustment in renal failure
- Extensive first-pass metabolism producing active metabolites
Correct Answer: Improved bioavailability with fatty meals due to high lipophilicity
Q8. Which of the following best explains why artemisinin derivatives require a partner drug in combination therapy?
- They have long half-lives that cause toxicity without a partner
- They have very short half-lives and need a partner to clear residual parasites and prevent recrudescence
- They are inactive against P. falciparum unless combined
- Partner drugs reduce their gastrointestinal side effects
Correct Answer: They have very short half-lives and need a partner to clear residual parasites and prevent recrudescence
Q9. Delayed hemolytic anemia has been reported after which antimalarial therapy for severe malaria?
- Oral pyrimethamine–sulfadoxine
- Intravenous artesunate
- Atovaquone monotherapy
- Artemether–lumefantrine only
Correct Answer: Intravenous artesunate
Q10. A known resistance mechanism to atovaquone in Plasmodium involves mutations in:
- Dihydrofolate reductase gene
- Cytochrome b gene of the mitochondrial electron transport chain
- Heme polymerase gene
- Apicoplast ribosomal RNA
Correct Answer: Cytochrome b gene of the mitochondrial electron transport chain
Q11. Which adverse effect is most characteristically associated with sulfonamide combinations with pyrimethamine?
- Stevens–Johnson syndrome and severe cutaneous reactions
- Ototoxicity and tinnitus
- Nephrogenic diabetes insipidus
- Mitochondrial myopathy
Correct Answer: Stevens–Johnson syndrome and severe cutaneous reactions
Q12. Artemether is commonly formulated and administered as:
- Intramuscular oil-based injection and oral formulations
- Continuous IV infusion only
- Topical gel for cutaneous malaria lesions
- Subcutaneous depot implant
Correct Answer: Intramuscular oil-based injection and oral formulations
Q13. Which drug interaction is important for atovaquone when co-administered with rifampicin?
- Rifampicin increases atovaquone levels leading to toxicity
- Rifampicin reduces atovaquone absorption leading to therapeutic failure
- They form an inactive complex increasing atovaquone half-life
- No significant interaction exists
Correct Answer: Rifampicin reduces atovaquone absorption leading to therapeutic failure
Q14. Folinic acid (leucovorin) rescue is used with pyrimethamine therapy to:
- Reverse neurotoxicity
- Prevent or treat marrow suppression and megaloblastic anemia
- Enhance antiparasitic activity synergistically
- Prevent GI upset associated with therapy
Correct Answer: Prevent or treat marrow suppression and megaloblastic anemia
Q15. Which antimalarial is most likely to be used as a component of “Malarone” combination therapy?
- Pyrimethamine
- Atovaquone combined with proguanil
- Artesunate combined with doxycycline
- Chloroquine combined with mefloquine
Correct Answer: Atovaquone combined with proguanil
Q16. Which statement about artemisinin-induced neurotoxicity is most accurate for clinical practice?
- Severe, irreversible neurotoxicity is common in humans
- Neurotoxicity was seen in animal studies, but clinically significant neurotoxicity in humans is rare
- All artemisinins are contraindicated due to proven human neurotoxicity
- Neurotoxicity can be prevented by co-administration of pyrimethamine
Correct Answer: Neurotoxicity was seen in animal studies, but clinically significant neurotoxicity in humans is rare
Q17. When prescribing artemether–lumefantrine, which advice improves absorption of lumefantrine?
- Take with a high-fat meal
- Take on an empty stomach
- Co-administer with antacids
- Avoid dairy during therapy
Correct Answer: Take with a high-fat meal
Q18. A B. Pharm student asked which laboratory parameter to monitor in a patient on long-term pyrimethamine therapy. The most relevant test is:
- Liver function tests only
- Complete blood count with reticulocyte count
- Serum creatinine only
- Serum bilirubin only
Correct Answer: Complete blood count with reticulocyte count
Q19. Which of the following is a correct statement about pharmacokinetics of artesunate?
- Artesunate has a very long half-life and accumulates with repeat dosing
- Artesunate is rapidly converted to an active metabolite, dihydroartemisinin, with a short half-life
- Artesunate is primarily renally excreted unchanged
- Artesunate requires hepatic activation to an inactive form
Correct Answer: Artesunate is rapidly converted to an active metabolite, dihydroartemisinin, with a short half-life
Q20. Which clinical scenario is most appropriate for atovaquone–proguanil use?
- Treatment of severe cerebral malaria requiring ICU care
- Uncomplicated P. falciparum malaria and prophylaxis in travelers
- Treatment of P. vivax hypnozoites in the liver
- First-line therapy for neonatal malaria
Correct Answer: Uncomplicated P. falciparum malaria and prophylaxis in travelers
Q21. Resistance to pyrimethamine most commonly arises from mutations in:
- Plasmodial dihydrofolate reductase (DHFR)
- Plasmodial cytochrome b
- Host folate transporters
- Parasite hemoglobinase enzymes
Correct Answer: Plasmodial dihydrofolate reductase (DHFR)
Q22. Which adverse effect is a recognized concern with atovaquone–proguanil therapy?
- Severe megaloblastic anemia due to folate antagonism
- GI disturbances and rare hepatotoxicity
- Ototoxicity causing irreversible hearing loss
- Severe aplastic anemia in most patients
Correct Answer: GI disturbances and rare hepatotoxicity
Q23. In the management of severe malaria, what is the recommended initial antimalarial of choice according to WHO guidelines?
- Oral chloroquine
- Intravenous artesunate
- Atovaquone monotherapy
- Intramuscular pyrimethamine
Correct Answer: Intravenous artesunate
Q24. The role of pyrimethamine when combined with a sulfonamide is primarily to:
- Inhibit folate synthesis sequentially at two steps for synergistic effect
- Enhance heme detoxification
- Act as a membrane stabilizer to reduce hemolysis
- Function as an antiparasitic vaccine adjuvant
Correct Answer: Inhibit folate synthesis sequentially at two steps for synergistic effect
Q25. Which statement about oral artemether pharmacology is correct?
- Artemether has a long elimination half-life and single-dose cures malaria
- Artemether acts rapidly but requires a partner drug to prevent recrudescence
- Artemether is ineffective against P. falciparum
- Artemether works by chelating iron in host erythrocytes
Correct Answer: Artemether acts rapidly but requires a partner drug to prevent recrudescence
Q26. Which monitoring is particularly important after IV artesunate therapy for severe malaria?
- Serial hemoglobin monitoring for delayed hemolysis
- Daily serum creatinine only
- Weekly audiometry for ototoxicity
- No monitoring is necessary after successful treatment
Correct Answer: Serial hemoglobin monitoring for delayed hemolysis
Q27. Which of the following reduces the bioavailability of atovaquone significantly?
- Co-administration with fatty meals
- Administration with antacids or drugs that accelerate gastric emptying
- Taking atovaquone with a protein-rich snack
- Concurrent use of oral contraceptives
Correct Answer: Administration with antacids or drugs that accelerate gastric emptying
Q28. Artemisinin-based combination therapy (ACT) selection should primarily consider:
- Partner drug half-life, resistance patterns, and patient tolerability
- Only the cost of the regimen
- Whether the patient has a history of malaria >10 years ago
- Patient blood type
Correct Answer: Partner drug half-life, resistance patterns, and patient tolerability
Q29. Which of the following is a contraindication or caution for pyrimethamine–sulfonamide use?
- Severe folate deficiency and pregnancy without medical supervision
- Use in adults over 65 only
- Concomitant use with artesunate increases efficacy without risk
- History of childhood measles
Correct Answer: Severe folate deficiency and pregnancy without medical supervision
Q30. Which laboratory change is most likely during effective therapy with artemisinin derivatives as parasites are cleared?
- Progressive leukocytosis with eosinophilia
- Rapid fall in peripheral parasitemia and improvement in lactate and metabolic acidosis
- Sudden rise in bilirubin due to hepatic necrosis
- Gradual decline in serum creatinine due to drug nephroprotection
Correct Answer: Rapid fall in peripheral parasitemia and improvement in lactate and metabolic acidosis
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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