Malaria: antimalarial therapy and resistance management MCQs With Answer

Malaria: antimalarial therapy and resistance management MCQs With Answer is designed for M.Pharm students to deepen understanding of current antimalarial pharmacotherapy, mechanisms of action, pharmacokinetics, adverse effects and strategies to manage and monitor drug resistance. This collection emphasizes clinical decision-making, molecular markers of resistance, safe use in special populations (pregnancy, G6PD deficiency), prophylaxis for travellers, and public-health approaches such as combination therapy policies and surveillance. Each question tests higher-order thinking relevant to therapeutics, drug interactions and stewardship to prepare you for research, clinical pharmacy practice, and policy roles. Answers are provided to facilitate self-assessment and focused revision for Pharmacotherapeutics II (MPP 202T).

Q1. What is the primary molecular mechanism responsible for chloroquine resistance in Plasmodium falciparum?

  • Increased drug efflux mediated by amplified pfmdr1 copies
  • Mutations in the kelch13 propeller domain
  • Mutations in the pfcrt gene leading to decreased drug accumulation in the digestive vacuole
  • Overexpression of parasite dihydrofolate reductase (DHFR)

Correct Answer: Mutations in the pfcrt gene leading to decreased drug accumulation in the digestive vacuole

Q2. For uncomplicated falciparum malaria in many endemic regions, the WHO recommends first-line therapy consisting of which of the following?

  • High-dose chloroquine monotherapy
  • Artemisinin-based combination therapy (ACT), e.g., artemether-lumefantrine
  • Quinine monotherapy for 7 days
  • Primaquine single dose

Correct Answer: Artemisinin-based combination therapy (ACT), e.g., artemether-lumefantrine

Q3. Which antimalarial is required for radical cure of Plasmodium vivax to eliminate hepatic hypnozoites, and what important test must be done before administration?

  • Tafenoquine without any testing
  • Primaquine after confirming normal G6PD status
  • Chloroquine with liver function tests
  • Mefloquine with cardiac ECG monitoring

Correct Answer: Primaquine after confirming normal G6PD status

Q4. Artemisinin derivatives exert their antimalarial effect primarily by which mechanism?

  • Inhibition of dihydrofolate reductase (DHFR)
  • Interference with heme polymerization like chloroquine
  • Generation of free radicals following cleavage of an endoperoxide bridge by ferrous iron/heme
  • Blockade of the parasite electron transport chain at cytochrome b

Correct Answer: Generation of free radicals following cleavage of an endoperoxide bridge by ferrous iron/heme

Q5. Partial artemisinin resistance in Plasmodium falciparum has been associated with mutations in which gene?

  • pfcrt (chloroquine resistance transporter)
  • kelch13 (PfK13 propeller domain)
  • pfmdr1 (multidrug resistance protein 1)
  • dhfr (dihydrofolate reductase)

Correct Answer: kelch13 (PfK13 propeller domain)

Q6. The recommended treatment for severe falciparum malaria in hospitalized patients is:

  • Oral artemether-lumefantrine
  • Intravenous quinidine
  • Intravenous artesunate
  • Intramuscular chloroquine

Correct Answer: Intravenous artesunate

Q7. The most clinically important adverse reaction of primaquine that requires screening prior to therapy is:

  • Severe hepatotoxicity
  • Hemolytic anemia in G6PD-deficient patients
  • Prolonged QT interval
  • Nephrotoxicity

Correct Answer: Hemolytic anemia in G6PD-deficient patients

Q8. Amplification (increased copy number) of which parasite gene is commonly linked to mefloquine resistance?

  • pfcrt
  • pfmdr1
  • kelch13
  • dhps (dihydropteroate synthase)

Correct Answer: pfmdr1

Q9. Tafenoquine distinguishes itself from primaquine because it:

  • Does not require G6PD testing
  • Is approved as a single-dose radical cure for P. vivax due to its long half-life but still requires G6PD testing
  • Is safe in pregnancy
  • Acts primarily by inhibiting parasite DHFR

Correct Answer: Is approved as a single-dose radical cure for P. vivax due to its long half-life but still requires G6PD testing

Q10. In ACTs, the role of the non-artemisinin partner drug is primarily to:

  • Provide immediate rapid parasite clearance within hours
  • Prevent relapse from hypnozoites
  • Eliminate residual parasites with a longer half-life and reduce selection of resistant mutants
  • Act as an antidote to artemisinin toxicity

Correct Answer: Eliminate residual parasites with a longer half-life and reduce selection of resistant mutants

Q11. Lumefantrine is primarily metabolized by which cytochrome P450 enzyme, with clinical implications for drug interactions?

  • CYP2D6
  • CYP3A4
  • CYP1A2
  • CYP2C9

Correct Answer: CYP3A4

Q12. Which patient group should not receive primaquine for radical cure due to risk to the fetus?

  • Children under 2 years
  • Pregnant women
  • Breastfeeding mothers
  • Patients with controlled hypertension

Correct Answer: Pregnant women

Q13. For a traveler to an area with chloroquine-resistant P. falciparum, which prophylactic regimen is commonly recommended?

  • Chloroquine weekly
  • Atovaquone-proguanil daily
  • Primaquine single dose before travel
  • High-dose mefloquine daily

Correct Answer: Atovaquone-proguanil daily

Q14. Which of the following is a key strategy to delay or manage antimalarial drug resistance at the population level?

  • Widespread use of monotherapy with artemisinin derivatives
  • Use of artemisinin-based combination therapies with surveillance of efficacy and molecular markers, plus ensuring full treatment adherence
  • Banning all antimalarial use in endemic areas
  • Using subtherapeutic dosing to decrease selection pressure

Correct Answer: Use of artemisinin-based combination therapies with surveillance of efficacy and molecular markers, plus ensuring full treatment adherence

Q15. The mechanistic basis of the atovaquone-proguanil combination is best described as:

  • Both drugs inhibit heme polymerization
  • Atovaquone inhibits mitochondrial cytochrome bc1 (electron transport); proguanil’s metabolite inhibits dihydrofolate reductase (DHFR)
  • Both drugs are rapid-acting endoperoxides
  • Atovaquone is a folate antagonist; proguanil blocks protein synthesis

Correct Answer: Atovaquone inhibits mitochondrial cytochrome bc1 (electron transport); proguanil’s metabolite inhibits dihydrofolate reductase (DHFR)

Q16. Which antimalarial is classically associated with the syndrome of “cinchonism” (tinnitus, headache, nausea, visual disturbances)?

  • Artemisinin
  • Primaquine
  • Quinine
  • Atovaquone

Correct Answer: Quinine

Q17. The single amino acid substitution most commonly used as a molecular marker for chloroquine resistance is:

  • K76T mutation in pfcrt
  • N86Y mutation in pfmdr1
  • C580Y mutation in kelch13
  • S108N mutation in dhfr

Correct Answer: K76T mutation in pfcrt

Q18. What is the recommended therapy for uncomplicated P. falciparum malaria in the first trimester of pregnancy?

  • Artemisinin-based combination therapy (ACT) such as artemether-lumefantrine
  • Quinine combined with clindamycin
  • Primaquine single dose
  • Atovaquone-proguanil

Correct Answer: Quinine combined with clindamycin

Q19. Effective national monitoring for emerging antimalarial resistance should include which of the following components?

  • Only passive case reporting of treatment failures
  • Therapeutic efficacy studies combined with molecular marker surveillance and pharmacovigilance
  • Restricting diagnostics to microscopy only
  • Exclusive reliance on in vitro drug sensitivity testing without clinical correlation

Correct Answer: Therapeutic efficacy studies combined with molecular marker surveillance and pharmacovigilance

Q20. Co-administration of a strong CYP3A4 inducer (e.g., rifampicin) is likely to have which effect on an ACT containing lumefantrine?

  • Increase lumefantrine plasma concentrations and risk toxicity
  • Reduce lumefantrine plasma concentrations, potentially decreasing ACT efficacy
  • Have no clinically significant effect on lumefantrine levels
  • Convert lumefantrine into a more active metabolite enhancing efficacy

Correct Answer: Reduce lumefantrine plasma concentrations, potentially decreasing ACT efficacy

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