The study of antimalarial drugs — mechanism of action and resistance — is essential for B.Pharm students preparing for careers in pharmacology, clinical pharmacy, and drug development. This introduction covers key keywords: antimalarial drugs, mechanism of action, Plasmodium biology, heme detoxification, artemisinin, chloroquine, sulfadoxine‑pyrimethamine, atovaquone, primaquine, molecular markers (PfCRT, PfMDR1, K13), resistance mechanisms, cross‑resistance, and combination therapy. Understanding how drugs act at molecular targets and how Plasmodium evolves resistance helps students interpret pharmacokinetics, resistance surveillance, and rational therapy design. Practical knowledge of laboratory assays and resistance markers is also highlighted. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which primary mechanism explains chloroquine’s antimalarial activity?
- Inhibition of dihydrofolate reductase (DHFR)
- Interference with heme detoxification in the parasite food vacuole
- Blockade of mitochondrial electron transport at cytochrome bc1
- Generation of reactive oxygen species through endoperoxide activation
Correct Answer: Interference with heme detoxification in the parasite food vacuole
Q2. Resistance to chloroquine in Plasmodium falciparum is most commonly associated with mutations in which gene?
- k13 (Kelch propeller)
- pfcrt (chloroquine resistance transporter)
- dhps (dihydropteroate synthase)
- cytb (cytochrome b)
Correct Answer: pfcrt (chloroquine resistance transporter)
Q3. Artemisinin derivatives exert rapid parasiticidal effects primarily by:
- Inhibiting protein synthesis at the 80S ribosome
- Alkylation of heme and generation of free radicals after activation by iron
- Blocking folate synthesis by competitive inhibition of PABA
- Disrupting DNA replication by intercalation
Correct Answer: Alkylation of heme and generation of free radicals after activation by iron
Q4. The validated molecular marker associated with artemisinin partial resistance (delayed clearance) is:
- Mutations in pfcrt
- Amplification of pfmdr1
- Mutations in the k13 propeller domain
- Point mutations in cytb
Correct Answer: Mutations in the k13 propeller domain
Q5. Sulfadoxine‑pyrimethamine combination targets which two enzymes in folate pathway?
- Dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR)
- DNA gyrase and topoisomerase IV
- Heme polymerase and plasmepsin
- Cytochrome P450 and monoamine oxidase
Correct Answer: Dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR)
Q6. Atovaquone’s antimalarial action is mainly due to inhibition of:
- Mitochondrial cytochrome bc1 complex (cytochrome b)
- Parasite ribosomal 30S subunit
- Food vacuole heme polymerase
- Glucose uptake transporters
Correct Answer: Mitochondrial cytochrome bc1 complex (cytochrome b)
Q7. A common resistance mechanism to atovaquone involves point mutations in:
- Plasmodium falciparum mitochondrial cytochrome b (cytb)
- pfcrt transporter protein
- Human CYP3A4 enzyme
- Parasite dihydrofolate reductase
Correct Answer: Plasmodium falciparum mitochondrial cytochrome b (cytb)
Q8. Mefloquine resistance is frequently linked to which genetic change?
- Amplification (increased copy number) of pfmdr1
- Deletion of k13 gene
- Point mutation in DHFR
- Loss of mitochondrial DNA
Correct Answer: Amplification (increased copy number) of pfmdr1
Q9. Primaquine is unique among antimalarials because it:
- Specifically targets gametocytes and hypnozoites (liver stages)
- Is a quinoline that accumulates in the food vacuole
- Inhibits the parasite cytochrome bc1 complex
- Acts purely as a blood schizonticide like chloroquine
Correct Answer: Specifically targets gametocytes and hypnozoites (liver stages)
Q10. Which safety test is essential before administering primaquine or tafenoquine?
- Pregnancy test only
- Liver function tests exclusively
- Glucose‑6‑phosphate dehydrogenase (G6PD) deficiency screening
- Renal clearance measurement
Correct Answer: Glucose‑6‑phosphate dehydrogenase (G6PD) deficiency screening
Q11. Piperaquine resistance in P. falciparum has been associated with:
- Point mutations in k13 only
- Amplification of plasmepsin II/III genes and changes in pfcrt
- Human host CYP polymorphisms
- Loss of mitochondrial function
Correct Answer: Amplification of plasmepsin II/III genes and changes in pfcrt
Q12. Which assay is commonly used to detect artemisinin resistance characterized by survival of early ring stages?
- IC50 parasite growth inhibition assay
- Ring‑stage survival assay (RSA)
- Disk diffusion assay
- ELISA for antimalarial antibodies
Correct Answer: Ring‑stage survival assay (RSA)
Q13. Which of the following describes a resistance mechanism that reduces drug accumulation in the Plasmodium food vacuole?
- Overexpression of human drug efflux pumps
- Mutations in pfcrt and pfmdr1 altering transporter function
- Increased hepatic metabolism in the human host
- Mutations in parasite ribosomal RNA
Correct Answer: Mutations in pfcrt and pfmdr1 altering transporter function
Q14. The partner drug in artemisinin-based combination therapy (ACT) is chosen primarily to:
- Shorten absorption time of artemisinin
- Provide a longer half‑life to clear residual parasites and prevent resistance
- Enhance artemisinin activation by heme
- Reduce artemisinin side effects by competition
Correct Answer: Provide a longer half‑life to clear residual parasites and prevent resistance
Q15. Which antimalarial acts by inhibiting plasmodial dihydroorotate dehydrogenase (DHODH)?
- Proguanil
- DSM265 (investigational DHODH inhibitor)
- Chloroquine
- Artemether
Correct Answer: DSM265 (investigational DHODH inhibitor)
Q16. The mechanism of action of proguanil’s active metabolite (cycloguanil) is:
- Inhibition of dihydrofolate reductase (DHFR)
- Direct disruption of heme polymerization
- Inhibition of mitochondrial ATP synthase
- Chelation of iron in the food vacuole
Correct Answer: Inhibition of dihydrofolate reductase (DHFR)
Q17. Cross‑resistance between chloroquine and amodiaquine is mainly due to:
- Similar activation by cytochrome P450
- Shared target in folate synthesis
- Convergent mutations affecting drug transporters like PfCRT
- Identical chemical structures
Correct Answer: Convergent mutations affecting drug transporters like PfCRT
Q18. Which pharmacokinetic property of partner drugs in ACTs is most important for preventing the emergence of resistance?
- Very rapid hepatic metabolism
- Long elimination half‑life to maintain therapeutic concentrations after artemisinin clearance
- Extensive protein binding only
- High volume of distribution without plasma persistence
Correct Answer: Long elimination half‑life to maintain therapeutic concentrations after artemisinin clearance
Q19. A clinician suspects treatment failure with sulfadoxine‑pyrimethamine. Molecular testing reveals mutations in both dhfr and dhps. This indicates:
- Increased susceptibility to SP
- Multigenic resistance leading to SP treatment failure
- Resistance to atovaquone instead
- Only host metabolic issues, not parasite resistance
Correct Answer: Multigenic resistance leading to SP treatment failure
Q20. The role of PfMDR1 in antimalarial resistance includes:
- Encoding the heme polymerase enzyme
- Acting as an ATP‑binding cassette transporter affecting multiple drug susceptibilities
- Serving as a mitochondrial electron carrier
- Direct activation of artemisinin endoperoxide bond
Correct Answer: Acting as an ATP‑binding cassette transporter affecting multiple drug susceptibilities
Q21. Which drug is recommended for radical cure of P. vivax hypnozoites (with G6PD testing)?
- Chloroquine alone
- Primaquine or tafenoquine
- Amodiaquine
- Mefloquine
Correct Answer: Primaquine or tafenoquine
Q22. Drug tolerance leading to delayed parasite clearance during ACT therapy is most concerning because it:
- Indicates immediate treatment success
- May facilitate selection of parasites with higher-level resistance
- Is only a pharmacokinetic issue in the host
- Is always reversible without changing therapy
Correct Answer: May facilitate selection of parasites with higher-level resistance
Q23. Which laboratory measure quantifies the concentration of drug that inhibits 50% of parasite growth in vitro?
- Minimum inhibitory concentration (MIC)
- IC50 (half maximal inhibitory concentration)
- Area under the curve (AUC)
- Therapeutic index (TI)
Correct Answer: IC50 (half maximal inhibitory concentration)
Q24. Combination therapy reduces the risk of resistance mainly by:
- Using two drugs with identical mechanisms
- Applying multiple selective pressures making simultaneous resistance less likely
- Lowering drug doses to subtherapeutic levels
- Targeting human enzymes to slow parasite evolution
Correct Answer: Applying multiple selective pressures making simultaneous resistance less likely
Q25. Which antimalarial drug’s efficacy is most reduced by mutations in parasite folate pathway enzymes?
- Atovaquone
- Sulfadoxine‑pyrimethamine
- Artemisinin
- Piperaquine
Correct Answer: Sulfadoxine‑pyrimethamine
Q26. Which statement about halofantrine is true in the context of resistance and safety?
- It has no cardiac effects and is safe in all patients
- Resistance is widespread due to k13 mutations
- Its use is limited by cardiotoxicity (QT prolongation) despite efficacy
- It targets mitochondrial DHODH specifically
Correct Answer: Its use is limited by cardiotoxicity (QT prolongation) despite efficacy
Q27. A rise in IC50 values in field isolates over time suggests:
- Increasing parasite susceptibility to the drug
- Emerging reduced susceptibility or resistance to the drug
- Improved host immunity only
- Laboratory contamination of cultures
Correct Answer: Emerging reduced susceptibility or resistance to the drug
Q28. Which factor contributes to the selection of resistant Plasmodium strains in the community?
- Complete adherence to recommended combination therapy
- Monotherapy with long half‑life drugs and subtherapeutic dosing
- Use of bed nets exclusively
- Rapid diagnosis and effective treatment with ACTs
Correct Answer: Monotherapy with long half‑life drugs and subtherapeutic dosing
Q29. Which antimalarial requires metabolic activation by human hepatic enzymes to form its active metabolite cycloguanil?
- Primaquine
- Proguanil
- Chloroquine
- Artesunate
Correct Answer: Proguanil
Q30. In surveillance of antimalarial resistance, which combined approach yields the most reliable data?
- Clinical therapeutic efficacy studies, in vitro susceptibility testing, and molecular marker monitoring
- Only in vitro IC50 testing
- Relying solely on patient self‑reports of fever resolution
- Measuring serum drug levels without parasite testing
Correct Answer: Clinical therapeutic efficacy studies, in vitro susceptibility testing, and molecular marker monitoring
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.
Mail- Sachin@pharmacyfreak.com