Primaquine and Pamaquine – mechanism and toxicity MCQs With Answer

Primaquine and Pamaquine – mechanism and toxicity MCQs With Answer

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Introduction

Primaquine and pamaquine are 8‑aminoquinoline antimalarials important in the pharmacology curriculum for B. Pharm students. This topic covers mechanism of action — hepatic bioactivation to oxidative metabolites that target hypnozoites and gametocytes — and key toxicity issues including hemolysis in G6PD deficiency, methemoglobinemia, gastrointestinal effects, and drug interactions (notably CYP2D6-related activation). Understanding pharmacokinetics, contraindications (pregnancy, infants), monitoring, and management of adverse effects is essential for safe clinical use. These focused MCQs reinforce concepts of radical cure, metabolic activation, toxicity screening, and therapeutic decisions in antimalarial pharmacotherapy. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary mechanism by which primaquine exerts its antimalarial activity against hypnozoites?

  • Inhibition of heme polymerization in the parasite food vacuole
  • Intercalation into parasite DNA preventing replication
  • Hepatic biotransformation to oxidative metabolites that generate reactive oxygen species damaging parasite organelles
  • Blockade of folate synthesis by dihydropteroate synthase inhibition

Correct Answer: Hepatic biotransformation to oxidative metabolites that generate reactive oxygen species damaging parasite organelles

Q2. Pamaquine (plasmoquine) is best described as:

  • A widely used first‑line antimalarial in current WHO guidelines
  • An older 8‑aminoquinoline similar to primaquine but largely abandoned due to high toxicity
  • A 4‑aminoquinoline used primarily for chloroquine‑resistant falciparum malaria
  • An antimalarial that acts exclusively on blood schizonts with no hepatic activity

Correct Answer: An older 8‑aminoquinoline similar to primaquine but largely abandoned due to high toxicity

Q3. Which malaria stages are specifically targeted by primaquine?

  • Only erythrocytic asexual blood stages
  • Hypnozoites in the liver and gametocytes in the blood
  • Trophozoites in the mosquito midgut
  • Only sporozoites in the mosquito salivary glands

Correct Answer: Hypnozoites in the liver and gametocytes in the blood

Q4. Activation of primaquine to its active metabolites primarily depends on which cytochrome P450 enzyme?

  • CYP3A4
  • CYP1A2
  • CYP2D6
  • CYP2C9

Correct Answer: CYP2D6

Q5. The most clinically important toxicity of primaquine is:

  • Hepatotoxicity with elevated transaminases
  • Severe renal failure
  • Oxidative hemolysis in individuals with G6PD deficiency
  • Cardiac arrhythmias due to QT prolongation

Correct Answer: Oxidative hemolysis in individuals with G6PD deficiency

Q6. Before prescribing primaquine, which test is essential to minimize risk of severe hemolysis?

  • Serum creatinine measurement
  • Liver function tests (ALT/AST)
  • G6PD enzyme activity assay
  • Electrocardiogram (ECG)

Correct Answer: G6PD enzyme activity assay

Q7. Primaquine is contraindicated in pregnancy primarily because:

  • It causes teratogenic malformations in the first trimester
  • Fetal G6PD status is unknown and the fetus is at risk of hemolysis
  • It is ineffective during pregnancy due to hormonal changes
  • It causes uterine contractions leading to preterm labor

Correct Answer: Fetal G6PD status is unknown and the fetus is at risk of hemolysis

Q8. Methemoglobinemia produced by primaquine results from oxidation of hemoglobin iron to which state?

  • Ferrous (Fe2+) species that bind oxygen tightly
  • Ferric (Fe3+) species that cannot bind oxygen effectively
  • Manganese‑bound hemoglobin complex
  • Porphyrin‑bound ferrous complex

Correct Answer: Ferric (Fe3+) species that cannot bind oxygen effectively

Q9. Which laboratory pattern is most consistent with intravascular hemolysis due to primaquine in a susceptible patient?

  • Rising hemoglobin with low indirect bilirubin
  • Falling hemoglobin, elevated indirect bilirubin and low haptoglobin
  • Isolated thrombocytopenia without hemoglobin change
  • Increased albumin with normal bilirubin

Correct Answer: Falling hemoglobin, elevated indirect bilirubin and low haptoglobin

Q10. Immediate management when hemolysis is suspected after primaquine administration includes:

  • Continue drug and increase dose to overcome resistance
  • Stop primaquine, provide supportive care and consider blood transfusion if severe
  • Give high‑dose aspirin to reduce hemolysis
  • Administer cholestyramine to bind primaquine in the gut

Correct Answer: Stop primaquine, provide supportive care and consider blood transfusion if severe

Q11. Standard adult dosing of primaquine for radical cure of P. vivax (typical regimen) is:

  • Single dose of 600 mg base
  • 15 mg base orally daily for 14 days
  • 500 mg intravenously once weekly for 4 weeks
  • 50 mg orally once monthly for 6 months

Correct Answer: 15 mg base orally daily for 14 days

Q12. Compared with primaquine, pamaquine was historically associated with:

  • Lesser risk of hemolysis and better safety profile
  • Greater toxicity and worse tolerability leading to limited use
  • Specific activity only against P. falciparum blood stages
  • Use as a combination therapy with artemisinin derivatives

Correct Answer: Greater toxicity and worse tolerability leading to limited use

Q13. Tafenoquine is related to primaquine in that it:

  • Is a 4‑aminoquinoline used only for blood schizonts
  • Is an 8‑aminoquinoline with activity against hypnozoites and can be single‑dose for radical cure
  • Has no risk of hemolysis and is safe in G6PD deficiency
  • Is administered topically for cutaneous leishmaniasis

Correct Answer: Is an 8‑aminoquinoline with activity against hypnozoites and can be single‑dose for radical cure

Q14. A patient who is a CYP2D6 poor metabolizer is likely to experience which consequence when given primaquine?

  • Increased production of toxic metabolites and worse hemolysis
  • Decreased conversion to active metabolites and reduced antimalarial efficacy
  • Immediate hypersensitivity reaction independent of metabolism
  • Enhanced renal excretion causing acute kidney injury

Correct Answer: Decreased conversion to active metabolites and reduced antimalarial efficacy

Q15. The most common gastrointestinal adverse effects of primaquine include:

  • Constipation and biliary colic
  • Nausea, abdominal pain and epigastric discomfort
  • Severe pancreatitis in most patients
  • Painless hematemesis

Correct Answer: Nausea, abdominal pain and epigastric discomfort

Q16. Which organ is the primary site of primaquine metabolism and bioactivation?

  • Kidneys
  • Spleen
  • Liver
  • Lung

Correct Answer: Liver

Q17. Concomitant use of potent CYP2D6 inhibitors with primaquine would most likely result in:

  • Increased formation of active metabolites and greater efficacy
  • Reduced generation of active metabolites and potential treatment failure
  • Rapid renal clearance and increased toxicity
  • No change since primaquine is not metabolized by CYP enzymes

Correct Answer: Reduced generation of active metabolites and potential treatment failure

Q18. In G6PD deficiency, which erythrocyte population is most susceptible to oxidative damage from primaquine?

  • Young reticulocytes with high G6PD activity
  • Older erythrocytes with lower residual G6PD activity
  • Platelets rather than erythrocytes
  • Leukocytes exclusively

Correct Answer: Older erythrocytes with lower residual G6PD activity

Q19. The principal biochemical basis for primaquine‑induced hemolysis is:

  • Inhibition of erythropoietin production
  • Oxidative stress from reactive metabolites causing membrane lipid peroxidation
  • Autoimmune antibody formation against hemoglobin
  • Direct inhibition of hemoglobin synthesis genes

Correct Answer: Oxidative stress from reactive metabolites causing membrane lipid peroxidation

Q20. A symptomatic patient with methemoglobinemia due to primaquine and normal G6PD activity should be treated with:

  • Methylene blue administration
  • High‑dose vitamin K
  • Oral iron supplementation only
  • Immediate exchange transfusion as first‑line without other measures

Correct Answer: Methylene blue administration

Q21. Which clinical sign is characteristic of methemoglobinemia seen with primaquine toxicity?

  • Bluish/gray discoloration of skin and chocolate‑colored blood with low pulse oximetry readings
  • Flushed skin and rapid bradycardia
  • High oxygen saturation (>99%) with severe dyspnea
  • Petechial rash with severe thrombocytopenia

Correct Answer: Bluish/gray discoloration of skin and chocolate‑colored blood with low pulse oximetry readings

Q22. Primaquine should be avoided in neonates because:

  • They have enhanced CYP2D6 activity causing toxicity
  • Neonates commonly have unknown or low G6PD activity increasing hemolysis risk
  • Primaquine is ineffective in neonatal physiology
  • It causes permanent tooth discoloration

Correct Answer: Neonates commonly have unknown or low G6PD activity increasing hemolysis risk

Q23. Which statement about pamaquine’s current clinical use is correct?

  • It is commonly used as first‑line radical cure worldwide
  • It has been largely discontinued due to severe toxicity and replaced by safer alternatives
  • It is used exclusively for prophylaxis in travellers
  • It is the preferred therapy in pregnant patients

Correct Answer: It has been largely discontinued due to severe toxicity and replaced by safer alternatives

Q24. Primaquine is classified pharmacologically as a:

  • Blood schizonticide only
  • Tissue hypnozoiticide and gametocytocide (radical cure agent)
  • Direct antitoxin agent neutralizing malaria toxins
  • Parasite cell wall synthesis inhibitor

Correct Answer: Tissue hypnozoiticide and gametocytocide (radical cure agent)

Q25. Radical cure with primaquine is specifically indicated to eradicate latent liver forms of which species?

  • Plasmodium falciparum only
  • Plasmodium vivax and Plasmodium ovale
  • Plasmodium malariae only
  • All parasitic protozoa including Leishmania

Correct Answer: Plasmodium vivax and Plasmodium ovale

Q26. A drug that strongly inhibits CYP2D6 is co‑administered with primaquine. The most likely clinical effect is:

  • Increased risk of primaquine‑induced hemolysis
  • Reduced antirelapse efficacy of primaquine
  • Enhanced gastrointestinal absorption of primaquine
  • Shorter half‑life of primaquine due to autoinduction

Correct Answer: Reduced antirelapse efficacy of primaquine

Q27. Populations with high prevalence of G6PD deficiency (and thus at risk for primaquine hemolysis) include:

  • Northern European populations only
  • African, Mediterranean and some Asian populations
  • Only native populations of South America
  • All populations are equally affected worldwide

Correct Answer: African, Mediterranean and some Asian populations

Q28. During primaquine therapy, which monitoring parameter should be checked to detect early hemolysis?

  • Serum amylase weekly
  • Hemoglobin or hematocrit and signs of jaundice
  • Blood glucose hourly
  • Serum potassium every 24 hours

Correct Answer: Hemoglobin or hematocrit and signs of jaundice

Q29. Both primaquine and pamaquine belong to which chemical class of antimalarials?

  • 4‑Aminoquinolines
  • 8‑Aminoquinolines
  • Artemisinin derivatives
  • Sulfonamides

Correct Answer: 8‑Aminoquinolines

Q30. For a patient with confirmed G6PD deficiency who requires treatment for P. vivax, the best immediate approach regarding primaquine is:

  • Start standard primaquine regimen without testing
  • Administer a higher dose of primaquine to overcome resistance
  • Avoid primaquine due to hemolysis risk and manage blood stages while consulting a specialist for safe radical‑cure options
  • Give methylene blue prophylactically alongside primaquine to prevent hemolysis

Correct Answer: Avoid primaquine due to hemolysis risk and manage blood stages while consulting a specialist for safe radical‑cure options

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