Quinine sulfate – chemistry and mechanism is an essential topic for B.Pharm students studying antimalarial pharmacology and medicinal chemistry. Quinine, a chiral cinchona alkaloid (base formula C20H24N2O2), is converted to a sulfate salt to improve aqueous solubility for oral and parenteral use. Its pharmacodynamics involve accumulation in the Plasmodium food vacuole, binding hematin and inhibiting hemozoin formation, leading to toxic heme buildup. Understanding quinine’s structure-activity relationships, stereochemistry, salt chemistry, metabolism (CYP-mediated), resistance mechanisms (pfcrt/pfmdr1), drug interactions, and adverse effects (cinchonism, QT prolongation, hypoglycemia) is vital for safe clinical use. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the molecular formula of quinine (base)?
- C20H24N2O2
- C19H22N2O2
- C21H26N2O3
- C20H22N2O
Correct Answer: C20H24N2O2
Q2. Quinine sulfate as a pharmaceutical salt typically exists in which stoichiometric ratio?
- One quinine molecule per one sulfate ion
- Two quinine molecules per one sulfate (dihydrogen sulfate) molecule
- One quinine molecule per two sulfate ions
- Three quinine molecules per one sulfate molecule
Correct Answer: Two quinine molecules per one sulfate (dihydrogen sulfate) molecule
Q3. Which key functional group is present in the quinine molecule and important for its protonation in acidic vacuoles?
- Secondary alcohol
- Carboxylic acid
- Primary amine
- Amide
Correct Answer: Secondary alcohol
Q4. What is the primary molecular mechanism by which quinine exerts antimalarial effects?
- Inhibition of folate synthesis
- Binding heme/hematin and inhibiting hemozoin formation
- Blocking microtubule polymerization
- Direct inhibition of ribosomal protein synthesis
Correct Answer: Binding heme/hematin and inhibiting hemozoin formation
Q5. In which intracellular compartment of Plasmodium does quinine primarily accumulate to exert its effect?
- Parasite mitochondrion
- Food (digestive) vacuole
- Endoplasmic reticulum
Correct Answer: Food (digestive) vacuole
Q6. The toxic species that accumulates in the parasite due to quinine action is:
- Hemozoin crystals
- Free heme/hematin
- Unfolded proteins
- Reactive oxygen radicals exclusively
Correct Answer: Free heme/hematin
Q7. Quinine resistance in Plasmodium falciparum is commonly associated with mutations in which genes?
- pfmdr1 and pfcrt
- dhfr and dhps
- k13 and atp6
- g6pd and mdr2
Correct Answer: pfmdr1 and pfcrt
Q8. Which cytochrome P450 enzyme is most implicated in the hepatic metabolism of quinine?
- CYP3A4
- CYP2D6
- CYP1A2
- CYP2E1
Correct Answer: CYP3A4
Q9. “Cinchonism” caused by quinine typically includes which symptoms?
- Tinnitus and headache
- Renal colic and hematuria
- Dry mouth and constipation only
- Brittle nails and hair loss
Correct Answer: Tinnitus and headache
Q10. A serious cardiovascular adverse effect of quinine is:
- QT interval prolongation
- Hypertrophic cardiomyopathy
- Aortic stenosis
- Pericarditis
Correct Answer: QT interval prolongation
Q11. Why is quinine commonly administered as the sulfate salt in formulations?
- To decrease potency
- To increase aqueous solubility and enable oral/parenteral dosing
- To prevent metabolism by the liver
- To increase lipophilicity for CNS penetration
Correct Answer: To increase aqueous solubility and enable oral/parenteral dosing
Q12. Quinine is stereochemically characterized as:
- A chiral molecule with multiple stereocenters
- An achiral planar molecule
- A racemic mixture in natural form
- A symmetrical meso compound
Correct Answer: A chiral molecule with multiple stereocenters
Q13. Quinine accumulates in the parasite food vacuole because it is a:
- Strong acid that diffuses into vacuole
- Weak base that becomes protonated and trapped in acidic vacuole
- Neutral lipid-soluble molecule that partitions in membranes
- Metal chelator that binds ferric ions
Correct Answer: Weak base that becomes protonated and trapped in acidic vacuole
Q14. Quinine mainly targets which stage of Plasmodium in human infection?
- Exoerythrocytic liver schizonts
- Asexual erythrocytic stages (blood schizonts)
- Gametocytes only
- Hypnozoites in the liver
Correct Answer: Asexual erythrocytic stages (blood schizonts)
Q15. Which metabolic consequence can occur as an adverse effect of quinine therapy?
- Hyperglycemia due to insulin resistance
- Hypoglycemia due to stimulated insulin release
- Severe lactic acidosis by mitochondrial inhibition
- Hyperuricemia due to decreased excretion
Correct Answer: Hypoglycemia due to stimulated insulin release
Q16. A severe hematological complication occasionally linked to quinine is:
- Pancytopenia due to bone marrow aplasia
- Hemolytic anemia and blackwater fever
- Polycythemia vera
- Iron deficiency anemia
Correct Answer: Hemolytic anemia and blackwater fever
Q17. Which analytical technique is most appropriate for precise assay of quinine in pharmaceutical formulations?
- High-performance liquid chromatography (HPLC)
- Turbidimetric titration
- Simple gravimetric analysis
- Paper chromatography
Correct Answer: High-performance liquid chromatography (HPLC)
Q18. Quinine exhibits which photochemical property relevant to handling and analysis?
- Complete photostability under sunlight
- Photodegradation and characteristic fluorescence under UV
- Becomes colorless when exposed to UV
- Forms stable photoisomers with no activity change
Correct Answer: Photodegradation and characteristic fluorescence under UV
Q19. For severe malaria requiring parenteral therapy, which quinine form is typically used?
- Quinine base as oral tablets
- Quinine sulfate solution for IV/IM administration
- Quinine phosphide for inhalation
- Quinine acetate transdermal patch
Correct Answer: Quinine sulfate solution for IV/IM administration
Q20. Pharmacologically, quinine is classified as which type of antimalarial?
- Primaquine-like hypnozoitocide
- Blood schizonticide
- Sporozoitocide
- Antifolate inhibitor
Correct Answer: Blood schizonticide
Q21. The direct binding target of quinine in the parasite is:
- Hematin (ferriprotoporphyrin IX) derived from hemoglobin digestion
- Parasite DNA polymerase
- Parasite tubulin exclusively
- Plasmodium ribosomal RNA
Correct Answer: Hematin (ferriprotoporphyrin IX) derived from hemoglobin digestion
Q22. Concomitant administration of which of the following is most likely to increase plasma quinine levels?
- A CYP3A4 inducer such as rifampicin
- A CYP3A4 inhibitor such as ketoconazole
- A cholestyramine resin that binds quinine in the gut
- Activated charcoal administered days after dosing
Correct Answer: A CYP3A4 inhibitor such as ketoconazole
Q23. A parasite resistance mechanism that reduces quinine accumulation is best described as:
- Enhanced DNA repair enzymes
- Mutations increasing efflux via transport proteins (e.g., pfmdr1 amplification)
- Increased heme polymerization efficiency only
- Complete loss of hemoglobin digestion
Correct Answer: Mutations increasing efflux via transport proteins (e.g., pfmdr1 amplification)
Q24. Major route of elimination for quinine and its metabolites is:
- Hepatobiliary excretion of unchanged parent only
- Renal excretion of metabolites and some unchanged drug
- Exhalation via lungs
- Sequestration in adipose with no excretion
Correct Answer: Renal excretion of metabolites and some unchanged drug
Q25. Is quinine effective against chloroquine-resistant Plasmodium falciparum?
- No, quinine is ineffective against chloroquine-resistant strains
- Yes, quinine is often effective though resistance can develop
- Only effective when combined with primaquine
- Only effective against liver stages
Correct Answer: Yes, quinine is often effective though resistance can develop
Q26. Which symptom is an early indicator of quinine toxicity (cinchonism)?
- Severe hypertension
- Tinnitus (ringing in the ears)
- Persistent hyperthermia
- Profuse sweating without other signs
Correct Answer: Tinnitus (ringing in the ears)
Q27. A notable physical property of quinine useful for qualitative labs is:
- It is nonpolar and insoluble in organic solvents
- It fluoresces under ultraviolet light
- It forms an insoluble precipitate with sodium chloride
- It lacks any UV absorbance signal
Correct Answer: It fluoresces under ultraviolet light
Q28. Which specific biochemical polymerization step is inhibited by quinine in Plasmodium?
- Polymerization of actin filaments
- Polymerization of heme into inert hemozoin
- Polymerization of nucleotides into DNA
- Polymerization of peptidoglycan in the parasite cell wall
Correct Answer: Polymerization of heme into inert hemozoin
Q29. For severe falciparum malaria in adults, which route of quinine administration is commonly used initially?
- Topical application
- Intravenous infusion
- Intranasal spray
- Rectal suppository only
Correct Answer: Intravenous infusion
Q30. Which laboratory/clinical monitoring is essential during quinine therapy due to its known toxicities?
- Serial liver biopsy
- ECG monitoring for QT interval prolongation
- Daily chest X-ray
- Continuous measurement of intracranial pressure
Correct Answer: ECG monitoring for QT interval prolongation
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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