Natural Products as Leads: Cardiovascular drugs (Lovastatin, Dicoumarol) MCQs With Answer

Introduction: This quiz collection focuses on “Natural Products as Leads: Cardiovascular drugs (Lovastatin, Dicoumarol) MCQs With Answer” tailored for M.Pharm students preparing for MPC 104T Chemistry of Natural Products. It covers biosynthetic origins, structural features, mechanisms of action, pharmacokinetics, drug interactions, adverse effects, SAR and analytical considerations for lovastatin and dicoumarol. Questions are designed to deepen understanding of how natural molecules became therapeutic leads, their chemical transformations (prodrug activation, metabolic pathways), monitoring strategies and clinical implications. Use these MCQs to test core concepts, reinforce critical thinking for exams and practical applications in drug development and therapeutics.

Q1. Which statement best describes the origin and primary class of lovastatin?

• A synthetic bile-acid sequestrant produced by chemical synthesis
• An HMG-CoA reductase inhibitor produced by the fungus Aspergillus terreus
• A plant-derived alkaloid that blocks adrenergic receptors
• A peptide antibiotic isolated from Streptomyces

Correct Answer: An HMG-CoA reductase inhibitor produced by the fungus Aspergillus terreus

Q2. What is the primary biochemical mechanism by which lovastatin reduces plasma cholesterol?

• Inhibition of intestinal cholesterol absorption via NPC1L1 blockade
• Competitive inhibition of HMG-CoA reductase, decreasing mevalonate synthesis
• Activation of lipoprotein lipase to increase triglyceride clearance
• Upregulation of CETP activity to enhance HDL metabolism

Correct Answer: Competitive inhibition of HMG-CoA reductase, decreasing mevalonate synthesis

Q3. Lovastatin is administered as a lactone. Which statement describes its activation in vivo?

• The lactone is excreted unchanged and is the active inhibitor
• Hepatic esterases hydrolyze the lactone to the active β‑hydroxy acid form
• Cytochrome P450 oxidizes the lactone to an active epoxide
• Gut microbiota reduce the lactone to an active alcohol

Correct Answer: Hepatic esterases hydrolyze the lactone to the active β‑hydroxy acid form

Q4. Dicoumarol is historically associated with which natural event leading to toxicity?

• Consumption of improperly fermented soy leading to alkaloid poisoning
• Ingestion of spoiled sweet clover hay producing a natural anticoagulant
• Eating moldy grains producing aflatoxin-mediated hemorrhage
• Drinking water contaminated with nitrates causing methemoglobinemia

Correct Answer: Ingestion of spoiled sweet clover hay producing a natural anticoagulant

Q5. What is the primary molecular target and consequence of dicoumarol action?

• Inhibition of thrombin directly, preventing fibrin formation
• Antagonism of vitamin K epoxide reductase, reducing γ‑carboxylation of clotting factors
• Activation of plasminogen to plasmin, increasing fibrinolysis
• Blocking platelet GP IIb/IIIa receptors to inhibit aggregation

Correct Answer: Antagonism of vitamin K epoxide reductase, reducing γ‑carboxylation of clotting factors

Q6. Which adverse effect is characteristically associated with statins like lovastatin and is increased by certain drug interactions?

• Severe thrombocytopenia exacerbated by penicillins
• Myopathy/rhabdomyolysis risk, increased with CYP3A4 inhibitors or fibrates
• QT prolongation potentiated by macrolides
• Bronchospasm aggravated by β‑agonists

Correct Answer: Myopathy/rhabdomyolysis risk, increased with CYP3A4 inhibitors or fibrates

Q7. Which hepatic enzyme system is primarily responsible for metabolism of lovastatin?

• CYP2D6
• CYP1A2
• CYP3A4
• CYP2C9

Correct Answer: CYP3A4

Q8. In the structure–activity relationship (SAR) of statins, which moiety is critical for mimicking the HMG-CoA substrate and binding HMG-CoA reductase?

• A lipophilic polycyclic decalin ring only
• The dihydroxyheptanoic acid (HMG-like) moiety
• An aromatic nitro group at the para position
• A sulfhydryl group chelating magnesium

Correct Answer: The dihydroxyheptanoic acid (HMG-like) moiety

Q9. Which laboratory test is primarily used to monitor anticoagulant effect in patients on dicoumarol-like vitamin K antagonists?

• Activated partial thromboplastin time (aPTT)
• Thrombin time (TT)
• Prothrombin time/International Normalized Ratio (PT/INR)
• Bleeding time

Correct Answer: Prothrombin time/International Normalized Ratio (PT/INR)

Q10. Clinically, lovastatin is most effective at lowering which lipid parameter?

• HDL cholesterol (major increase)
• LDL cholesterol (primary reduction)
• Serum free fatty acids
• Chylomicron remnants exclusively

Correct Answer: LDL cholesterol (primary reduction)

Q11. Which interaction increases the anticoagulant effect of dicoumarol in patients?

• Concurrent broad‑spectrum antibiotic therapy reducing gut vitamin K synthesis
• High dietary vitamin K intake from leafy greens
• Use of sucralfate binding dicoumarol in the gut decreasing absorption
• Concurrent administration of rifampicin inducing dicoumarol levels

Correct Answer: Concurrent broad‑spectrum antibiotic therapy reducing gut vitamin K synthesis

Q12. The biosynthetic pathway that produces lovastatin in filamentous fungi primarily involves which enzymatic assembly line?

• Nonribosomal peptide synthetase (NRPS) pathway
• Shikimate pathway enzymes
• Polyketide synthase (PKS) pathway
• Terpene cyclase pathway

Correct Answer: Polyketide synthase (PKS) pathway

Q13. Dicoumarol’s chemical structure is best described as which of the following?

• A monomeric 4‑hydroxycoumarin with a nitro substituent
• A dimer of 4‑hydroxycoumarin linked by a methylene bridge (3,3’‑methylenebis(4‑hydroxycoumarin))
• A linear polyphenolic chain derived from cinnamic acid
• A tricyclic lactone unrelated to coumarins

Correct Answer: A dimer of 4‑hydroxycoumarin linked by a methylene bridge (3,3’‑methylenebis(4‑hydroxycoumarin))

Q14. Compared to the lactone form, the open β‑hydroxy acid form of lovastatin has which pharmacological property?

• It is inactive and has no affinity for HMG-CoA reductase
• It is the active form with higher affinity for the enzyme
• It causes immediate immune-mediated hepatotoxicity
• It loses lipid-lowering activity but gains anticoagulant effect

Correct Answer: It is the active form with higher affinity for the enzyme

Q15. What is the recommended antidote for bleeding due to dicoumarol overdose?

• Protamine sulfate
• Vitamin K1 (phytonadione)
• Idarucizumab
• Fresh frozen plasma is contraindicated

Correct Answer: Vitamin K1 (phytonadione)

Q16. Which monitoring parameter is routinely recommended when initiating or increasing the dose of lovastatin?

• Serum creatine kinase only, without liver tests
• Complete blood count weekly
• Baseline and periodic liver function tests (transaminases)
• Serum amylase monthly to check for pancreatitis

Correct Answer: Baseline and periodic liver function tests (transaminases)

Q17. Genetic variation in which hepatic transporter is linked to increased statin myopathy risk due to altered hepatic uptake (notably for simvastatin and related statins)?

• SLCO1B1 (OATP1B1)
• ABCB1 (P‑glycoprotein)
• CFTR chloride channel
• SLC6A4 serotonin transporter

Correct Answer: SLCO1B1 (OATP1B1)

Q18. Which statement correctly contrasts dicoumarol and warfarin?

• Dicoumarol is a synthetic derivative developed after warfarin
• Warfarin is a naturally occurring dimeric coumarin like dicoumarol
• Dicoumarol is the naturally occurring prototype vitamin K antagonist; warfarin is a later synthetic 4‑hydroxycoumarin analogue
• Both are direct thrombin inhibitors with identical pharmacokinetics

Correct Answer: Dicoumarol is the naturally occurring prototype vitamin K antagonist; warfarin is a later synthetic 4‑hydroxycoumarin analogue

Q19. Beyond LDL reduction, statins such as lovastatin exhibit pleiotropic effects that include:

• Pro‑inflammatory cytokine upregulation and plaque destabilization
• Anti‑inflammatory effects, improved endothelial function and plaque stabilization
• Direct vasoconstriction via calcium channel blockade
• Impaired wound healing due to collagen synthesis inhibition

Correct Answer: Anti‑inflammatory effects, improved endothelial function and plaque stabilization

Q20. For quantitative analysis of lovastatin in pharmaceutical formulations and plasma, which analytical technique provides the best sensitivity and specificity?

• Thin‑layer chromatography with visual staining only
• HPLC coupled with mass spectrometric detection (HPLC‑MS/MS)
• Titrimetric assay against a strong base
• Naked-eye color comparison against standards

Correct Answer: HPLC coupled with mass spectrometric detection (HPLC‑MS/MS)

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