Reversible inhibitors – Tacrine hydrochloride MCQs With Answer

Reversible inhibitors – Tacrine hydrochloride MCQs With Answer

Tacrine hydrochloride, a classic reversible acetylcholinesterase inhibitor, played a landmark role in Alzheimer’s pharmacology. This concise introduction covers mechanism of action, central nervous system penetration, metabolic pathways, safety concerns like hepatotoxicity, and fundamental enzyme kinetics relevant to B. Pharm students. Keywords: Reversible inhibitors, Tacrine hydrochloride, acetylcholinesterase inhibitor, Alzheimer’s disease, hepatotoxicity, enzyme kinetics, IC50, Ki, B. Pharm MCQs. The questions that follow probe pharmacodynamics, pharmacokinetics, monitoring, drug interactions, assays and clinical implications to deepen understanding and exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary pharmacological action of tacrine hydrochloride?

• Beta-adrenergic receptor agonist
• Monoamine oxidase inhibitor
• Acetylcholinesterase inhibitor
• NMDA receptor antagonist

Correct Answer: Acetylcholinesterase inhibitor

Q2. Tacrine is best described chemically as which of the following?

• 1,2,3,4-tetrahydroacridine (THA)
• Benzodiazepine derivative
• Phenothiazine analog
• Macrolide antibiotic

Correct Answer: 1,2,3,4-tetrahydroacridine (THA)

Q3. Which clinical condition was tacrine primarily developed to treat?

• Parkinson’s disease
• Alzheimer’s disease
• Major depressive disorder
• Epilepsy

Correct Answer: Alzheimer’s disease

Q4. Tacrine’s inhibition of acetylcholinesterase is classified as which type?

• Irreversible covalent inhibition
• Reversible non-covalent inhibition
• Suicide substrate inhibition
• Irreversible chelation

Correct Answer: Reversible non-covalent inhibition

Q5. Which adverse effect led to limited use and regulatory concerns for tacrine?

• Severe renal toxicity
• Hepatotoxicity with elevated liver enzymes
• Ototoxicity and hearing loss
• Severe neutropenia

Correct Answer: Hepatotoxicity with elevated liver enzymes

Q6. Tacrine increases central acetylcholine levels primarily by which mechanism?

• Stimulating acetylcholine synthesis
• Blocking acetylcholine release
• Inhibiting acetylcholinesterase that degrades acetylcholine
• Increasing choline transporter activity

Correct Answer: Inhibiting acetylcholinesterase that degrades acetylcholine

Q7. Which laboratory test should be monitored because of tacrine’s known toxicity?

• Serum creatinine
• Liver function tests (ALT, AST)
• Complete blood glucose
• Thyroid stimulating hormone

Correct Answer: Liver function tests (ALT, AST)

Q8. Tacrine is able to exert central nervous system effects because it has which property?

• Strong P-glycoprotein substrate activity
• High molecular weight (>1000 Da)
• Ability to cross the blood–brain barrier
• Exclusive peripheral distribution

Correct Answer: Ability to cross the blood–brain barrier

Q9. Which enzyme system is primarily responsible for tacrine metabolism?

• CYP2D6
• CYP3A4
• CYP1A2
• CYP2C19

Correct Answer: CYP1A2

Q10. A reversible enzyme inhibitor is characterized by which interaction with the enzyme?

• Covalent bond formation leading to permanent inactivation
• Non-covalent, often reversible binding to the enzyme
• Enzyme degradation via proteolysis
• Alkylation of active-site residues

Correct Answer: Non-covalent, often reversible binding to the enzyme

Q11. Which clinical sign is most consistent with cholinergic excess from tacrine overdose?

• Dry mouth and constipation
• Mydriasis and tachycardia
• Salivation, sweating, bronchospasm and bradycardia
• Hyperactivity and insomnia

Correct Answer: Salivation, sweating, bronchospasm and bradycardia

Q12. The standard laboratory assay widely used to measure acetylcholinesterase activity in research is:

• ELISA for acetylcholine
• Ellman’s colorimetric method using DTNB
• Western blot for enzyme protein
• Mass spectrometry for acetylcholine fragments

Correct Answer: Ellman’s colorimetric method using DTNB

Q13. In enzyme kinetics, a competitive inhibitor typically produces which effect on Km and Vmax?

• Km increases, Vmax unchanged
• Km decreases, Vmax decreases
• Km unchanged, Vmax decreases
• Km decreases, Vmax increases

Correct Answer: Km increases, Vmax unchanged

Q14. Which drug interaction is most likely to increase tacrine plasma concentrations?

• Co-administration with a potent CYP1A2 inhibitor
• Co-administration with CYP1A2 inducer
• Concurrent antacids that reduce absorption
• Concurrent use of cholinergic agonists

Correct Answer: Co-administration with a potent CYP1A2 inhibitor

Q15. Which monitoring advice is essential when initiating tacrine therapy historically?

• Weekly renal ultrasound
• Periodic liver enzyme monitoring during therapy
• Daily EEG monitoring
• Monthly bone density scans

Correct Answer: Periodic liver enzyme monitoring during therapy

Q16. Which of the following best defines IC50 in inhibitor studies?

• Concentration required to kill 50% of cells
• Concentration at which 50% of enzyme activity is inhibited
• Concentration at which 50% of drug is metabolized
• Concentration resulting in 50% bioavailability

Correct Answer: Concentration at which 50% of enzyme activity is inhibited

Q17. Ki is best described as:

• Rate constant for enzyme turnover
• Equilibrium dissociation constant for inhibitor binding
• Plasma half-life of the inhibitor
• Maximum inhibitory effect achievable

Correct Answer: Equilibrium dissociation constant for inhibitor binding

Q18. Tacrine’s withdrawal from widespread clinical use was mainly due to:

• Lack of efficacy in symptomatic relief
• Severe hepatotoxicity limiting safe dosing
• Excessive sedative effects
• Unmanageable psychosis induction

Correct Answer: Severe hepatotoxicity limiting safe dosing

Q19. Which physiological receptor effects mediate many peripheral adverse effects of tacrine?

• Muscarinic receptor stimulation
• Beta-2 adrenergic stimulation
• GABA-A receptor agonism
• Histamine H1 receptor antagonism

Correct Answer: Muscarinic receptor stimulation

Q20. An advantage of reversible inhibitors like tacrine over irreversible inhibitors is:

• Permanent enzyme inactivation after a single dose
• Ability to reverse effects by drug discontinuation or dilution
• No potential for drug interactions
• Unlimited therapeutic index

Correct Answer: Ability to reverse effects by drug discontinuation or dilution

Q21. Which patient condition would raise concern before prescribing tacrine?

• History of well-controlled hypertension
• Active hepatic disease or elevated baseline LFTs
• Corrected mild anemia
• Uncomplicated osteoarthritis

Correct Answer: Active hepatic disease or elevated baseline LFTs

Q22. Which pharmacokinetic property explains tacrine’s central activity?

• High plasma protein binding prevents CNS entry
• High lipid solubility enabling blood–brain barrier penetration
• Rapid renal excretion without metabolism
• Poor oral absorption with no systemic exposure

Correct Answer: High lipid solubility enabling blood–brain barrier penetration

Q23. Which clinical test could indicate tacrine’s therapeutic effect in Alzheimer’s patients?

• Improvement in cognitive scores (e.g., MMSE)
• Increased fasting blood glucose
• Reduction in platelet count
• Elevation of creatine kinase

Correct Answer: Improvement in cognitive scores (e.g., MMSE)

Q24. The term “reversible inhibitor” implies which experimental observation?

• Enzyme activity cannot be restored once inhibited
• Enzyme activity recovers after removing inhibitor or dilution
• Inhibitor permanently modifies the active-site serine
• Enzyme is rapidly degraded by proteases

Correct Answer: Enzyme activity recovers after removing inhibitor or dilution

Q25. Which symptom is least likely to be caused by tacrine’s cholinergic effects?

• Diarrhea
• Bradycardia
• Constipation
• Nausea

Correct Answer: Constipation

Q26. Tacrine interaction with what type of drugs could reduce its therapeutic effect by pharmacodynamic antagonism?

• Anticholinergic drugs like atropine
• SSRIs like fluoxetine
• Proton pump inhibitors like omeprazole
• Statins like atorvastatin

Correct Answer: Anticholinergic drugs like atropine

Q27. In research, reversible inhibition can be distinguished from irreversible by which experimental approach?

• Measuring enzyme protein by Western blot only
• Dialysis or dilution to see recovery of enzyme activity
• Observing color change without activity measurement
• Measuring body temperature changes

Correct Answer: Dialysis or dilution to see recovery of enzyme activity

Q28. Which of the following best describes tacrine’s selectivity?

• Highly selective for monoamine oxidase B
• Primarily inhibits acetylcholinesterase with central effects
• Selective beta-1 adrenergic blocker
• Specific histamine H2 receptor antagonist

Correct Answer: Primarily inhibits acetylcholinesterase with central effects

Q29. Which therapeutic strategy reduces the risk of tacrine-induced hepatotoxicity?

• Empirical high initial dosing without monitoring
• Frequent liver enzyme monitoring and dose adjustment/withdrawal
• Co-administration of nephrotoxic drugs
• Avoiding all dietary protein

Correct Answer: Frequent liver enzyme monitoring and dose adjustment/withdrawal

Q30. Which statement about tacrine’s half-life and dosing considerations is true in general pharmacology context?

• Short half-life may require multiple daily dosing to maintain effect
• Extremely long half-life allows once-monthly dosing
• Half-life is irrelevant for dosing frequency
• Half-life prevents CNS penetration

Correct Answer: Short half-life may require multiple daily dosing to maintain effect

Q31. Which agent is used to treat severe muscarinic symptoms of cholinesterase inhibitor overdose?

• Physostigmine
• Atropine
• Neostigmine
• Oximes like pralidoxime only

Correct Answer: Atropine

Q32. Tacrine structural modifications in medicinal chemistry aim to improve which properties?

• Reduce BBB penetration and increase hepatotoxicity
• Increase potency, selectivity for AChE, and reduce toxicity
• Eliminate binding to acetylcholinesterase entirely
• Increase non-specific protein alkylation

Correct Answer: Increase potency, selectivity for AChE, and reduce toxicity

Q33. Which pharmacodynamic effect is expected with central acetylcholinesterase inhibition?

• Reduced synaptic acetylcholine leading to sedation
• Enhanced cholinergic neurotransmission improving cognition temporarily
• Primary dopaminergic surge causing psychosis
• Direct opioid receptor agonism

Correct Answer: Enhanced cholinergic neurotransmission improving cognition temporarily

Q34. Which experimental parameter indicates reversible competitive inhibition when plotting Lineweaver-Burk graphs?

• Lines intersect on the x-axis, indicating Km unchanged
• Lines intersect on the y-axis, indicating Vmax unchanged
• Parallel lines indicating same slope
• Curved plots not fitting linear behavior

Correct Answer: Lines intersect on the y-axis, indicating Vmax unchanged

Q35. In structure-activity relationship (SAR) studies, replacing which property often affects BBB penetration?

• Increasing molecular polarity
• Decreasing molecular polarity
• Adding bulky charged groups increases penetration
• Increasing degree of ionization at physiological pH

Correct Answer: Decreasing molecular polarity

Q36. Tacrine’s effect on peripheral cholinergic receptors can lead to which cardiovascular effect?

• Hypertension due to vasoconstriction
• Bradycardia due to vagal stimulation
• Reflex tachycardia due to beta stimulation
• Complete AV block always

Correct Answer: Bradycardia due to vagal stimulation

Q37. Which urine or plasma marker is directly indicative of acetylcholinesterase inhibition?

• Increased acetylcholine concentrations in plasma/CSF
• Elevated serum creatinine
• High urinary glucose
• Raised plasma albumin

Correct Answer: Increased acetylcholine concentrations in plasma/CSF

Q38. A drug that competes with substrate for the same active site would most likely show what behavior when substrate concentration is increased?

• Inhibition is overcome at high substrate concentration
• Inhibition becomes irreversible
• Inhibition increases with higher substrate
• Enzyme is degraded instantly

Correct Answer: Inhibition is overcome at high substrate concentration

Q39. Which monitoring frequency was recommended historically during the initial months of tacrine therapy?

• No monitoring required
• Liver enzymes every 1–2 weeks initially
• Daily MRI scans
• Yearly ophthalmic exams only

Correct Answer: Liver enzymes every 1–2 weeks initially

Q40. Which of the following is NOT a typical sign of peripheral cholinergic stimulation?

• Excessive salivation
• Bronchoconstriction
• Pupil dilation (mydriasis)
• Increased gastrointestinal motility

Correct Answer: Pupil dilation (mydriasis)

Q41. Tacrine’s hydrochloride form primarily confers what pharmaceutical advantage?

• Increased volatility for inhalation delivery
• Enhanced water solubility for oral formulation
• Guaranteed bypass of first-pass metabolism
• Intrinsic antidotal properties

Correct Answer: Enhanced water solubility for oral formulation

Q42. Which pharmacological class of drugs would likely worsen tacrine-associated bradycardia?

• Beta-blockers
• Nitrates
• Loop diuretics
• Proton pump inhibitors

Correct Answer: Beta-blockers

Q43. Which experimental outcome supports a reversible binding model for a small-molecule inhibitor?

• Permanent loss of enzyme after short exposure
• Rapid restoration of activity after removing inhibitor by dialysis
• Formation of covalent adducts detected by mass spectrometry exclusively
• Loss of enzyme gene expression

Correct Answer: Rapid restoration of activity after removing inhibitor by dialysis

Q44. In medicinal chemistry, improving selectivity toward central AChE over peripheral AChE aims to:

• Increase peripheral adverse effects
• Reduce peripheral cholinergic side effects and increase CNS benefit
• Make the drug more hepatotoxic
• Prevent crossing the BBB

Correct Answer: Reduce peripheral cholinergic side effects and increase CNS benefit

Q45. Which animal model outcome would indicate potential cognitive benefit of a new tacrine derivative?

• Impaired maze learning and memory
• Improved performance in memory tasks like the Morris water maze
• Reduced locomotor activity only
• Increased food consumption with no cognitive testing

Correct Answer: Improved performance in memory tasks like the Morris water maze

Q46. Which statement about tacrine and butyrylcholinesterase (BuChE) is most accurate?

• Tacrine exclusively inhibits BuChE and not AChE
• Tacrine may inhibit both AChE and BuChE to varying degrees
• Tacrine activates BuChE activity
• Tacrine is degraded by BuChE rather than inhibiting it

Correct Answer: Tacrine may inhibit both AChE and BuChE to varying degrees

Q47. Which property of tacrine analogs would medicinal chemists modify to reduce hepatotoxicity risk?

• Increase formation of reactive metabolites
• Alter metabolic hotspots to reduce reactive metabolite formation
• Increase lipophilicity without regard to metabolism
• Introduce strongly electrophilic moieties

Correct Answer: Alter metabolic hotspots to reduce reactive metabolite formation

Q48. For reversible inhibitors, which kinetic parameter directly reflects binding affinity?

• Vmax
• Km only
• Ki (inhibition constant)
• pKa of the inhibitor

Correct Answer: Ki (inhibition constant)

Q49. Which is a rational step in developing safer tacrine-like drugs for Alzheimer’s therapy?

• Ignore metabolism studies and focus solely on potency
• Optimize brain selectivity, minimize hepatic reactive metabolites, and improve therapeutic index
• Maximize peripheral cholinergic activity to enhance digestion
• Design irreversible covalent inhibitors to avoid monitoring

Correct Answer: Optimize brain selectivity, minimize hepatic reactive metabolites, and improve therapeutic index

Q50. Which teaching point best summarizes tacrine’s role in pharmacology education?

• Example of an irreversible enzyme inhibitor with excellent safety
• Historic example of a centrally acting reversible AChE inhibitor illustrating efficacy vs toxicity trade-offs
• Primarily used as an antibiotic model drug
• Prototype for modern proton pump inhibitors

Correct Answer: Historic example of a centrally acting reversible AChE inhibitor illustrating efficacy vs toxicity trade-offs

G S Sachin

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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