SAR of beta blockers MCQs With Answer

The Structure-Activity Relationship (SAR) of beta blockers MCQs With Answer is essential reading for B. Pharm students preparing for exams and practical prescribing knowledge. This focused introduction explains how structural features—aryloxypropanolamine core, hydroxyl group, basic amine substituents, aromatic substitutions, stereochemistry, lipophilicity and hydrogen-bonding—determine beta-adrenergic receptor affinity, beta1/beta2 selectivity, intrinsic sympathomimetic activity (ISA) and CNS penetration. Understanding these SAR principles links molecular design to pharmacological effects, metabolism and clinical choice of agents like propranolol, metoprolol and pindolol. These SEO-rich notes help you master both concept and application. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which functional motif forms the core pharmacophore of most classical beta blockers?

• Aryloxypropanolamine
• Beta-lactam
• Quinolone
• Sulfonylurea

Correct Answer: Aryloxypropanolamine

Q2. Which receptor residue commonly forms an ionic interaction with the protonated amine of beta blockers?

• Serine in TM5
• Aspartate in TM3
• Tyrosine in TM7
• Glycine in TM1

Correct Answer: Aspartate in TM3

Q3. The secondary alcohol (-OH) in the aryloxypropanolamine scaffold primarily contributes to:

• Increasing lipophilicity
• Hydrogen bonding with receptor serines
• Blocking metabolism by CYPs
• Forming a covalent bond with the receptor

Correct Answer: Hydrogen bonding with receptor serines

Q4. Increasing the bulk of the N-substituent (e.g., tert-butyl) on the amine tends to:

• Decrease beta-blocking potency
• Increase beta2 selectivity exclusively
• Alter beta receptor subtype selectivity and often increase potency
• Convert the drug into an agonist

Correct Answer: Alter beta receptor subtype selectivity and often increase potency

Q5. Which stereochemistry of many beta blockers is generally more potent at beta receptors?

• R-enantiomer
• S-enantiomer
• Both enantiomers are equally active
• Racemic mixtures are always inactive

Correct Answer: S-enantiomer

Q6. Intrinsic sympathomimetic activity (ISA) in some beta blockers means the drug:

• Is a full antagonist only
• Has partial agonist activity at beta receptors
• Is rapidly metabolized to an inactive form
• Only blocks alpha receptors

Correct Answer: Has partial agonist activity at beta receptors

Q7. Which physicochemical property most strongly predicts CNS penetration of beta blockers?

• High molecular weight
• High lipophilicity
• High aqueous solubility
• High polarity

Correct Answer: High lipophilicity

Q8. Pindolol’s partial agonism (ISA) is mainly attributed to which structural feature?

• Presence of a bulky quaternary ammonium
• An indole ring that stabilizes a partial agonist conformation
• Absence of the propanolamine side chain
• A terminal carboxylic acid group

Correct Answer: An indole ring that stabilizes a partial agonist conformation

Q9. Replacing the aromatic ring oxygen linkage (aryloxy) by a direct carbon bond typically:

• Enhances hydrogen bonding to the receptor
• Reduces beta-blocker activity
• Converts the compound to a beta agonist
• Has no effect on activity

Correct Answer: Reduces beta-blocker activity

Q10. Which modification is commonly used to increase beta1-selectivity over beta2?

• Small N-methyl substitution
• Bulky branched N-substituent like isopropyl or tert-butyl
• Removal of the hydroxyl group
• Conversion to a quaternary ammonium

Correct Answer: Bulky branched N-substituent like isopropyl or tert-butyl

Q11. Atenolol’s relative hydrophilicity compared to propranolol results in:

• Greater CNS side effects
• Less CNS penetration and fewer central adverse effects
• Higher membrane-stabilizing activity
• Increased renal clearance only

Correct Answer: Less CNS penetration and fewer central adverse effects

Q12. Membrane-stabilizing (local anesthetic) activity of some beta blockers is associated with:

• High polarity and lack of aromatic ring
• Lipophilic aromatic structures that block sodium channels
• Presence of a carboxylate group
• Quaternary ammonium formation

Correct Answer: Lipophilic aromatic structures that block sodium channels

Q13. A beta blocker with a permanently charged quaternary ammonium is likely to:

• Have high oral bioavailability
• Fail to cross the blood-brain barrier and show limited oral absorption
• Be highly lipophilic
• Be metabolized into an active lipophilic form

Correct Answer: Fail to cross the blood-brain barrier and show limited oral absorption

Q14. Which interaction helps stabilize beta blocker binding via the aromatic ring?

• Pi–pi stacking with receptor aromatic residues
• Disulfide bond formation
• Covalent acylation of the receptor
• Metal coordination

Correct Answer: Pi–pi stacking with receptor aromatic residues

Q15. Shortening the oxyalkyl chain from propanolamine to ethanolamine in beta blockers generally:

• Improves potency
• Reduces binding affinity
• Has no effect
• Converts to an agonist

Correct Answer: Reduces binding affinity

Q16. The presence of a para-substituent on the aromatic ring often affects:

• Only the drug’s melting point
• Receptor affinity and selectivity
• The drug’s color only
• Ability to form salts

Correct Answer: Receptor affinity and selectivity

Q17. Which structural feature favors beta2 selectivity rather than beta1?

• Small N-alkyl groups and certain aryl substituents
• Large bulky N-tert-butyl groups only
• Removal of the hydroxyl group
• Quaternization of the amine

Correct Answer: Small N-alkyl groups and certain aryl substituents

Q18. Metoprolol’s selectivity for beta1 is mainly due to:

• A rigid bicyclic core
• Specific aryl and N-substituent pattern in the aryloxypropanolamine scaffold
• A carboxylic acid moiety at para position
• Being a quaternary ammonium salt

Correct Answer: Specific aryl and N-substituent pattern in the aryloxypropanolamine scaffold

Q19. Which is an expected effect of increasing polar surface area in a beta blocker?

• Increased CNS penetration
• Decreased oral absorption and reduced BBB crossing
• Increased lipophilicity
• Increased membrane-stabilizing action

Correct Answer: Decreased oral absorption and reduced BBB crossing

Q20. Prodrugs of beta blockers are sometimes designed to:

• Increase immediate receptor agonism
• Improve oral bioavailability or reduce GI irritation
• Decrease plasma protein binding to zero
• Convert to quaternary ammonium pre-systemically

Correct Answer: Improve oral bioavailability or reduce GI irritation

Q21. Removal of the secondary alcohol (-OH) on the propanolamine chain typically causes:

• Retention of full potency
• Marked loss of receptor affinity
• Conversion to inverse agonist
• Increased beta1 selectivity

Correct Answer: Marked loss of receptor affinity

Q22. Which physicochemical change generally increases hepatic metabolism by CYPs?

• High polarity and hydrophilicity
• Increased lipophilicity and aromatic substitution
• Quaternary ammonium formation
• Conjugation with glucuronic acid prior to dosing

Correct Answer: Increased lipophilicity and aromatic substitution

Q23. Which class of beta blockers typically shows significant first-pass hepatic metabolism and variable oral bioavailability?

• Hydrophilic beta blockers like atenolol
• Lipophilic beta blockers like propranolol
• Quaternary ammonium beta blockers
• All beta blockers have identical first-pass effects

Correct Answer: Lipophilic beta blockers like propranolol

Q24. Beta-blocker binding often involves hydrogen bonding to serine residues in which transmembrane helix?

• TM1
• TM5
• TM2
• TM7

Correct Answer: TM5

Q25. Which change is likely to reduce oral clearance and prolong half-life?

• Increasing polar surface area
• Designing a drug resistant to oxidative metabolism (steric hindrance)
• Converting to an ester readily hydrolyzed by plasma esterases
• Adding multiple ionizable groups for renal excretion

Correct Answer: Designing a drug resistant to oxidative metabolism (steric hindrance)

Q26. Which beta blocker characteristic correlates with a higher risk of bronchoconstriction in asthmatic patients?

• High beta1-selectivity
• Non-selective beta1/beta2 blockade
• High ISA
• Poor oral absorption

Correct Answer: Non-selective beta1/beta2 blockade

Q27. Which structural modification favors peripheral selectivity and lower CNS effects?

• Increased lipophilicity
• Quaternary ammonium or increased polarity
• Smaller molecular size
• Removal of aromatic ring

Correct Answer: Quaternary ammonium or increased polarity

Q28. For beta blockers, tertiary amines that are protonated at physiological pH mainly serve to:

• Permit ionic interaction with acidic receptor residues
• Block hepatic uptake transporters
• Cause irreversible binding to receptor
• Eliminate renal clearance

Correct Answer: Permit ionic interaction with acidic receptor residues

Q29. Which property generally enhances oral absorption of beta blockers?

• Extremely high polarity and multiple charges
• Moderate lipophilicity and balanced polarity
• Permanent positive charge as quaternary ammonium
• Large molecular weight (>1000 Da)

Correct Answer: Moderate lipophilicity and balanced polarity

Q30. A bulky heteroaryl substituent on the aryloxy ring can:

• Increase selectivity or confer ISA depending on orientation
• Always convert the drug into a beta agonist
• Remove any membrane-stabilizing activity
• Prevent oral absorption completely

Correct Answer: Increase selectivity or confer ISA depending on orientation

Q31. Which of the following best describes membrane-stabilizing activity in some beta blockers?

• Blocking of cardiac sodium channels similar to local anesthetics
• Enhanced stimulation of beta receptors
• Rapid hydrolysis in the stomach
• Formation of insoluble complexes in plasma

Correct Answer: Blocking of cardiac sodium channels similar to local anesthetics

Q32. Why is the protonated amine important for beta blocker-receptor binding?

• It improves oral solubility only
• It forms an ionic bond with a conserved acidic residue in the receptor
• It prevents metabolism by CYP enzymes
• It blocks renal excretion

Correct Answer: It forms an ionic bond with a conserved acidic residue in the receptor

Q33. Which structural change would you predict to increase water solubility for a beta blocker?

• Adding polar functional groups such as amides or hydroxyls
• Increasing aromatic ring substitution with lipophilic groups
• Converting tertiary amine to bulky hydrophobic substituent
• Adding more fused aromatic rings

Correct Answer: Adding polar functional groups such as amides or hydroxyls

Q34. Selectivity for beta1 over beta2 receptors can reduce which adverse effect?

• Bradycardia
• Bronchoconstriction in susceptible patients
• Hypoglycemia masking
• Hypotension

Correct Answer: Bronchoconstriction in susceptible patients

Q35. Which metabolic pathway commonly inactivates many lipophilic beta blockers?

• Phase III efflux only
• Oxidative metabolism by cytochrome P450 enzymes
• Direct renal excretion without metabolism
• Photodegradation in the gut

Correct Answer: Oxidative metabolism by cytochrome P450 enzymes

Q36. A beta blocker designed with reduced lipophilicity is expected to have which of the following?

• Increased CNS adverse effects
• Lower BBB penetration and fewer central side effects
• Higher membrane-stabilizing activity
• Greater passive tissue distribution into brain

Correct Answer: Lower BBB penetration and fewer central side effects

Q37. Which experimental change would most likely convert a beta blocker into a partial agonist?

• Add a permanent positive charge
• Modify the aryl or heteroaryl ring to stabilize an active-like receptor conformation
• Remove the propanolamine side chain entirely
• Increase molecular weight beyond 800 Da

Correct Answer: Modify the aryl or heteroaryl ring to stabilize an active-like receptor conformation

Q38. Which beta blocker property enhances oral absorption but may increase first-pass metabolism?

• High hydrophilicity
• High lipophilicity
• Permanent ionic charge
• Extensive conjugation to polar groups

Correct Answer: High lipophilicity

Q39. Which functional group change often reduces affinity dramatically in the beta blocker scaffold?

• Retention of the aryloxy linkage
• Elimination of the secondary hydroxyl on the propanolamine chain
• Optimizing N-substituent size
• Para-substitution of the aromatic ring

Correct Answer: Elimination of the secondary hydroxyl on the propanolamine chain

Q40. In SAR terms, what is the role of an electron-donating para substituent on the phenyl ring?

• Always abolishes receptor binding
• Can modulate potency and selectivity depending on steric and electronic effects
• Converts the molecule into a diuretic
• Prevents protonation of the amine

Correct Answer: Can modulate potency and selectivity depending on steric and electronic effects

Q41. Which experimental observation supports the importance of stereochemistry in beta blocker activity?

• Both enantiomers show identical receptor binding in all cases
• One enantiomer frequently shows greater affinity and intrinsic activity than the other
• Racemates are always inactive
• Stereochemistry is irrelevant to pharmacokinetics

Correct Answer: One enantiomer frequently shows greater affinity and intrinsic activity than the other

Q42. An N-isopropyl substituent on the amine commonly contributes to:

• Beta-adrenergic antagonism and altered subtype selectivity
• Complete agonism of alpha receptors
• Removal of all acidic functional groups
• Reducing oral bioavailability to zero

Correct Answer: Beta-adrenergic antagonism and altered subtype selectivity

Q43. Which structural attribute is least compatible with good oral bioavailability?

• Moderate lipophilicity
• Multiple charged centers and very high polarity
• Balanced hydrogen bond donors and acceptors
• Reasonable molecular weight

Correct Answer: Multiple charged centers and very high polarity

Q44. Beta blockers that are substrates for P-glycoprotein efflux will likely show:

• Enhanced BBB penetration
• Reduced brain accumulation and lower CNS effects
• Increased intrinsic sympathomimetic activity
• Complete avoidance of hepatic metabolism

Correct Answer: Reduced brain accumulation and lower CNS effects

Q45. Which clinical advantage is associated with beta blockers having ISA?

• Greater suppression of resting heart rate at all times
• Potentially less resting bradycardia and less disturbance of basal cardiac output
• Complete elimination of hypotension risk
• No interaction with other cardiovascular drugs

Correct Answer: Potentially less resting bradycardia and less disturbance of basal cardiac output

Q46. Designing a selective beta1-blocker for elderly patients would favor which properties?

• High lipophilicity and high CNS penetration
• Beta1-selectivity, moderate hydrophilicity, and predictable renal clearance
• Strong membrane-stabilizing activity
• Permanent quaternary ammonium structure

Correct Answer: Beta1-selectivity, moderate hydrophilicity, and predictable renal clearance

Q47. Which modification often reduces first-pass hepatic metabolism and increases renal excretion?

• Increase lipophilicity
• Increase hydrophilicity (e.g., polar substituents)
• Convert tertiary amine to quaternary salt that is highly lipophilic
• Fuse additional aromatic rings

Correct Answer: Increase hydrophilicity (e.g., polar substituents)

Q48. Beta blockers that are highly lipophilic are more likely to:

• Be excreted unchanged in urine
• Accumulate in fatty tissues and cross the BBB
• Have no interaction with hepatic enzymes
• Be completely inactive pharmacologically

Correct Answer: Accumulate in fatty tissues and cross the BBB

Q49. Which experimental SAR approach can identify residues important for ligand binding in the beta receptor?

• Site-directed mutagenesis of receptor amino acids
• Increasing only the molecular weight of ligands
• Randomly adding bulky groups without testing
• Changing solvent conditions only

Correct Answer: Site-directed mutagenesis of receptor amino acids

Q50. For a novel beta blocker, which combined SAR knowledge best predicts a safe profile for asthmatic patients?

• Non-selective beta2 blockade and high lipophilicity
• High beta1-selectivity with low beta2 affinity and limited pulmonary effects
• Strong membrane-stabilizing activity and high BBB penetration
• High ISA primarily at beta2 receptors

Correct Answer: High beta1-selectivity with low beta2 affinity and limited pulmonary effects

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.

Mail- Sachin@pharmacyfreak.com