Protein binding and biological action MCQs With Answer

Protein binding and biological action MCQs With Answer is a focused study resource for B.Pharm students exploring how drugs interact with plasma proteins and how those interactions affect pharmacokinetics and pharmacodynamics. This introduction covers key concepts such as plasma protein binding, albumin and alpha-1 acid glycoprotein (AAG) roles, free drug fraction, displacement interactions, and clinical implications for dosing, toxicity, and therapeutic drug monitoring. Emphasis on methods (equilibrium dialysis, ultrafiltration), binding constants and disease- or age-related changes ensures practical understanding for exams and clinical practice. Targeted keywords: protein binding, drug-protein interactions, plasma protein binding, pharmacokinetics, pharmacodynamics, B.Pharm, MCQs. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is meant by ‘protein binding’ of a drug in plasma?

• The reversible association of drug molecules with plasma proteins
• The irreversible covalent bonding of drugs to tissue proteins
• The total elimination of a drug by the liver
• The uptake of drug into red blood cells

Correct Answer: The reversible association of drug molecules with plasma proteins

Q2. Which plasma protein primarily binds acidic drugs?

• Alpha-1 acid glycoprotein (AAG)
• Albumin
• Transferrin
• Fibrinogen

Correct Answer: Albumin

Q3. Which type of drugs preferentially bind to alpha-1 acid glycoprotein?

• Neutral lipophilic drugs
• Acidic drugs
• Basic (cationic) drugs
• Highly polar drugs

Correct Answer: Basic (cationic) drugs

Q4. What is the clinical significance of a high fraction unbound (fu) of a drug?

• Lower pharmacologic effect because bound drug is active
• Higher free concentration leading to greater effect and clearance
• No change in drug distribution or elimination
• Increased protein synthesis

Correct Answer: Higher free concentration leading to greater effect and clearance

Q5. How does hypoalbuminemia affect total and free concentrations of a highly albumin-bound drug?

• Total concentration increases while free concentration decreases
• Total and free concentrations remain unchanged
• Total concentration decreases but free concentration may remain similar or increase
• Both total and free concentrations decrease equally

Correct Answer: Total concentration decreases but free concentration may remain similar or increase

Q6. Which method is commonly used to measure the free (unbound) fraction of a drug?

• Mass spectrometry without separation
• Equilibrium dialysis
• Thin-layer chromatography
• pH titration

Correct Answer: Equilibrium dialysis

Q7. What does a high association constant (Ka) indicate about a drug–protein interaction?

• Weak affinity for the protein
• Strong affinity for the protein
• No specific binding sites
• Inability to displace other drugs

Correct Answer: Strong affinity for the protein

Q8. Which equation relates free drug concentration (Cu) to total concentration (Ct) and bound concentration?

• Ct = Cu + Cbound
• Ct = Cu × Vd
• Ct = Ka / Fu
• Ct = Cl × AUC

Correct Answer: Ct = Cu + Cbound

Q9. Which drug is classically known to be ~99% albumin-bound?

• Paracetamol
• Warfarin
• Gentamicin
• Metformin

Correct Answer: Warfarin

Q10. Displacement of one drug from albumin by another usually leads to what immediate effect?

• Decrease in free drug concentration
• Increase in free drug concentration
• Immediate increased protein synthesis
• Permanent loss of binding sites

Correct Answer: Increase in free drug concentration

Q11. Which clinical factor commonly increases alpha-1 acid glycoprotein levels?

• Chronic liver failure
• Acute inflammation or trauma
• Nephrotic syndrome
• Hypoalbuminemia due to malnutrition

Correct Answer: Acute inflammation or trauma

Q12. How does increased free fraction affect clearance for a low extraction drug?

• Clearance remains the same regardless of fu
• Clearance decreases because bound drug is cleared faster
• Clearance increases proportionally with free fraction
• Clearance becomes independent of hepatic blood flow

Correct Answer: Clearance increases proportionally with free fraction

Q13. Which statement about protein binding and pharmacologic action is correct?

• Only bound drug is pharmacologically active
• Only unbound drug can cross membranes and produce effect
• Bound drug increases tissue penetration directly
• Protein binding prevents renal filtration of unbound drug

Correct Answer: Only unbound drug can cross membranes and produce effect

Q14. Which laboratory technique separates free drug from bound drug using pressure and a semipermeable membrane?

• High-performance liquid chromatography (HPLC)
• Ultrafiltration
• Gel electrophoresis
• Western blotting

Correct Answer: Ultrafiltration

Q15. What is the typical effect of uremia on drug–protein binding?

• Increased binding due to accumulation of binding proteins
• No effect on binding
• Decreased binding due to accumulation of endogenous inhibitors like uremic toxins
• Irreversible protein modification increases binding

Correct Answer: Decreased binding due to accumulation of endogenous inhibitors like uremic toxins

Q16. Which force is NOT typically involved in reversible drug–protein binding?

• Hydrophobic interactions
• Hydrogen bonding
• Covalent bonding
• Electrostatic interactions

Correct Answer: Covalent bonding

Q17. In neonates, protein binding of drugs is often reduced. What is a consequence for dosing of highly protein-bound drugs?

• Smaller free fraction, so increase dose
• Reduced free drug, so no dose change needed
• Increased free fraction, may require lower dose to avoid toxicity
• No clinical relevance

Correct Answer: Increased free fraction, may require lower dose to avoid toxicity

Q18. Which of the following drugs is known to bind strongly to alpha-1 acid glycoprotein?

• Phenytoin
• Propranolol
• Penicillin
• Gentamicin

Correct Answer: Propranolol

Q19. What is ‘fraction unbound’ (fu) defined as?

• The ratio of bound drug to total drug
• The ratio of unbound drug concentration to total drug concentration
• The total plasma concentration of drug
• The volume of distribution normalized to body weight

Correct Answer: The ratio of unbound drug concentration to total drug concentration

Q20. Which change is most likely to increase the free fraction of an acidic, albumin-bound drug?

• Increase in plasma albumin concentration
• Hypoalbuminemia
• Decrease in free fatty acids
• Alkalinization of plasma

Correct Answer: Hypoalbuminemia

Q21. If two drugs compete for the same albumin binding site, co-administration may cause:

• Reduced free fraction of both drugs
• Increased free fraction of the displaced drug
• Complete inhibition of metabolism
• Enhanced covalent binding to albumin

Correct Answer: Increased free fraction of the displaced drug

Q22. Which parameter does protein binding directly influence?

• Glomerular filtration rate
• Unbound drug clearance and distribution
• Absorption pH only
• Active secretion exclusively

Correct Answer: Unbound drug clearance and distribution

Q23. How is ‘scatchard plot’ used in studying drug–protein interactions?

• To determine membrane permeability
• To estimate binding affinity and number of binding sites
• To measure drug metabolism rates
• To calculate renal clearance

Correct Answer: To estimate binding affinity and number of binding sites

Q24. For a drug with low hepatic extraction ratio, what is the effect of increased free fraction on hepatic clearance?

• No effect on hepatic clearance
• Hepatic clearance increases because it is dependent on free concentration
• Hepatic clearance decreases proportionally
• Hepatic clearance equals renal clearance

Correct Answer: Hepatic clearance increases because it is dependent on free concentration

Q25. Which clinical measurement is more informative for drugs with significant protein binding?

• Total drug concentration alone
• Only the dose administered
• Free (unbound) drug concentration
• Proteinuria level

Correct Answer: Free (unbound) drug concentration

Q26. Phenytoin is highly albumin-bound. In hypoalbuminemia, monitoring which value is most appropriate?

• Total phenytoin concentration only
• Free phenytoin concentration
• Serum creatinine
• Serum potassium

Correct Answer: Free phenytoin concentration

Q27. Which physiological change during pregnancy affects drug–protein binding?

• Increase in albumin concentration
• Decrease in plasma volume
• Decrease in albumin concentration leading to increased free fraction
• Constant protein levels with no effect

Correct Answer: Decrease in albumin concentration leading to increased free fraction

Q28. What role do free fatty acids play in drug–albumin binding?

• They enhance binding of all drugs to albumin
• They can displace drugs from albumin, reducing binding
• They covalently modify albumin to increase binding
• They are irrelevant to drug binding

Correct Answer: They can displace drugs from albumin, reducing binding

Q29. Which of the following is TRUE about stereoselective protein binding?

• Enantiomers always have identical protein binding
• One enantiomer may bind more strongly than the other, affecting pharmacokinetics
• Stereochemistry has no clinical relevance
• Only racemic mixtures bind proteins

Correct Answer: One enantiomer may bind more strongly than the other, affecting pharmacokinetics

Q30. How does chronic liver disease typically affect drug–protein binding?

• Increase in albumin leading to more binding
• Decrease in albumin leading to higher free fractions
• No effect on plasma proteins
• Conversion of albumin to AAG

Correct Answer: Decrease in albumin leading to higher free fractions

Q31. Which statement best describes the relationship between protein binding and volume of distribution (Vd)?

• Higher plasma protein binding typically increases Vd
• Higher plasma protein binding typically decreases Vd
• Protein binding has no effect on Vd
• Only tissue binding affects Vd

Correct Answer: Higher plasma protein binding typically decreases Vd

Q32. Which drug interaction is most likely to produce clinically significant displacement from albumin?

• Two drugs both 30% bound
• Co-administration of two drugs both >95% bound with similar binding sites
• Combination of hydrophilic antibiotics
• Two drugs eliminated exclusively by the kidney

Correct Answer: Co-administration of two drugs both >95% bound with similar binding sites

Q33. In an acute-phase reaction, what happens to albumin and AAG levels respectively?

• Albumin increases, AAG decreases
• Albumin decreases, AAG increases
• Both increase equally
• Both decrease equally

Correct Answer: Albumin decreases, AAG increases

Q34. Valproic acid is highly albumin-bound. Which factor can increase free valproate and risk toxicity?

• Concurrent hypoalbuminemia or displacement by another drug
• Decreased renal clearance only
• Increased albumin synthesis
• Administration with food only

Correct Answer: Concurrent hypoalbuminemia or displacement by another drug

Q35. For drugs with high protein binding, therapeutic drug monitoring should consider:

• Only trough total concentrations
• Free concentration measurement or correction for albumin
• Only dose adjustments based on age
• Ignoring protein levels as irrelevant

Correct Answer: Free concentration measurement or correction for albumin

Q36. Which experimental artifact can falsely increase measured bound fraction during ultrafiltration?

• Non-specific adsorption of drug to filter membranes
• Complete equilibrium across the membrane
• Using physiological temperature
• Correct sample pH

Correct Answer: Non-specific adsorption of drug to filter membranes

Q37. Why might an increase in free drug not always lead to a proportional increase in pharmacologic effect?

• Because bound drug becomes instantly active
• Because clearance may increase and free drug may be rapidly eliminated
• Because free drug cannot cross membranes
• Because protein binding determines receptor affinity

Correct Answer: Because clearance may increase and free drug may be rapidly eliminated

Q38. Which mathematical expression approximates the fraction unbound (fu) if binding sites are not saturated?

• fu = 1 / (1 + Ka × [P]) where [P] is protein concentration
• fu = Ka × [P]
• fu = Vd / Cl
• fu = AUC × dose

Correct Answer: fu = 1 / (1 + Ka × [P]) where [P] is protein concentration

Q39. In which condition is the clinical relevance of protein binding least significant?

• Drug is highly protein bound and low extraction
• Drug is highly protein bound but HD clearance is low
• Drug is low protein bound and high extraction
• Drug with narrow therapeutic index

Correct Answer: Drug is low protein bound and high extraction

Q40. Which drug pair is known for clinically important protein displacement interactions?

• Warfarin and ibuprofen
• Amoxicillin and clavulanate
• Metformin and glibenclamide
• Insulin and glucagon

Correct Answer: Warfarin and ibuprofen

Q41. Which factor does NOT influence drug–albumin binding?

• pH of plasma
• Presence of endogenous ligands like bilirubin
• Ambient temperature in physiological range
• Genetic polymorphism in albumin structure

Correct Answer: Ambient temperature in physiological range

Q42. How does acute inflammation affect dosing of a basic drug highly bound to AAG?

• May reduce free fraction and require higher dose to maintain effect
• Always increases free fraction leading to toxicity
• Has no effect on AAG-bound drugs
• Causes irreversible binding and drug accumulation

Correct Answer: May reduce free fraction and require higher dose to maintain effect

Q43. Which analytical consideration is important when measuring free drug in plasma samples?

• Diluting the sample extensively before separation
• Maintaining physiological temperature and pH to preserve equilibrium
• Adding excess protein to shift equilibrium
• Freezing and thawing multiple times to free bound drug

Correct Answer: Maintaining physiological temperature and pH to preserve equilibrium

Q44. What effect will increased non-specific tissue binding have on apparent volume of distribution?

• Decrease Vd because drug remains in plasma
• Increase Vd as more drug is sequestered in tissues
• No effect on Vd
• Reduce half-life to zero

Correct Answer: Increase Vd as more drug is sequestered in tissues

Q45. Which of the following is a consequence of stereoselective binding for chiral drugs?

• Both enantiomers have identical clearance
• Different enantiomers may have different free fractions and effects
• Only the racemate binds proteins
• Stereoselectivity only affects metabolism, not binding

Correct Answer: Different enantiomers may have different free fractions and effects

Q46. For a drug with fu = 0.01, what percent is bound to protein?

• 1%
• 10%
• 99%
• 50%

Correct Answer: 99%

Q47. Which procedure would you choose for rapid bedside estimation of free drug if lab resources are limited?

• Equilibrium dialysis in a research lab
• Use validated correction formulas based on albumin and total concentration for some drugs
• Mass spectrometry without separation
• Performing protein electrophoresis

Correct Answer: Use validated correction formulas based on albumin and total concentration for some drugs

Q48. Which drug property most strongly predicts extensive plasma protein binding?

• High water solubility
• High lipophilicity and affinity for binding sites
• Rapid renal elimination
• Low molecular weight only

Correct Answer: High lipophilicity and affinity for binding sites

Q49. Which clinical scenario increases the likelihood that measuring free drug concentration will change management?

• Patient with normal albumin and stable dosing
• Patient with hypoalbuminemia, polypharmacy and critical illness receiving a highly bound drug
• Patient on a water-soluble antibiotic with low binding
• Routine screening in healthy volunteers

Correct Answer: Patient with hypoalbuminemia, polypharmacy and critical illness receiving a highly bound drug

Q50. Which best summarizes why B.Pharm students must understand protein binding?

• It explains only the chemical synthesis of drugs
• It is essential for predicting drug distribution, interactions, dosing and therapeutic monitoring
• It replaces the need to learn pharmacodynamics
• It only matters for veterinary drugs

Correct Answer: It is essential for predicting drug distribution, interactions, dosing and therapeutic monitoring

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