Introduction
Plasma and tissue protein binding of drugs is a key topic in pharmacokinetics and pharmacology for B. Pharm students. Understanding plasma protein binding, primarily to albumin and alpha-1 acid glycoprotein, and tissue binding to lipids, bone, and intracellular proteins helps predict free drug concentration, volume of distribution, clearance, and drug interactions. Concepts such as binding affinity, fraction unbound (fu), displacement, non-linear binding, and methods like equilibrium dialysis and ultrafiltration are essential. Clinical factors—disease states, age, pregnancy, and drug physicochemical properties—influence binding and therapeutic response. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the clinical significance of plasma protein binding for a drug?
- It determines the color of the drug solution
- It affects the free (unbound) concentration and pharmacologic effect
- It only influences drug taste
- It prevents drug metabolism completely
Correct Answer: It affects the free (unbound) concentration and pharmacologic effect
Q2. Which plasma protein is primarily responsible for binding acidic drugs?
- Alpha-1 acid glycoprotein
- Globulin
- Albumin
- Fibrinogen
Correct Answer: Albumin
Q3. Alpha-1 acid glycoprotein mainly binds which type of drugs?
- Neutral hydrophilic drugs
- Basic (cationic) lipophilic drugs
- Acidic drugs
- Metals
Correct Answer: Basic (cationic) lipophilic drugs
Q4. The fraction unbound (fu) is defined as:
- Total drug concentration divided by unbound concentration
- Unbound drug concentration divided by total drug concentration
- Bound drug concentration divided by unbound concentration
- Volume of distribution divided by clearance
Correct Answer: Unbound drug concentration divided by total drug concentration
Q5. Which method is considered a gold standard for measuring plasma protein binding?
- Equilibrium dialysis
- High-performance liquid chromatography (HPLC) without separation
- Colorimetric assay
- Mass spectrometry without separation
Correct Answer: Equilibrium dialysis
Q6. A drug with high plasma protein binding (≥99%) typically has which characteristic?
- Very large fraction unbound
- Small change in total concentration produces large change in unbound concentration
- Large free fraction and short half-life
- No clinical relevance
Correct Answer: Small change in total concentration produces large change in unbound concentration
Q7. Tissue binding increases a drug’s:
- Clearance without affecting volume of distribution
- Volume of distribution (Vd)
- Plasma protein concentration
- Renal filtration rate
Correct Answer: Volume of distribution (Vd)
Q8. Which parameter is NOT directly altered by changes in plasma protein binding for low extraction drugs?
- Unbound clearance (CLu)
- Plasma total concentration
- Free fraction (fu)
- Unbound concentration at steady state (Css,u)
Correct Answer: Unbound clearance (CLu)
Q9. Displacement interactions at protein binding sites are most likely to cause a clinically important effect when:
- Both drugs are weakly bound (<50%)
- The displaced drug has a narrow therapeutic index and low clearance
- The displaced drug is rapidly eliminated with high clearance
- Both drugs are hydrophilic and do not bind tissues
Correct Answer: The displaced drug has a narrow therapeutic index and low clearance
Q10. Non-linear (saturable) protein binding means:
- Binding sites increase as concentration decreases
- Binding is constant irrespective of concentration
- Fraction unbound increases at higher concentrations due to saturation
- The drug binds irreversibly to proteins
Correct Answer: Fraction unbound increases at higher concentrations due to saturation
Q11. Which factor commonly decreases plasma albumin concentration and thereby increases drug free fraction?
- Hypoalbuminemia due to liver disease
- Increased albumin synthesis
- Hyperbilirubinemia
- Administration of albumin infusions
Correct Answer: Hypoalbuminemia due to liver disease
Q12. Equilibrium dialysis separates free from bound drug based on:
- Size exclusion in a chromatographic column
- Diffusion across a semipermeable membrane until free drug equilibrates
- Centrifugation of protein complexes
- Magnetic separation
Correct Answer: Diffusion across a semipermeable membrane until free drug equilibrates
Q13. Which statement best defines the free drug hypothesis?
- Only bound drug produces pharmacologic effect
- Both bound and unbound drug equally cross membranes
- Only unbound drug is pharmacologically active and available for clearance
- Protein-bound drug is rapidly metabolized
Correct Answer: Only unbound drug is pharmacologically active and available for clearance
Q14. Lipophilicity of a drug generally leads to:
- Decreased tissue binding and smaller Vd
- Increased tissue binding and larger Vd
- No change in distribution
- Only increased renal elimination
Correct Answer: Increased tissue binding and larger Vd
Q15. Scatchard analysis is used to determine:
- Drug solubility in water
- Binding affinity and number of binding sites
- Metabolic pathway of a drug
- Renal clearance
Correct Answer: Binding affinity and number of binding sites
Q16. In neonates, plasma protein binding is often reduced because of:
- Higher albumin levels than adults
- Lower concentrations and immature binding sites
- Excess alpha-1 acid glycoprotein
- Increased competition from other drugs
Correct Answer: Lower concentrations and immature binding sites
Q17. Which tissue is well known for acting as a reservoir for lipophilic drugs?
- Bone
- Fat (adipose) tissue
- Cartilage
- Blood plasma only
Correct Answer: Fat (adipose) tissue
Q18. A drug with high tissue binding but low plasma protein binding is expected to have:
- Small Vd and short half-life
- Large Vd and prolonged tissue residence
- No distribution outside plasma
- Only renal excretion
Correct Answer: Large Vd and prolonged tissue residence
Q19. Which condition can increase alpha-1 acid glycoprotein levels and thus affect binding of basic drugs?
- Acute inflammation or stress
- Hypothyroidism
- Chronic malnutrition
- Hemorrhage only
Correct Answer: Acute inflammation or stress
Q20. If two highly protein-bound drugs compete for the same albumin site, the immediate effect is:
- Decrease in unbound concentration of both drugs
- No change in free concentration but decreased total concentration
- Increase in free concentration of the displaced drug
- Permanent elimination of the displaced drug
Correct Answer: Increase in free concentration of the displaced drug
Q21. Which analytical artifact can cause overestimation of protein binding when using ultrafiltration?
- Non-specific adsorption of drug to the filter membrane
- Perfect recovery of free drug
- Complete equilibrium across membrane
- Use of isotonic buffer
Correct Answer: Non-specific adsorption of drug to the filter membrane
Q22. A basic, lipophilic drug is likely to bind preferentially to:
- Albumin only
- Alpha-1 acid glycoprotein and lipid-rich tissues
- Glucose transporter proteins
- Only to renal tubule cells
Correct Answer: Alpha-1 acid glycoprotein and lipid-rich tissues
Q23. Which kinetic constant describes the strength of drug-protein binding?
- Vmax
- Ka (association constant) or Kd (dissociation constant)
- Clearance (CL)
- Half-life (t1/2)
Correct Answer: Ka (association constant) or Kd (dissociation constant)
Q24. Why is monitoring total plasma concentration sometimes misleading for highly protein-bound drugs?
- Total concentration directly reflects pharmacologic effect
- Changes in protein binding can alter total but not unbound concentration
- Total concentration is always equal to unbound concentration
- Protein binding has no impact on therapeutic outcomes
Correct Answer: Changes in protein binding can alter total but not unbound concentration
Q25. Tissue binding to bone or teeth often involves which mechanism?
- Partitioning into adipose lipid only
- Chelation or ionic binding to mineral components
- Binding exclusively to plasma albumin
- Transport via P-glycoprotein
Correct Answer: Chelation or ionic binding to mineral components
Q26. During hypoalbuminemia, which of the following is expected for a low extraction, highly albumin-bound drug?
- Decrease in unbound concentration due to increased clearance
- Increase in free fraction and possible increase in pharmacologic effect
- No change in free fraction
- Immediate renal excretion of bound drug
Correct Answer: Increase in free fraction and possible increase in pharmacologic effect
Q27. Which experimental condition helps prevent artifactual displacement during protein binding assays?
- Using very high drug concentrations above therapeutic range
- Maintaining physiologic pH and temperature and using relevant protein concentrations
- Using extreme pH to denature proteins
- Omitting protein from the assay
Correct Answer: Maintaining physiologic pH and temperature and using relevant protein concentrations
Q28. The term ‘apparent volume of distribution’ (Vd) is influenced by:
- Only renal clearance
- Plasma protein binding, tissue binding, and lipophilicity
- Only the drug’s pKa
- Dietary intake exclusively
Correct Answer: Plasma protein binding, tissue binding, and lipophilicity
Q29. Which drug property favors high plasma protein binding?
- High polarity and low lipophilicity
- High lipophilicity and specific affinity for protein binding sites
- Rapid renal excretion unchanged
- Very small molecular size only
Correct Answer: High lipophilicity and specific affinity for protein binding sites
Q30. Why are free drug concentrations more predictive of effect than total concentrations?
- Because bound drug rapidly diffuses into tissues to exert effect
- Only unbound drug can cross membranes, bind receptors, and be cleared
- Total concentration is identical to free concentration
- Protein-bound drug is the primary active species
Correct Answer: Only unbound drug can cross membranes, bind receptors, and be cleared
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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