Distribution of drugs and tissue permeability MCQs With Answer

Distribution of drugs and tissue permeability are core topics in pharmacokinetics for B.Pharm students. Mastery of concepts such as plasma protein binding, volume of distribution (Vd), blood–brain barrier, membrane permeability, partition coefficient, tissue binding, and pH-dependent ionization clarifies how drugs reach targets, accumulate, or form tissue reservoirs. Key determinants include organ blood flow, capillary type, transporters (e.g., P-gp), and disease states like edema or inflammation that modify rate and extent of distribution. Understanding these principles informs dosing, interactions, toxicity, dialysis removal, and drug delivery design. This concise, concept-driven review links theory to clinical application. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What does the volume of distribution (Vd) primarily represent?

• The apparent volume in which a drug is distributed based on plasma concentration
• The actual physical volume of blood in the body
• The rate at which a drug is eliminated
• The total volume of extracellular fluid only

Correct Answer: The apparent volume in which a drug is distributed based on plasma concentration

Q2. Which factor most increases a drug’s Vd?

• High plasma protein binding
• Extensive tissue binding
• Low lipid solubility
• Restricted capillary permeability

Correct Answer: Extensive tissue binding

Q3. Which statement best describes perfusion-limited distribution?

• Distribution rate is limited by capillary permeability rather than blood flow
• Distribution rate is limited by organ blood flow when membranes are highly permeable
• Distribution is independent of blood flow and permeability
• Distribution only occurs via active transport

Correct Answer: Distribution rate is limited by organ blood flow when membranes are highly permeable

Q4. pH partitioning affects drug distribution by?

• Altering drug molecular weight
• Changing drug ionization and membrane permeability
• Modifying plasma protein levels directly
• Increasing blood flow to tissues

Correct Answer: Changing drug ionization and membrane permeability

Q5. Which tissue barrier has the tightest junctions limiting drug permeability?

• Skeletal muscle capillaries
• Renal glomerular capillaries
• Blood–brain barrier
• Liver sinusoidal endothelium

Correct Answer: Blood–brain barrier

Q6. High plasma protein binding of a drug typically results in:

• Increased free fraction and faster clearance
• Decreased Vd and limited tissue uptake
• Greater renal filtration of the drug
• Increased membrane permeability

Correct Answer: Decreased Vd and limited tissue uptake

Q7. Which transporter is a major efflux pump at the blood–brain barrier affecting drug distribution?

• GLUT1
• P-glycoprotein (P-gp)
• Na+/K+ ATPase
• Organic cation transporter 2 (OCT2)

Correct Answer: P-glycoprotein (P-gp)

Q8. A drug with high lipid solubility and low plasma protein binding would most likely have:

• Small Vd and confinement to plasma
• Large Vd due to extensive tissue penetration
• Rapid renal excretion unchanged
• Distribution limited to extracellular fluid

Correct Answer: Large Vd due to extensive tissue penetration

Q9. Which condition can increase free drug concentration by reducing plasma protein binding?

• Dehydration
• Hypoalbuminemia
• Hyperbilirubinemia
• Polycythemia

Correct Answer: Hypoalbuminemia

Q10. Ion trapping leads to accumulation of a weak base in an acidic compartment because:

• The base becomes more lipid soluble in acid
• The base becomes ionized and less able to cross membranes
• The base is actively transported into the compartment
• The base binds to intracellular proteins preferentially

Correct Answer: The base becomes ionized and less able to cross membranes

Q11. Which best describes permeability-limited distribution?

• Distribution rate determined by tissue blood perfusion only
• Distribution rate limited by membrane permeability and diffusion into tissue
• Distribution independent of drug lipophilicity
• Only applies to highly lipophilic drugs

Correct Answer: Distribution rate limited by membrane permeability and diffusion into tissue

Q12. How does inflammation generally affect tissue permeability for drugs?

• Decreases permeability due to vasoconstriction
• Increases capillary permeability enhancing distribution
• Has no effect on drug distribution
• Reduces tissue blood flow and distribution uniformly

Correct Answer: Increases capillary permeability enhancing distribution

Q13. Which class of drugs is most likely to cross the placenta by passive diffusion?

• Highly ionized, hydrophilic large molecules
• Small, lipophilic, non-ionized molecules
• Drugs transported only by P-gp out of fetal circulation
• Protein-bound macromolecules

Correct Answer: Small, lipophilic, non-ionized molecules

Q14. A high tissue-to-plasma concentration ratio indicates:

• Preferential tissue uptake or binding
• Poor tissue penetration
• Exclusive plasma confinement
• Rapid renal elimination

Correct Answer: Preferential tissue uptake or binding

Q15. Which measurement method is commonly used to estimate Vd experimentally?

• Urine excretion rate only
• Plasma concentration after intravenous bolus and dose
• Skin biopsy concentration
• Saliva drug levels

Correct Answer: Plasma concentration after intravenous bolus and dose

Q16. Which physiological change in elderly patients commonly alters drug distribution?

• Increased total body water
• Decreased body fat percentage
• Reduced plasma albumin leading to higher free fraction for some drugs
• Enhanced hepatic blood flow increasing tissue uptake

Correct Answer: Reduced plasma albumin leading to higher free fraction for some drugs

Q17. Which of the following shifts drug from plasma to tissues, potentially prolonging duration of action?

• Competitive displacement from tissue binding sites
• Redistribution into adipose tissue due to lipophilicity
• Increased renal clearance of free drug
• Enhanced hepatic metabolism

Correct Answer: Redistribution into adipose tissue due to lipophilicity

Q18. Which is true about plasma protein binding and dialysis removal?

• Highly protein-bound drugs are easily removed by dialysis
• Only unbound drug is removed efficiently by dialysis
• Protein binding increases dialysis clearance
• Dialysis removes both bound and unbound drug equally

Correct Answer: Only unbound drug is removed efficiently by dialysis

Q19. The apparent Vd of a drug is 5 L. This suggests the drug is primarily:

• Distributed mainly in plasma
• Widely distributed into fat and tissues
• Restricted to extracellular fluid
• Confined to intracellular compartment

Correct Answer: Distributed mainly in plasma

Q20. Which factor most reduces a drug’s ability to penetrate the central nervous system?

• High lipid solubility
• Strong P-gp efflux at the BBB
• Low plasma protein binding
• Small molecular size

Correct Answer: Strong P-gp efflux at the BBB

Q21. Tissue reservoirs of drugs can lead to:

• Reduced half-life and rapid offset of effect
• Prolonged elimination and potential delayed toxicity
• Complete protection from metabolism
• Immediate increase in plasma concentration after dosing

Correct Answer: Prolonged elimination and potential delayed toxicity

Q22. How does edema influence drug distribution?

• Increases distribution to adipose tissue only
• Expands extracellular fluid volume, altering distribution of hydrophilic drugs
• Reduces distribution of hydrophilic drugs by shrinking interstitial space
• Does not affect drug distribution

Correct Answer: Expands extracellular fluid volume, altering distribution of hydrophilic drugs

Q23. When two drugs compete for the same plasma protein binding site, the immediate effect is:

• Permanent increase in Vd of both drugs
• Transient increase in free fraction of the displaced drug
• Reduction in renal clearance of the displaced drug
• Decreased pharmacologic effect of the displaced drug

Correct Answer: Transient increase in free fraction of the displaced drug

Q24. Which physicochemical property most favors rapid passive diffusion across cell membranes?

• High molecular weight and high polarity
• Low lipid solubility and high ionization
• Small size and high lipophilicity
• Strong binding to extracellular matrix

Correct Answer: Small size and high lipophilicity

Q25. Which statement about volume of distribution and loading dose is correct?

• Loading dose = Target plasma concentration × clearance
• Loading dose is independent of Vd
• Loading dose = Target plasma concentration × Vd
• Loading dose equals maintenance dose always

Correct Answer: Loading dose = Target plasma concentration × Vd

Q26. Which organ’s capillary structure generally allows greatest drug access to tissue?

• Brain with continuous tight junctions
• Liver with fenestrated sinusoidal endothelium
• Muscle with tight capillaries
• Skin with multilayered barriers

Correct Answer: Liver with fenestrated sinusoidal endothelium

Q27. A drug showing a very large Vd (>100 L) most likely:

• Is confined to the vascular compartment
• Is extensively distributed into tissues and fat
• Is hydrophilic and restricted to extracellular fluid
• Is rapidly excreted unchanged in urine

Correct Answer: Is extensively distributed into tissues and fat

Q28. Which clinical implication follows from a drug that is highly protein bound?

• It has a large free fraction and rapid clearance
• Small changes in binding can significantly alter free drug levels
• Protein binding does not affect drug interactions
• Protein-bound drug is readily removed by dialysis

Correct Answer: Small changes in binding can significantly alter free drug levels

Q29. Which is a characteristic of drugs undergoing permeability-limited distribution into the brain?

• Rapid equilibration with plasma
• Penetration limited by tight junctions and low membrane permeability
• No influence of efflux transporters
• Distribution determined solely by lipophilicity

Correct Answer: Penetration limited by tight junctions and low membrane permeability

Q30. Which change would decrease the plasma clearance of a drug but likely increase its Vd?

• Increased plasma albumin concentration
• Enhanced tissue binding and sequestration
• Improved renal filtration of unbound drug
• Increased hepatic metabolism rate

Correct Answer: Enhanced tissue binding and sequestration

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