Tissue-binding interactions and implications MCQs With Answer

Tissue-binding interactions and implications MCQs With Answer

This quiz collection is designed for M.Pharm students to deepen understanding of tissue-binding mechanisms and their pharmacokinetic and pharmacodynamic consequences. Questions focus on molecular determinants of tissue binding (lipophilicity, ionization, protein and phospholipid interactions), experimental approaches (equilibrium dialysis, ultrafiltration, microdialysis, autoradiography, Scatchard analysis), and clinical implications such as volume of distribution, drug accumulation, tissue reservoirs, toxicity, and drug–drug interactions. Emphasis is on how binding affinity, capacity, and experimental artifacts influence interpretation of tissue distribution data and dosing decisions. Use these MCQs to test conceptual knowledge and prepare for advanced bioanalytical problem-solving.

Q1. Which physicochemical property most strongly promotes accumulation of a basic drug in acidic intracellular organelles (e.g., lysosomes)?

• High lipophilicity with neutral pKa
• Acidic pKa causing ionization in cytosol
• Basic pKa leading to ion trapping in acidic compartments
• High molecular weight preventing membrane permeation

Correct Answer: Basic pKa leading to ion trapping in acidic compartments

Q2. Which experimental technique allows continuous sampling of free (unbound) drug concentrations in interstitial fluid of living tissue?

• Equilibrium dialysis of tissue homogenate
• Microdialysis
• Autoradiography of frozen sections
• Ultracentrifugation of plasma

Correct Answer: Microdialysis

Q3. In Scatchard analysis, a curvilinear plot often indicates which of the following binding characteristics?

• Single-site, non-cooperative binding
• Homogeneous high-affinity binding only
• Multiple binding sites or heterogeneous affinity
• No specific binding present

Correct Answer: Multiple binding sites or heterogeneous affinity

Q4. High tissue binding with low free fraction in tissue is most likely to produce which pharmacokinetic effect?

• Rapid renal clearance due to filtration of bound drug
• Large apparent volume of distribution and prolonged terminal half-life
• Decreased tissue half-life and rapid equilibration with plasma
• Increased oral bioavailability due to tissue reservoirs

Correct Answer: Large apparent volume of distribution and prolonged terminal half-life

Q5. Which tissue component commonly contributes to strong binding of lipophilic basic drugs and can lead to long-term retention?

• Plasma albumin
• Adipose tissue triglycerides
• Bone mineral (hydroxyapatite)
• Melanin and phospholipids in pigment tissues

Correct Answer: Melanin and phospholipids in pigment tissues

Q6. When measuring tissue binding using homogenates, which artifact can falsely increase the apparent extent of binding?

• Maintaining physiological temperature during incubation
• Non-specific adsorption to labware or filters
• Using equilibrium dialysis with intact tissue slices
• Correcting for tissue water content

Correct Answer: Non-specific adsorption to labware or filters

Q7. A drug shows stereoselective tissue binding where one enantiomer binds more tightly to tissue components. Clinically this may result in:

• Identical pharmacokinetics for both enantiomers
• Enantioselective distribution and potentially different toxicity profiles
• Faster renal elimination of the more tissue-bound enantiomer
• No change in pharmacodynamics since binding is irreversible

Correct Answer: Enantioselective distribution and potentially different toxicity profiles

Q8. Which parameter obtained from tissue binding studies quantifies the maximum binding capacity of tissue binding sites?

• KD (dissociation constant)
• Bmax (maximum binding capacity)
• fu (fraction unbound in plasma)
• Clint (intrinsic clearance)

Correct Answer: Bmax (maximum binding capacity)

Q9. How does high plasma protein binding relative to tissue binding generally affect drug distribution into tissues?

• Increases free drug in plasma and tissue penetration
• Decreases free plasma fraction and may limit tissue uptake
• Has no influence because only total drug concentration matters
• Always increases volume of distribution

Correct Answer: Decreases free plasma fraction and may limit tissue uptake

Q10. Which of the following best explains why lipophilic drugs often show slow release from adipose tissue?

• Rapid metabolism within adipocytes
• High perfusion rate of adipose tissue leading to quick equilibration
• Strong partitioning into lipid stores creating a low unbound fraction and slow diffusion back to plasma
• Active transporters in adipose pumping drug into circulation

Correct Answer: Strong partitioning into lipid stores creating a low unbound fraction and slow diffusion back to plasma

Q11. Autoradiography in tissue distribution studies primarily provides which type of information?

• Quantitative free fraction of drug in plasma
• Spatial localization and semi-quantitative distribution of radiolabeled drug within tissue sections
• Real-time free drug concentration in interstitial fluid
• Affinity constants (KD) for specific binding sites

Correct Answer: Spatial localization and semi-quantitative distribution of radiolabeled drug within tissue sections

Q12. A high-affinity, low-capacity tissue binding site will most likely affect a drug by:

• Sequestering large amounts of drug regardless of dose
• Influencing initial distribution at low concentrations but saturating at higher doses
• Having no effect on free concentrations at any dose
• Increasing renal clearance via binding to tubular proteins

Correct Answer: Influencing initial distribution at low concentrations but saturating at higher doses

Q13. Which in vitro method is commonly used to separate free drug from tissue-bound drug based on size exclusion rather than binding equilibrium?

• Equilibrium dialysis
• Ultrafiltration
• Scatchard plot analysis
• Autoradiography

Correct Answer: Ultrafiltration

Q14. How can tissue binding influence the interpretation of therapeutic drug monitoring (TDM) from plasma concentrations?

• Tissue binding has no effect, so plasma total concentration always reflects therapeutic effect
• High tissue binding may mean plasma total concentrations poorly predict active free drug at target sites
• TDM should always measure only bound drug for accuracy
• Tissue binding increases free plasma concentration making TDM unnecessary

Correct Answer: High tissue binding may mean plasma total concentrations poorly predict active free drug at target sites

Q15. Which tissue is characteristically a long-term reservoir for lipophilic drugs and can cause prolonged terminal elimination phases?

• Liver due to rapid metabolism
• Adipose tissue due to lipid partitioning
• Kidney cortex due to filtration
• Plasma proteins due to reversible binding

Correct Answer: Adipose tissue due to lipid partitioning

Q16. Non-specific binding in an assay system primarily affects which experimental outcome?

• Underestimation of drug metabolism rate only
• Overestimation of free fraction and underestimation of bound drug
• Apparent loss of drug leading to underestimation of free concentration and biased binding parameters
• Improved accuracy in KD determination

Correct Answer: Apparent loss of drug leading to underestimation of free concentration and biased binding parameters

Q17. Which concept explains why two drugs that bind to the same tissue site can alter each other’s distribution when co-administered?

• pH partition hypothesis
• Competitive displacement leading to changes in free fraction and distribution
• First-pass metabolism interactions only
• Increased renal secretion of the displaced drug

Correct Answer: Competitive displacement leading to changes in free fraction and distribution

Q18. Binding of a drug to tissue phospholipids is often driven by which molecular interactions?

• Only covalent bond formation
• Electrostatic attraction, hydrophobic interactions, and hydrogen bonding with polar headgroups and lipid tails
• Direct enzymatic conjugation to phospholipids
• Hydrolytic cleavage of drug to form lipid-soluble metabolites

Correct Answer: Electrostatic attraction, hydrophobic interactions, and hydrogen bonding with polar headgroups and lipid tails

Q19. In vivo, rapid equilibration between plasma and tissue free drug is most likely when which conditions are met?

• Low tissue perfusion and high tissue binding capacity
• High tissue perfusion and low tissue binding (high fu in tissue)
• Extensive intracellular trapping and slow diffusion
• High molecular weight and charged drug at physiological pH

Correct Answer: High tissue perfusion and low tissue binding (high fu in tissue)

Q20. Which parameter is most directly altered when a drug binds irreversibly to a tissue macromolecule?

• Reversible KD value remains unchanged
• Apparent volume of distribution decreases without affecting clearance
• Drug is effectively removed from the free pool, potentially reducing free concentration and prolonging apparent exposure until synthesis of the macromolecule
• Increases immediate renal filtration of the drug

Correct Answer: Drug is effectively removed from the free pool, potentially reducing free concentration and prolonging apparent exposure until synthesis of the macromolecule

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