Welcome, PharmD students, to your MCQ quiz on Drug Distribution! Once a drug enters the systemic circulation, it doesn’t stay confined there. The process of distribution describes how a drug reversibly moves from the bloodstream into various tissues and fluids of the body. Understanding the factors that govern drug distribution, such as tissue permeability, blood flow, and protein binding, along with key concepts like the volume of distribution, is crucial for predicting drug concentrations at the site of action and for effective dose individualization. This quiz will test your knowledge of these fundamental pharmacokinetic principles. Let’s explore how drugs navigate the body!
1. Drug distribution in pharmacokinetics refers to the process by which a drug:
- a) Is eliminated from the body.
- b) Moves from the site of administration into the bloodstream.
- c) Is chemically altered by enzymes in the body.
- d) Reversibly leaves the bloodstream and enters the interstitial and intracellular fluids and tissues.
Answer: d) Reversibly leaves the bloodstream and enters the interstitial and intracellular fluids and tissues.
2. Which of the following factors generally promotes wider distribution of a drug into body tissues?
- a) High degree of ionization at physiological pH
- b) High lipid solubility
- c) Large molecular size
- d) High binding to plasma proteins
Answer: b) High lipid solubility
3. The apparent volume of distribution (Vd) is defined as:
- a) The actual physiological volume of body water.
- b) The rate at which a drug is cleared from the plasma.
- c) The theoretical volume that would be required to contain the total amount of drug in the body at the same concentration as it is in the plasma.
- d) The fraction of drug absorbed into the systemic circulation.
Answer: c) The theoretical volume that would be required to contain the total amount of drug in the body at the same concentration as it is in the plasma.
4. A drug with a very high volume of distribution (e.g., > 42 L in a 70 kg person) suggests that the drug:
- a) Is largely confined to the plasma compartment.
- b) Distributes extensively into tissues and may be sequestered there.
- c) Is rapidly eliminated by the kidneys.
- d) Is poorly absorbed after oral administration.
Answer: b) Distributes extensively into tissues and may be sequestered there.
5. Which of the following plasma proteins is a major carrier for acidic drugs?
- a) Alpha-1-acid glycoprotein
- b) Hemoglobin
- c) Albumin
- d) Lipoproteins
Answer: c) Albumin
6. The extent of plasma protein binding of a drug primarily affects its:
- a) Rate of metabolism only.
- b) Free (unbound) concentration, which is pharmacologically active and available for distribution and elimination.
- c) Chemical stability.
- d) Route of administration.
Answer: b) Free (unbound) concentration, which is pharmacologically active and available for distribution and elimination.
7. If a drug is 99% bound to plasma proteins, what percentage of the drug in plasma is free and pharmacologically active?
- a) 99%
- b) 50%
- c) 10%
- d) 1%
Answer: d) 1%
8. The blood-brain barrier (BBB) restricts the entry of many drugs into the central nervous system primarily due to:
- a) High permeability of brain capillaries.
- b) Presence of tight junctions between endothelial cells and active efflux transporters.
- c) Abundant fenestrations in brain capillaries.
- d) Low blood flow to the brain.
Answer: b) Presence of tight junctions between endothelial cells and active efflux transporters.
9. Which of the following types of drugs would most easily cross the blood-brain barrier?
- a) Highly ionized, water-soluble drugs
- b) Large molecular weight drugs
- c) Small, lipid-soluble (lipophilic) drugs
- d) Drugs extensively bound to plasma proteins
Answer: c) Small, lipid-soluble (lipophilic) drugs
10. The rate of drug distribution to different tissues is primarily determined by:
- a) Only the drug’s pKa.
- b) Only the drug’s molecular weight.
- c) Tissue perfusion (blood flow) and permeability of tissue membranes to the drug.
- d) Only the volume of the tissue.
Answer: c) Tissue perfusion (blood flow) and permeability of tissue membranes to the drug.
11. For a drug that binds extensively to tissues, its apparent volume of distribution (Vd) would likely be:
- a) Very small (e.g., < 5 L)
- b) Equal to plasma volume
- c) Very large (e.g., > 100 L)
- d) Equal to total body water
Answer: c) Very large (e.g., > 100 L)
12. The placental barrier is a specialized barrier that separates maternal and fetal circulation. Most drugs can cross the placental barrier to some extent, primarily by:
- a) Active transport only
- b) Simple diffusion, depending on lipid solubility and ionization
- c) Facilitated diffusion only
- d) Pinocytosis only
Answer: b) Simple diffusion, depending on lipid solubility and ionization
13. If the Vd of Drug A is 10 L and the Vd of Drug B is 500 L in the same patient, which drug is more extensively distributed into tissues outside the plasma?
- a) Drug A
- b) Drug B
- c) Both distribute equally.
- d) Cannot be determined from Vd.
Answer: b) Drug B
14. Conditions such as hypoalbuminemia (low plasma albumin levels) can affect drug distribution by:
- a) Decreasing the free fraction of highly protein-bound acidic drugs, reducing their effect.
- b) Increasing the free fraction of highly protein-bound acidic drugs, potentially increasing their effect or toxicity.
- c) Increasing the total amount of drug in the body.
- d) Decreasing the rate of drug metabolism.
Answer: b) Increasing the free fraction of highly protein-bound acidic drugs, potentially increasing their effect or toxicity.
15. The initial, rapid decline in plasma drug concentration seen with some IV drugs, before the slower elimination phase, is often attributed to:
- a) Drug absorption
- b) Drug metabolism only
- c) Drug distribution from the central compartment to peripheral tissues
- d) Saturation of elimination pathways
Answer: c) Drug distribution from the central compartment to peripheral tissues
16. Which body compartment would a highly water-soluble drug with low lipid solubility and significant ionization at physiological pH primarily distribute into if it does not bind extensively to plasma proteins?
- a) Adipose tissue
- b) Intracellular fluid
- c) Extracellular fluid (plasma and interstitial fluid)
- d) Bone
Answer: c) Extracellular fluid (plasma and interstitial fluid)
17. The volume of distribution (Vd) is a key parameter used in calculating:
- a) The elimination rate constant.
- b) The oral bioavailability.
- c) An appropriate loading dose to rapidly achieve a target plasma concentration.
- d) The time to reach peak plasma concentration.
Answer: c) An appropriate loading dose to rapidly achieve a target plasma concentration.
18. If a drug is highly sequestered in a specific tissue (e.g., digoxin in muscle tissue), it will have a:
- a) Small apparent Vd.
- b) Large apparent Vd.
- c) Vd equal to plasma volume.
- d) Vd primarily determined by its clearance.
Answer: b) Large apparent Vd.
19. The phenomenon where a drug initially distributes to highly perfused organs (like brain, heart, liver, kidneys) and then more slowly redistributes to less perfused tissues (like muscle, fat) is known as:
- a) First-pass effect
- b) Enterohepatic circulation
- c) Redistribution
- d) Bioinactivation
Answer: c) Redistribution
20. Which of the following statements about drug distribution is TRUE?
- a) All drugs distribute uniformly throughout all body tissues.
- b) Distribution is an irreversible process.
- c) Only unbound (free) drug can typically cross cell membranes and exert a pharmacological effect.
- d) Plasma protein binding always increases the Vd of a drug.
Answer: c) Only unbound (free) drug can typically cross cell membranes and exert a pharmacological effect.
21. A drug with a Vd of approximately 3-5 Liters in an adult is likely distributed primarily in the:
- a) Total body water
- b) Extracellular fluid
- c) Plasma compartment
- d) Adipose tissue
Answer: c) Plasma compartment
22. The binding of drugs to tissue components (e.g., proteins, nucleic acids, fats) will tend to:
- a) Decrease the apparent volume of distribution.
- b) Increase the apparent volume of distribution.
- c) Increase the rate of drug elimination.
- d) Decrease the drug’s half-life.
Answer: b) Increase the apparent volume of distribution.
23. P-glycoprotein (P-gp) is an efflux transporter found in various tissues, including the BBB and placenta. Its action generally leads to:
- a) Increased drug penetration into these tissues.
- b) Decreased drug penetration into these tissues by pumping drugs out of cells.
- c) Enhanced drug metabolism within these tissues.
- d) Increased drug binding to plasma proteins.
Answer: b) Decreased drug penetration into these tissues by pumping drugs out of cells.
24. The Vd can be calculated using the formula: Vd = Dose / C0. What does C0 represent?
- a) Steady-state concentration
- b) Minimum effective concentration
- c) Initial plasma drug concentration (at time zero) after IV bolus administration, assuming instantaneous distribution.
- d) Concentration at half-life
Answer: c) Initial plasma drug concentration (at time zero) after IV bolus administration, assuming instantaneous distribution.
25. Displacement of a highly protein-bound drug (Drug A) by another drug (Drug B) that also binds to the same plasma protein site can lead to:
- a) A decrease in the free concentration of Drug A.
- b) An increase in the free concentration of Drug A, potentially leading to increased effects or toxicity.
- c) A decrease in the Vd of Drug A.
- d) An increase in the metabolism of Drug B.
Answer: b) An increase in the free concentration of Drug A, potentially leading to increased effects or toxicity. (This is clinically significant mainly for drugs with narrow therapeutic indices and high protein binding).
26. For a drug that is primarily distributed within the extracellular fluid, its Vd would be approximately:
- a) 3-5 L
- b) 10-20 L (in a 70 kg adult)
- c) 42 L
- d) >100 L
Answer: b) 10-20 L (in a 70 kg adult) (Plasma volume ~3L, Interstitial fluid ~12-15L)
27. The distribution of drugs into breast milk is a concern for nursing mothers. Drugs that readily pass into breast milk are typically:
- a) Highly ionized and water-soluble.
- b) Large molecular weight proteins.
- c) Lipid-soluble, non-ionized, and not highly protein-bound in maternal plasma.
- d) Only administered intravenously.
Answer: c) Lipid-soluble, non-ionized, and not highly protein-bound in maternal plasma.
28. Pathological conditions like severe burns or trauma can alter drug distribution by:
- a) Only decreasing drug metabolism.
- b) Altering plasma protein concentrations (e.g., decreased albumin) and capillary permeability.
- c) Only increasing renal clearance.
- d) Making all drugs distribute solely to adipose tissue.
Answer: b) Altering plasma protein concentrations (e.g., decreased albumin) and capillary permeability.
29. If a drug has a Vd equal to the total body water (approx. 0.6 L/kg or 42 L in a 70 kg adult), it suggests the drug distributes:
- a) Only in the plasma.
- b) Throughout the total body water, including intracellular and extracellular fluids.
- c) Primarily into adipose tissue.
- d) Only to highly perfused organs.
Answer: b) Throughout the total body water, including intracellular and extracellular fluids.
30. The rate and extent of drug distribution are important because they influence:
- a) Only the color of the final drug product.
- b) The onset, intensity, and duration of drug action.
- c) Only the cost of the drug.
- d) The manufacturing process.
Answer: b) The onset, intensity, and duration of drug action.
31. What is the relationship between the fraction unbound (fu) of a drug in plasma and its Vd when tissue binding is significant?
- a) Vd is directly proportional to fu.
- b) Vd is inversely proportional to fu.
- c) Vd is independent of fu.
- d) The relationship is complex and depends on the fraction unbound in tissue as well.
Answer: d) The relationship is complex and depends on the fraction unbound in tissue as well. (Vd = Vp + Vt * (fu / fut))
32. The concept of “one-compartment model” for drug distribution implies that:
- a) The drug distributes into multiple body compartments at different rates.
- b) The body acts as a single, uniform compartment into which the drug distributes rapidly and homogeneously.
- c) The drug does not distribute outside the plasma.
- d) Distribution is the rate-limiting step in elimination.
Answer: b) The body acts as a single, uniform compartment into which the drug distributes rapidly and homogeneously.
33. A “two-compartment model” (central and peripheral) is often used when drug distribution into certain tissues is:
- a) Instantaneous
- b) Slower and rate-limiting compared to elimination from the central compartment
- c) Non-existent
- d) Only occurring via active transport
Answer: b) Slower and rate-limiting compared to elimination from the central compartment
34. Alpha-1-acid glycoprotein (AAG) is an important plasma protein for binding:
- a) Acidic drugs
- b) Basic (cationic) and neutral lipophilic drugs
- c) Only very large protein drugs
- d) Only drugs administered IV
Answer: b) Basic (cationic) and neutral lipophilic drugs
35. If the loading dose (LD) is calculated as LD = Target Concentration × Vd, a larger Vd will require:
- a) A smaller loading dose.
- b) A larger loading dose to achieve the same target concentration.
- c) No change in the loading dose.
- d) A loading dose equal to the maintenance dose.
Answer: b) A larger loading dose to achieve the same target concentration.
36. Which of the following best describes tissue permeability as a factor in drug distribution?
- a) The ease with which a drug passes through cell membranes to enter a tissue.
- b) The blood supply to a tissue.
- c) The binding of a drug to plasma proteins.
- d) The volume of a specific tissue.
Answer: a) The ease with which a drug passes through cell membranes to enter a tissue.
37. Factors that can increase the permeability of the blood-brain barrier to drugs include:
- a) Decreased lipid solubility of the drug.
- b) Inflammation (e.g., in meningitis).
- c) Increased activity of efflux transporters like P-glycoprotein.
- d) High degree of drug ionization.
Answer: b) Inflammation (e.g., in meningitis).
38. The distribution of a drug can be affected by the patient’s age. For example, neonates may have:
- a) Increased plasma protein binding capacity.
- b) A higher proportion of body fat compared to adults.
- c) A higher proportion of total body water and potentially different protein binding, leading to altered Vd for some drugs.
- d) More efficient blood-brain barrier.
Answer: c) A higher proportion of total body water and potentially different protein binding, leading to altered Vd for some drugs.
39. Drug accumulation in adipose tissue is more likely for drugs that are:
- a) Highly water-soluble
- b) Highly lipid-soluble (lipophilic)
- c) Rapidly metabolized
- d) Excreted unchanged by the kidney
Answer: b) Highly lipid-soluble (lipophilic)
40. The passage of drugs into the cerebrospinal fluid (CSF) is restricted by:
- a) The hepatic portal system.
- b) The blood-brain barrier and the blood-CSF barrier (choroid plexus).
- c) High protein content in the CSF.
- d) Rapid metabolism within the CSF.
Answer: b) The blood-brain barrier and the blood-CSF barrier (choroid plexus).
41. The Vd is an “apparent” volume because:
- a) It represents a true physiological space in all cases.
- b) It is a proportionality constant and may not correspond to any real anatomical volume, especially if it’s very large.
- c) It can only be measured for IV drugs.
- d) It changes with every dose administered.
Answer: b) It is a proportionality constant and may not correspond to any real anatomical volume, especially if it’s very large.
42. If a drug binds avidly to tissue proteins but has low plasma protein binding, its Vd is expected to be:
- a) Small
- b) Large
- c) Equal to plasma volume
- d) Primarily dependent on its clearance
Answer: b) Large
43. Perfusion-rate limited distribution occurs when:
- a) The drug has difficulty crossing cell membranes.
- b) The delivery of the drug to a tissue is limited by the blood flow to that tissue, typically for small, lipophilic drugs that readily cross membranes.
- c) The drug only distributes to the plasma.
- d) The drug is actively transported out of tissues.
Answer: b) The delivery of the drug to a tissue is limited by the blood flow to that tissue, typically for small, lipophilic drugs that readily cross membranes.
44. Permeability-rate limited distribution occurs when:
- a) Blood flow to the tissue is very high.
- b) The drug’s ability to cross the cell membrane is the main factor limiting its entry into a tissue, often for polar drugs or well-perfused tissues with tight barriers.
- c) The drug is extensively bound to plasma proteins.
- d) The drug is rapidly metabolized in the blood.
Answer: b) The drug’s ability to cross the cell membrane is the main factor limiting its entry into a tissue, often for polar drugs or well-perfused tissues with tight barriers.
45. The extent of drug distribution can impact the time it takes to reach steady state because:
- a) Drugs with larger Vd take longer to distribute and reach equilibrium throughout the body.
- b) Drugs with smaller Vd are eliminated faster.
- c) Distribution does not affect time to steady state, only half-life does.
- d) Steady state is only relevant for IV drugs.
Answer: a) Drugs with larger Vd take longer to distribute and reach equilibrium throughout the body. (While half-life is the primary determinant for time to Css, distribution contributes to the half-life value).
46. Which type of drug interaction related to distribution involves competition for plasma protein binding sites?
- a) Alteration of gastric pH
- b) Induction of metabolic enzymes
- c) Displacement of one drug from plasma proteins by another, increasing the free fraction of the displaced drug
- d) Inhibition of renal transporters
Answer: c) Displacement of one drug from plasma proteins by another, increasing the free fraction of the displaced drug
47. When interpreting Vd values, it’s important to remember that it’s a parameter that reflects:
- a) The rate of drug elimination.
- b) The extent to which a drug partitions between plasma and tissue compartments.
- c) The absolute amount of drug in the body.
- d) The drug’s bioavailability.
Answer: b) The extent to which a drug partitions between plasma and tissue compartments.
48. For drugs that accumulate in certain tissues, these tissues can act as a:
- a) Primary site of elimination.
- b) Reservoir, potentially prolonging the drug’s duration of action or leading to delayed toxicity.
- c) Barrier to absorption.
- d) Site for first-pass metabolism.
Answer: b) Reservoir, potentially prolonging the drug’s duration of action or leading to delayed toxicity.
49. Changes in body composition (e.g., increased adipose tissue in obesity) can significantly alter the Vd of which type of drugs?
- a) Highly water-soluble drugs
- b) Highly lipid-soluble (lipophilic) drugs
- c) Drugs that do not bind to plasma proteins
- d) Drugs eliminated only by the kidneys
Answer: b) Highly lipid-soluble (lipophilic) drugs
50. Understanding drug distribution is critical for pharmacists to:
- a) Only determine the selling price of a medication.
- b) Predict potential for drug accumulation, design loading doses, and understand how various patient factors can alter drug disposition.
- c) Compound all medications from raw ingredients.
- d) Perform surgery.
Answer: b) Predict potential for drug accumulation, design loading doses, and understand how various patient factors can alter drug disposition.