BPP III

Question 1

In a 70 kg man, what is the potential volume of distribution for a drug in the plasma, interstitial fluid, and cell? What are examples of drugs that could get through all three compartments, just two of them, and only plasma?

Answer 1

3 L, 9 L, 28 L (40 L total); small and/or lipid soluble could get through all three, lipid-insoluble molecules would get stopped at the cell membrane, and protein-bound drugs would be stuck in the plasma

Question 2

What two things determine a drug’s Vd?

Answer 2

How well it diffuses and how it is transported

Question 3

What is the relationship between a drug’s plasma concentration and a drug’s volume of distribution (think of the equation)?

Answer 3

Inverse

Question 4

What is a drug’s Vd if it has high protein binding? What about if there is a high degree of tissue binding?

Answer 4

3L; 40 L

Question 5

What are factors that would affect drug volume of distribution?

Answer 5

Blood flow (drugs will go to more vascular organs with higher blood flow),
ability of drug to enter fluid space (pH, binding, transport, lipid solubility),
time after administration (equilibrium with various compartments could take some time),
redistribution (drug will distribute from initial compartments to target tissue)

Question 6

What types of drugs can sneak through placenta? What do babies not have yet that makes this a problem? What types of other EFFECTS might you need to consider for distribution?

Answer 6

Those with <1000 in molecular weight and lipid-soluble; Immature fetal liver and kidney;
Teratogenic (especially in first trimester, look for abnormal tissue differentiation) and toxic (acute = addiction, birth weight, specific organ abnormalities, chronic = respiratory depression, hyperbilirubinemia, etc.)

Question 7

What does the blood brain barrier consist of and where are these found? How can drugs get through?

Answer 7

Tight junctions that are found between capillary endothelial cells and choroid plexus in ventricles;
use carrier mechanisms or be lipid soluble

Question 8

What are consequences of dealing with drugs that could cross BBB?

Answer 8

1. Affect apparent drug potency (dose-related)
2. Could need lipid soluble precursors of the active drug
3. Problems in treating overdoses of lipid soluble or electrolyte drugs
4. Might need direct injection of certain drugs into CNS (ie intrathecal)

Question 9

In terms of protein binding, what would hydrophilic molecules bind to? Steroid hormones? Lipids, cholesterol, fat-soluble stuff?

Answer 9

Mostly albumin; some albumin, alpha proteins; alpha and beta proteins

Question 10

Plasma drug concentration = ____ + _____ drug; which is the pharmacologically active moiety? What is a loading dose?

Answer 10

bound; free; free; enough drug to fill up the protein binding sites before you have distribution to the target tissue proper