Unit 1 - Volume of Distribution

Question 1

what is volume of distribution?

Answer 1

shows how spread out the dose of drug goes

-Vd = dose / concentration in plasma

Question 2

what is the Vd if the drug…

• remains in plasma
• permeates ECF
• permeates total body water

assuming a 70 kg man

Answer 2

plasma only: 3 L
permeates ECF: 12 L
permeates TBL: 40 L

Question 3

what are 5 factors affecting distribution?

Answer 3

1. blood flow - drugs distribute first to more vascular organs with higher blood flow
2. ability of drug to enter fluid space - pH, binding, transport, lipid solubility
3. time after administration - equilibrium with various compartments may take a long time to achieve
4. redistribution - drug may have to distribute from initial compartments to target tissue
5. size of aptient - Vd can vary with size of patient - many drugs dosed on basis of weight or body surface area (esp. pediatrics or chemotherapy)

Question 4

what should be considered drug-wise about the placenta

Answer 4

no barrier to drugs that are < 1000 MW, or lipid soluble

• fetal liver and kidney are immature
• teratogenic effects especially in first trimester, abnormal tissue differentiation
• toxic effects may be chronic (addition, birth weight, specific organ abnormalities) or acute (respiratory depression, hyperbilirubinemia, vascular problems)

Question 5

what should be considered drug-wise about the BBB?

Answer 5

“tight junctions” between capillary endothelial cells and between choroid plexus cells in ventricles

• to enter CNS, a drug must be lipid soluble or transported by carrier mediated mechanism (perhaps as a precursor)
• can affect apparent drug potency, and creates special problems in treating overdoses of lipid soluble or electrolyte drugs
• may necessitate direct injection of certain drugs into CNS

Question 6

how do you change drug distribution by pH manipulation?

Answer 6

for if overdosed, causing CNS toxicity

1. weak acid drug: counter by increasing plasma pH with HCO3-, shifting from brain to plasma
2. weak base drug: counter by decreasing plasma pH with H+, shifting from brain to plasma

Question 7

protein binding of drugs

Answer 7

binding can change apparent Vd

• larger if tissue binding occurs, due to reservoir (potential prolonged toxicity)
• smaller if plasma protein binding occurs

Question 8

what is the concept of a “loading dose”?

Answer 8

may need to fill storage sites before enough free drug is available to interact with receptor

• short term: protein binding
• long term: lipid binding or bone

Question 9

what are the different types of proteins drugs can bind to?

Answer 9

albumin - majority
alpha1 - steroid hormones (transcortin), B12, Sialic acid, thyroxine
alpha2 - hemoglobin (haptoglobin)
beta1
beta2 - Fe++ (transferrin)