Basic Principles of Pharmacology IV

Question 1

Distribution of fluid in body

Answer 1

Total body water ~ 40L.

3L in plasma, 9L in interstitial fluid, 28L in intracellular fluid

Question 2

Volume of distribution equation

Answer 2

Vd = Dose/Cp

• If drug remains in plasma, Vd = 3L
• If drug permeates extracellular fluid, Vd = 12L
• If drug permeates total body water, Vd = 40L

Question 3

Factors affecting drug distribution

Answer 3

• Blood flow: drugs distribute 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 may take a long time to achieve
• Redistribution – drug may have to distribute from initial compartments to target tissues
• Size of pt – many drugs are dosed based on weight

Question 4

Can drugs pass placenta?

Answer 4

Drugs

Question 5

Blood brain barrier

Answer 5

An anatomical protective barrier created by the existence of “tight junctions” between the capillary endothelial cells and between the choroid plexus cells in the ventricles
- to enter CNS drug must be lipid soluble or transported by a carrier

Question 6

Consequences of BBB

Answer 6

• can affect apparent drug potency
• may need to use lipid soluble precursor of active drug
• will create special problems in treating overdoses or lipid soluble or electrolyte drugs
• may necessitate direct injection of drugs into CNS

Question 7

How do you change pH to reverse overdose of weak acid drug

Answer 7

Increase plasma pH, shifts weak acid from brain to plasma

Question 8

How do you change pH to reverse overdose of weak base drug

Answer 8

Decrease plasma pH, shifts weak base from brain to plasma

Question 9

Protein binding of drugs

Answer 9

• only free drug can interact with receptor

- can change apparent Vd (larger if tissue binding occurs, smaller if plasma protein binding occurs)

Question 10

Loading dose

Answer 10

may need to fill the storage sites before enough free drug is available to interact with the receptor
Short term: protein binding, long term: lipid binding or bone

Question 11

What effect does drug displacement have on pharmacologic response?

Answer 11

Drug displacement –> more free drug at receptor –> GREATER pharmacological response