Transfer of drugs across membranes ++

Question 1

Examples of zero-order drugs

Answer 1

Ethanol, phenytoin

Question 2

Which are affected by change in absorption?

AUC, tmax, F, V, CL, T_1/2

Answer 2

AUC, tmax, F

Question 3

Which are affected in change in distribution?

AUC, tmax, F, V, CL, T1/2

Answer 3

V, T1/2

Question 4

Which are affected in change in elimination?

AUC, tmax, F, V, CL, T1/2

Answer 4

AUC, CL, T1/2

Question 5

Possible mechanisms for transfer of drugs across membranes?

Answer 5

• Pinocytosis: not very relevant
• Filtration: requires high pressure, glomerulus
• Active: Drugs structurally related to endogenous molecules
• Bulk flow of water: low MW
• Passive diffusion: Most drugs, maintained by blood flow

Question 6

Rate of passive diffusion depends on

Answer 6

• Concentration gradient across membrane (blood flow)
• Surface area
• Thickness of membrane
• Diffusion constant - Size and solubility

Question 7

Characteristics of weak acid absorption:

Answer 7

• Absorption from stomach and intestine
• Largely ionized at blood pH
• Ulikely to enter brain

Question 8

Characteristics of weak base absorption:

Answer 8

• Negligable absorption from stomach
• Good absorption from intestine
• Unionized in blood
• Likely to enter brain
• Secreted in stomach and saliva

Question 9

Which drugs are likely to be absorbed in stomach

Answer 9

pH 1.5

• Weak acids predominantly unionized and absorbed
• Weak bases predominantly ionized and not absorbed

Question 10

An example of acid labile drug

Answer 10

PPI

Question 11

Special adaptations for omeprazole

Answer 11

Given as acid resistant capsule - degrades at pH 5 in duodenum

Avoids first past metabolism

Question 12

Features of percutaneous absorption

Answer 12

• Dermis almost totally permeable to drugs, acts as a simple lipid bilayer
• Inflamed skin more permeable to drugs than normal
• E.g. conjuctival sac for timolol