PED1003/L05 Drug Elimination I

Question 1

Give the 3 factors that affect a drug’s distribution.

Answer 1

Blood perfusion of organ/tissue
Ability to cross a cell membrane
Plasma protein binding ability

Question 2

Describe the blood brain barrier.

Answer 2

Continuous layer of epithelial cells that makes the brain inaccessible to many drugs

Question 3

What 3 factors does the amount of drug bound to plasma proteins depend on?

Answer 3

Concentration of free drug
Affinity for binding site
Concentration of protein

Question 4

Describe albumin. (2)

Answer 4

Binds mostly acidic drugs
Binds small number of basic drugs

Question 5

Describe a1 acid glycoprotein. (2)

Answer 5

Binds most basic and neutral drugs
Increased inflammatory disease

Question 6

Define apparent volume of distribution (Vd).

Answer 6

Volume of fluid that would be required to contain the amount of drug in the body (Q) at the same concentration as that present in the plasma (Cp)

Question 7

What is the equation for Vd?

Answer 7

Vd = Q/Cp

Question 8

What kind of drug is not eliminated by the kidney?

Answer 8

Lipophilic drugs

Question 9

What occurs to lipophilic drugs before they can be excreted?

Answer 9

Metabolised to more polar products

Question 10

Describe the 2 phases of drug metabolism in the liver.

Answer 10

Phase I: catabolic, mostly mediated by Cytochrome P450 enzymes
Phase II: anabolic conjugation reactions

Question 11

Define hydroxylation.

Answer 11

Conversion of a hydrogen to hydroxyl group

Question 12

Define deamination.

Answer 12

Conversion of an amino group to a carbonyl group

Question 13

Define dehydrogenation.

Answer 13

Conversion of a hydroxyl group to a carbonyl group

Question 14

Describe Cytochrome P450s. (3)

Answer 14

Large family of related but distinct enzymes
Embedded in SER
Require oxygen, NADPH & NADPH-P450 reductase

Question 15

Give 3 reasons for variations in cytochrome P450.

Answer 15

Species differences
Genetic polymorphisms
Environmental factors
Other drugs

Question 16

What is the function of butrylcholinesterase (plasma cholinesterase)?

Answer 16

Hydrolyses suxamethonium
Overactivates cholinergic receptors on muscles to cause paralysis

Question 17

What is the function of aspirin esterase?

Answer 17

Hydrolyses aspirin to salicylate

Question 18

What is the function of alcohol dehydrogenase? (2)

Answer 18

Oxidises ethanol to acetalehdye
Requires NAD+

Question 19

Where do phase II reactions usually take place?

Answer 19

Liver, also in lungs/kidneys

Question 20

What are the usual products of phase II reactions?

Answer 20

Inactive

Question 21

Give 3 methods of elimination.

Answer 21

Mass transport in gut
Water soluble filtered out in kidney
Volatile gases
Secreted into glands

Question 22

Define clearance (Cl).

Answer 22

Volume of plasma (or blood) cleared of the drug per unit of time to achieve overall elimination of drug from body

Question 23

What is elimination rate constant?

Answer 23

Fraction of drug eliminated per unit time at any time point