EXAM 5 - Drug Metabolism 1

Question 1

The properties that enable xenobiotics/drugs to be ____ are also going to be an obstacle for _____.

Answer 1

absorbed (lipophilicity)
elimination (too lipophilic to be eliminated)
* the elimination of any xenobiotics depends on their conversion to more water-soluble compounds

Question 2

Describe the relation between pro-drugs and metabolism.

Answer 2

Many drugs (pro-drugs) must undergo biotransformation/metabolism to exert their therapeutic/toxic effects.
* determines intensity and duration of action of drugs and play a key role in chemical toxicity

Question 3

Explain why we have drug metabolizing enzymes.

Answer 3

these enzymes have evolved to metabolize any drug
* to protect from toxicity
* to convert to energy

Question 4

Describe the 4 reasons that drug metabolism is important.

Answer 4

A. Influences pharmacokinetics of drug (action of body on drug).
* rate of absorption, distribution, and elimination is dependent on chemical structure –> can be changed by metabolism

B. Influences pharmacodynamics (drug action on body).
* receptor binding, duration of action, efficacy and potency depend on chemical structure –> can be changed by metabolism

C. Changes toxicology of drug (adverse reactions). Toxicity could decrease, increase, or stay the same; or site of toxicity changed.

D. Pharmacogenetics - variability between different people in their response to drug treatment due to genetic differences in drug metabolism

Question 5

Name the 5 basic properties of drug metabolizing enzymes.

Answer 5

1. Most have broad substrate specificity/selectivity
2. Most are expressed constitutively (all the time)
3. Some play important roles in normal physiology
4. Many have no know physiological function (except to metabolize xenobiotics)
5. Can increase or decrease therapeutic effect and/or toxic effect of drugs.

Question 6

Describe Phase 1 biotransformation.

Answer 6

Phase 1 reactions introduce functional groups, such as OH, NH2, O, or COOH
* result in a small increase in water solubility

Question 7

Describe Phase 2 biotransformations.

Answer 7

Phase 2 reactions require cofactors that react with functional groups (previously present or introduced during phase 1).
* result in large increase in water solubility

Question 8

Describe Phase 3 biotransformation.

Answer 8

Phase 3 reactions result in cellular efflux of polar xenobiotics by membrane bound transporters.
* transported out the cell to get eliminated bc after phase 1&2, it is too hydrophilic to transport across membrane alone.

Question 9

Define microsome.

Answer 9

Fragment of ER and attached ribosomes obtained by centrifugation of homogenized cells.

Question 10

Explain the distribution of drug biotransforming enzymes.

Answer 10

Majority in liver, but also in most other tissues/organs.
* location and amount of a particular biotransformation enzyme can explain tissue-specific action and/or injury

Question 11

Describe the metabolism of acetaminophen.

Answer 11

2 Phase II and Phase 1 enzyme reactions happen at the same time in the liver.

Question 12

Answer 12

B. elimination

Question 13

Answer 13

D. All of the above

Question 14

Answer 14

D. All of the above

Question 15

Answer 15

D. glycine

Question 16

Describe the metabolism of acetaminophen.

Answer 16

2 Phase II and Phase 1 enzyme reactions happen at the same time in the liver.