Drug Metabolism

Question 1

What is the function of inactivation?

Answer 1

Facilitate elimination - inactive metabolite is more easily eliminated. Lipid-soluble (hydrophobic) drugs converted to water soluble (hydrophilic) metabolite.

Question 2

Where does drug metabolism primarily occur?

Answer 2

Liver

Question 3

Where does drug elimination primarily occur?

Answer 3

Kidney

Question 4

Where are Phase I enzymes found?

Answer 4

Mainly endoplasmic reticulum

Question 5

Where are Phase II enzymes found?

Answer 5

Mainly cytoplasm

Question 6

What occurs during Phase I?

Answer 6

Drugs are made more hydrophilic and the addition of functional groups

Question 7

What occurs during Phase II?

Answer 7

Conjugation with endogenous substances occurs onto the functional group

Question 8

What is the main system that mediates Phase I reactions?

Answer 8

Mixed Function Oxidase System (MFO)

Question 9

What are the 4 main elements of the MFO?

Answer 9

• Cytochrome P450 Hemoprotein
• NADPH Cytochrome P450 Reductase
• NADPH
• O2

Question 10

What is the fate of O2 during the MFO reactions?

Answer 10

One O atom is placed onto the drug and one O atom is turned into H2O.

Question 11

What does non-microsomal oxidation occur on?

Answer 11

Alcohol

Question 12

What is the function of conjugations in Phase II?

Answer 12

Create a highly polar conjugate to excrete

Question 13

First-pass effect

Answer 13

Many orally administered drugs will be extensively biotransformed before they reach the systemic circulation due to biotransformation in the G.I. tract and liver

Question 14

What is the net equation of the Phase I reaction?

Answer 14

RH + O2 + NADPH + H+ -> ROH + H2O + NADP+

Question 15

What is PABA structurally similar to?

Answer 15

Sulfonamides

Question 16

What are some drug-age interactions in neonates and the elderly?

Answer 16

Slow biotransformation in neonates and elderly patients leads to increased susceptibility to drug toxicity

Question 17

What happens when drugs compete for metabolism?

Answer 17

Accumulation of both drugs, may lead to toxicity

Question 18

What can inhibit CYP3A4?

Answer 18

Grapefruit Juice

Question 19

What is an example of drug induction?

Answer 19

Drugs can induce the expression of cytochrome P450

Question 20

What is the end result of the metabolism of the drugs?

Answer 20

ACTIVE DRUG
1) very lipid-soluble
2) less polar
3) less ionized
4) weak electrolyte
5) more able to penetrate
cell membrane

Convert to….

INACTIVE DRUG
1) less lipid-soluble
2) more polar
3) more ionized
4) strong electrolyte
5) less able to penetrate
cell membranes