Drug Metabolism

Question 1

Define metabolism.

Answer 1

Disappearance of a drug by chemically changing it into another cmpd called a metabolite.

Question 2

Define xenobiotics.

Answer 2

Foreign substances that are absorbed or ingested.

Question 3

Define pro-drug. What are its 3 purposes?

Answer 3

Cmpd w/ little or no activity that is metabolized to an active species in order to 1) promote absorption, 2) prevent acid destruction, 3) minimize exposure toxicity

Question 4

Define biological half-life.

Answer 4

that period of time in which half of the amount of a drug disappears; a function of its rate of metabolism and its rate of excretion

Question 5

Define first-pass effect. What organ is usually involved?

Answer 5

occurs when more than half of the amount of a drug is metabolized on its 1st pass through an organ (usually the liver)

Question 6

Almost all drugs are metabolized to compounds that are: (name 3)

Answer 6

1. more polar than the parent compound
2. not as well reabsorbed and therefore more efficiently excreted
3. many will become inactive or less active than their parent compound

Question 7

What are the three possible outcomes of hepatic metabolism of pharmacologic cmpds?

Answer 7

1. Activation
2. Degradation into active or inactive metabolites
3. Degradation to a toxic metabolite, including carcinogens

Question 8

What is the most important organ for elimination of drugs and their metabolites?

Answer 8

Kidney

Question 9

What are the three processes involved in the excretion of drugs and metabolites in the urine? Which is affected most by drug metabolism? Why?

Answer 9

• glomerular filtration
• active tubular secretion
• passive tubular reabsorption

Passive tubular reabsorption - b/c metabolite is more polar than the drug that was administered

Question 10

What is the major diff between Phase I and Phase II rxns?

Answer 10

Phase II needs a donor molecule, Phase I reactions act on the drug alone

Question 11

Where do enzymes that participate in hydrolysis act?

Answer 11

Plasma & cytoplasm

Question 12

What are the reaction classes of Phase I and Phase II?

Answer 12

Phase I - oxidation, reduction, hydrolysis

Phase II - conjugation

Question 13

What order are the kinetics of drug metabolism reactions at therapeutic doses?

Answer 13

First order

Question 14

What order are the kinetics of drug metabolism reactions at saturation?

Answer 14

Zero order

Question 15

What organ has the highest level of drug-metabolizing activity?

Answer 15

Liver

Question 16

What system can oxidize drugs? What are its two requirements?

Answer 16

Monooxygenase or cytochrome P450 system

1. Reduced NADPH
2. Oxygen

Question 17

What drug was removed from the market due to a P450-based toxicity? What condition did it make them susceptible to?

Answer 17

Seldane

Cardiac arrhythmias

Question 18

What chemical group is inserted in oxidation?

Answer 18

Hydroxyl group

Question 19

What is removed in reduction?

Answer 19

Oxygen

Question 20

What does hydrolysis involve?

Answer 20

Cleavage w/ addition of water

Question 21

What reaction type frequently uses transferase enzymes? Phase I or II?

Answer 21

Phase II

Question 22

What are 4 factors in neonates that makes their drug metabolism capabilities different than adults?

Answer 22

1. Absorption - gastric pH varies
2. Distribution - body water is greater
3. Metabolism - p450 is developed, but functions slower; glucuronidation is immature
4. Excretion - renal blood flow, GFR, tubular function are reduced

Question 23

What are 5 factors in elderly that make their drug metabolism capabilities different than adults?

Answer 23

1. Absorption - may be less efficient
2. Distribution - can be altered by hypoalbuminemia, changes in drug-binding sites, changes in protein/fat mass ratio
3. Metabolism - reduced hepatic mass, enzyme activity, and blood flow to liver
4. Excretion - reduced renal blood flow
5. Receptor sensitivity - reduced

Question 24

What are the acute and chronic effects of ethyl alcohol on drug metabolism?

Answer 24

Acute - inhibits drug metabolism

Chronic - induces hepatic drug metabolizing activity (drugs are not effective)

Question 25

How does grapefruit juice affect drug metabolism?

Answer 25

Flavinoids inhibit metabolism of Ca2+ channel blockers and caffeine by inhibiting CYP3A

Question 26

Which of the following drugs will cause an increased metabolism of combination pill oral contraceptives?

A. ampicillin
B. ciprofloxacin
C. erythromycin
D. tetracycline

Answer 26

A and D