Pharmacokinetics - Drug Metabolism

Question 1

3 routes of drug elimination

Answer 1

1. Hepatic metabolism
2. Bile elimination
3. Urine elimination

Question 2

Clearance

Answer 2

The amount of drug cleared from the body per unit of time

Question 3

Pathway of liver metabolization

Answer 3

1. Drug taken orally
2. Drug enters portal vein
3. Cycles through metabolism in liver
4. Enters back into blood stream

Question 4

What does 1st pass do to the bioavailability

Answer 4

Extensively decreases the amount of drug that will go into circulation

Question 5

Drugs that exhibit high first-pass metabolism are….

Answer 5

Metabolized in extremely large amounts by the liver. EX: Nitroglycerin - 90% metabolized. Must give sublingual to avoid this

Question 6

Examples of high first pass drugs

Answer 6

1. Lidocaine
2. Morphine
3. Metoprolol

Question 7

What must happen to a lipid soluble drug in order for it to be excreted

Answer 7

Must be metabolized into a polar (hydrophilic) substance in Phase I and II in order for them to be eliminated in the kidneys (because kidney cannot get ride of lipophilics)

Question 8

Phase I reactions of metabolism

Answer 8

Converts lipophilic molecules into more polar molecules (oxidation/reduction/hydrolysis)

Question 9

What catalyzes the phase I reactions

Answer 9

Cytochrome P450 enzyme

Question 10

Phase II reaction sof metabolism

Answer 10

If metabolites from phase I are still too lipophilic, a conjugate acid is added to the substance to make it more polar and usually more water soluble

Question 11

What happens if the drug already has an -OH, -NH2, -COOH?

Answer 11

It can bypass Phase I and may enter phase II directly and conjugate immediately

Question 12

Difference between drug and metabolites

Answer 12

The metabolites are much more polar than parent drug and are more readily excreted

Question 13

Pro-drug

Answer 13

Inactive form of a drug that is converted to the active form via metabolism

Question 14

What happens to active drugs during metabolism

Answer 14

They can become active metabolites (oxycodone)

Question 15

Active drug to toxic metabolite

Answer 15

After active drug is metabolized, it may turn into a metabolite that exerts toxic effects on the body

Question 16

Metabolism induction

Answer 16

When enzymes (p450) are enhanced or stimulated and results in an increased rate of metabolism of the drug

Question 17

What affect does induction have on drug concentration

Answer 17

Decreases concentration

Question 18

What effect does induction have on clinical efficacy

Answer 18

decreases it

Question 19

Metabolism inhibition

Answer 19

When metabolic enzymes are deactivated by the drug.

Question 20

What does inhibition result in

Answer 20

Decreased metabolism, Increase in drug concentration, Increase in clinical efficacy. May be potentially toxic

Question 21

Where is the Cytochrome P450 enzyme located

Answer 21

In the lipid bilayer of ER of many cells

Question 22

Where is the highest concentration of P450 enzymes

Answer 22

Liver and SI

Question 23

Role of P450

Answer 23

Is the enzyme that catalyzes the Phase I reactions (breaking down the lipophilic drugs by converting them into more polar molecules)

Question 24

How does conjugation enhance ability to of drug to be eliminated by kidney

Answer 24

By adding a conjugate (most often an acid of some kind), it allows for the molecules to become even less lipophilic and more polar, which will allow the drug to remain in the kidney tubule for excretion

Question 25

What is the effect of cells with high expression of P-glycoproteins

Answer 25

It reduces drug absorption because it is a multi drug transmembrane protein that moves drugs across the cells membrane and into cells for excretion

Question 26

P-glycoproteins in the SI will….

Answer 26

Reduce drug absorption in the blood, but will transport drugs into the lumen