4- Drug Metabolism

Question 1

How does the body convert a drug from an active to an inactive form?

Answer 1

Phase I and II reactions (talked about last chapter)

Question 2

What is first pass extraction?

Answer 2

When drugs are taken orally or rectally, they are taken up by the portal system and metabolized in the liver. This means less drug will be delivered to the blood stream that you put in because an amount of it will be inactivated by the liver.

Question 3

What type of administration bypasses the first pass extraction?

Answer 3

IV administration of a drug

Question 4

What does oxidation reactions do to the drug for metabolization?

Answer 4

more hydrophilic metabolites by adding or exposing polar functional groups

Question 5

Where does conjugation and hydrolysis take place in the liver for phase II reactions?

Answer 5

in both the cytosol and ER

Question 6

Since neonates don’t have the capacity to conjugate, what do they used to conjugate bilirubin to excrete it?

Answer 6

UDGPT

Question 7

What happens if a neonate doesnt have UDGPT yet?

Answer 7

They get jaundice.

Question 8

What is the Multidrug resistant protein 1 ( MDR1)?

Answer 8

ABC family of efflux transporters, actively transports compounds back into the intestinal lumen

Question 9

What is the Organic anion transporting polypeptide (OATP)?

Answer 9

Help transport drugs from portal circulation into hepatocytes

Question 10

What is induction?

Answer 10

chronic drug exposure (barbs, alcohol, coffee) creates more enzymes to increase the metabolism of the drug in the next initial dose. This means you need more of the drug to produce the same effects as the initial dose as they are quickly metabolized by the surplus of enzymes.

Question 11

What is an example of a drug that speeds up its own metabolism via P450 3A4 induction?

Answer 11

Carbamazepine

Question 12

What is significant about P450 3A4?

Answer 12

It’s responsible for metabolizing more than 50% of prescribed drugs

Question 13

What is a drug that induces P450 3A4, used in HIV therapy, and induces the metabolism of other drugs?

Answer 13

Rifampin/St. Johns wort

Question 14

Why is the induction of other drugs bad?

Answer 14

Induction can reduce other drug concentrations below their therapeutic level if standard doses of the drugs are administered

Question 15

What is inhibition?

Answer 15

Sometimes drugs inhibit enzymes that other drugs use for metabolism. This leads to a toxicity of the drug.

Question 16

What is an example of an antifungal drug that inhibits P450 enzymes?

Answer 16

Ketoconazole

Question 17

What are prodrug metabolites?

Answer 17

Prodrug is inactive compounds that are metabolized by the body into their active, therapeutic forms

Question 18

What are toxic metabolites?

Answer 18

drug metabolites have adverse effect

Question 19

What is an example of a famous toxic metabolite that injures the liver when the levels exceed the therapeutic range?

Answer 19

Acetaminophen. Excessive accumulation of acetaminophen metabolites that are not conjugated side reacts and causes harm to the liver

Question 20

What is the role of genetics in drug metabolism?

Answer 20

Certain population exhibit polymorphism mutation in one or more enzymes of drug metabolism, changing the rate of these reactions and eliminating others altogether

Question 21

What is the role of race in drug metabolism?

Answer 21

Race may be a key consideration in choosing drug treatment or doses.
Ex: P450 2D6 is functionally inactive in 8% Caucasians while in Asians only 1%.

Question 22

What is the role of age in drug metabolism?

Answer 22

In young children and elderly, they have slow biotransformation reaction. Neonates are not able to carry out all oxidative reaction. Elderly has decline in function

Question 23

What is the role of diet in drug metabolism?

Answer 23

Both diet and environment can alter drug metabolism by inducing or inhibiting enzyme of the P450 system

Question 24

What is the role of the patient’s health in drug metabolism?

Answer 24

This is important because much disease state can affect the rate and extent of drug metabolism in the body. Especially liver disease because liver is the main site of biotransformation.

Question 25

What is an important nolecule that Fe in P450 uses to split the O2 molecule?

Answer 25

NADPH

Question 26

What are poisons?

Answer 26

poisons are substances that can cause damage, illness, or death to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism

Question 27

What are toxins?

Answer 27

A toxin is a poisonous substance produced by living cells or organisms that is active at very low concentrations.