57. Phase 1 and Phase 2 Metabolism

Question 1

what does ADME stand for

Answer 1

Absorption, Distribution, Metabolism and Excretion

Question 2

what is drug metabolism

Answer 2

drug transformation by metabolism by the liver and other tissues
the enzymatic conversion of the drug to another chemical entity

Question 3

which organ is the most important for drug metabolism

Answer 3

liver

Question 4

Metabolism in the liver (and/or gut) reduces the ‘………..’of drugs when administered by the enteral (oral) rout

Answer 4

Bioavailability

Question 5

what has 100% bioavailability

Answer 5

Intravenous administration

Question 6

what is bioavailability

Answer 6

The amount of drug that eventually reaches systemic circulation (and hence is available for drug action on the target) of an administered dose of the drug

Question 7

what is the bioavailability equation

Answer 7

(Bioavailability) F= quantity of drug reaching systemic circulation/quantity of drug administered (DOSE)

AKA
Amount of drug in systemic Circ
F= ——————————————–
Quantity of drug administered

Question 8

what is first pass metabolism

Answer 8

Occurs with oral administration;

The drug is absorbed in the gut and transported to the liver,

Reducing bioavailability.

This may require higher doses or alternative routes of administration

Question 9

systemic metabolism occurs in ….. phases

Answer 9

2

Question 10

Phase one and two mainly take part where?

Answer 10

the liver

Question 11

Phase 1 of systemic metabolism is (3)

Answer 11

oxidation, reduction and hydrolysis

Question 12

Phase 2 of systemic metabolism is

Answer 12

Conjunction with polar molecules to form water soluble metabolites

Question 13

explain phase 1 oxidation

Answer 13

by cytochrome P450 enzymes, incorporation 1 atom of O2 to the drug to form a hydroxyl group

Question 14

explain phase 1 reduction

Answer 14

this reaction occurs less than oxidation.

Question 15

explain phase 1 hydrolysis

Answer 15

Ester and amide bonds are hydrolyzed, occurring in plasma and other tissues.
Usually forms chemically reactive metabolites that can be active or toxic.

Question 16

so oxidation phase one can produce good metabolites?

Answer 16

No, they are harmful

Question 17

what is an example of harmful oxidation of drugs in metabolism 1

Answer 17

paracetamol
cytochrome P450 2E1 causes NAPQI which is a toxic metabolite of paracetamol

Question 18

Cytochrome P450 enzymes are ‘…….’ proteins

Answer 18

Haem

Question 19

Name some CYP (Cytochrome P450) gene families involved in drug metabolism in the liver

Answer 19

CYP1, CYP2, CYP3

Question 20

P450 activity is genetically determined so when people lack this activity it leads to

Answer 20

higher drug plasma levels

Question 21

P450 activity is genetically determined so when people have very high levels of this activity it leads to

Answer 21

lower plasma levels (reduced drug action)

Question 22

what are you blood plasma levels

Answer 22

When you take a drug, it enters your bloodstream and is carried throughout your body. The blood plasma level is the amount of the drug present in the liquid part of your blood (plasma) at any given time.

Question 23

Why Are Blood Plasma Levels Important? 2 reasons

Answer 23

Effectiveness: The drug needs to reach a certain level in your blood to be effective. If the level is too low, the drug might not work. If it’s too high, it could be toxic.

Timing: Understanding how long a drug stays in your blood helps determine how often you need to take it.

Question 24

drugs can induce or inhibit P450 activity, which ……

Answer 24

affects drug metabolism.

Question 25

explain phase 2 reactions f metabolism

Answer 25

• Involves conjugation with polar molecules to form water-soluble metabolites.
• Usually terminates biological activity.
• Conjugated products are readily excreted via the kidney.

Question 26

what does conjunction mean

Answer 26

conjugation refers to Phase II reactions where a drug or its Phase I metabolite is combined with another substance to form a more water-soluble compound. This process helps in the elimination of the drug from the body. Here are some key points: