ADME 5

Question 1

what is drug metabolism?

Answer 1

Overall process by which a living system acquires and utilises the free energy needed to carry out various functions

Question 2

what is anabolism?

Answer 2

Biosynthesis•Biomolecules are synthesised from simpler components

Question 3

what is catabolism?

Answer 3

Degradation•Nutrients are broken down to salvage components and energy•Carbohydrates, lipids, proteins are all converted to the same common intermediate•Acetyl CoA

Question 4

what is the purpose of drug metabolism?

Answer 4

Aids elimination of drugs and foreign compounds
Detoxification process
A drug is often metabolised into many products

Question 5

do most drugs emerge from a patient unchanged after matabolism?

Answer 5

rare- most drugs undergo a chemical change to produce metabolites

Question 6

why does is the purpose of making the drug more hydrophilic functionality?

Answer 6

to excrete urine

Question 7

how do you slow the rate of metabolism?

Answer 7

modify its structure

Question 8

why are metabolites often eliminated quicker than the drug?

Answer 8

more water soluble

Question 9

what 4 things influence drug metabolism

Answer 9

genetic/ physiological/Pharmacodynamics/ environmental factors

Question 10

what happens if the rate of metabolism decreases?

Answer 10

increased intensity and duration of drug action

•increased accumulation of parent drug in the plasma, increased toxicity risk

Question 11

what happens if the rate of metabolism increases?

Answer 11

decreased intensity and duration of drug action

•toxicity may increase owing to production of toxic metabolites

Question 12

what are the sites of metabolism?

Answer 12

liver
Endoplasmic reticulum (microsomes)
Cytosol
Non-specific enzymes

Question 13

what happens when you introduce polar groups to molecules?

Answer 13

oxidative, hydrolytic (hydrolysis/hydration), reductive, isomerisatio

Question 14

why would you convert one functional group into another?

Answer 14

Increases a molecules polarity
May not produce metabolites for excretion
Provides a site for Phase II metabolism

Question 15

what are esters hydrolised to?

Answer 15

alcohols, phenols and carboxylic acids

Question 16

what are amines hydrolized to?

Answer 16

amines and carboxylic acids

Question 17

what reaction is slower? amides/ester hydrolysis?

Answer 17

amides

Question 18

what does cytochrome P450 do?

Answer 18

addition of oxygen

Mixed function oxidases or monooxygenases located in the liver hepatocyte endoplasmic reticulum

Question 19

what is required for P450 oxidation?

Answer 19

require NADH or NADPH and O2as cofactors

•Cytochrome P-450 (or cytochrome b5) enzyme needed

Question 20

what kind of an enzyme is cytochrom P450?

Answer 20

iron containing porphyrin

Question 21

where does all activated chemistry occur in the pathway of P450?

Answer 21

occurs at the iron centre heme with oxygen transfer to the protein bound substrate

Question 22

what is P450 drug-drug interaction?

Answer 22

involving induction or inhibition of metabolism of one drug by co-administration of another

Question 23

what s involved in biotransformation of ~60% of drugs undergoing oxidative metabolism ?

Answer 23

CYP3A4

Question 24

why is there some genetic variation with the CYP2D6 drug?

Answer 24

8% Caucasians, 4% African-Americans, 1% Asians are poor metabolisers through CYP2D6

Question 25

what is an inducer and an inhibitor?

Answer 25

inducer•Activity is increased and rate of metabolism increases
Inhibitor•Activity is decreased and rate of metabolism decreases