Drug Metabolism Flashcards Preview

Principles of Disease > Drug Metabolism > Flashcards

Flashcards in Drug Metabolism Deck (67)
Loading flashcards...
1

What is drug metabolism

A biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity

2

Why is metabolism an essential pharmacokinetic process

It limits the life of a substance in the body, by rendering lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted

3

What happens to lipid soluble substances

They are passively reabsorbed from renal or extra renal excretory sites back into the blood

4

What are important sites in drug metabolism

Liver
Lining of gut
Kidneys
Lungs

5

What happens to most drugs before excretion

They are metabolised

6

What is the purpose of drug metabolism

To increase water solubility and so aid excretion
Or to deactivate compounds (which may involve a number of steps)

7

What happens to prodrugs following metabolism

They are activated

8

What happens to some drugs following metabolism

They form active metabolites

9

Give examples of prodrugs

Codeine
Enalapril
Simvastatin
Sacubitril

10

What are the effects of drug metabolism

The loss of pharmacological activity
A decrease in activity, with metabolites that show some activity
Increase in activity, more active metabolites (activation of a prodrug)
Production of toxic metabolites

11

What can the production of toxic metabolites in drug metabolism cause

Direct toxicity
Carcinogenesis
Teratogenesis

12

What can metabolising enzymes be divided into

Families and sub-families

13

What type of specificity do metabolising enzymes have

Wide substrate specificity
Individual drugs can be metabolised by more than one

14

Where is enzyme activity control regulated

At several levels

15

How are some enzymes expressed

Constitutively
Some are expressed or induced in the presence of a particular substrate

16

How many phases are there in enzyme metabolism

2
Phase 1
Phase 2

17

What occurs in phase 1

Oxidation, reduction and hydrolysis reactions
It increases the polarity of the compound and provides an active site for Phase 2 metabolism

18

What enzymes super family are important metabolising enzymes

Cytochrome P-450 enzymes

19

How is drug specificity determined

By the isoform of the cytochrome P-450

Specificity tends to be relative rather than absolute

20

What are the three most important families of the cytochrome P-450 superfamily that have been identified as important in oxidative drug metabolism

CYP1: isoform CYP1A2
CYP2: isoform CYP2D6
CYP3: isoform CYP3A4

21

What is the drug substrate for CYP1: isoform CYP1A2

Theophylline

22

What is the drug substrate for CYP2: isoform CYP2D6

Codeine

23

What is the drug substrate for CYP3: isoform CYP3A4

Cyclosporine

24

What is CYP3A4

The major constitutive enzyme in human liver and contributes to the metabolism of a wide range of drugs

25

Where can CYP3A4 be found

Liver
Gut

26

What is CYP3A4 also responsible for

The pre-sysytemic metabolism of several drugs

27

Give examples of drugs which use CYP3A4

Diazepam
Methadone
Simvastatin
CCBs

28

What is CYP2D6 responsible for

The metabolism of some antidepressants, antipsychotics and the conversion of codeine to morphine

29

What is found in 5-10% of the population in regards to CYP2D6

Reduced or absent expression so they may be immune to the analgesic actions of codeine

30

What is CYP1A2 induced by

Smoking so smokers will require a higher dose of theophylline than non smokers