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Principles of disease JK > Drug Metabolism > Flashcards

Flashcards in Drug Metabolism Deck (18):
1

Drug metabolism

Biochemical modification of pharmaceutical substances by living organisms usually through specialised enzymatic activity

2

How does drug metabolism limit life of substance in the body?

Rendering lipid soluble compounds water soluble to be excreted

3

Lipid soluble drug reabsorption

Passively from renal or extra renal back into blood

4

Where are most drugs metabolised before excretion?

Liver, lining of gut, kidneys, lungs

5

Pro drugs

Some drugs are pro drugs and only become active after metabolism eg codeine

6

What are some effects of toxic metabolites

Direct toxicity
Carcinogenesis
Teratogenesis

7

Metabolising enzymes

- wide substrate specificity and many metabolise a drug
- Expressed constantly or when needed

8

Phase 1 metabolism steps

- Oxidation
- reduction
- hydrolysis

9

What does phase 1 metabolism do?

Increases polarity and provides an active site
Introduce or expose polar groups

10

Cytochrome p450

Enzymes in liver which are important in oxidative drug metabolism
Isoform determines drug specifity

11

CYP 1

CYP1A2 induced by smoking so a higher dose of theophylline needed

12

CYP2

CYP2D6 metabolise antidepressants and codeine and are reduced in 5-10% of population and are induced by smoking q

13

CYP3A4

Major liver enzyme works on a wide range of drugs eg cyclosporine and also found in gut for pre systemic metabolism

14

Phase 2 reactions

Conjugation - Eg acetate, sulphate attached to metabolite from phase 1

15

What does phase 2 reactions do?

Increase water solubility and enhance secretion of metabolised compound
Mostly inactivation although sometimes activation

16

What do endogenous substances do in phase 2?

Donates portion of itself to the foreign molecule

17

What factors affect metabolism?

Age, sex, ethnicity, pregnancy, liver disease, genetics, other drugs

18

Drugs which can inhibit drug metabolising enzymes

Erythromycin
Grapefruit