Drug Metabolism

Question 1

Purpose of Metabolism

Answer 1

Increase water solubility/aid secretion
de-activate compounds/
activate compounds +/- produce active metabolites

Increased Met = Increased activity of drug (e.g.pro-drug)

Question 2

Main oxidative drug metabolising enzyme (phase 1)

Answer 2

cytochrome p450 (CYP)

Question 3

________ determines drug specificity

Answer 3

isoform of cytochrome p450

Question 4

Name 3 common prodrug (activated when metabolised)

Answer 4

Codeine, Enalapril, aspirin

Question 5

If first pass met is really active/efficient/high, the drug either:

a. has low effect
b. is toxic

Answer 5

Has low effect - metabolism high - excreted high rate

Question 6

Is Metabolism part of Elimination?

Answer 6

Yes

Excretion/Elimination also part of Elimination

Question 7

Phase 1 or 2?
Hydrolysis, Hydroxylation
Oxidation
Reduction
Increased polarity

Answer 7

Phase 1 met

Question 8

Phase 1 or 2?
Conjugation UDP-GT
Increased H2O solubility + Increased excretion of metabolised compound

Answer 8

Phase 2 met

UDP-GT - polar group, glucuronic acid grp - increase hydrophillic - water soluble -> excretion

Question 9

1st Pass met
major enzyme in liver
found in gut - presystemic met
increased effectiveness in female

Answer 9

CYP3A4

diazepam, methadone, simvastin, CCM

CYP3A4 induced by phenytoin

Question 10

metabolises - Antidepressants, antipsychotics

codeine -> morphine

Answer 10

CYP2D6

Induced by Smoking - increased smokers - mental patients - drugs metabolism increase so the effect of anti-depressant not as effective - so higher conc administered to have a therapeutic effect. If the patients stops smoking, then the therapeutic dose has to be lowered = otherwise toxic!!

Low expression of CYP2D6: immune to analgesic act of codeine

Question 11

Metabolise Theophyllin and caffeine

Answer 11

CYP1A2

Induced by Smoking - Smokers require higher dose of medication

Question 12

Increased metabolism of drug - reduce drug effect as enzyme induced

CRAP GPS induce me to madness!!

Carbemazepines (anti-epileptics) and antidepressants (St Johs worts), Rifampicin, Alcohol (chronic), Phenytoin & Primidone (Anti-epileptics)

GI drugs (omeprazole), Phenobarbitone, Sulphonylureas and Smoking

Answer 12

Enzyme inDucEr

Phenytoin- an inducer of the CYP3A4

Question 13

Decreased metabolism of drug - quick and rapid effect - TOXIC
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Sodium valproate , Isoniazid (antibact), Cimetidine (GI drugs), Ketoconazole

Fluconazole (antifungals), Alcohol, Chloramphenicol, (Erythromycin, Clarithroymycin (Antibact)), Sulfonamides

CPX (antibact), Omeprazole (GI), MTZ (anti-bact), Grapefruit juice

Answer 13

Enzyme inhiBitors

anti bacts, fungs

Question 14

Factors affecting metabolism

Answer 14

Other drugs
Hepatic blood flow/Liver disease
Ethnicity
Age (foetus - low metabolising enzyme - require lower [drug]; child to pubery - high met; elderly - multi-drug therapy, lower lean mass)
pregnancy (increased liver met - may require higher dose)
Genetics