CYP450

Question 1

Xenobiotics

Answer 1

mechanism by which a foreign agent such as a drug molecule is metabolized and eliminated from the body

Question 2

Phase 1 metabolisation

Answer 2

• oxidation, reduction and hydrolysis

- a molecule suitable for conjugation is produced

Question 3

Direct phase 2 reactions

Answer 3

• some drugs go straight to phase 2 reactions
  e. g lorazepam, temazepam and oxazepam
• in patients with alcoholic liver disease, oxazepam is favoured for alcohol detoxidication instead of cholordiazepoxide which requires intact liver enzymes for phase 1 clearance

Question 4

Phase 2 metabolism

Answer 4

• involves conjugation reactions such as glucoronidation

- polar compounds (mostly inactive) are produced and are excretable in bile or urine

Question 5

Cytochrome P450 enzymes

Answer 5

• most psychotherapeutic drugs are oxidized by the hepatic cytochrome P450 enzyme system
• this is a family of enzymes
• CYP2D6 and CYP3A4 contribute to 90% of psychotropic metabolism

Question 6

Genetic variations

Answer 6

• 5-10% caucasians lack CYP2D6

- 15-20% east asians are poor metabolizers of CYP2C19 substrates

Question 7

SSRIs

Answer 7

• inhibit CYP system
• fluoxetine increases plasma tricyclic antidepressants via 2D6 and 2C19
• fluvoxamine increases plasma clozapine concentrations
• clozapine levels increase 10x by fluvoxamine-induces seizures
• inhibit the metabolism of warfarin-may cause serious bleeding

Question 8

Carbamazepine

Answer 8

• decreases plasma concentrations of several drugs including contraceptive pills
• carbamazepine and phenobarbitol an induce their own metabolism

Question 9

CYP inducers

Answer 9

Sulphonylureas
Carbamezapine
Rifampin
Alcohol
Phenytoin

Griseofulvin
Phenobarbital
and brussel sprouts! (SCRAP GP)

Question 10

CYP inhibitors

Answer 10

Sodium valproate
Isoniazid
Cimetidine
Ketoconazole

Fluconazole
Alcohol..binge drinking
Chloramphenicol
Erythromycin
Sulfonamides
.
Ciprofloxacin
Omeprazole
Metronidazole

SICK FACES .COM
and grapefruit juice/caffeine

Question 11

CYP2D6

Answer 11

-metabolises all TCAs, fluoxetine, paroxetine, trazodone, nefazodone, valproate, all neuroleptics, risperidone

Question 12

CYP3A4

Answer 12

-metabolises clomipramine, fluvoxamine, mirtazapine, carbamazepine and most benzodiazepines

Question 13

Smoking and caffeine

Answer 13

• both affect glucoronidation reaction via UGT enzyme and CYP1A2
• affects clozapine and and olanzapine as these are metabolised by CYP1A2
• caffeine inhibits CYP1A2 and solevels of clozapine and olanzapine rise
• cigarettes (PAH) induce the enzyme