Metabolism

Question 1

Cytochrome P450

Answer 1

Group of enzymes located in the SER
Highly conserved
Oxidation reactions

Question 2

CYP1A2

Answer 2

Oxidation reactions
Metabolized Clozapine
Smoking cigarettes increases transcription of CYP1A2

Question 3

CYP2D6

Answer 3

Metabolizes risperidone and paroxetine
Paroxetine outcompetes risperidone causing toxicity
7-10% of caucasians are poor metabolizers (will still have pain with codeine)
Metabolizes haloperidol and fluoxeting
Fluoxetine is a competitive inhibitor

Question 4

CYP3A4

Answer 4

Largest metabolizer
Metabolizes methadone and nefazodone (people would ask for Nefazodone as an antidepressant because it would make them high on methadone)

Question 5

Major Inducers

Answer 5

mnemonic = CPPPR
Carbamazepine (3A4)
Primidone
Phenobarbital
Phenytoin (in lots of anti-epileptics)
Rifampimycin (antibiotic)
CIgarettes
Chronic alcohol use (increases all CYPs)
St. John's Wort

Question 6

Major Inhibitors

Answer 6

Antifungals
Antibiotics (erythromycin)
Valproic acid
Fluvoxemine
15-20% of Asians are poor metabolizers of CYP2C19

Question 7

Antidepressants with very few drug-drug interactions

Answer 7

Venlafaxine
Citalopram
Mirtazapine

Question 8

Phase 2

Answer 8

Takes metabolites from Phase 1 and glucoconjugates them with glucuronic acid using uridine glucuronate transferase (UGT)
Can be induced or inhibited

Question 9

Phase 2

Answer 9

Takes metabolites from Phase 1 and glucoconjugates them with glucuronic acid using uridine glucuronate transferase (UGT)
Can be induced or inhibited

Question 10

Carbamazepine

Answer 10

Produces 10-11 epoxy-carbamazepine if there is a phase 2 block
Toxic
Carbamazepine is auto-inducing, meaning it induces the enzyme that metabolizes it, bringing its half-life from 20 hours initially to 17 hours 3 weeks later

Question 11

Allegra (Fexofenadine)

Answer 11

Phase one derivative of terfenadine

Terfenadine is toxic

Question 12

Oxazepam

Answer 12

First pass metabolite of diazepam