drug actions 1 exam 1

what are the strong inducers of CYP2C19?

1. rifampin (rifadin, rimactane); common substrates affected: clopidogrel (activation decreases), PPIs, phenytoin; key clinical pearl —> decreased antiplatelet effect

2. carbamazepine (tegretol); common substrates affected: PPIs, clopidogrel; key clinical pearl —> enzyme induction

3. phenytoin (dilantin); common substrates affected: PPIs, diazepam; key clinical pearl —> bidirectional

drugs levels go DOWN.

what are the strong inhibitors of CYP2C19?

1. omeprazole (prilosec); common substrates affected: clopidogrel (activation decreases), diazepam, phenytoin; key clinical pearl —> decreased antiplatelet effect

2. esomeprazole (nexium); common substrates affected: same as omeprazole; key clinical pearl —> avoid with clopidogrel

3. fluconazole (diflucan); common substrates affected: phenytoin, warfarin; key clinical pearl —> narrow TI risk

4. voriconazole (vfend); common substrates affected: warfarin, phenytoin; key clinical pearl —> strong inhibitor

5. cimetidine (tagamet); common substrates affected: warfarin, theophylline; key clinical pearl —> non-specific

6. modafinil (provigil); common substrates affected: diazepam, phenytoin; key clinical pearl —> also induces CYP3A4

drug levels go UP

cimetidine is a strong inhibitor of many CYP enzymes, like?

CYP1A2, CYP2C19, CYP2D6, CYP2C9, CYP2E1, CYP3A4

modafinil is a inducer of _____ and an inhibitor of ____

CYP3A4; CYP2C19

what are the strong inducers of CYP3A4?

1. rifampin (rifadin, rimactane); common substrates affected: oral contraceptives, tacrolimus, cyclosporine, midazolam, protease inhibitors, statins; key clinical pearl —> most potent inducer (induces other CYP enzymes as well)

2. carbamazepine (tegretol); common substrates affected: OCPs, antipsychotics, steroids, warfarin; key clinical pearl —> autoinduction

3. phenytoin (dilantin); common substrates affected: OCPs, steroids, warfarin, azoles; key clinical pearl —> narrow TI

4. phenobarbital (luminal); common substrates affected: warfarin, steroids, azoles; key clinical pearl —> long-lasting induction

5. st. john’s wort; common substrates affected: OCPs, cyclosporine, antiretrovirals; key clinical pearl —> OTC exam favorite

what are the strong inhibitors of CYP3A4

1. ketoconazole (nizoral); common substrates affected: statins, benzodiazepines, QT-risk drugs; key clinical pearl —> classic inhibitor

2. itraconazole (sporanox); common substrates affected: statins, CCBs, warfarin; key clinical pearl —> QT prolongation

3. clarithromycin (biaxin); common substrates affected: statins, CCBs, theophylline; key clinical pearl —> avoid with statins

4. ritonavir (norvir); common substrates affected: protease inhibitors, anticoagulants, steroids; key clinical pearl —> PK booster

5. cobicistat (tybost); common substrates affected: protease inhibitors; key clinical pearl —> no antiviral activity

6. grapefruit juice; common substrates affected: statins, CCbs, benzodiazepines; key clinical pearl —> intestinal CYP3A4 only

7. cimetidine (tagamet); common substrates affected: warfarin, theophylline; key clinical pearl —> non-specific

what are the strong inducers of CYP2D6?

none

what are the strong inhibitors of CYP2D6?

1. fluoxetine (prozac); common substrates affected: atomoxetine, TCAs, antipsychotics, amphetamines; key clinical pearl —> long-half life

2. paroxetine (paxil); common substrates affected: atomoxetine, TCAs, metoprolol; key clinical pearl —> strongest SSRI

3. bupropion (wellbutrin); common substrates affected: atomoxetine, TCAs, antipsychotics; key clinical pearl —> common exam trap

4. quinidine (generic); common substrates affected: TCAs, antiarrhythmics; key clinical pearl —> classic example

5. ritonavir (norvir); common substrates affected: antipsychotics, TCAs; key clinical pearl —> multi-CYP effects

6. cimetidine (tagamet); common substrates affected: warfarin, theophylline; key clinical pearl —> non-specific