Cytochrome P450 Inhibitors and Inducers

Cytochrome P450

A family of iso-enzymes found in the liver that metabolise/break down drugs from their lipophilic form to a more water soluble form so that they can be excreted via urine.

Cytochrome P450 Enzyme Inhibitors Mnemonic

SICKFACES.COM

Cytochrome P450 Enzyme Inducers Mnemonic

CRAP GPS

SICKFACES.COM (Mnemonic for Cytochrome P450 Enzyme Inhibitors)

Sodium Valproate (CYP 2C9)

Isoniazid (CYP 2C19)

Cimetidine (CYP 1A2)

Ketoconazole (CYP 3A4)

Fluconazole (CYP 3A4 & 2C9)

Amiodarone (CYP 2C9 & 3A4)

Ciprofloxacin (CYP 1A2)

Erythromycin (CYP 3A4)

Sulfonamides (CYP 2C9)

Calcium Channel Blockers (CYP 3A4)

Omeprazole (CYP 2C19)

Metronidazole (CYP 2C9)

CRAP GPS (Mnemonic for Cytochrome P450 Enzyme Inducers)

Carbamazepine (CYP 3A4)

Rifampicin (CYP 3A4)

Alcohol* (CYP 2E1)

Phenytoin (CYP 3A4)

Griseofulvin (CYP 3A4)

Phenobarbital (CYP 3A4)

St. John's Wort (CYP 3A4)

*Alcohol acts as an inducer with chronic use but as an inhibitor in acute use.

Which cytochrome P450 enzyme metabolises the largest proportion of drugs?

CYP 3A4

A patient taking warfarin is started on metronidazole. What is the most likely effect?

- Metronidazole is a CYP 2C9 inhibitor and Warfarin is metabolised by CYP 2C9

- Therefore, CYP 2C9 is inhibited so warfarin metabolism is reduced.

- Serum-Warfarin concentration would build up in the body and cause an increase in INR, increasing the risk of bleeding.

A patient taking codeine reports poor pain relief after starting fluoxetine. What is the reason?

- Codeine is a prodrug metabolised by CYP 2D6 into its active form, morphine.

- Fluoxetine is a potent CYP 2D6 inhibitor, therefore codeine cannot be metabolised into its active form and exert a therapeutic effect, leading to little pain relief.

Which enzyme is primarily responsible for activating clopidogrel?

CYP 2C19

A patient who smokes heavily requires increasing doses of theophylline. Which enzyme explains this?

- Theophylline is metabolised by CYP 1A2.

- Smoking is a CYP 1A2 inducer increasing the effect of CYP 1A2, subsequently theophylline is metabolised more rapidly, reducing theophylline plasma concentrations and therapeutic effect.

Rifampicin reduces the effectiveness of the oral contraceptive pill because it...

- Rifampicin is a potent CYP 3A4 inducer.

- The oral contraceptive pill is metabolised by CYP 3A4 enzyme.

- Rifampicin increases the effect of the CYP 3A4 enzyme, causing the contraceptive pill to be metabolised more rapidly, reducing its effectiveness.