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Pharmacology CYP 450

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What do the different letters/numbers in CYP 3A4 represent?
C - gene for cytrochrome 3 - family A - subfamily 4 - specific enzyme
What type of metabolism reaction are CYP P450 responsible for?
Phase 1 reactions (oxidation, reduction, hydrolysis)
Where are CYP P450 enzyme systems located?
- primarily located in the membranes of the smooth endoplastic reticulum - located in the liver, small intestines, brain
What type of metabolism do elderly patients lose?
Phase I
What type of reactions are Phase II reactions?
synthesis and oxidation
What is induction?
- a substance that stimulates the synthesis of the enzyme and the metabolic capacity of that substance is increased - inducing the metabolism of a drug increases the rate of elimination of that drug
What is inhibition?
- competitive binding at an enzyme site - will slow metabolism of a drug (increases drug level in the body because drug is not being eliminated)
Which CYP-450 isoenzyme is most abundant?
CYP 3A4
Name some drugs that are metabolized by 3A4
1. macrolides - clarithromycin 2. Fluoxetine (Prozac) 3. Indanivir - protease inhibitor in HIV 4. Itraconazole (Sporanox) 5. Ketonazole (or Nizoral)- antifungal 6. Ritonavir - protease inhibitor
Name some CYP-450 1A2 inhibitors
- Cimetidine (Tagemet) - quinolones (Levaquin)
Name some inhibitors of CYP 450 2C10
- Fluoxetine (Prozac) - Ketocanazole - Lansoprazole
Name some inhibitors of CYP 450 2C9
- Amiodarone (Cordarone) - Fluconazole (Diflucan) - Isoniazid (INH)
Name some inhibitors of the CYP450 2D6
- Amiodarone - Cimetidine (Tagmet) - Clomipramine (Anafranil): a tricyclic antidepressant - Paroxetine (Paxil): SSRI - Ritonavir (a very potent inhibitor used to keep other antiviral drugs in the system)
Name some CYP450 3A4 inhibitors
- protease inhibitors - Amiodarone (Cordarone) - Clarithromycin - Erythromycin
What dosage adjustment need to be made if a patient is given Amiodarone and Coumadin?
- decrease dosage of Coumadin (Warfarin) by 25% because Amiodarone is an inhibitor of Coumadin
What is the safest macrolide to use to avoid drug interactions?
Azithromycin (Zithromax)
Name an inducer of CYP 450 1A2
tobacco
Name an inducer of CYP 450 2C9
Rifampin (potent inducer) - a antimicrobial agent
Name some inducers of CYP-450 2E1
- ethanol (acute) - isoniazid (chronic)
Name an inducer of CYP-450 3A4
- Carbamazipine - Barbituates (phenobarbital) - Rifampin
What is the pneumonic for remembering inducers?
Barbie's Car Goes Real F(Ph)ast Barbituates Carbamazepine Griseofulvin Rifampin Phenytoin
What is pneumonic for remembering inhibitors?
Ken's Car is Equally F(Ph)ast Ketocanazole Carbamazepine Ethambutol Phenytoin

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