About : Cyt P450 isozymes are major enzymes involved in Phase I Reaction. They can be stimulated or inhibited by hydroxylation or dealkylation.
Location: Smooth Endoplasmic Reticulum of Liver > GI > Lungs > Kidney.
Requirement: Oxygen and NADPH
General Inducers: Barbiturates, Phenytoin, Carbamazepine, Rifampin, CHRONIC Alcohol, Smoking, Halothane, Isoflurane
General Inhibitors: Cimetidine, Omeprazole, Macrolids (Erythromycin (no longer use as an antibiotic use, only use for post-diabetic gastroparesis) > Clarithromycin > Azithromycin), Protease Inhibitors (eg. Ritonavir), Ketoconazole, Acute Alcohol, Amiodarone, Quinolones, Quinidine, Haloperidol, Disulfram, Fluoxetine, Grapefruit Juice
***Underlined drugs are HY for USMLE or any other medical board.
Geriatric patients: have decreased Phase I metabolism and thus drugs metabolized via phase I reactions have longer half-lives.
Medications that are prodrugs requiring activation through hepatic metabolism may be less effective in older people.
Medications that are metabolized for biliary or renal excretion may require lower or less frequent doses in older people.
P450 Inhibitor : Cimetidine in Elderly Patients
Cimetidine is widely prescribed but has numerous potential side effects, especially in elder patients, who require a lower dosage, e.g., 300 mg twice daily. Antacids may be more effective than cimetidine in preventing acute gastrointestinal bleeding in critically ill elderly patients. Cimetidine increases the risk of toxicity of other commonly used drugs such as phenytoin, diazepam, chlordiazepoxide, propranolol, theophylline, warfarin, and carbamazepine. Elderly patients taking cimetidine are at risk for neuropsychiatric changes, which may be temporarily reversed by physostigmine. Other side effects and indications for use are reviewed.
P450 Inducer : Carbamazepine in Elderly Patients
In Elderly patients, there is a reduction in the rate of Cytochrome P450 mediated drug metabolism. As a result of this, patients in old age will require lower CBZ dosages to achieve serum concentrations comparable with those found in nonelderly adults.
Clinical Exp. in some of this drugs has not identified differences in responses between the elderly and younger patients, However caution should be taken while prescribing any drug metabolized by this system.
Article By : Chirag Navadia MD, founder of MedRx Education (www.medrx-education).com