Week 1 1. Describe the cytochrome P450 system. Describe how inducers and inhibitors affect the cytochrome system and how that affects the half-life of medications. Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Fluoxetine, sertraline, and fluvoxamine are believed to inhibit cytochrome P450 2C because of observed interactions with phenytoin, diazepam, and other drugs metabolized by these enzymes. Rifampicin and isoniazid are key drugs used in the treatment of tuberculosis, while rifampicin is highly effective in inducing hepatic, drug metabolic P450 enzyme. The mnemonic SICKFACES.COM can be used to easily remember common cytochrome P450 inhibitors. 1. Sodium valproate. 2. Isoniazid. 3. Cimetidine. 4. Ketoconazole. 5. Fluconazole. 6. Alcohol & Grapefruit juice. 7. Chloramphenicol. 8. Erythromycin. 2. Describe the affect on low and high albumin levels on active drug levels especially for drugs that are highly protein bound. Albumin is the plasma protein with the greatest capacity for binding drugs. Binding to plasma proteins affects drug distribution into tissues, because only drug that is not bound is available to penetrate tissues, bind to receptors, and exert activity. As free drug leaves the bloodstream, more bound drug is released from binding sites. Some drugs have a high affinity for binding to serum proteins and may be 95% to 98% protein bound. With highly protein bound drugs, low albumin levels (as in protein-calorie malnutrition, or chronic illness) may lead to toxicity because there are fewer than the normal sites for the drug to bind. The amount of free drug is significantly increased in that case. Competition for binding sites is one important way that drugs might interact. If a patient is using two highly protein bound drugs at the same time, there will be competition for binding sites on the albumin. The drug with the greatest affinity for the albumin