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. a. Cytochrome p450 system is a series of enzymes used to metabolize medications. b. Drugs that cause CYP450 metabolic drug interactions are referred to as either inhibitors or inducers. Inducers increase CYP450 enzyme activity by increasing enzyme synthesis c. Inhibitors block the metabolic activity of one or more CYP450 enzymes 2. Describe the affect on low and high albumin levels on active drug levels especially for drugs that are highly protein bound. a. Albumin is the plasma protein with the greatest capacity for binding drugs. i. 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. b. Highly protein bound drugs, low albumin levels (w/ malnutrition, or chronic illness) may lead to toxicity because there are fewer than the normal sites for the drug to bind 3. Describe ways to lessen the hepatic first pass effect: metabolism during first pass through the liver a. Alternative routes (suppository, intravenous, intramuscular, inhalational aerosol, transdermal, and sublingual) avoid the first-pass effect allow drugs to be absorbed directly into the systemic circulation 4. Be able to calculate creatinine clearance using the Cockgraft Gault equiation: a. Male = ([140-age] × weight in kg)/(serum creatinine × 72) b. Female = CrCl (male) × 0.85 5. Describe what determines the frequency of drug administration: a. Drug half-life, plasma concentration 6. Be familiar with the Beers criteria and how to use it: a. Potentially Inappropriate Medication Use in Older Adults i. to call attention to medications that are commonly problematic, and thus should be avoided in most older adults 7. Describe factors that affect absorption, distribution, metabolism and excretion: a. Absorption low blood state (shock or arrest); contact time with GI tract too fast (diarrhea = can’t absorb); delayed stomach emptying (large meal = delayed absorption); drug-drug or drug-food interactions b. Metabolism genetics, age, organ function c. Distribution low albumin levels, body composition, cardiac decomp (HF), and age d. Excretion affected by abnormal kidney or liver function; age, drug inter