LEIK Pharmacology Review with 100% correct answers

First Pass Metabolism GI Tract ---> Portal Circulation ---> Liver --->Metabolized ---> Systemic Circulation 1st pass metabolism lowers the amount of drug available. If high first-pass effect, mostly becomes inactivated and cannot be used, these meds cannot be given orally. Example: Insulin Drug Metabolism The most active organ is the LIVER (Cytochrome P450 enzyme system) Others are Kidneys, GI Tract, Lungs Coumadin and Bactrim Sulfa drugs will interact with warfarin (increases the blood level) which results in: *Elevation of INR and Risk of Bleeding! Potent Inhibitors of the cytochrome P450 (CYP450) System *Responsible for a number of drug to drug interactions ■ Macrolides (erythromycin, clarithromycin, pediazole) ■ Antifungals (ketoconazole, fluconazole) ■ Cimetidine (Tagament) ■ Citaprolam (Celexa) ■ Cisapride (Propulsid). This drug has been pulled from the U.S. market. Pharmacology terms ■ Half-life (t½): the amount of time in which drug concentration decreases by 50%. ■ Area under the curve (AUC): the average amount of a drug in the blood after a dose is given. It is a measure of the availability (bioavailability) of a drug after it is administered. ■ Minimum inhibitory concentration (MIC): the lowest concentration of an antibiotic that will inhibit the growth of organisms (after overnight incubation). ■ Maximum concentration: the highest concentration of a drug after a dose. ■ Trough (minimum concentration): the lowest concentration of a drug after a dose. Narrow Therapeutic Index Drugs* ■Warfarin sodium (Coumadin): monitor INR. ■ Digoxin (Lanoxin): monitor digoxin level, EKG, electrolytes (potassium, magnesium, calcium). ■ Theophylline: monitor blood levels. ■ Carbamezapine (Tegretol) and phenytoin (Dilantin): monitor blood levels. ■ Levothyroxine: monitor TSH. ■ Lithium: monitor blood levels, TSH (risk of HYPOthyroidism). Safety Issues: Thiazolidinediones (TZDs) Pioglitazone (Actos) *Insulin Sensitizer Can Cause or exacerbate CHF in some patients. *Do not use if NYHA Class III or IV heart failure STOP if: c/o dyspnea, weight gain, cough (HEART FAILURE) Safety Issues: Atypical antipsychotics Risperidone (Risperdal) Olanzapine (Zyprexa) Quietipine (Seroquel) High risk of WEIGHT GAIN, metabolic syndrome, and type 2 diabetes. Monitor weight every 3 months. Black Box Warning: higher mortality in elderly patients. Monitor: TSH, lipids, weight/body mass index (BMI) Safety Issues: Biphosphonates Alendronate (Fosamax) Risedronate (Actonel) Jaw pain (JAW NECROSIS). Chest pain, difficulty swallowing, burning mid-back (perforation). Take ALONE upon awakening with 8 oz glass water (NOT JUICE) before breakfast. Do not lie down x 30 minutes afterward. Do not mix with other drugs). Take FIRST thing in the morning before breakfast Safety Issues: Statins Atorvastatin (Lipitor) Lovastatin (Mevacor) Rosuvastatin (Crestor) Simvastatin (Zocor) Do NOT mix with GRAPEFRUIT juice Drug-induced hepatitis or rhabdomyolysis higher if mixed with AZOLE antifungals High-dose Zocor (80 mg) has highest risk of rhabdomyolysis (muscle pain/tenderness) CK (creatine kinase) level goes up. Safety Issues: Lincosamides Clindamycin (Cleocin) Higher risk of Clostridium difficile-associated diarrhea (CDAD) Metronidazole (Flagyl) PO TID × 10-14 days Probiotics daily—BID × few weeks Drugs used to treat heart disease ■ Cardiac Glycosides: Digoxin (Lanoxin) ■ Anticoagulants: Warfarin Sodium (Coumadin) ■ Thiazide Diuretics ■ Potassium-Sparing Diuretics ■ Loop Diuretics ■ Aldosterone Antagonists Cardiac Glycosides: Digoxin (Lanoxin) Treats atrial fibrillation. - Digoxin has a narrow therapeutic range (0.5-2.0 ng/mL). *NOT a first-line drug for heart rate control in atrial fibrillation. Signs and symptoms of digoxin overdose: - Initial symptoms are GASTROINTESTINAL (anorexia, nausea/vomiting, abdominal pain). Others are arrhythmias, confusion, and VISUAL CHANGES (yellowish green tinged-color vision, scotomas). Severe toxicity Severe toxicity is treated with digoxin-binding antibodies (Digibind). What laboratory test should be ordered if digoxin toxicity is suspected? Order a digoxin level, electrolytes (potassium, magnesium, calcium), creatinine, and serial EKGs. Anticoagulants: Warfarin Sodium (Coumadin) ■ Decreases emboli/thrombi formation (atrial fibrillation, stroke, pulmonary emboli). ■ For atrial fibrillation, the target INR is from 2.0 to 3.0. A patient has an INR of 8.0. Physical examination is negative for petechiae, bleeding gums, bruising, or dark stools. What is the best treatment plan for this patient? - INR between 5.0 and 9.0 (without bleeding): Hold the warfarin for 1 to 2 doses. Recheck INR every 2 to 3 days until it is stable (INR between 2.0 and 3.0). Another option is to hold the warfarin and add a small dose of oral vitamin K. Limit and/or avoid high vitamin K foods (green leafy vegetables, broccoli, brussels sprouts, cabbage). After the INR becomes stable, recheck it monthly.* Clinical Tips ■ INR values BELOW 2.0 increase stroke risk SIXFOLD. ■ There is a higher risk of hemorrhage with high INRs in the elderly (age greater than 70 years). ■ Mayonnaise, canola oil, and soybean oil also have high levels of vitamin K. Thiazide Diuretics ■ Uncomplicated hypertension (FIRST line), heart failure (FIRST line), edema. ■ Hypertension accompanied by OSTEOPOROSIS. ■ Hydrochlorothiazide (HCTZ) 12.5 to 25 mg PO daily. ■ Chlorthalidone 12.5 to 25 mg PO daily. ■ Indapamide (Lozol) PO daily.