Cardiovascular Drug Introduction Cardiovascular medications can be broken down into the following categories Antiarrhythmics Antihypertensives Inotropes Vasodilators Diuretics Antihyperlipidemics Anti-plateletes Thrombolytics Introduction HMG-CoA reductase inhibitors Examples "statins" - lovastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin, atorvastatin Mechanism inhibition of cholesterol synthesis HMG-CoA reductase is the rate-limiting step of cholesterol synthesis causes ↑ in LDL-receptor synthesis Change in LDL Change in HDL Change in triglycerides ↓↓↓ ↑ ↓ Indications LDL is > 70 mg/dL TG > 150 mg/dL coronary artery disease diabetes mellitus peripheral vascular disease Toxicity myalgia/myopathy (monitor serum CK) rhabdomyolysis teratogenic hepatotoxic (↑ LFTs) inhibitors of P450 can ↑ serum concentration Bile acid sequestrants Examples cholestryramine, colestipol, colesevelam remember: act in the colon (col) Mechanism bind bile acids in the intestine to prevent reabsorbtion and recycling forces liver to consume cholesterol in the process of making more bile salts causes ↑ in LDL-receptor synthesis Change in LDL Change in HDL Change in triglycerides ↓↓ slightly ↑ slightly ↓ Toxicity GI distrubances ↓ absorbtion of fat soluble vitamins and drugs Niacin Mechanism ↓ lipolysis in adipose tissue ↓ hepatic VLDL synthesis/secretion into circulation Change in LDL Change in HDL Change in triglycerides ↓↓ ↑↑ ↓ Toxicity flushed face ↓ by aspirin tolerance develops over long-term use hyperglycemia acanthosis nigricans hyperuricemia worsens gout pruritis Fibrates Examples gemfibrozil, fenofibrate Mechanism activate lipoprotein lipase via activation of PPAR-α results in ↑ TG clearance Change in LDL Change in HDL Change in triglycerides ↓ ↑ ↓↓↓ Toxicity myopathy ↑ risk when combined with statins gallstones can ↑ LDL so not often used as monotherapy Ezetimibe Mechanism blocks cholesterol reabsorption at small intestine brush border Change in LDL Change in HDL Change in triglycerides ↓↓ - - Toxicity hepatotoxic ↑ risk when combined with statins