Drugs for Hyperlipidemia Flashcards
Statins
HMG-CoA reductase inhibitos
Atorvastatin Fluvastatin Lovastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin
Statins - MoA
HMG-CoA reductase converts HMG-CoA to mevalonic acid and is the rate-limiting enzyme in cholesterol biosynthesis. By competitively inhibiting this enzyme, statins reduce hepatic cholesterol biosynthesis and the amount of cholesterol available for incorporation into VLDL. This leads to compensatory increase in the number of hepatic LDL receptors, which increases hepatic uptake of LDL-C. Together, these actions cause a substantial reduction in LDL-C.
In patients with hypercholesterolemia, statins typically decrease LDL-C levels by 20% to 60%, whereas HDL-C levels are increased by up to 10%
The statins also reduce serum triglycerides but are usually not a sufficient treatment for hypertriglyceridemia
Statins - Clinical use
Reduce blood cholesterol levels in persons with Hypercholesterolemia.
Slow the progression of atherosclerosis, reduce the risk of CHD and other atherosclerotic vascular diseases, and reduce cardiac mortality rate.
May protect against osteoporosis and certain forms of cancer.
Statins - Adverse effects
GI problems; abdominal cramps, constipation, diarrhea, heartburn.
Hepatitis and elevated liver enzymes Rhabdomyolysis Muscle myopathy(earliest stage is myalgia, which consists of muscle ache or weakness without creatine kinase levels)
Myalgia can be followed by myositis or muscle inflammation accompanied by muscle pain, leakage of muscle creatine kinase into the plasma, and elevated creatine kinase levels
Myositis can eventually lead to rhabdomyolysis in which muscle cells disintegrate, thereby releasing myoglobin into the circulation
Myoglobin then accumulates in the kidneys and cause acute kidney failure
10-25% risk in incidence of diabetes
Statins - Interactions
Atrovastatin, lovastatin and simvastatin are metabolized by CYP3A4, plasma levels increases strong by inhibitors of this isozyme; erythromycin, itraconazole, ritonavir
Fluvastatin is metabolized by CYP2C9, and its plasma levels may be increased by inhibitors of this CYP, including some NSAIDs
They increase warfarin levels slightly by inhibiting warfarin metabolism.
Statins - Contraindications
Because statins , fibric acid derivatives, and niacin may cause myopathies, the combined use of drugs should be undertaken with greater caution using lower doses of each agent employed
Which statins are used for mixed hyperlipidemia?
Atorvastation and Rosuvastatin
Most potent statin
Second most potent satin
Rosuvastatin
Atorvastatin
Which statins crosses the blood brain barrier and can cause sleep disturbances?
Lovastatin and Simvastatin
Lovastatin - Interactions
Should be taken with evening meal to facilitate its absorption
Bile Acid-Bindings Resins
Cholestyramine
Colestipol
Colesevelam
Bile Acid-Bindings Resins - MoA
After resins bind to bile acids, the bile acid-resin complex is excreted. This action prevents the enterohepatic cycling of bile acid and obligates the liver to synthesize replacement bile acid from cholesterol. To obtain more cholesterol for this purpose, the liver increases the number of LDL receptors. Then the levels of LDL-C in the blood are reduced as more cholesterol is delivered to the liver
Bile Acid-Bindings Resins - Clinical use
Hypercholesterolemia in pat who cannot tolerate other drugs and in patients who are young.
Chronic diarrhea due to bile acid malabsorption
Bile Acid-Bindings Resins - Adverse effects
Constipation Fecal impaction GI side effect, nausea, vomiting. Irritation of the perianal area Skin rash
Bile Acid-Bindings Resins - Interactions
Decrease absorption of digoxin, thyroxin and warfarin.
Decreases absorption of fat soluble vitamins; A, D, E
Cholestyramine and Colestipol - Interactions
Bind to digoxin, thyroxin, warfarin and other drugs. For this reason, it is best to take the resins 2 hours before or after taking other medications
Ezetimibe - MoA
Absorbed from the intestines after oral adm, and mostly is converted to active ezetimibe-glucuronide. This metabolite is distributed by the circulation to the small intestines, where it localizes in the brush border and inhibits absorption of both biliary and dietary cholesterol. Acts by disrupting two protein, annexin-2 and caveolin-1, which mediates cholesterol transport in intestinal brush border cells.
Ezetimibe - Clinical use
Hypercholesterolemia
Ezetimibe - Adverse effects
Increases serum hepatic transaminase levels
Headache
Myalgia
Niacin - Classification
Vitamine B3
Niacin - MoA
Inhibiting the formation and secretion of hepatic VLDL, the major carrier of plasma triglycerides and the precursor of LDL. The effect on VLDL secretion is caused by inhibition of lipolysis in adipose tissue. This action reduces the supply of circulating free fatty acids that the liver uses to synthesize triglycerides for incorporation into VLDL. The inhibition of lipolysis has been attributed to the binding of niacin to a G-protein coupled receptor in adipose tissue. Niacin decreases LDL-C levels and LDL associated with atherosclerosis, at the same time it increases HDL-C levels. Decreases lipoprotein (a)
Niacin - Clinical use
Hypertriglycerdemia
Increase HDL-C levels in persons with abnormally low levels of this lipoprotein.
Primary hyperlipidemia
Mixed dyslipidemia
Reduce the risk of pancreatitis in pat with high triglyceride levels.
Reduces risk of myocardial infaction among men with hypercholesterolemia and atherosclerosis, and is decreased total mortality
Niacin - Adverse effects and Interactions
Vasodilation and flushing of the skin accompanied by pruritus and a feeling of warmth and tingling.
Elevate serum transaminase levels and cause hepatitis
Gastric distress Trigger peptic ulcers Increase glucose levels, but well tolerated in diabetes. Hyperuricemia and gout Myopathy
Interactions:
Fibrates or statins increase risk of myopathy
Avoid in pt w: PUD, acute liver disease, Pregnancy, Arterial bleeding
Fibric acid derivatives
Gemfibrozil
Fenofibrate
