Adverse Reactions In clinical trials, all doses of colesevelam were generally well tolerated. Colesevelam is not absorbed in the digestive tract, reducing the potential for systemic adverse side effects. Also, its water-retaining ability creates a soft, gelatinous material that minimizes the potential for gastrointestinal irritation. The most common side effects reported by patients in clinical trials of colesevelam HCl were flatulence (12% for colesevelam vs. 14% for placebo) and constipation (11% for colesevelam vs. 7% for placebo). The incidence of gastrointestinal side effects was less than that associated with other drugs in its class. Less than 3% of the trial patients discontinued colesevelam therapy as a result of GI tract adverse …
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Pharmacology and Pharmacokinetics Bile acids are formed from cholesterol in a series of reactions regulated by the enzyme 7-alpha- hydroxylase. During normal digestion, bile acids are secreted into the intestine. A major portion of bile acids are then absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation. Colesevelam is a hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not absorbed (less than 0.05% absorption) from the GI tract. It binds bile acids in the intestine, impeding their reabsorption and facilitating elimination. As the bile acid pool becomes depleted, the hepatic enzyme cholesterol 7-alpha-hydroxylase is upregulated, increasing the conversion of cholesterol to bile …
[ Continue Reading... ]What does the pharmacist need to know to counsel patients about colesevelam? Development Epidemiological studies have established that elevated levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipo-protein B (Apo B), as well as decreased levels of HDL-cholesterol (HDL-C), are associated with an increased risk of atherosclerosis and cardiovascular-related mortality. Furthermore, it has been documented through numerous trials that aggressive reduction of lipid levels can significantly reduce the risk of cardiovascular disease. It is estimated that more than 50 million Americans currently have at least mild elevations of cholesterol (hyper-cholesterolemia or Fredrickson Type IIa hyperlipidemia) and would benefit from some form of lipid-lowering therapy. Diet and lifestyle changes generally represent the …
[ Continue Reading... ]By lowering cholesterol, drug reduces stroke events. By analyzing 28 studies involving use of HMGcoA reductase inhibitors or other anti-lipidemic agents in more than 100,000 patients, researchers have concluded that those patients given the HMGcoA inhibitors were 0.76 times as likely to develop strokes as those in the control groups. The stroke rate in patients given fibrates, resins or dietary intervention did not significantly differ from the control groups. Patients given the reductase inhibitors were also less likely to die of coronary heart disease or from other causes. Their analysis of these studies, said the authors, indicates that elevated cholesterol levels are a risk factor for stroke and may have a …
[ Continue Reading... ]Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) have traditionally been used to decrease serum cholesterol levels and to reduce morbidity and mortality associated with cardiovascular disease in patients with hyperlipidemia. Animal and human studies also suggest that HMG-coenzyme A reductase inhibitors may increase bone formation and bone mineral density. In humans, an increase in bone mineral density can decrease the risk of fractures, especially in patients with osteoporosis. Fracture risk is increased 1.5-2.5 times for every standard deviation below average peak bone mass. Osteoporotic fractures are recognized as a common and important cause of disability and death; 1.5 million fractures are attributed to osteoporosis annually. Although several recently approved medications effectively prevent and …
[ Continue Reading... ]Atorvastatin (Lipitor) is a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor or “statin.” HMG-CoA reductase is the enzyme responsible for converting HMG-CoA to mevalonate; this occurs at an early and rate-limiting step in the biosynthesis of cholesterol (see figure). Although a number of “statins” are now available, atorvastatin is the only drug in this class indicated as an adjunct to diet in the reduction of elevated total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), and triglyceride (TG) levels in patients with primary hypercholesterolemia and mixed dyslipidemia. It is the first drug of its class specifically indicated for lowering both low-density lipoprotein cholesterol and triglyceride levels. It is also the only statin …
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