HMG-CoA reductase inhibitors

HMG-CoA reductase inhibitors

HMG-CoA reductase inhibitors (also known as the statins) lower lipid levels by interfering with cholesterol synthesis. These drugs include atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.

Pharmacokinetics

Each drug has slightly different pharmacokinetic properties. With the exception of pravastatin, all are highly bound to plasma proteins and undergo extensive first-pass metabolism. However, plasma levels don’t correlate with the drugs’ abilities to lower cholesterol.

 

Pharmacodynamics

HMG-CoA reductase inhibitors inhibit the enzyme responsible for the conversion of HMG-CoA to mevalonate, an early step in the synthesis of cholesterol.

 

Pharmacotherapeutics

Statins are used primarily to reduce LDL cholesterol and total blood cholesterol levels. These agents also produce a mild increase in HDL cholesterol levels.

Statins are used to treat primary hypercholesterolemia (types IIa and IIb). Because of their effect on LDL and total cholesterol, these drugs are also used to reduce the risk of CAD and to prevent MI or stroke in patients with high cholesterol levels.

 

Drug interactions

• Taking a statin drug with amiodarone, clarithromycin, cyclosporine, erythromycin, fluconazole, gemfibrozil, itraconazole, ketoconazole, or niacin increases the risk of myopathy or rhabdomyolysis (a potentially fatal breakdown of skeletal muscle, causing renal failure).
• Lovastatin, rosuvastatin and simvastatin may increase the risk of bleeding when administered with warfarin.
• All of these drugs should be administered 1 hour before or 4 hours after the administration of bile-sequestering drugs (cholestyramine, colesevelam, and colestipol). 

Warning!

Adverse reactions to HMG-CoA reductase inhibitors

HMG-CoA reductase inhibitors may alter liver function studies, increasing aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin levels. Other hepatic effects may include pancreatitis, hepatitis, and cirrhosis.

 

Myalgia is the most common musculoskeletal effect, although arthralgia and muscle cramps may also occur. Myopathy and rhabdomyolysis are rare, but potentially severe, reactions that may occur with these drugs.

 

Possible adverse GI reactions include nausea, vomiting, diarrhea, abdominal pain, flatulence, and constipation.

 

Nicotinic acid

Also known as niacin, nicotinic acid is a water-soluble vitamin that decreases cholesterol, triglyceride, and apolipoprotein B-100 levels and increases the HDL level. The drug is available in immediate-release and extended-release tablets.

 

Pharmacokinetics

Nicotinic acid is rapidly and extensively absorbed following oral administration. It’s moderately bound to plasma proteins; its overall binding ranges from 60% to 70%. The drug undergoes rapid metabolism by the liver to active and inactive metabolites. About 75% of the drug is excreted in urine.

 

Pharmacodynamics

The mechanism of action by which nicotinic acid lowers triglyceride and apolipoprotein levels is unknown. However, it may work by inhibiting hepatic synthesis of lipoproteins that contain apolipoprotein B-100, promoting lipoprotein lipase activity, reducing free fatty acid mobilization from adipose tissue, and increasing fecal elimination of sterols.

 

Pharmacotherapeutics

Nicotinic acid is usually used in combination with other drugs to lower triglyceride levels in patients with type IV or V hyperlipidemia who are at high risk for pancreatitis and to lower cholesterol and LDL levels in patients with hypercholesterolemia. It may also be used with other antilipemics to boost HDL levels.

Nicotinic acid is contraindicated in patients who are hypersensitive to nicotinic acid and in those with hepatic dysfunction, active peptic ulcer disease, or arterial bleeding.

 

Warning!

Adverse reactions to nicotinic acid

High doses of nicotinic acid may produce vasodilation and cause flushing. Extendedrelease forms tend to produce less severe vasodilation than immediate-release forms do. To help minimize flushing, administer aspirin 30 minutes before nicotinic acid, or give the extendedrelease form at night.

Nicotinic acid can cause hepatotoxicity; the risk of this adverse reaction is greater with extended-release forms.

Other adverse reactions include nausea, vomiting, diarrhea, and epigastric or substernal pain.

 

Drug interactions

• Together, nicotinic acid and an HMG-CoA reductase inhibitor may increase the risk of myopathy or rhabdomyolysis.
• Bile-sequestering drugs (cholestyramine, colesevelam, and colestipol) can bind with nicotinic acid and decrease its effectiveness.
• When given with nicotinic acid, kava may increase the risk of hepatotoxicity.