HMG CoA reductase inhibitor

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

In Scheme 10, HMG-CoA reductase inhibitor 92 was synthesized via a Suzuki coupling approach. Hiyama s group also carried out a Hiyama coupling to make the same compound (93TL8263). Vinylsilane 119 was prepared by platinum-catalyzed reaction from terminal alkyne 89. 

The search for inhibitors of this pathway began with the first key regulatory enzyme, HMG CoA reductase. Several clinically useful inhibitors of HMG CoA reductase are now known. One of the most successful, Mevacor, produced by Merck, is one of the pharmaceutical industry s best selling products. However, the problem with inhibiting a branched biosynthetic pathway at an early point is that the biosynthesis of other crucial biomolecules may also be inhibited. Indeed, there is some evidence that levels of ubiquinone and the dolichols are affected by some HMG CoA reductase inhibitors. Consequently, efforts have recently been directed towards finding inhibitors of squalene synthase, the enzyme controlling the first step on the route to cholesterol after the FPP branch point. 

HMG-CoA-Reductase-Inhibitors Peroxisome Proliferator-Activated Recqrtors (PPARs) ACE Inhibitors Antiplatelet Drugs... 

HMG-CoA reductase inhibitors (statins). This effect has been suggested to account for some of the side effects of statins like myositis or rhabdomyolysis. 

Peroxisome Proliferator-Activated Receptor (PPARs) HMG-CoA Reductase Inhibitors... 

HMG-CoA-Reductase Inhibitors. Figure 1 Mechanism of action of statins - cholesterol synthesis pathway. The conversion of acetyl CoA to cholesterol in the liver. The step of cholesterol biosynthesis inhibited by HMG-CoA reductase inhibitors (statins) is shown. 

HMG-COA-Reductase Inhibitors Low-Density Lipoprotein Receptor Gene Family... 

HMG-CoA-Reductase-Inhibitors Lipoprotein Metabolism Lipid Transfer Proteins... 

HMG CoA-Reductase HMG-CoA-Reductase Inhibitors Homologous Desensitization Homologous Proteins Homologous Recombination Homology Modeling Hormonal Contraceptives Hormone Replacement Therapy (HRT)... 

HMG-CoA reductase inhibitors are usually well tolerated. Adverse reactions, when they do occur, are often mild and transient and do not require discontinuing therapy. The more common adverse reactions include nausea, vomiting, constipation, abdominal pain or cramps, and... 

The HMG-CoA reductase inhibitors are contraindicated in individuals with hypersensitivity to the drugs, serious liver disorders, and during pregnancy (Pregnancy... 

Category X) and lactation. The HMG-CoA reductase inhibitors are used cautiously in patients with a history of alcoholism, acute infection, hypotension, trauma, endocrine disorders, visual disturbances, and myopathy. 

The HMG-CoA reductase inhibitors have an additive effect when used with the bile acid sequestrants, which may provide an added benefit in treating hypercholesterolemia that does not respond to a single-drug regimen. There is an increased risk of myopathy (disorders of the striated muscle) when the HMG-CoA reductase inhibitors are administered with erythromycin, niacin, or cyclosporin a When the HMG-CoA reductase inhibitors are administered with oral anticoagulants, there is an increased anticoagulant effect. 

When administering the HMG-CoA reductase inhibitors and the fibric acid derivatives, the nurse monitors the patient s fiver function by obtaining serum transaminase levels before the drug regimen is started, at 6 and 12 weeks, then periodically thereafter because of the possibility of liver dysfunction with the drugs. If aspartate aminotransferase (AST) levels increase to three times normal, the primary care provider in notified immediately because the HMG-CoA reductase inhibitor therapy may be discontinued. 

HMG-CoA REDUCTASE INHIBITORS AND FlBRIC ACID DERIVATIVES. The antihyperlipidemic drugp, particularly die HMG-CoA reductase inhibitors, have been associated with skeletal muscle effects leading to rhab-domyolysis. Rhabdomyolysis is a very rare condition in which muscle damage results in die release of muscle cell contents into die bloodstream. Rhabdomyolysis may precipitate renal dysfunction or acute renal failure The nurse is alert for unexplained muscle pain, muscle tenderness, or weakness, especially if tiiey are accompanied by malaise or fever. These symptoms should be reported to die primary health care provider because the drug may be discontinued. 

Goldberg Arnold R, Kaniecki D, Tak Piech C, et al. An economic evaluation of HMG-CoA reductase inhibitors for cholesterol reduction in the primary prevention of coronary heart disease. 11th International Conference on Pharmacoepidemiology. Montreal, Quebec, Canada, 1995. 

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