HMG-CoA reductase inhibitor therapy

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. 

Ordovas JM, Lopez-Miranda J, Perez-Jimenez F, Rodriguez C, Park JS, Cole T, et al. Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy. Atherosclerosis 1995 113 157-166. 

A 53-year-old male patient with elevated levels of low-density lipoprotein (LDL) cholesterol, signs of premature cholesterol gallstone disease and substantially elevated triglycerides visited his physician for a follow-up to check his current status. The patient had received various statin, HMG-CoA-reductase inhibitors therapies for the past 2 years. However, after blood work done at this follow-up visit, complications had still not subsided. This patient has similar problems as two of his siblings. Which of the following best explains this patients dyslipidemia ... 

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... 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

The NKF suggests that CKD should be classified as a coronary heart disease (CHD) risk equivalent and the goal LDL-C level should be below 100 mg/dL in all patients with CKD.22 The most frequently used agents for the treatment of dyslipidemias in patients with CKD are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ( statins ) and the fibric acid derivatives. However, other treatments have been studied in patients with CKD and should be considered if first-line therapies are contraindicated. 

From the preceding sections, it is clear that chemokines are important players in atherosclerotic disease and, as such, are being considered as possible targets in the treatment of this prevalent inflammatory condition. Under consideration at this time are both traditional nonspecific therapies [e.g., 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, fibrates, etc.], as well as chemokine specific approaches (142). 

As discussed above, obesity is associated with dyslipidemia, a condition where high levels of low-density lipoprotein cholesterol (LDL-C) is common. Elevated LDL-C is strongly associated with an elevated risk of coronary artery disease and for this reason a number of lipid-lowering therapies that target LDL-C have been developed. These include bile-acid sequestrants (BAS), statins (HMG-CoA reductase inhibitors), cholesterol absorption inhibitors, and fibrates. ... 

Combination therapy - For maximal therapeutic effect in combination with an HMG-CoA reductase inhibitor, the recommended dose of colesevelam is 3 tablets taken twice daily with meals or 6 tablets taken once daily with a meal. Doses of 4 to 6 tablets/day have been shown to be safe and effective when coadministered with an HMG-CoA reductase inhibitor or when the 2 drugs are dosed apart. 

Antihyperlipidemics Use HMG-CoA reductase inhibitors in addition to a diet restricted in saturated fat and cholesterol when diet and other nonpharmacological therapies alone have produced inadequate responses. Refer to individual product monographs. ... 

Combination therapy with HMG-CoA reductase inhibitors - In combination with an HMG-CoA reductase inhibitor as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and nonfamilial) hypercholesterolemia. 

Monitoring When ezetimibe is coadministered with an HMG-CoA reductase inhibitor, perform liver function tests at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor. At the time of hospitalization for an acute coronary event, take lipid measures on admission or within 24 hours. Liver enzymes Wnen ezetimibe is coadministered with an HMG-CoA reductase inhibitor, perform liver function tests at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor. 

Chang JT, Staffa JA, Parks MD, et al. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol. 

In one of our other studies [37], the 6 months therapy with 0,4 mg daily of other HMG-CoA-reductase inhibitor cerivastatin, which is more effective than pravastatin as cholesterol-lowering drug, sharply increased the level of LDL lipohydroperoxides in the blood plasma of patients [37] (Figure 18). At the same time administration of cerivastatin in combination with synthetic antioxidant probucol in daily dose 250 mg did not produce the increase of the LDL lipohydroperoxide level in the plasma during all time of the observation [37] (Figure 18). 

As appears from the above, for prevention of atherogenic oxidative modification of LDL in the blood of patients with atherosclerosis HMG-CoA-reductase inhibitors must be used in combination with antioxidants. The most attractive conclusion is that synthetic antioxidant probucol may act in the LDL as a trap for lipid free radicals and may be effective in the prevention of LDL peroxidation in atherogenesis and during cholesterollowering therapy. 

Although nicotinic acid and niacin are usually the drugs of choice, a combination therapy such as gemfibrozil and resins or gemfibrozil and an HMG-CoA reductase inhibitor can also be used. ... 

Hasunuma, T., Nakamura, M., Yachi, T., Arisawa, N., Fukushima, K. and Iijima, H. (2003) The drug-drug interactions of pitavastatin (NK-104), a novel HMG-CoA reductase inhibitor and cyclosporine. Journal of Clinical Therapy Medicine, 19, 381-389. 

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