McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

process that generates atheromas in vessel walls. That exact mechanism of action is not understood. These drugs are indicated as adjuncts with diet and exercise for the treatment of increased cholesterol and LDL levels that are unresponsive to dietary restrictions alone. Pravastatin and simvastatin are indicated for indi- viduals with documented CAD to slow progression of the disease. These two agents and atorvastatin are used to prevent a first myocardial infarction (MI) in people who have multiple risk factors for developing CAD. Table 47.3 discusses usual indications for each of the HMG-CoA reductase inhibitors. Several of the statin drugs have been formulated as combination therapy. Examples of combination therapy are highlighted in Box 47.6. In recent years, combination therapy for reducing the risk of atherosclerosis in people with multiple risk factors has been introduced in Australia. It has been thought that the convenience of taking one tablet each day would improve compliance with the lipid-lowering therapy and other complementary medicines. Newer combination drugs for treating CAD • Caduet and Cadatin are combinations of 5 or 10 mg amlodipine and 10, 20, 40 or 80 mg atorvastatin. The person should first be stabilised on the individual drugs before the correct combination is selected. The combination provides the blood pressure–lowering and antianginal effect of the amlodipine with the lipid-lowering effects of the atorvastatin. The usual adult dose is 5 to 10 mg amlodipine with 10 to 80 mg atorvastatin, based on the individual’s response. The recommended dose in children 10 to 17 years of age is 2.5 to 5 mg amlodipine with 10 to 20 mg atorvastatin. • Vytorin , introduced in 2005, is a combination of ezetimibe and simvastatin, and was approved to help lower lipid levels in people who did not have good results with single-drug therapy. Ezetimibe decreases the absorption of cholesterol, and simvastatin decreases the body’s production of cholesterol. The drug is available in tablets that contain 10 mg ezetimibe and 10, 20, 40 or 80 mg simvastatin. Dose should be determined based on lipid levels. The ENHANCE study reported disappointing effectiveness of this combination. • Juvicor is a combination of 100 mg sitagliptin and 10, 20 or 40 mg simvastatin. This drug is used to manage type 2 diabetes mellitus as well as reducing serum cholesterol levels. Only Vytorin is available in New Zealand at time of publication. ■■ BOX 47.6  Combination therapy for lowering cholesterol levels

Evaluation

■■ Bile acid sequestrants prevent the reabsorption of bile salts, which are very high in cholesterol. Consequently, the liver will pull cholesterol from the blood to make new bile acids, lowering the serum cholesterol level. ■■ People receiving bile acid sequestrants need to learn how to mix the powders or, if taking the tablet form, the importance of swallowing the tablet whole and not cutting, crushing or chewing it. Doses should not be taken with other drugs to avoid problems with absorption. ■■ GI problems are often reported when using bile acid sequestrants, including nausea, bloating and constipation. HMG-C o A reductase inhibitors The HMG-CoA reductase inhibitors include atorva­ statin ( Lipitor ), fluvastatin ( Lescol ), pravastatin ( Cholstat , Pravachol ), rosuvastatin ( Crestor ) and sim- vastatin ( Simvar , Zocor ). Therapeutic actions and indication The early rate-limiting step in the synthesis of cellular cholesterol involves the enzyme HMG-CoA reductase. If this enzyme is blocked, serum cholesterol and LDL levels decrease because more LDLs are absorbed by the cells for processing into cholesterol. In contrast, HDL levels increase slightly with this alteration in fat metabo- lism. HMG-CoA reductase inhibitors block HMG-CoA reductase from completing the synthesis of cholesterol (see Figure 47.2). Most of these drugs are chemical modi­ fications of compounds produced by fungi. As a group, they are frequently referred to as “statins”. Because these drugs undergo a marked first-pass effect in the liver, most of their effects are seen in the liver (see Adverse effects). These drugs may also have some effects on the ■ ■ Monitor response to the drug as appropriate (reduction in serum cholesterol levels). ■ ■ Monitor for adverse effects (headache, vitamin deficiency, increased bleeding times, constipation, nausea, rash). ■ ■ Evaluate the effectiveness of the teaching plan (person can name drug, dosage, adverse effects to watch for and specific measures to avoid them; person understands the importance of continued follow-up). ■ ■ Monitor the effectiveness of comfort measures and compliance with the regimen. KEY POINTS