Other Lipid-Lowering Agents

Several other agents have beneficial effects on plasma lipid profiles occurring through various cellular mechanisms.89 Cholestyramine (Questran), for example, attaches to bile acids within the gastrointestinal lumen and increases the fecal excretion of these acids. This action leads to decreased plasma cholesterol concentrations because cholesterol breakdown is accelerated to replace the bile acids that are lost in the feces. 

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Another therapeutic class to be briefly discussed is that of the lipid-lowering agents known as fibrates, e.g., clofibrate and fenofibrate (8.5). Here also, the acidic metabolite is the active form clofibrate (an ethyl ester) is rapidly hydrolyzed to clofibric acid by liver carboxylesterases and blood esterases [11], Human metabolic studies of fenofibrate (8.5), the isopropyl ester of fenofibric acid, showed incomplete absorption after oral administration, while hydrolysis of the absorbed fraction was quantitative [12], This was followed by other reactions of biotransformation, mainly glucuronidation of the carboxylic acid group. 

Many lipid-lowering agents are used alone or in combination to achieve lipid goals (Table 4). Although numerous lipid-lowering agents are available, which are used alone and in combination, additional therapies are required to decrease other atherogenic components and to enhance reverse cholesterol transport. 

NMDA receptor modulators (47-50)], monoamine oxidase B (MAO B) inhibitors (51-55), antioxidants (52, 56-59), nootropics (41, 60), lipid-lowering agents (e.g., statins) (61), insulin (62), anti-inflammatory agents (63-67), and estrogen supplementation (63, 65, 66, 68, 69). Because several other reviews are available that compare these therapeutic approaches (70-77), the remainder of the present chapter focuses on ion channel modulation approaches to cognition enhancement. 

Drug therapy is generally reserved for patients who fail to respond to diet or other measures described above. Lipid-lowering agents are described in Table 4.8. Strategies for reducing lipid levels include ... 

Recent literature does not point to side effects of nicotinic acid and its derivatives other than those which were reviewed in SED VIII (p. 936). The field has been reviewed by Parsons (26 ), who has stressed the need for a major study to determine the long-term effects of nicotinic acid as compared with other lipid-reducing agents. One of the few long-term studies recently reported, that of Zbllner et al. (27 ) is a follow-up on 37 patients who had been treated for hypercholesterolaemia with nicotinyl alcohol for between 6 and 8 years. Those who had taken more than 0.9 g daily still had a lower serum cholesterol than at the beginning of treatment, and there was no evidence of long-term adverse effects. 

The ocular hypotensive lipids in typical ophthalmology practice are considered first-line alternatives to topical P-blockers because of their superior efficacy and safety profiles. Many clinicians may choose to use the ocular hypotensive lipids as first-line agents, especially in patients that have an initial requirement to lower IOP by more than 25%, or in patients that have relative or absolute contraindications to topical P-blockers. However, latanoprost is currently the only ocular hypotensive lipid drug that has a Food and Drug Administration (FDA) indication for first-line therapy. Bimatoprost and travoprost are indicated by the FDA for patients who are intolerant of other IOP-lowering therapy or insufficiently responsive to another IOP-lowering medication.10,38... 

In vitro, allicin and related compounds inhibit HMG-CoA reductase, which is involved in cholesterol biosynthesis (see Chapter 35 Agents Used in Hyperlipidemia). Several clinical trials have investigated the lipid-lowering potential of garlic. Some have shown significant reductions in cholesterol and others no effect. The most recent meta-analysis suggested a minor (5%) reduction of total cholesterol that was insignificant when dietary controls were in place. 

The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was the deciding evidence that the JNC7 used to justify thiazide diuretics as first-line therapy." It was designed to test the hypothesis that newer antihypertensive agents (an a-blocker, ACE inhibitor, and dihydropyridine CCB) would be superior to thiazide diuretic therapy. The primary objective was to compare the combined end point of fatal coronary heart disease and nonfatal myocardial infarction. Other hypertension-related complications (e.g., heart failure and stroke) were evaluated as secondary end points. This was the largest hypertension trial ever conducted and included 42,418 patients aged 55 years and older with hypertension and one additional cardiovascular risk factor. This prospective, double-blind trial randomized patients to chlorthalidone (a thiazide diuretic), amlodipine (dihydropyridine CCB), doxazosin (a-blocker), or lisinopril (ACE inhibitor) for a mean follow-up of 4.9 years. 

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