Hyperlipidemia-controlling drugs

Derivatives of clofibric acid were used in earlier times as hyperlipidemia-controlling drugs. Currently more interest is shown in the synthesis of 2-methyl-2-aryloxypropanoic acids because these classes of compounds are being considered as possible remedies for type II diabetes. The earlier GSK process involves reacting 2-bromo-2-methylpropanoic acid with a phenolic compound at 50°C, where both compounds are suspended in 2-butanone solvent. The acid is expensive, and large volumes of the organic solvent are also required. 

The cornerstone of treatment in primary hyperlipidemia is diet restriction and weight reduction. Limit or eliminate alcohol intake. Use drug therapy in conjunction with diet, and after maximal efforts to control serum lipids by diet alone prove unsatisfactory, when tolerance to or compliance with diet is poor or when hyperlipidemia is severe and risk of complications is high. Treat contributory diseases such as hypothyroidism or diabetes mellitus. 

Hyperlipidemia, secondary causes Prior to initiating therapy, exclude secondary causes of hyperlipidemia (eg, poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) and measure total-C, HDL-C, and triglycerides. 

Prazosin may be particularly useful when patients cannot tolerate other types of antihypertensive agents or when blood pressure is not well controlled by other drugs. Since prazosin does not significantly influence blood uric acid or glucose levels, it can be used in hypertensive patients whose condition is complicated by gout or diabetes meUitus. Prazosin treatment is associated with favorable effects on plasma lipids. Thus, it may be of particular importance in managing patients with hyperlipidemia. 

Although it is not exactly clear how much these agents can reduce the risk of a major cardiac event (e.g., infarction, stroke), these drugs will probably remain the first choice for people with certain hyper-lipidemias (e.g., increased triglycerides). These drugs are likewise advocated for mixed hyperlipidemias that are common in metabolic disorders such as type 2 diabetes mellitus (see Chapter 32).32,141 Certain fibrates can be used with other drugs, such as statins, to provide more comprehensive pharmacologic control of certain lipid disorders.30,147... 

Nephrotic hyperlipidemia is accompanied with increased risk of cardiovascular complications and should be treated in all patients with persistent nephrotic syndrome. The putative positive effect of hypolipidemic drugs (namely statins) on the cardiovascular risk and potentially also on the rate of progression of chronic renal failure remains to be demonstrated in prospective controlled studies. 

In lipid metabolism, there is elegant balance in the levels of end-product lipids, and the enzymes and genes involved in their biosynthesis, as well as close cooperation with other metabolisms to maintain homeostasis. When the balance is lost, obesity or hyperlipidemia will develop, leading to a variety of serious diseases including atherosclerosis, hypertension, diabetes, functional depression of certain organs, and so on. Therefore, the control of lipid metabolism by drugs could lead to the prevention or treatment of these diseases. 

For diabetic patients with chronic kidney disease (CKD) stages 1-11 (Creatinine clearance betwem normal and 60 mL/min/1.73 m ), stage-independent actions such as control of cardiovascular risk factors (hypertension, hyperlipidemia, and smoking), avoidance of drug toxicity and diagnostic injury, control of progression, and reduction of proteinuria are essential. 

Levels of lipoproteins in the blood are controlled by (1) diet, (2) a number of hormones, (3) age, (4) weight change, (5) emotions and stress, (6) exercise, (7) drugs, (8) illness, and (9) heredity. Excessive concentration of one or more of the lipoproteins is termed hyperlipoproteinemia. There are six of these (1) hyperchylomicronemia (2) hyperbetalipo-proteinemia or hypercholesterolemia (3) hyperlipidemia or hypercholesterolemia with hyperglyceridemia (4) broad beta (5) hyperbetaliproteinemia and (6) mixed hyperlipe-demia. These hyperlipoproteinemias cause numerous health... 

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