Fredrickson’s type

All HMGRIs are approved for the treatment of primary hypercholesterolemia and familial combined hyperlipidemia (Fredrickson s type Ha and lib) (Table 30.2) In patients who have not responded to diet, exercise, and other non pharmacological methods (Table 30.6) (15,21). They may be used either alone or In combination with bile acid sequestrants, ezetimibe, or niacin. As previously mentioned, they should be administered at least 1 hour before or 4 to 6 hours after bile acid sequestrants when this combination Is desired. Fluvastatin, lovastatin, pravastatin, and simvastatin have been specifically Indicated to reduce the mortality of CHD and stroke. By reducing plasma LDL levels, these compounds slow the progression of atherosclerosis and reduce the risk of myocardial Infarction and other ramifications of vascular occlusion. Atorvastatin, rosuvastatin, and simvastatin have been shown to be effective In homozygous familial hyperlipidemia and are Indicated for this use. Additionally, atorvastatin, pravastatin, and simvastatin are Indicated for primary dysbetallpoprotelnemla (Fredrickson s type III) (Table 30.2). Finally, atorvastatin, pravastatin, rosuvastatin, and simvastatin are Indicated for the treatment of hypertriglyceridemia. 

Fibrates are approved to treat hypertriglyceridemia and familial combined hyperlipidemia (Fredrickson s type lla, lib, IV, and V) (Table 30.2) in patients who are at risk of pancreatitis and have not responded to dietary adjustments or in patients who are at risk of CHD and have not responded to weight loss, dietary adjustments, and other pharmacological treatment. They can be used either alone or in combination with niacin, bile acid sequestrants, or FlMGRIs. If used with bile acid sequestrants, fibrates must be taken either 1 hour before or 4 to 6 hours after the sequestrant. As discussed previously and reemphasized below, caution should be used it fibrates are combined with HMGRIs. Fibrates are not effective in the treatment of hypertriglyceridemia associated solely to elevated chylomicron levels (Fredrickson s type I). 

Nicotinic acid is approved for the treatment of hyper-cholesterolemia, hypertriglyceridemia, and familial combined hyperlipidemia (Fredrickson s type lla, Mb, IV, and V) (Table 30.2) in patients who have not responded to diet, exercise, and other nonpharmacological methods. It also is approved for nutritional supplementation, the prevention of pellagra, and as adjunct therapy for peripheral vascular disease and circulatory disorders. It is contraindicated in patients with hepatic disease and peptic ulcer disease. Additionally, because of its ability to elevate glucose and uric acid levels, especially when taken in large doses, nicotinic acid should be used with caution in patients who have or are predisposed to diabetes mellitus and gout (15,20,21). 

Dextrothyroxine has largely fallen into disuse because of its property in raising the metabolic rate, commonly in individuals (e.g. with a history of myocardial infarct) in whom this is something which one must scrupulously avoid (SED VIII, p. 936). It may occasionally be useful in Fredrickson s type II hyperlipoproteinaemia if other therapy for any reason is not feasible, but coronary disease must be rigidly excluded and patients kept under strict control. 

The most recent contribution to the separation of lipoproteins and to the study of lipoprotein patterns in various forms of hyperlipidemias is that of Fredrickson s (1966) group. Using a modified form of paper electrophoresis, Fredrickson and Lees (1966) described 5 different types of familial hyperlipoproteinemia, type II of which corresponds to EFH and is characterized by an intensely staining beta-band in their system. 

This grouping is possibly not homogenous and may subsequently be subdivided. It includes subjects who have been described as having mixed hyperlipemia by Kuo and Basset (1963), calorie induced hyperlipemia by Kin sell and Schlierf (1965) and probably type V of Fredrickson s and Lees classification (1965). Whatever the homogeneity, it appears that these individuals accumulate very low density lipoproteins in plasma under essentially all dietary conditions except absolutely or relatively low calorie intake, and in some except during the administration of insulin. 

For many of the drugs of interest, action occurs presumably only during some fraction of the cell mitotic cycle. Most often this is considered to be the DNA production or S-phase of the total Gi-S-G2-M cycle. A useful model, therefore, should at least be able to incorporate this type of information—e.g., the structured models of Tsuchiya, Fredrickson, and Aris (3). This means that simple gross descriptions, such as Michaelis-Menten-Monod models are not sufficient, and some attention must be paid to the cells during growth. We assume here for a first approximation that a single cell age or maturation variable is sufficient. 

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