Used in the Treatment of Hyperlipidemias

Describe the proposed role of lipoproteins in the formation of atherosclerotic plaques. 

List the four main classes of drugs used to treat hyperlipidemia and describe their mechanism of action, effects upon serum lipid concentrations, and adverse effects. 

Based on a set of baseline serum lipid values, propose a rational drug treatment regimen. 

Argue the merits of combined drug therapy for some diseases and list three rational drug combinations. 

Apolipoproteins Profeins located on the surface of iipoproteins they play critical roles in the regulation of lipoprotein metabolism and uptake into cells 

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Nicotinic acid is used in the treatment of hyperlipidemia. It causes various changes in lipid and lipoprotein metabolism when administered in high doses (up to 5 g/d) ... 

Nicotinamide should not be used in the treatment of hyperlipidemia because it does not effectively lower cholesterol or triglyceride levels. 

TIVniXSH Comparison of Drugs Used in the Treatment of Hyperlipidemia ... 

PUFAs are potent inhibitors of the HMG-CoA reductase enzyme and similar to statins are useful in the treatment of hyperlipidemias (99-102). Statins enhance plasma AA levels and decrease the ratio of EPA to AA significantly (100). This finding suggests that PUFAs mediate many actions of statins (103) and that this could be one mechanism by which they lower cholesterol levels. Statins and PUFAs have many overlap actions such as the inhibition of IL-6 and TNF-a production and NF-kB activation plus the ability to enhance eNO production thus, both possess anti-inflammatory actions and both are useful in atherosclerosis, coronary heart disease, osteoporosis, stroke, Alzheimer s disease, and inflammatory conditions such as lupus and cancer (3, 4, 94, 104-121). These similar and overlap actions strongly indicate that the molecular mechanisms of actions of statins and PUFAs are similar, if not identical. Furthermore, when a combination of statins and PUFAs are given together, a synergistic beneficial effect was seen in patients with combined hyperlipemia (122). 

Vitamin E is the common name for o-a-tocopherol and is an oily liquid at room temperature and is also an antioxidant. Alfacalcidol, a dehydroxy derivative of calcitriol, is formulated as a solution in a mixture of sesame oil and a-tocopherol in 0.25 pg, 0.5 pg, and 1.0 pg One-Alpha soft gelatin capsules. Ethyl icosapen-tate is used in the treatment of hyperlipidemia and arteriosclerosis obliterans, and exists as a liquid at ambient room temperature that is formulated as a solution in a-tocopherol in 300 mg Epadel soft gelatin capsules. 

He flJiH npoflami cksh m fleacaBra-KOHEepcMH MyCAHfl 3T 4>poHT.py >— DRUGS USED IN THE TREATMENT OF HYPERLIPIDEMIAS / 317... 

Photodecarboxylation of 2-(3-benzoyl)phenylpropionate, the ketoprofen anion, was studied in water by time-resolved, laser-induced optoacoustic spectroscopy (LIOAS). The various transient species involved in the title reaction were identified and their Hfetimes measured. The intrinsic photoreactivity of the 2-benzoylthiophene chromophore of the photosensitizing drug, tiaprofenic acid, was also studied. The observed photoprocesses account readily for the biological photosensitization reactions such as membrane damage and protein modification. The transient photochemistry in photodecarboxylation of rufloxacin (a fluoroquinolone antibacterial drug), fenofibric acid (used in the treatment of hyperlipidemia), and tohnetin has also been reported. 

The bile acid sequestering resins lower elevated LDL cholesterol and therefore are useful in the treatment of type Ila hyperlipoproteinemia. However, because the resins can raise plasma VLDL in some patients, they are not recommended for treatment of combined hyperlipidemias (type Ilb) when both LDL cholesterol and VLDL triglycerides are high or in other conditions of elevated triglycerides. 

The fibrates are mainly used to treat two hyperlipi-demias, familial hypertriglyceridemia (type IV) and dysbetalipoproteinemia (type III). They are also useful in the treatment of hypertriglyceridemia associated with type II diabetes (secondary hyperlipidemia). The fibrates are the drugs of choice in treating hypertriglyceridemias, particularly those associated with low levels of HDL cholesterol. The fibrates additionally appear to... 

The drugs discus.sed in this chapter arc used for their action on the heart or other parts of the vascular system, to modify the total output of the heart or the distribution of blood to the circulatory system. These drugs are used in the treatment of angina, cardiac arrhythmias, hypertension, hyperlipidemias. and di.sorders of blood coagulation. This chapter also includes a discu.ssion of hypoglycemic agents, thyroid hormones, and antithyroid drugs. 

Niacin, a B-complex vitamin, is used in the treatment of pellagra, peripheral vascular disease, and circulatory disorders, and as an adjunctive treatment of hyperlipidemias, especially those associated with hypercholesterolemia. Niacin, nicotinic acid (pyridine-3-carboxylic acid), is one of the oldest drugs used to treat dyslipidemia and favorably affects virtually all lipid parameters. 

While the fibric acid derivatives have antihyperlipidemic effects, their use varies depending on the drug. For example, Clofibrate (Atromid-S) and gemfibrozil (Lopid) are used to treat individuals with very high serum triglyceride levels who present a risk of abdominal pain and pancreatitis and who do not experience a response to diet modifications. Clofibrate is not used for the treatment of other types of hyperlipidemia and is not thought to be effective for prevention of coronary heart disease. Fenofibrate (Tricor) is used as adjunctive treatment for the reduction of LDL, total cholesterol, and triglycerides in patients with hyperlipidemia. 

Atypical antipsychotics such as aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are effective as monotherapy or adjunctive therapy with lithium and valproate in the treatment of acute mania. Some antipsychotics have the potential to cause adverse effects such as extrapyramidal reactions, sedation, depression, emotional blunting, sexual dysfunction, weight gain, and orthostatic hypotension. Prophylactic use of antipsychotics may be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed because of long-term adverse effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). ... 

The fruit body of Ganoderman lucidum (Fr.) Karst has been used for the treatment of hypertension, hyperlipidemia, arthritis, bronchitis, arteriosclerosis, diabetes and cancer. I previously reported that an aqueous extract of G lucidum reduced the elevation of blood glucose without elevating blood insulin in a test utilizing an intravenous infusion of adrenaline and an oral infusion of glucose [4], The polysaccharide... 

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). 

The principal use of niacin is for mixed hyperlipidemia or as a second-line agent in combination therapy for hypercholesterolemia. It is a first-line agent or alternative for the treatment of hypertriglyceridemia and diabetic dyslipidemia. 

These drugs are used for treatment of hyperlipidemia. They lower the levels of lipoproteins and lipids in blood. The plasma lipids are present in lipoproteins after combining with apoproteins. They are high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL). 

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