Lowering Agents

Brand Name Mevacor (lovastatin) Pravachol (pravastatin) 

Mechanism of Action Inhibit HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate, an early step in cholesterol biosynthesis Depletion of cellular cholesterol stimulates the production of cell surface receptors that recognize LDL, leading to increased catabolism of LDL cholesterol  

Contraindications Hypersensitivity to any component of these medications Active liver disease Pregnancy and lactation (Pregnancy Category X)  

Warnings Liver function tests should be performed prior to treatment, at 6 and 12 weeks after initiation of therapy and periodically thereafter. Rhabdomyolysis with acute renal failure has been reported with related drugs in this class.  

Adverse Reactions Headache Flatus Abdominal pain and cramps Diarrhea Rash/Pruritus Constipation Nausea Dyspepsia Myalgia Dizziness Heartburn Blurred vision Muscle cramps Localized pain Nausea/vomiting Common cold Diarrhea Headache Abdominal pain Cardiac chest pain Constipation Chest pain Flatulence Dizziness Heartburn Myalgia Influenza Urinary abnormality 

The total fat intake must be reduced to achieve weight reduction by diet therapy.70 Dietary recommendations also include a reduction in saturated fatty acids. Drug therapy must be started only after confirmation of lipid levels such as cholesterol, triglycerides, LDL, and HDL. Adequate trial must be initiated with modification of dietary therapy, only failing which drug therapy must be started. 

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The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

Ciprofibrate (48), a more potent lipid-lowering agent clofibrate, is prepared from Simmons-Smith product by Sandmeyer replacement of the amino group by a hydroxyl via the diazonium salt. Phenol undergoes the Reimer-Thiemann like process common to these agents upon alkaline treatment with acetone and chloroform to complete the synthesis of ci profib-rate (48). 

A lipid lowering agent of potential value in hypercholesterolemia is cetaben (31). It is synthesized facilely by monoalkylation of ethyl -aminobenzoate with hexadecyl bromide and then saponification. " ... 

The cholesterol-lowering agents called statins, such as simvastatin (Zocor) and pravastatin (Pravachol), are among the most widely prescribed drugs in the world. Identify the functional groups in both, and tell how the two substances differ. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Elkind MS, Flint AC, Sciacca RR, Sacco RL. Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality. Neurology 2005 65 253-258. 

JARIWALLA R (1999) Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid lowering agent. Anticancer Research, 19 3699-702. 

Lipid-lowering agents, 40 (2002) 1 5-Lipoxygenase inhibitors and their antiinflammatory activities, 29 (1992) 1 Literature of medicinal chemistry, 6 (1969) 266... 

Often used to augment blood pressure lowering, CCBAs are most commonly used as add-on therapy for patients who are in need of further blood pressure lowering above and beyond that afforded by diuretics or other antihypertensives. Nonetheless, they have demonstrated their efficacy in select patient populations as very effective blood pressure lowering agents. 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

Clofibrate (91) has been in clinical use for several years as a serum triglyceride lowering agent. This drug is an important hypocholesteremic... 

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