1,721,110 research outputs found
Best practice--ongoing polemics
No full textCurrent treatment strategies and disease management programs for hyperlipidemia employ a range of lipid-lowering drugs. Results from early lipid-lowering trials using diet, fibrates, niacin and other classes of drug showed that lowering plasma cholesterol can significantly reduce the risk of developing ischemic cardiovascular events. The landmark statin trials have clearly demonstrated the benefits of lipid-lowering therapy in coronary heart disease (CHD) prevention and unlike early lipid-lowering studies, a reduction in mortality may become evident with statin therapy during the first year of treatment. The number of successful lipid-intervention trials continues to increase and evidence is accumulating that lipid modification can also reduce the risk of cardiovascular events among individuals with only modest degrees of blood-lipid abnormalities. With increasingly powerful drugs to modify blood lipids, the potential levels at which to initiate treatment and the appropriate target levels are rapidly changing and debate surrounds the question of where the line to initiate treatment should be drawn. The relative lack of major adverse events with statin therapy means that the level of CHD risk at which clinical benefit occurs cannot be determined by the degree of risk at which benefit exceeds adverse events. Therefore, patients with only moderately raised cholesterol levels can be treated because statin treatment is well tolerated. One of the most important aspects of the statin trials is the finding that clinical events, such as death and disability due to coronary artery disease, may be preventable or limited in a significant number of patients if they receive aggressive therapy. Current goals for cholesterol levels in patients with established CHD are rarely achieved with non-aggressive treatment; however, with aggressive lipid lowering statins can achieve these goals in a safe and effective manner
Drug-drug interaction with statins
No full text3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors (the so-called statins: atorvastatin, fluvastatin, pravastatin, lovastatin, rosuvastatin and simvastatin) are a well-established class of drugs in the treatment of hypercholesterolemia. Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Since statins are prescribed on a long-term basis, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. Moreover, a combination of therapy between statins and other classes of lipid-lowering agents (e.g., ezetimibe, fibrates, resins and nicotinic acid) is recommended for some patients by current guidelines. Therefore, the potential for drug-drug interactions emerges as a relevant factor in determining the safety profile of statins. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions
Lipophilic calcium antagonists in antiatherosclerotic therapy
No full textTwo key events in atherosclerotic plaque formation are the deposition of lipids in cells of the vascular wall, and migration and proliferation of arterial smooth muscle cells from the tunica intima toward the media. It has been shown that various calcium-channel antagonists may delay plaque formation in animal models. Among these, the new and highly lipophilic calcium antagonists, such as lacidipine and lercanidipine, display the most promising antiatherosclerotic activities. This paper will review and discuss these beneficial effects
Cholesterol : its regulation and role in central nervous system disorders
Full text linkCholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer's disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions
Statin drug interactions and related adverse reactions
No full textIntroduction: Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, their possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. Areas covered: This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions and related adverse reactions. Expert opinion: Avoiding drugdrug interactions and consequent adverse drug reactions is essential in order to optimize compliance, and thus improve the treatment of patients at high cardiovascular risk. The different pharmacokinetic profiles among statins should be carefully considered, in order to understand the possible spectrum of drug interactions. The growing trend toward earlier statin treatment for the prevention of cardiovascular disease means that physicians must anticipate future polypharmacy when their patients require additional medications for comorbid conditions
Modulation of macrophage function and metabolism
No full textSeveral drugs or pharmacologically active molecules such as statins, calcium antagonists, and PPAR agonists have been shown to affect macrophage functions that contribute to atherosclerosis and modulate plaque stability. For example, the modulation of matrix metalloproteinase secretion and cholesterol metabolism in macrophages may help to prevent cardiovascular disease independently of the correction of risk factors
Pharmacological interactions of statins
No full textThe 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in reducing the risk of coronary events, and are generally very well tolerated. However, simvastatin, lovastatin, cerivastatin and atorvastatin are biotransformed in the liver primarily by cytochrome P450 (CYP) 3A4, and clinical experience has shown that the risk of adverse effect, such as myopathy, increases with concomitant use of statins with drugs that substantially inhibit CYP 3A4 at therapeutic doses. Indeed, pharmacokinetic interactions (e.g. increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin and cyclosporine A, mibefradil or nefazodone. In contrast, fluvastatin (mainly metabolized by CYP 2C9) and pravastatin (eliminated by other metabolic routes) are less subject to this interaction. Nevertheless, an increase in pravastatin bioavailability has been reported in the presence of cyclosporine A, possibly because of an interaction at the level of biliary excretion. In summary, some statins may have lower adverse drug interaction potential than others, which is an important determinant of safety during long-term therapy
Safety of statins: focus on clinical pharmacokinetics and drug interactions
Full text linkStatin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions
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