Document Detail


Statins and myotoxicity: a therapeutic limitation.
MedLine Citation:
PMID:  16907655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level. Although statin-associated myotoxicity affects compliance, quality of life of patient and discontinuation rate, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins. Medical management of myotoxicity seems to be pivotal for the proper compliance of patients with statin treatment. The appropriate and judicious use of drugs would substantially reduce the likelihood of developing clinically important myopathy.
Authors:
Atul Tiwari; Vinay Bansal; Anita Chugh; Kasim Mookhtiar
Related Documents :
22642305 - The natural history of motor neuron disease: assessing the impact of specialist care.
22811625 - A quarter century of hospice care: the southern california kaiser permanente experience.
22438595 - Individualized education and competency development of croatian community pharmacists u...
22897205 - Living with locked-in syndrome: an explorative study on health care situation, communic...
9094845 - Adequacy of prenatal care utilization, maternal ethnicity, and infant birthweight in ch...
22781015 - Activities in daily life and changes in care level among users of preventive care servi...
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on drug safety     Volume:  5     ISSN:  1744-764X     ISO Abbreviation:  Expert Opin Drug Saf     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-15     Completed Date:  2006-08-23     Revised Date:  2008-04-14    
Medline Journal Info:
Nlm Unique ID:  101163027     Medline TA:  Expert Opin Drug Saf     Country:  England    
Other Details:
Languages:  eng     Pagination:  651-66     Citation Subset:  IM    
Affiliation:
Ranbaxy Research Laboratories, Metabolic & Urology Group, New Drug Discovery Research, Gurgaon-122001, Haryana, India. atul_tri@rediffmail.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Biological Availability
Drug Interactions
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*,  pharmacokinetics,  therapeutic use
Hyperlipidemias / drug therapy
Liver / drug effects*,  metabolism
Myositis / chemically induced*,  physiopathology
Pharmacogenetics
Rhabdomyolysis / chemically induced*,  physiopathology
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Angiotensin-converting enzyme inhibitor-related angioedema: how to deal with it.
Next Document:  Side effects of using nitrates to treat angina.