Statin induced myopathy: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
Statin induced myopathies has a complex poorly understood multifactorial pathophysiology. It is postulated that statin causes myopathy through the following changes: | |||
* Changes in cholesterol content and alteration of the membrane fluidity of skeletal muscle cells which disrupts their normal function | |||
* Changes in skeletal muscle cells membrane electrical properties | |||
* Changes in Na+/K+ pump density resulting in decreased production of ATP | |||
* Changes in the excitation-contraction coupling | |||
* Changes in the cell surface receptor transduction cascades | |||
* Decreased synthesis of ubiquinone (Q10), a component of the mitochondrial electron transport chain, leading to decreased ATP production and decreased free radical scavenging | |||
* Increased intracellular calcium causing apoptosis of the skeletal muscle cells | |||
* Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in apoptosis of skeletal muscle cells<ref name="pmid16885396">{{cite journal| author=Dirks AJ, Jones KM| title=Statin-induced apoptosis and skeletal myopathy. | journal=Am J Physiol Cell Physiol | year= 2006 | volume= 291 | issue= 6 | pages= C1208-12 | pmid=16885396 | doi=10.1152/ajpcell.00226.2006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16885396 }} </ref> | |||
==Treatment== | ==Treatment== | ||
Revision as of 02:17, 28 November 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby
Overview
Definition
Statin induced myopathy is a spectrum of muscular problems caused by the intake of statin. Myopathy by definition is the abnormal function of the muscle. The spectrum of statin induced myopathy includes:
Myalgia
- Myalgia is defined as one or combination of muscle weakness, tenderness or pain.
- Patients usually complain of cramping feeling in the muscles.
- Creatine kinase may be normal or minimally elevated.
Asymptomatic increase in creatine kinase
Myositis
- Myositis is the inflammation of the muscle characterised by muscular complaints in the setting of elevated creatine kinase up to ten folds.
Rhabdomyositis
- Rhabdomyositis is the acute degeneration of the skeletal muscle.
- It is a potentially lethal condition due to its associated nephrotoxicity caused by myoglobinuria and myoglobinemia.
- Creatine kinase is elevated in rhabdomyosistis similarly to myositis.
- The complications of rhabdomyositis are acute tubular necrosis, hypocalcemia, hyperkalemia, metabolic acidosis, hyperuricemia, DIC and cardiomyopathy.[1]
Other Statin Induced Myopathies
- Elevated creatine kinase after statin withdrawal[2]
- Autoimmune myopathy requiring immunosuppressive therapy[3]
Prevalence
Risk Factors
Pathophysiology
Statin induced myopathies has a complex poorly understood multifactorial pathophysiology. It is postulated that statin causes myopathy through the following changes:
- Changes in cholesterol content and alteration of the membrane fluidity of skeletal muscle cells which disrupts their normal function
- Changes in skeletal muscle cells membrane electrical properties
- Changes in Na+/K+ pump density resulting in decreased production of ATP
- Changes in the excitation-contraction coupling
- Changes in the cell surface receptor transduction cascades
- Decreased synthesis of ubiquinone (Q10), a component of the mitochondrial electron transport chain, leading to decreased ATP production and decreased free radical scavenging
- Increased intracellular calcium causing apoptosis of the skeletal muscle cells
- Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in apoptosis of skeletal muscle cells[4]
Treatment
References
- ↑ Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.
- ↑ Thompson PD, Clarkson P, Karas RH (2003). "Statin-associated myopathy". JAMA. 289 (13): 1681–90. doi:10.1001/jama.289.13.1681. PMID 12672737.
- ↑ Radcliffe KA, Campbell WW (2008). "Statin myopathy". Curr Neurol Neurosci Rep. 8 (1): 66–72. PMID 18367041.
- ↑ Dirks AJ, Jones KM (2006). "Statin-induced apoptosis and skeletal myopathy". Am J Physiol Cell Physiol. 291 (6): C1208–12. doi:10.1152/ajpcell.00226.2006. PMID 16885396.