Statin induced myopathy: Difference between revisions

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{{CMG}}; {{AE}} [[User:Rim Halaby|Rim Halaby]]
{{CMG}}; {{AE}} [[User:Rim Halaby|Rim Halaby]]


==Overview==
{{Statin induced myopathy}}


==Definition==
==[[Statin induced myopathy overview|Overview]]==
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====
==[[Statin induced myopathy classification|Classification]]==
====Myositis====
* Myositis is the inflammation of the muscle characterised by muscular complaints in the setting of elevated creatine kinase up to ten folds.


====Rhabdomyositis====
==[[Statin induced myopathy pathophysiology|Pathophysiology]]==
* 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.<ref name="baker">Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.</ref>


====Other Statin Induced Myopathies====
==[[Statin induced myopathy epidemiology and demographics|Epidemiology & Demographics]]==
* Elevated creatine kinase after statin withdrawal<ref name="pmid12672737">{{cite journal| author=Thompson PD, Clarkson P, Karas RH| title=Statin-associated myopathy. | journal=JAMA | year= 2003 | volume= 289 | issue= 13 | pages= 1681-90 | pmid=12672737 | doi=10.1001/jama.289.13.1681 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12672737  }} </ref>
* Autoimmune myopathy requiring immunosuppressive therapy<ref name="pmid18367041">{{cite journal| author=Radcliffe KA, Campbell WW| title=Statin myopathy. | journal=Curr Neurol Neurosci Rep | year= 2008 | volume= 8 | issue= 1 | pages= 66-72 | pmid=18367041 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18367041  }} </ref>


==Prevalence==
==[[Statin induced myopathy epidemiology and demographics|Risk Factors]]==
The prevalence of statin induced myopathy, described as a spectrum of clinical conditions ranging from myalgia to myositis and rhabdomyolysis, is almost 10-15%<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837  }} </ref>


==Risk Factors==
==[[Statin induced myopathy screening|Screening]]==
* Age more than 80<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515  }} </ref>
* Genetics (single nucleotide polymorphism of the gene SLCO1B1)<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837  }} </ref>*High dose of statin<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837  }} </ref>
* Concurrent use of hepatic [[cytochrome P450 inhibitors]]
* Concurrent use of [[fibrates]]
* Cerivastatin use especially in combination with [[gemfibrosil]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9| pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079  }} </ref>* Major trauma<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079  }} </ref>
*Polypharmacy<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837  }} </ref>
* Small body size<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515  }} </ref>
* [[Surgery]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079  }} </ref>
* Systemic disease
**[[Liver]] disease
**[[Kidney]] disease
**[[Diabetes]]
**[[Hypothyroidism]]<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515  }} </ref>


==Pathophysiology==
==[[Statin induced myopathy differential diagnosis|Differentiating Statin induced myopathy from other Diseases]]==
[[Statin induced myopathy]] has a complex poorly understood multifactorial pathophysiology. It is postulated that [[statin induced myopathy]] is caused by [[apoptosis]] of the skeletal muscle cells because of disrupted intracellular calcium signaling and mitochondrial dysfunction due to depletion of mevalonate metabolism products, notably isoprenoids.<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>
 
The following changes are caused by [[statin]]:
* 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<ref name="baker">Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.</ref>
* Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in the [[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>
;Shown below is an image depicting the mechanism of statin induced myopathy through increasing the intracellular calcium concentration.
[[Image:Statin_induced_myopathy.png|center|Statin induced myopathy through increased intracellular calcium]]


==Diagnosis==
[[Statin induced myopathy history and symptoms|History & Symptoms]] | [[Statin induced myopathy laboratory tests|Lab Tests]]
==Treatment==
==Treatment==
[[Statin induced myopathy medical therapy|Medical Therapy]]


==References==
==References==
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[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Drugs]]
[[Category:Drugs]]
[[Category:Disease]]
[[Category:Up-To-Date cardiology]]
[[Category:Up-To-Date]]

Latest revision as of 16:18, 30 November 2012