Sympathetic nervous system: Difference between revisions

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{{main|G-protein-coupled receptor kinase}}
{{main|G-protein-coupled receptor kinase}}
Polymorphisms of [[G-protein-coupled receptor kinase]] (GRK5) may underlie racial differences in the affect of treatment of [[heart failure]].<ref>{{OMIM|600870}}</ref> There is conflicting evidence whether [[beta-blocker]]s [[medication]]s are as effective in African-American patients as in Anglo patients.<ref name="pmid12742294">{{cite journal |author=Shekelle PG, Rich MW, Morton SC, ''et al'' |title=Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials |journal=J. Am. Coll. Cardiol. |volume=41 |issue=9 |pages=1529–38 |year=2003 |pmid=12742294 |doi=}}</ref>  GRK5 may confer a natural "genetic beta-blockade".<ref name="pmid18425130">{{cite journal |author=Liggett SB, Cresci S, Kelly RJ, ''et al.'' |title=A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure |journal=Nat. Med. |volume=14 |issue=5 |pages=510–7 |year=2008 |month=May |pmid=18425130 |pmc=2596476 |doi=10.1038/nm1750 |url=http://dx.doi.org/10.1038/nm1750 |issn=}}</ref>
Polymorphisms of [[G-protein-coupled receptor kinase]] (GRK5) may underlie racial differences in the affect of treatment of [[heart failure]].<ref>{{OMIM|600870}}</ref> There is conflicting evidence whether [[beta-blocker]]s [[medication]]s are as effective in African-American patients as in Anglo patients.<ref name="pmid12742294">{{cite journal |author=Shekelle PG, Rich MW, Morton SC, ''et al'' |title=Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials |journal=J. Am. Coll. Cardiol. |volume=41 |issue=9 |pages=1529–38 |year=2003 |pmid=12742294 |doi=}}</ref>  GRK5 may confer a natural "genetic beta-blockade".<ref name="pmid18425130">{{cite journal |author=Liggett SB, Cresci S, Kelly RJ, ''et al.'' |title=A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure |journal=Nat. Med. |volume=14 |issue=5 |pages=510–7 |year=2008 |month=May |pmid=18425130 |pmc=2596476 |doi=10.1038/nm1750 |url=http://dx.doi.org/10.1038/nm1750 |issn=}}</ref>
G protein–coupled [[cell surface receptor]] kinase 2 (GRK2) [[genetic polymorphism]]s may also affect the response to [[adrenergic beta-antagonist]]s.<ref>{{OMIM|109635}}</ref>


[[Genetic polymorphism]]s of the protein kinase associated with β-2 [[adrenergic receptor]]s may affect the response in [[asthma]] to [[adrenergic beta-agonist]]s by patients of African descent.<ref name="pmid18622265">{{cite journal |author=Wang WC, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB |title=A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors |journal=Pharmacogenet. Genomics |volume=18 |issue=8 |pages=729–32 |year=2008 |month=August |pmid=18622265 |doi=10.1097/FPC.0b013e32830967e9 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1744-6872&volume=18&issue=8&spage=729 |issn=}}</ref>
[[Genetic polymorphism]]s of the protein kinase associated with β-2 [[adrenergic receptor]]s may affect the response in [[asthma]] to [[adrenergic beta-agonist]]s by patients of African descent.<ref name="pmid18622265">{{cite journal |author=Wang WC, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB |title=A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors |journal=Pharmacogenet. Genomics |volume=18 |issue=8 |pages=729–32 |year=2008 |month=August |pmid=18622265 |doi=10.1097/FPC.0b013e32830967e9 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1744-6872&volume=18&issue=8&spage=729 |issn=}}</ref>
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===Cytochrome P-450===
===Cytochrome P-450===
{{main|cytochrome P-450}}
{{main|cytochrome P-450}}
Polymorphisms of the [[cytochrome P-450]], such as CYp2D6<ref>{{OMIM|124030}}</ref>, are eligible for more drug interactions<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref><ref name="pmid12571261">{{cite journal |author=Weinshilboum R |title=Inheritance and drug response |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=529–37 |year=2003 |month=February |pmid=12571261 |doi=10.1056/NEJMra020021 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=12571261&promo=ONFLNS19 |issn=}}</ref> and more inherited variation in metabolism<ref name="pmid16220080">{{cite journal |author=Nozawa T, Taguchi M, Tahara K, ''et al'' |title=Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol |journal=J. Cardiovasc. Pharmacol. |volume=46 |issue=5 |pages=713–20 |year=2005 |month=November |pmid=16220080 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0160-2446&volume=46&issue=5&spage=713 |issn=}}</ref>.<ref>{{OMIM|104250}}</ref>
Polymorphisms of the [[cytochrome P-450]], such as CYp2D6<ref>{{OMIM|124030}}</ref>, are eligible for more drug interactions<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing drug-related side effects and adverse reactionss: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref><ref name="pmid12571261">{{cite journal |author=Weinshilboum R |title=Inheritance and drug response |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=529–37 |year=2003 |month=February |pmid=12571261 |doi=10.1056/NEJMra020021 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=12571261&promo=ONFLNS19 |issn=}}</ref> and more inherited variation in metabolism<ref name="pmid16220080">{{cite journal |author=Nozawa T, Taguchi M, Tahara K, ''et al'' |title=Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol |journal=J. Cardiovasc. Pharmacol. |volume=46 |issue=5 |pages=713–20 |year=2005 |month=November |pmid=16220080 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0160-2446&volume=46&issue=5&spage=713 |issn=}}</ref>.<ref>{{OMIM|104250}}</ref>


==References==
==References==
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The sympathetic nervous system is part of the autonomic nervous system has the following functions:

The autonomic nervous system
Blue = parasympathetic
Red = sympathetic
  • Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction.
  • Blood flow to skeletal muscles, the lung is not only maintained, but enhanced (by as much as 1200%, in the case of skeletal muscles).
  • Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange.
  • Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for the enhanced blood flow to skeletal muscles.
  • Dilates pupils and relaxes the lens, allowing more light to enter the eye.

Molecular biology

The pharmacogenetics of adrenergic beta-antagonist medications have been reviewed.[1]

Adrenergic receptor

For more information, see: adrenergic receptor.

Polymorphisms of the adrenergic receptor may affect clinical outcomes.[2]

Genetic polymorphisms of beta-1 (ADRB1) may affect the response to adrenergic beta-antagonist treatment of heart failure.[3]

Genetic polymorphisms of alpha-2C (ADRA2C) may affect the response to adrenergic beta-antagonist treatment of heart failure.[4]

G-protein-coupled receptor kinase

For more information, see: G-protein-coupled receptor kinase.

Polymorphisms of G-protein-coupled receptor kinase (GRK5) may underlie racial differences in the affect of treatment of heart failure.[5] There is conflicting evidence whether beta-blockers medications are as effective in African-American patients as in Anglo patients.[6] GRK5 may confer a natural "genetic beta-blockade".[7]

G protein–coupled cell surface receptor kinase 2 (GRK2) genetic polymorphisms may also affect the response to adrenergic beta-antagonists.[8]

Genetic polymorphisms of the protein kinase associated with β-2 adrenergic receptors may affect the response in asthma to adrenergic beta-agonists by patients of African descent.[9]

Cytochrome P-450

For more information, see: cytochrome P-450.

Polymorphisms of the cytochrome P-450, such as CYp2D6[10], are eligible for more drug interactions[11][12] and more inherited variation in metabolism[13].[14]

References

  1. ↑ Shin J, Johnson JA (June 2007). "Pharmacogenetics of beta-blockers". Pharmacotherapy 27 (6): 874–87. DOI:10.1592/phco.27.6.874. PMID 17542770. Research Blogging.
  2. ↑ Zaugg M, Bestmann L, Wacker J, et al (July 2007). "Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up". Anesthesiology 107 (1): 33–44. DOI:10.1097/01.anes.0000267530.62344.a4. PMID 17585213. Research Blogging.
  3. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 109630. World Wide Web URL: http://omim.org/.
  4. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 104250. World Wide Web URL: http://omim.org/.
  5. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 600870. World Wide Web URL: http://omim.org/.
  6. ↑ Shekelle PG, Rich MW, Morton SC, et al (2003). "Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials". J. Am. Coll. Cardiol. 41 (9): 1529–38. PMID 12742294. [e]
  7. ↑ Liggett SB, Cresci S, Kelly RJ, et al. (May 2008). "A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure". Nat. Med. 14 (5): 510–7. DOI:10.1038/nm1750. PMID 18425130. PMC 2596476. Research Blogging.
  8. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 109635. World Wide Web URL: http://omim.org/.
  9. ↑ Wang WC, Mihlbachler KA, Bleecker ER, Weiss ST, Liggett SB (August 2008). "A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors". Pharmacogenet. Genomics 18 (8): 729–32. DOI:10.1097/FPC.0b013e32830967e9. PMID 18622265. Research Blogging.
  10. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124030. World Wide Web URL: http://omim.org/.
  11. ↑ Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (November 2001). "Potential role of pharmacogenomics in reducing drug-related side effects and adverse reactionss: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893. [e]
  12. ↑ Weinshilboum R (February 2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. DOI:10.1056/NEJMra020021. PMID 12571261. Research Blogging.
  13. ↑ Nozawa T, Taguchi M, Tahara K, et al (November 2005). "Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol". J. Cardiovasc. Pharmacol. 46 (5): 713–20. PMID 16220080. [e]
  14. ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 104250. World Wide Web URL: http://omim.org/.
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