Pharmacogenomics: Difference between revisions
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==Drug toxicity== | ==Drug toxicity== | ||
{{main|Drug toxicity}} | {{main|Drug toxicity}} | ||
Among drugs frequently cited in adverse | Among drugs frequently cited in drug-related side effects and adverse reactionss, 60% are metabolized by enzymes with genetic variations in metabolism. 7% to 22% of randomly selected have such variation.<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 |pmid=11710893 |doi=}}</ref> | ||
Examples include: | Examples include: | ||
* The SLCO1B1 Variants and statin-induced myopathy<ref name="pmid18650507"> The SEARCH Collaborative Group. (2008) [http://content.nejm.org/cgi/content/full/NEJMoa0801936 SLCO1B1 Variants and Statin-Induced Myopathy]. New Eng J Med. PMID 18650507</ref> | * The SLCO1B1 Variants and statin-induced myopathy<ref name="pmid18650507"> The SEARCH Collaborative Group. (2008) [http://content.nejm.org/cgi/content/full/NEJMoa0801936 SLCO1B1 Variants and Statin-Induced Myopathy]. New Eng J Med. PMID 18650507</ref> | ||
* [[Toxic epidermal necrolysis]] (TEN) and [[Stevens-Johnson syndrome]] (SJS) patients with [[HLA]]-B*1502 allele who take [[carbamazepine]]<ref> | * [[Toxic epidermal necrolysis]] (TEN) and [[Stevens-Johnson syndrome]] (SJS) patients with [[HLA]]-B*1502 allele who take [[carbamazepine]]<ref name="urlTable of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers">{{cite web |url=http://www.fda.gov/cder/genomics/genomic_biomarkers_table.htm |title=Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-12}}</ref>. | ||
===Genotyping=== | ===Genotyping=== | ||
Examples are emerging where genotyping may improve drug dosing, although costs are a barrier.<ref name="urlTable of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers">{{cite web |url=http://www.fda.gov/cder/genomics/genomic_biomarkers_table.htm |title=Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-12}}</ref><ref>Lavine G. Jan 15, 2009. [http://www.ajhp.org/cgi/content/full/66/2/114 HHS panel examines effects of patents, licenses on genetic testing]. Am J Health Syst Pharm {{doi|10.2146/news090008}}</ref> Other issues in evaluating the role of genotyping have been discussed.<ref name="pmid18587383">{{cite journal |author=Weiss ST, McLeod HL, Flockhart DA, ''et al'' |title=Creating and evaluating genetic tests predictive of drug response |journal=Nat Rev Drug Discov |volume=7 |issue=7 |pages=568–74 |year=2008 |month=July |pmid=18587383 |doi=10.1038/nrd2520 |url=http://dx.doi.org/10.1038/nrd2520 |issn=}}</ref> | |||
[[Mass screening|Screening]] for [[HLA Antigens|HLA]]-B*5701 may reduce the incidence of [[hypersensitivity]] reactions to [[abacavir]] according to a [[randomized controlled trial]].<ref name="pmid18256392">{{cite journal |author=Mallal S, Phillips E, Carosi G, ''et al'' |title=HLA-B*5701 screening for hypersensitivity to abacavir |journal=N. Engl. J. Med. |volume=358 |issue=6 |pages=568–79 |year=2008 |month=February |pmid=18256392 |doi=10.1056/NEJMoa0706135 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18256392&promo=ONFLNS19 |issn=}}</ref> Six percent of the patients in this study had [[HLA Antigens|HLA]]-B*5701. | [[Mass screening|Screening]] for [[HLA Antigens|HLA]]-B*5701 may reduce the incidence of [[hypersensitivity]] reactions to [[abacavir]] according to a [[randomized controlled trial]].<ref name="pmid18256392">{{cite journal |author=Mallal S, Phillips E, Carosi G, ''et al'' |title=HLA-B*5701 screening for hypersensitivity to abacavir |journal=N. Engl. J. Med. |volume=358 |issue=6 |pages=568–79 |year=2008 |month=February |pmid=18256392 |doi=10.1056/NEJMoa0706135 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18256392&promo=ONFLNS19 |issn=}}</ref> Six percent of the patients in this study had [[HLA Antigens|HLA]]-B*5701. | ||
[[Mass screening|Screening]] for [[Cytochrome P-450]] 2C9 polymorphisms may improve [[warfarin]] dosing cmopared to the Ageno algorithm<ref name="pmid17851566">{{cite journal |author=Caraco Y, Blotnick S, Muszkat M |title=CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study |journal=Clin. Pharmacol. Ther. |volume=83 |issue=3 |pages=460–70 |year=2008 |month=March |pmid=17851566 |doi=10.1038/sj.clpt.6100316 |url=http://www.nature.com/clpt/journal/v83/n3/full/6100316a.html |issn=}}</ref> or may not improve [[warfarin]] dosing compared to the Kovacs 10 mg algorithm<ref name="pmid17989110">{{cite journal |author=Anderson JL, Horne BD, Stevens SM, ''et al'' |title=Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation |journal=Circulation |volume=116 |issue=22 |pages=2563–70 |year=2007 |month=November |pmid=17989110 |doi=10.1161/CIRCULATIONAHA.107.737312 |url=http://circ.ahajournals.org/cgi/content/full/116/22/2563 |issn=}}</ref>. | [[Mass screening|Screening]] for [[Cytochrome P-450]] 2C9 polymorphisms may improve [[warfarin]] dosing cmopared to the Ageno algorithm<ref name="pmid17851566">{{cite journal |author=Caraco Y, Blotnick S, Muszkat M |title=CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study |journal=Clin. Pharmacol. Ther. |volume=83 |issue=3 |pages=460–70 |year=2008 |month=March |pmid=17851566 |doi=10.1038/sj.clpt.6100316 |url=http://www.nature.com/clpt/journal/v83/n3/full/6100316a.html |issn=}}</ref> or may not improve [[warfarin]] dosing compared to the Kovacs 10 mg algorithm<ref name="pmid17989110">{{cite journal |author=Anderson JL, Horne BD, Stevens SM, ''et al'' |title=Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation |journal=Circulation |volume=116 |issue=22 |pages=2563–70 |year=2007 |month=November |pmid=17989110 |doi=10.1161/CIRCULATIONAHA.107.737312 |url=http://circ.ahajournals.org/cgi/content/full/116/22/2563 |issn=}}</ref>. However, even in the latter study a 2.4% absolute reduction in percent out-of-range [[International Normalized Ratio]]s, although statistically insignificant, occurred. | ||
==Drug efficacy== | ==Drug efficacy== | ||
| Line 20: | Line 22: | ||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 17:34, 10 February 2024
Pharmacogenomics, or pharmacogenetics, is the "branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (biotransformation)."[1]
Drug toxicity
Among drugs frequently cited in drug-related side effects and adverse reactionss, 60% are metabolized by enzymes with genetic variations in metabolism. 7% to 22% of randomly selected have such variation.[2]
Examples include:
- The SLCO1B1 Variants and statin-induced myopathy[3]
- Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) patients with HLA-B*1502 allele who take carbamazepine[4].
Genotyping
Examples are emerging where genotyping may improve drug dosing, although costs are a barrier.[4][5] Other issues in evaluating the role of genotyping have been discussed.[6]
Screening for HLA-B*5701 may reduce the incidence of hypersensitivity reactions to abacavir according to a randomized controlled trial.[7] Six percent of the patients in this study had HLA-B*5701.
Screening for Cytochrome P-450 2C9 polymorphisms may improve warfarin dosing cmopared to the Ageno algorithm[8] or may not improve warfarin dosing compared to the Kovacs 10 mg algorithm[9]. However, even in the latter study a 2.4% absolute reduction in percent out-of-range International Normalized Ratios, although statistically insignificant, occurred.
Drug efficacy
Heart failure and hypertension may be an examples were there are racial variations in responses to drugs. Presumably these variations are due to pharmacogenomics.
References
- ↑ Anonymous. Pharmacogenetics. National Library of Medicine. Retrieved on 2008-01-22.
- ↑ Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (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]
- ↑ The SEARCH Collaborative Group. (2008) SLCO1B1 Variants and Statin-Induced Myopathy. New Eng J Med. PMID 18650507
- ↑ 4.0 4.1 Anonymous. Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels, Drug Interactions: Table of Substrates, Inhibitors and Inducers. Food and Drug Administration. Retrieved on 2009-01-12.
- ↑ Lavine G. Jan 15, 2009. HHS panel examines effects of patents, licenses on genetic testing. Am J Health Syst Pharm DOI:10.2146/news090008
- ↑ Weiss ST, McLeod HL, Flockhart DA, et al (July 2008). "Creating and evaluating genetic tests predictive of drug response". Nat Rev Drug Discov 7 (7): 568–74. DOI:10.1038/nrd2520. PMID 18587383. Research Blogging.
- ↑ Mallal S, Phillips E, Carosi G, et al (February 2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N. Engl. J. Med. 358 (6): 568–79. DOI:10.1056/NEJMoa0706135. PMID 18256392. Research Blogging.
- ↑ Caraco Y, Blotnick S, Muszkat M (March 2008). "CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study". Clin. Pharmacol. Ther. 83 (3): 460–70. DOI:10.1038/sj.clpt.6100316. PMID 17851566. Research Blogging.
- ↑ Anderson JL, Horne BD, Stevens SM, et al (November 2007). "Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation". Circulation 116 (22): 2563–70. DOI:10.1161/CIRCULATIONAHA.107.737312. PMID 17989110. Research Blogging.