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Primun Non Nocere , Polypharmacy and Pharmacogenetics

2015; Future Medicine; Volume: 16; Issue: 17 Linguagem: Inglês

10.2217/pgs.15.137

1744-8042

María Isidoro‐García, Almudena Sánchez-Martín, Belén García‐Berrocal, Concepción Román‐Curto,

Pharmacological Effects and Toxicity Studies

PharmacogenomicsVol. 16, No. 17 Letter to the EditorFree AccessPrimun non nocere, polypharmacy and pharmacogeneticsMaría Isidoro-García, Almudena Sánchez-Martín, Belén García-Berrocal & Concepción Román-CurtoMaría Isidoro-García*Author for correspondence: E-mail Address: misidoro@usal.es Pharmacogenetics Unit, Department of Clinical Biochemistry, University Hospital of Salamanca, Salamanca, Spain Biomedical Institute of Salamanca IBSAL, Salamanca, Spain Department of Medicine, University of Salamanca, Salamanca, Spain, Almudena Sánchez-Martín Biomedical Institute of Salamanca IBSAL, Salamanca, Spain Department of Pharmacy, University Hospital of Salamanca, Salamanca, Spain, Belén García-Berrocal Pharmacogenetics Unit, Department of Clinical Biochemistry, University Hospital of Salamanca, Salamanca, Spain Biomedical Institute of Salamanca IBSAL, Salamanca, Spain & Concepción Román-Curto Biomedical Institute of Salamanca IBSAL, Salamanca, Spain Department of Dermatology, University Hospital of Salamanca, Salamanca, SpainPublished Online:10 Nov 2015https://doi.org/10.2217/pgs.15.137AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Figure 1. Patient and theoretical drug-drug interaction analysis, before and after the pharmacogenetic management.(A) Patient before pharmacogenetic management. (B) Patient after the treatment adjustment. (C) Theoretical drug–drug interaction analysis for P450 enzymes according to the superCYPplatform, before the treatment adjustment [1]. Enzyme names are shown in the first row (blue). Metabolic pathways from CYP1A1 to CYP3A7 are represented. All drugs prescribed during hospitalization before the adjustments are included in the same analysis. Colors show the degree of compromise. (D) Theoretical drug–drug interaction analysis after the treatment adjustment.ID: Inductor; IH: Inhibitor; pd: Per day; pw: Per week; S: Substrate.To the editorPrimun non nocere, first do no harm, is the oldest precept in medicine. This principle is especially important in polypharmacy, as increasing the number of drugs prescribed can increase the likelihood of adverse events. Personalized medicine offers new approaches to this old problem. Here, we show how the application of a personalized medicine approach helped avoid harm in the management of multiple medications.A 74-year-old woman with psoriasis was admitted to the cardiology department with congestive heart failure, atrial fibrillation and chronic renal failure. She had a previous history (8 years before) of adverse events with acitretin and cyclosporine. On admission, she was treated with acenocoumarol, bisoprolol, topical clobetasol, clorazepate, digoxin, diltiazem, enoxaparin, furosemide, hydrochlorothiazide, omeprazole and ramipril (Figure 1). Within a few days, she developed erythrodermic psoriasis. After treatment with oral prednisone and topical hydrocortisone, she presented uncontrolled euphoria and disorientation, for which she received alprazolam, which in turn resulted in severe drowsiness and stupor. Worsening erythema on the head, neck and upper chest was treated with methylprednisolone aceponate, which actually increased the severity of the lesions (Figure 1A). Shortly after methotrexate and folic acid were initiated, transaminase elevation and digitalis toxicity were observed.A personalized pharmacogenetics analysis of theoretical drug–drug interactions [1,2] showed significant compromise of the main steroid-metabolizing enzymes CYP3A4 and CYP3A53 [3] (Figure 1C), among others. We genotyped CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6 and MDR1. The patient was homozygous for CYP3A5*3 and heterozygous for 3435C>T MDR1. Treatment was readjusted (Figure 1D): omeprazole was replaced with sucralfate; hydrochlorothiazide, enoxaparin, prednisone and methylprednisolone aceponate were suspended; and topical fluocinolone acetonide (non-P450-metabolized steroid derivative) was introduced. Doses of bisoprolol, digoxin and methotrexate were readjusted. The patient improved remarkably with complete remission of cutaneous symptoms (Figure 1B) and control of cardiac, renal and hepatic problems.There is an increasingly clear understanding of the relationship between genetic variation and drug response [4]. Polypharmacy compromises metabolic pathways, especially in carriers of pharmacogenetic mutations, increasing the risk of adverse effects and consequently increasing costs. Our approach uses personalized drug–drug interaction analysis and pharmacogenotyping to rationalize drug choice and dosing. Although other genetic and nongenetic factors also influence drug response [5], there is an urgent need to translate pharmacogenetics to clinical practice [6]. Our approach has proven useful in recent years.Financial & competing interests disclosureThe authors have no relevant affiliations or financialinvolvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.The Immunoallergy Association of Salamanca provided funding (ASIAL/01/14) for writing assistance.References1 SuperCYP. A database on cytochrome P450 enzymes. http://bioinformatics.carite.de/supercyp/.Google Scholar2 Pharmgkb. The pharmacogenomics knowledge base. http://pharmgkb.org/.Google Scholar3 Kuehl P, Zhang J, Lin Y, Brockmoller J, Hustert E. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet. 27, 383–391 (2001).Crossref, Medline, CAS, Google Scholar4 Beitelshees AL, Veenstra DL. Evolving research and stakeholder perspectives on pharmacogenomics. JAMA 306, 1252–1253 (2011).Crossref, Medline, CAS, Google Scholar5 Wilkinson GR. Drug metabolism and variability among patients in drug response. N. Engl. J. Med. 352, 2211–2221 (2005).Crossref, Medline, CAS, Google Scholar6 Hamburg MA, Collins FS. The path to personalized medicine. N. Engl. J. Med. 363, 301–304 (2010).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByTen Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy11 January 2022 | Pharmaceutics, Vol. 14, No. 1Polypharmacy: a healthcare conundrum with a pharmacogenetic solution2 November 2019 | Critical Reviews in Clinical Laboratory Sciences, Vol. 57, No. 3Understanding the Medication List and Addressing Polypharmacy in Older Adults30 October 2019Physical Performance and Quality of Life in Older Adults: Is There Any Association between Them and Potential Drug Interactions in Polymedicated Octogenarians29 October 2019 | International Journal of Environmental Research and Public Health, Vol. 16, No. 21Farmacogenómica: la medicina personalizadaRevista del Laboratorio Clínico, Vol. 12, No. 3Pharmacogenetics and the treatment of asthmaMaría Isidoro-García, Almudena Sánchez-Martín, Asunción García-Sánchez, Catalina Sanz, Belén García-Berrocal & Ignacio Dávila4 August 2017 | Pharmacogenomics, Vol. 18, No. 13Pharmacogenetics to prevent maniac affective switching with treatment for bipolar disorder: CYP2D6Almudena Sánchez-Martín, Santiago Sánchez-Iglesias, Belén García-Berrocal, Carolina Lorenzo, Andrea Gaedigk & María Isidoro-García29 July 2016 | Pharmacogenomics, Vol. 17, No. 12Multiple drugs23 January 2016 | Reactions Weekly, Vol. 1585, No. 1 Vol. 16, No. 17 Follow us on social media for the latest updates Metrics History Published online 10 November 2015 Published in print November 2015 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financialinvolvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.The Immunoallergy Association of Salamanca provided funding (ASIAL/01/14) for writing assistance.PDF download