RESUMO
OBJECTIVE: To describe the legal use of opioids in adult patients before and after high-energy trauma. DESIGN: The study was a retrospective database study. SETTING: Clinical care outside hospitals. PATIENTS: All patients who suffered high-energy trauma and were brought to Odense University Hospital (OUH), Denmark, in 2007 and 2008 were retrieved from the trauma database. These patients were linked with data on opioid use from the regional prescription database. In all, 938 patients were included. MAIN OUTCOME MEASURE: Redemption of opioid prescription during the 6 months prior to a multitrauma or redemption of two or more prescriptions for opioids 6 months or later after a multitrauma. RESULTS: Of the 938 patients brought to OUH with severe trauma within the study period, 61 patients died (7 percent) and six of these had redeemed prescriptions for opioids within 6 months prior to the trauma (10 percent) compared to 65 patients of the 877 survivors (7 percent) (odds ratio 1.4, nonsignificant). In all, 62 patients (7 percent) redeemed opioid prescriptions later than 6 months after their trauma and in a multivariable analysis, severe injury itself and severe injuries of the lower extremities were associated with redemption of opioid prescription after the trauma. CONCLUSIONS: The authors did not find any correlation between death by trauma and redemption of opioid prescriptions within the 6 months before the trauma. More severe traumas and especially severe traumas to the lower extremities were associated with redemption of opioid prescriptions after multitrauma.
Assuntos
Analgésicos Opioides , Dor Crônica/tratamento farmacológico , Ferimentos e Lesões , Acidentes de Trânsito/estatística & dados numéricos , Adulto , Analgésicos Opioides/classificação , Analgésicos Opioides/uso terapêutico , Dor Crônica/etiologia , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Medicamentos sob Prescrição/classificação , Medicamentos sob Prescrição/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Índices de Gravidade do Trauma , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/mortalidadeRESUMO
PURPOSE: The aim of the study was to search for an association between the single-nucleotide polymorphisms A118G in OPRM1 and C3435T and G2677T/A in ABCB1 and the analgesic effect of intravenous oxycodone in postoperative pain. METHODS: There were 268 patients with postoperative pain after, primarily, thyroidectomy. At given times during the first 24 hours postoperatively, their pain was rated at rest and during activity according to a numeric rating scale (0 = no pain, 10 = worst possible pain) and calculated as pain time area under the curve0-24 hours . A negative answer in a final questionnaire and/or the use of rescue medication categorized a patient as a nonresponder. RESULTS: For OPRM1, there was no difference found between the wild type and the variant allele in the percentages of nonresponders (118AA = 16.4% vs 118AG/118GG = 17.0%, P = 1.0) or in the pain ratings. For ABCB1, no difference was found between the wild type and the variant alleles for single-nucleotide polymorphism tested as percentages of nonresponders (3435CC = 17.5% vs 3435CT/3435TT = 15.8%, P = .85; 2677GG = 17.8% vs 2677GT/2677TT = 15.8%, P = .74) or pain ratings. CONCLUSION: No association was found between the tested single-nucleotide polymorphisms in OPRM1 and ABCB1 and changes in the analgesic effect of oxycodone.
Assuntos
Analgésicos Opioides/uso terapêutico , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Receptores Opioides mu/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxicodona/efeitos adversos , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Analgésicos Opioides , Oxicodona , Dor/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Receptores Opioides mu/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Estudos Cross-Over , DNA/genética , Método Duplo-Cego , Feminino , Genótipo , Humanos , Masculino , Oxicodona/efeitos adversos , Oxicodona/farmacocinética , Oxicodona/uso terapêutico , Dor/etiologia , Dor/genética , Medição da Dor , Limiar da Dor , Adulto JovemRESUMO
Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.