Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Curr Pain Headache Rep ; 25(3): 16, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33630181

RESUMO

PURPOSE OF REVIEW: The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients. RECENT FINDINGS: Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.


Assuntos
Maconha Medicinal/administração & dosagem , Maconha Medicinal/normas , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/normas , Animais , Cannabis , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos
2.
J Clin Pharmacol ; 58(9): 1150-1156, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29775202

RESUMO

Aspirin remains the standard for stroke prophylaxis. However, as many as 20%-25% of patients may fail to show a full response to aspirin. Ideally, patients who are resistant to aspirin could be identified, then receive an increased dose of aspirin or be changed to an alternative therapy more efficiently. We have developed an in vitro assay that may make this possible. Healthy volunteers (n = 13) between 18 and 50 years of age were tested for both ex vivo and in vivo responses to aspirin. Dimethyl sulfoxide (DMSO) was selected as the solvent for aspirin in the assay. DMSO can exhibit antiplatelet effects, necessitating the use of a concentration low enough to avoid such antiplatelet effects. Blood samples were tested against DMSO 0%, 0.05%, 0.5%, and 1% w/v with and without aspirin 0, 50, and 100 µM. The effects of both agents were measured via whole-blood aggregometry. A 3-dimensional response model described the data well, quantifying the combinatorial effect of DMSO and aspirin on platelet aggregation. Across all participants, baseline aggregation stimulated with collagen 1 µM or arachidonate 0.5 mM was approximately 18 and 13 Ω, respectively. The response model showed that 0.05% DMSO with 100 µM aspirin would provide platelet aggregation of 3.4 Ω. A DMSO concentration of 0.05% in the absence of aspirin would result in no discernable effects on platelet aggregation (17.7 Ω). Overall, the use of 100 µM of aspirin in 0.05% DMSO provides a robust method to test for ex vivo inhibition of platelet aggregation.


Assuntos
Aspirina/administração & dosagem , Aspirina/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Adulto , Plaquetas/efeitos dos fármacos , Feminino , Humanos , Masculino , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária , Adulto Jovem
3.
J Clin Pharmacol ; 58(9): 1157-1163, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29775206

RESUMO

This study tested the capability of an assay to predict aspirin response and reduce ischemic events, and healthcare costs, and delays to optimal treatment. Patients who needed aspirin in the course of normal medical care were included. Patients were excluded if they had disorders affecting platelet function, alcohol use within 24 hours of a test, or NSAID use. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to 325 mg daily occurred based on the results of whole blood impedance aggregation testing to the agonists, collagen (1ug/mL, 5 ug/mL) and arachidonate (0.5 mM) after 10-14 days of treatment. The experimental in vitro test was conducted in triplicate by performing aggregometry on samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Of the 36 patients who were compliant 16 were found to be resistant to the antiplatelet effects of 81 mg daily aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose while six actually did. Predicted response to increased doses of aspirin was in good agreement with actual response. Sensitivity of the assay was 83% and specificity was 80%. Results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin necessitating an alternative antiplatelet regimen. Larger, multisite studies are inevitably needed.


Assuntos
Aspirina/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Adulto Jovem
4.
J Stroke Cerebrovasc Dis ; 27(6): 1582-1589, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29449127

RESUMO

BACKGROUND AND GOAL: Cytochrome P450 (CYP) enzymes are responsible for the conversion of clopidogrel into its active metabolite and the metabolism of proton pump inhibitors (PPIs), which may also inhibit CYP enzymes. A current Food and Drug Administration advisory suggests avoiding esomeprazole and omeprazole while taking clopidogrel because of concerns that PPIs may compromise clopidogrel's antiplatelet effects. The objective of the present study was to examine the robustness of this interaction using a well-controlled study design in a population of participants free of confounders. MATERIALS AND METHODS: Twenty-eight healthy male participants, with a mean age 24.2 ± 3.2, were randomized to an incomplete crossover design schedule. Participants underwent platelet aggregation testing after clopidogrel alone, while on clopidogrel in combination with 1 of 3 PPIs (40 mg of pantoprazole, 20 mg of omeprazole, 20 mg of rabeprazole, 40 mg of esomeprazole, 30 mg of lansoprazole, or 30 mg of dexlansoprazole), and during 1 week of clopidogrel-only washout periods. FINDINGS: The median platelet aggregation to adenosine diphosphate during a drug-free baseline was 10Ω (2.5 interquartile range) of impedance and decreased to 0Ω on clopidogrel alone. Aggregation did not significantly change with concomitant use of PPIs and clopidogrel. CONCLUSION: These data do not demonstrate a significant interaction between common individual PPIs and clopidogrel in healthy volunteers who respond to clopidogrel alone. This adds data to a growing body of evidence indicating that the addition of a PPI may have a weak effect on clopidogrel's antiplatelet properties, and may only be relevant in specific clinical circumstances.


Assuntos
Inibidores da Agregação Plaquetária/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Estudos Cross-Over , Interações Medicamentosas , Voluntários Saudáveis , Humanos , Masculino , New York , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Adulto Jovem
5.
Forensic Sci Med Pathol ; 9(1): 73-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22915321

RESUMO

The antiepileptic, carbamazepine, is extensively metabolized via hepatic enzymes in the cytochrome P450 family and is therefore subject to a myriad of drug interactions. Concomitant administration with phenytoin enhances carbamazepine metabolism thus reducing serum concentrations and necessitating the use of a higher maintenance dose. Removal of phenytoin therapy in the absence of anticipatory dose adjustments and careful monitoring of serum concentrations may result in catastrophic outcomes. Reported herein are the events leading to the death of a 23-month old child who suffered a fatal carbamazepine overdose following withdrawal of phenytoin therapy.


Assuntos
Anticonvulsivantes , Carbamazepina , Simulação por Computador , Modelos Biológicos , Fenitoína , Convulsões/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/intoxicação , Autopsia , Biotransformação , Carbamazepina/administração & dosagem , Carbamazepina/sangue , Carbamazepina/farmacocinética , Carbamazepina/intoxicação , Esquema de Medicação , Interações Medicamentosas , Monitoramento de Medicamentos , Overdose de Drogas/diagnóstico , Overdose de Drogas/etiologia , Overdose de Drogas/patologia , Quimioterapia Combinada , Evolução Fatal , Toxicologia Forense , Humanos , Lactente , Masculino , Método de Monte Carlo , Fenitoína/administração & dosagem , Fenitoína/sangue , Fenitoína/farmacocinética , Intoxicação/diagnóstico , Intoxicação/etiologia , Intoxicação/patologia
6.
Clin Pharmacokinet ; 47(2): 129-37, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18193919

RESUMO

OBJECTIVE: The objective of this study was to develop a mechanism-based pharmacodynamic model that characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. METHODS: Ten healthy volunteers were enrolled in a single-blinded, randomized, three-way crossover study. Treatments consisted of single doses of oral aspirin (325 mg) and ibuprofen (400 mg) and concomitant administration of aspirin (325 mg) and ibuprofen (400 mg). Ex vivo whole blood platelet aggregation induced by collagen (1 microg/mL) or arachidonic acid (0.5 mmol/L) was measured by impedance aggregometry. Model development and population parameter estimation were performed using nonlinear mixed-effects modelling implemented in NONMEM. RESULTS: Relatively complete inhibition of platelet aggregation was achieved following aspirin treatment (approximately 77% inhibition within 2 hours), and return to baseline values occurred within 72-96 hours after dosing. In contrast, treatment with ibuprofen alone or in combination with aspirin produced transient inhibition of platelet aggregation, with complete recovery observed in 6-8 hours. The final pharmacodynamic model was based on the turnover of cyclo-oxygenase-1 (COX-1) enzyme, and incorporated irreversible inhibition by aspirin and reversible binding and antiplatelet effects of ibuprofen. The temporal response profiles from all three study arms were well described by the final model, and the parameters were estimated with good precision. The apparent turnover rate constant for COX-1 (kout) and the irreversible inhibition rate constant for aspirin (K) were estimated to be 0.0209 h(-1) and 0.152 (mg/L)(-1).h(-1), with interindividual variability of 30.6% and 26.2%, respectively. Simulations were used to evaluate the influence of clinically relevant ibuprofen regimens on the antiplatelet effect of aspirin, confirming clinical reports that the antiplatelet effect of aspirin would be blocked when multiple daily doses of ibuprofen are given, even if taken after aspirin administration. CONCLUSIONS: A mechanism-based pharmacodynamic model has been developed that characterizes the antiplatelet effects of aspirin and ibuprofen, alone and concomitantly, and predicts a significant inhibition of aspirin antiplatelet effects in the presence of a typical ibuprofen dosing regimen.


Assuntos
Aspirina/farmacologia , Ibuprofeno/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Administração Oral , Adulto , Ácido Araquidônico/farmacologia , Aspirina/sangue , Aspirina/farmacocinética , Colágeno/farmacologia , Estudos Cross-Over , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacocinética , Inibidores de Ciclo-Oxigenase/farmacologia , Meia-Vida , Humanos , Ibuprofeno/sangue , Ibuprofeno/farmacocinética , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Método Simples-Cego , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...