RESUMO
PURPOSE: The transition from active cancer treatment to palliative care often results in a shift in drug risk-benefit assessment which requires the deprescribing of various medications. Deprescribing in palliative cancer patients can benefit patients by reducing their pill burden, decrease potential side effects, and potentially decrease healthcare costs. In addition, a change in patients' goals of care (GOC) necessitates the alteration of drug therapy which includes both deprescribing and the addition of medications intended to improve quality of life. Depending on a patient's GOC, a medication can be considered as inappropriate. OBJECTIVES: Primary: Comparison between potentially inappropriate medications (PIMs) prior to the palliative care consult (PCC) versus after the PCC. Secondary: Association between PIMs and GOC. METHODS: The study was a 1-year retrospective database review. The study included cancer patients seen by the PCC team at the University of Alberta Hospital. The OncPal guidelines were used to identify and determine the number of PIMs prior to the PCC and after the PCC. RESULTS: The reduction in PIMs prior to PCC versus after the PCC was statistically significant (p value < 0.001), demonstrating the PCC has a positive significant impact on deprescribing PIMs. For our secondary outcome, an overall decrease in PIMs was observed with the changes of GOC. The strength of the correlations was low (r < 0.1), and the p value was 0.056. CONCLUSION: This study shows the positive impact a PCC has on deprescribing and reveals the importance of using guidelines for deprescribing in palliative cancer patients.
Assuntos
Desprescrições , Prescrição Inadequada/tendências , Cuidados Paliativos/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Active rheumatoid arthritis (RA), obesity, and old age are associated with reduced responsiveness to the calcium channel antagonist verapamil despite increased drug concentrations. The diminishing effect appears to be associated with the severity of inflammation. We examined pharmacodynamics and pharmacokinetics of verapamil in patients with controlled RA. Volunteers included RA patients in remission: 12 on infliximab, 8 on other antirheumatic therapy, and 12 healthy subjects. Verapamil plasma concentrations and selected inflammatory mediators as well as blood pressure and electrocardiographic parameters were recorded after a single 80-mg dose of verapamil. Inflammatory mediators were all below what is reported for active RA, confirming that RA was controlled. The tumor necrosis factor-alpha concentration, however, was significantly higher in the infliximab group compared with other groups and the literature value for active RA. No significant difference was observed between groups in terms of percentage prolongation of PR interval despite a trend toward a lower response in the RA groups, the mean plasma concentrations, and the total and unbound area under the curve of verapamil. However, the slope of the S-verapamil concentration-effect curve was steeper for controls compared with the RA patients. Remission from active disease appears to restore plasma protein levels and hepatic drug metabolism activity in patients with RA, resulting in relatively normal verapamil pharmacokinetics.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/metabolismo , Bloqueadores dos Canais de Cálcio/farmacocinética , Verapamil/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Área Sob a Curva , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Disponibilidade Biológica , Bloqueadores dos Canais de Cálcio/sangue , Bloqueadores dos Canais de Cálcio/farmacologia , Feminino , Humanos , Infliximab , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Nitritos/sangue , Fator de Necrose Tumoral alfa/sangue , Verapamil/sangue , Verapamil/farmacologiaRESUMO
The objective of this study was to evaluate the suitability of the early phase of adjuvant arthritis (pre-AA) as a model of inflammation for pharmacokinetic studies. Pre-AA is associated with little or no pain and discomfort as compared with fully developed adjuvant arthritis. Pre-AA was induced in male Sprague-Dawley rats with a tail base injection of Mycobacterium butyricum. Animals were monitored for symptoms of arthritis and levels of the proinflammatory mediators, serum nitrite, C-reactive protein (CRP), and tumor necrosis factor alpha (TNFalpha). On day 6, rats were administered single i.v. (2 mg/kg) or oral (20 mg/kg) doses of racemic verapamil, and S- and R-verapamil concentrations were determined by high-performance liquid chromatography. Hepatic cytochrome P450 (P450) content and verapamil protein binding were also measured. All experiments were carried out in both pre-AA and control rats. Serum nitrite, CRP, and TNFalpha levels were significantly elevated in pre-AA rats while signs of pain and arthritis were absent. Pre-AA also significantly elevated plasma concentrations of S- and R-verapamil after both i.v. and oral doses, due, likely, to decreased drug clearance. This was accompanied by a significant reduction in hepatic cytochrome P450, CYP3A, and CYP1A content as well as significantly reduced verapamil free fraction in pre-AA. The early phase of AA is marked by increased proinflammatory mediators and reduced verapamil clearance, as well as decreased hepatic P450 enzymes. Hence, pre-AA is a suitable model of inflammation for pharmacokinetic studies that avoids unnecessary exposure of animals to the pain and distress of fully developed adjuvant arthritis.
Assuntos
Artrite Experimental/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Verapamil/farmacocinética , Administração Oral , Animais , Artrite Experimental/enzimologia , Artrite Experimental/microbiologia , Proteínas Sanguíneas/metabolismo , Técnicas In Vitro , Inflamação/enzimologia , Inflamação/metabolismo , Injeções Intravenosas , Masculino , Microssomos Hepáticos/enzimologia , Mycobacterium , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Verapamil/administração & dosagem , Verapamil/químicaRESUMO
PURPOSE: Stress increases plasma corticosterone concentration in rats. We studied the time-course of plasma corticosterone post jugular vein cannulation, a potential stress producing process, and after 1 h restraint stress using an improved assay. Current HPLC methods for corticosterone analysis require long extraction times with large volumes of solvent. METHODS: Adult male, Sprague-Dawley rats were used. Tail vein blood samples were collected from uncannulated rats (n=4). Other rats were cannulated in the right jugular vein, allowed to recover overnight and assigned to days 1, 2, 3 or 4 groups (n=4-6/group). Blood was sampled before and after exposure to 1 h of restraint stress. Plasma was separated and extracted with 5 mL ethyl acetate (betamethasone as internal standard), and then the extract was washed with sodium hydroxide (0.1 M) and water. After evaporation of ethyl acetate, the residue was dissolved in mobile phase (acetonitrile-water-acetic acid-TEA, 22:78:0.1:0.03, v/v) and injected into an isocratic HPLC consisting of a 10 cm C18 column, and UV detector at 254 nm. RESULTS: The minimum quantifiable concentration was 10 ng/mL of corticosterone based on 0.5 mL plasma. The standard curve was linear over the concentration range of 10-500 ng/mL. The extraction efficiency was 84-87%. The coefficient of variation for intra-day and inter-day precision was <10% with <8% error. Plasma corticosterone before cannulation (74 +/- 17 ng/mL) and those measured daily before restraint stress were not significantly different from one day to another (day 1, 60 +/- 21; day 2, 59 +/- 39, day 3, 45 +/- 23, and day 4, 41 +/- 8 ng/mL). Exposure to restraint stress elevated corticosterone (day 1, 122 +/- 33; day 2, 82 +/- 23; day 3, 148 +/- 33; and day 4, 134 +/- 20 ng/mL). Except on day 2, all concentrations were significantly elevated as compared to the pre-stress levels. CONCLUSIONS: Corticosterone concentrations were stable after jugular vein cannulation, and were increased by restraint stress. The present assay is a more convenient method as compared to those previously reported.