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1.
Anesthesiology ; 132(4): 692-701, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32022771

RESUMO

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Clonidina/administração & dosagem , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnóstico , Idoso , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Clonidina/efeitos adversos , Feminino , Seguimentos , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Tempo
2.
Methods Mol Biol ; 2059: 239-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31435926

RESUMO

Tizanidine hydrochloride is a skeletal muscle relaxant used for the treatment of spasm, a sudden involuntary muscle contraction leading to pain. The presently available oral dosage form has limitations such as high first pass metabolism resulting in low oral bioavailability. The short half-life necessitates its frequent administration to maintain the required plasma concentration. Transdermal delivery of drug avoids its first pass hepatic metabolism and gives controlled release, making it possible for reduction in dosing frequency. Drug delivery through transdermal route is severely limited by the presence of a tough stratum corneum barrier. A penetration enhancement approach is often necessary to achieve desired plasma concentrations. Microneedles are very short and sharp needles which do not cause pain. Thus, in the present investigation, preparation and evaluation of a transdermal delivery system for tizanidine hydrochloride based on microneedles are described.


Assuntos
Clonidina/análogos & derivados , Epiderme/efeitos dos fármacos , Microinjeções/instrumentação , Microinjeções/métodos , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Clonidina/farmacocinética , Liberação Controlada de Fármacos , Epiderme/ultraestrutura , Feminino , Membranas Artificiais , Microscopia Eletrônica de Varredura , Agulhas , Ratos , Ratos Wistar , Pele/patologia , Pele/ultraestrutura , Fluxo de Trabalho
3.
Int J Radiat Oncol Biol Phys ; 106(2): 320-328, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669562

RESUMO

PURPOSE: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. METHODS AND MATERIALS: Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 µg (n = 56), 100 µg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). RESULTS: SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. CONCLUSIONS: Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.


Assuntos
Quimiorradioterapia/efeitos adversos , Clonidina/administração & dosagem , Neoplasias de Cabeça e Pescoço/radioterapia , Protetores contra Radiação/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Estomatite/prevenção & controle , Administração Bucal , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Clonidina/efeitos adversos , Intervalos de Confiança , Transtornos de Deglutição/etiologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Protetores contra Radiação/efeitos adversos , Dosagem Radioterapêutica , Estomatite/etiologia , Comprimidos , Adulto Jovem
4.
Aerosp Med Hum Perform ; 90(11): 959-965, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31666158

RESUMO

INTRODUCTION: Exposure to high G force is a known safety hazard in military aviation as well as civilian aerobatic flight. Tolerance to high G forces has been well studied in military pilots, but there is little research directed at civilian pilots who may have medications or medical conditions not permitted in military pilots.METHODS: In this case-control study, we identified 89 fatal high-G aerobatic accidents and 4000 fatal control accidents from 1995 through 2018 from the NTSB accident database and the FAA autopsy database. We retrieved medications and medical conditions from the FAA's pilot medical databases. Logistic regression models were used to explore the associations of drugs, medical conditions, height, and medical waivers with high-G accidents.RESULTS: Seven drugs (alprazolam, clonidine, ethanol, meclizine, phentermine, triamterene, and zolpidem) reached statistical significance in our models, but had such small case counts that we consider these findings to be uncertain, except for ethanol, which was found in seven cases. Of these, only triamterene was known to the FAA. Statistically significant medical predictors included only alcohol abuse (seven cases) and liver disease (only two cases).DISCUSSION: Our analysis found that the drug ethanol and the condition alcohol abuse are significantly associated with high-G accidents. Seven other factors were statistically significant, but should only be considered as hypothesis generating due to very low case counts. Our study does not suggest that restricting pilots with otherwise permissible medications or medical conditions from aerobatics is warranted.Mills WD, Greenhaw RM, Wang JMP. A medical review of fatal high-G U.S. aerobatic accidents. Aerosp Med Hum Perform. 2019; 90(11):959-965.


Assuntos
Acidentes Aeronáuticos/mortalidade , Medicina Aeroespacial/estatística & dados numéricos , Hipergravidade/efeitos adversos , Pilotos/estatística & dados numéricos , Acidentes Aeronáuticos/prevenção & controle , Acidentes Aeronáuticos/estatística & dados numéricos , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Alprazolam/efeitos adversos , Estudos de Casos e Controles , Clonidina/efeitos adversos , Bases de Dados Factuais/estatística & dados numéricos , Etanol/efeitos adversos , Feminino , Humanos , Hepatopatias/complicações , Hepatopatias/fisiopatologia , Modelos Logísticos , Masculino , Meclizina/efeitos adversos , Pessoa de Meia-Idade , Fentermina/efeitos adversos , Triantereno/efeitos adversos , Estados Unidos/epidemiologia , Zolpidem/efeitos adversos
6.
Br J Anaesth ; 123(6): 795-807, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31623842

RESUMO

BACKGROUND: Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. METHODS: We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 µg kg-1 or with continuous administration alone. CONCLUSIONS: Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. PROTOCOL REGISTRATION: CRD42017071583.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Clonidina/efeitos adversos , Dexmedetomidina/efeitos adversos , Complicações Intraoperatórias/induzido quimicamente , Complicações Pós-Operatórias/induzido quimicamente , Bradicardia/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Período Pré-Operatório , Taquicardia/induzido quimicamente
9.
Eur Arch Otorhinolaryngol ; 276(11): 3095-3104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31363901

RESUMO

PURPOSE: Intense bleeding of the surgical field is a potential factor influencing success of functional endoscopic sinus surgery (FESS). Hypotensive anesthesia with α2 intravenous agonists reduces intraoperative bleeding, but which is the best agent is unknown. The main objective of this trial was to compare the current standard adjuvant drug for hypotensive anesthesia, clonidine, with the recently available alternative dexmedetomidine. METHODS: A randomized clinical trial compared the efficacy of clonidine and dexmedetomidine during FESS. Treatment was open label for the anesthesiologist and operating surgeon, but blind for an external evaluator who evaluated video-recorded surgeries. A Boezaart scale was assessed every 30 min during FESS until surgery completion. Main end-point was the proportion of patients with mean Boezaart scores > 2 (heavy bleeding) by external blinded evaluator. Secondary end-points included other bleeding parameters, surgery duration, hemodynamic measures and surgical complications. RESULTS: 94 patients were randomized. There were no significant differences in the proportion of patients with mean Boezaart scores > 2 in clonidine (42.6%) and dexmedetomidine (42.6%). Consistently, no differences were observed in secondary variables of bleeding, duration or complications. Small differences in mean heart rate were observed that might reflect different pharmacological profiles of the products, but are of uncertain clinical relevance. CONCLUSIONS: No significant differences were observed between clonidine and dexmedetomidine when used as anesthetic adjuvants in the reduction of surgical bleeding in FESS. A longer experience with clonidine and its lower costs suggest it may be a preferable option as an adjuvant for hypotensive anesthesia.


Assuntos
Anestesia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Clonidina , Dexmedetomidina , Endoscopia , Seios Paranasais/cirurgia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Doença Crônica , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Endoscopia/efeitos adversos , Endoscopia/métodos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Duração da Cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Resultado do Tratamento
10.
Eur J Anaesthesiol ; 36(8): 575-582, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274545

RESUMO

BACKGROUND: Intrathecal morphine (ITM) is a widely used technique for postcaesarean section analgesia but entails a high risk of postoperative nausea and vomiting (PONV). The transversus abdominis plane (TAP) block is an alternative. OBJECTIVE: We tested the hypothesis that a TAP block including clonidine reduces the incidence of PONV after caesarean section when compared with ITM. DESIGN: A randomised, controlled, double-blinded study. SETTING: Geneva University Hospitals, Switzerland, from October 2013 to February 2017. PATIENTS: A total of 182 patients undergoing elective caesarean section were studied. Reasons for noninclusion were complicated pregnancy, contraindication to spinal anaesthesia or TAP block, extreme weight or height, allergy to any medication or previous median abdominal incision. INTERVENTIONS: Patients were allocated randomly to one of two groups (quadruple blinded): 100 µg of morphine added to the spinal local anaesthetic or a bilateral TAP block with 20 ml of ropivacaine 0.375% + 75 µg of clonidine on each side. MAIN OUTCOME MEASURES: The primary outcome measure was the total number of patients presenting with PONV at 24 h. Secondary aims were to compare other adverse effects (pruritus, respiratory depression, hypotension, bradycardia, sedation), analgesic efficacy and the quality of postoperative recovery. RESULTS: At 24 h, there was no significant difference between ITM and TAP groups in the total number of patients presenting with PONV: 17/92 patients (18.5%, 95% confidence interval 11.1 to 27.9) and 27/88 patients (30.7%, 95% confidence interval 21.3 to 41.4) in TAP and ITM groups, respectively (P = 0.065). Pain scores at 6 h and cumulative morphine consumption at 24 h were lower in the ITM group (P < 0.0001 for morphine consumption at 24 h). The incidence of hypotension was higher in the TAP group (54.3 vs. 29.2%, P = 0.0006). Maternal satisfaction was high and not different between groups. CONCLUSION: A TAP block with clonidine and local anaesthetic does not reduce significantly the incidence of PONV compared with ITM. We confirm the superiority of ITM on acute postcaesarean section analgesia compared with a TAP block, even with clonidine as an adjunct. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01931215.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Bloqueio Nervoso/efeitos adversos , Dor Pós-Operatória/epidemiologia , Náusea e Vômito Pós-Operatórios/epidemiologia , Músculos Abdominais/inervação , Adulto , Anestesia Obstétrica/métodos , Raquianestesia/métodos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Injeções Espinhais , Morfina/administração & dosagem , Morfina/efeitos adversos , Bloqueio Nervoso/métodos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Gravidez , Estudos Prospectivos , Ropivacaina/administração & dosagem , Ropivacaina/efeitos adversos , Resultado do Tratamento
11.
BMJ Case Rep ; 12(6)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31243023

RESUMO

Compared with the general population, rates of pheochromocytoma are higher in neurofibromatosis type 1 (NF1) patients. However, pheochromocytoma testing is often plagued by false positive results. Here we present a patient with NF1, elevated urinary metanephrine levels, and an indeterminate adrenal nodule. Clonidine suppression testing aided diagnosis and led to definitive surgical treatment that confirmed a pheochromocytoma. Pheochromocytoma screening and clonidine suppression testing can both aid in the evaluation for catecholamine-secreting tumours.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Clonidina/farmacologia , Metanefrina/urina , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Clonidina/efeitos adversos , Reações Falso-Positivas , Feminino , Humanos , Pessoa de Meia-Idade , Neurofibromatose 1/complicações , Feocromocitoma/patologia , Feocromocitoma/cirurgia
12.
Curr Opin Anaesthesiol ; 32(3): 327-333, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31045639

RESUMO

PURPOSE OF REVIEW: Clonidine, an α2-receptor agonist is a widely used drug in pediatrics with a large scope of indications ranging from prevention of postoperative emergence agitation, analgesia, anxiolysis, sedation, weaning to shivering. In the era of 'opioid-free' medicine with much attention be directed toward increasing problems with opioid use, clonidine due to its global availability, low cost and safety profile has become an even more interesting option. RECENT FINDINGS: Increasing evidence from randomised clinical trials support the use of clonidine in healthy children in the perioperative setting. Clonidine appears to significantly reduce postoperative emergence agitation, opioid consumption, shivering, nausea and vomiting. In addition, emerging evidence support the use of clonidine for sedation of critically ill children in ICUs. In this review, the current evidence for clonidine in pediatrics is described and analyzed including a meta-analysis for prevention of emergence agitation. SUMMARY: Clonidine appears a safe and beneficial drug with moderate to high-quality evidence supporting its use in pediatric anesthesia. However, for some indications and populations such as children younger than 12 months old and those with hemodynamic instability, there is an urgent need for high-quality trials.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia/métodos , Clonidina/administração & dosagem , Delírio do Despertar/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Fatores Etários , Anestesia/efeitos adversos , Criança , Clonidina/efeitos adversos , Delírio do Despertar/etiologia , Humanos , Seleção de Pacientes , Náusea e Vômito Pós-Operatórios/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tremor por Sensação de Frio/efeitos dos fármacos
14.
J Nepal Health Res Counc ; 16(41): 428-433, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30739935

RESUMO

BACKGROUND: Caudal analgesia has long been the cornerstone to successful pain management in children undergoing abdominal and lower limb surgeries. Its analgesic duration with single shot injection is however limited. So adjuvants are used with local anesthetics in an attempt to increase the duration of caudal analgesia. This study aims to investigate the duration of analgesia provided by Clonidine when added to caudal Bupivacaine. METHODS: A randomized, double blinded, comparative study was conducted on 64 patients, aged two to seven years, scheduled for unilateral inguinal hernia repair. Patients were randomly allocated into two groups of 32 each, with group A receiving bupivacaine two milligram/kilogram and group B receiving bupivacaine two milligram/kilogram with one microgram/kilogramclonidine, (total volume of injectate was one milliliter/kilogram). Duration of analgesia, hemodynamic response and adverse effects, if any were noted. RESULTS: Mean duration of analgesia in group A was 264.12 ± 68.77 minutes and in group B was 520 ± 57.37 minutes, p-value <0.001.Incidence of vomiting was 9% in group A compared to 6% in group B. CONCLUSIONS: Clonidineas an adjuvant to caudal bupivacaine prolongs the duration of analgesia without increasing the adverse effects.


Assuntos
Analgésicos , Anestesia Caudal/métodos , Anestésicos Combinados , Bupivacaína , Clonidina , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anestesia Caudal/efeitos adversos , Anestésicos Combinados/administração & dosagem , Anestésicos Combinados/efeitos adversos , Bupivacaína/administração & dosagem , Bupivacaína/efeitos adversos , Criança , Pré-Escolar , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino
15.
Clin Pharmacol Ther ; 105(3): 703-709, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30223305

RESUMO

Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP) ≤ 70 mmHg during periods of drug co-exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33) than the cyclobenzaprine group (1.28%; n = 64); odds ratio (OR) = 1.60; P = 0.029. This difference remained statistically significant after adjustment for a log-transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications (OR = 1.57; P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.


Assuntos
Clonidina/análogos & derivados , Inibidores do Citocromo P-450 CYP1A2/efeitos adversos , Citocromo P-450 CYP1A2/metabolismo , Hipotensão/induzido quimicamente , Hipotensão/metabolismo , Relaxantes Musculares Centrais/efeitos adversos , Adulto , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Estudos de Coortes , Inibidores do Citocromo P-450 CYP1A2/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Hipotensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/administração & dosagem , Polimedicação , Estudos Retrospectivos , Fatores de Risco
16.
Curr Vasc Pharmacol ; 17(6): 573-578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30205798

RESUMO

INTRODUCTION: Menopause is associated with adverse effects on quality of life of perimenopausal and post-menopausal women. It also has an impact on the development of cardiovascular disease (CVD). Hormonal treatments are the most effective medications for menopausal symptoms relief. Given the fact that hormonal treatments are contraindicated for many women, non-hormonal treatment, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), gabapentin, pregabalin, clonidine and phytoestrogens, constitute alternative treatments. Nevertheless, little is known about their effects on CVD risk. METHODS: PubMed, EMBASE and Cochrane Library were searched for the effects of non-hormonal treatment on CVD risk, blood pressure, heart rate, lipids and glucose concentrations, weight gain, cardiovascular events, stroke, mortality and morbidity. RESULTS: Phytoestrogens, pregabalin and gabapentin seem to have no adverse effects on the cardiovascular system. Phytoestrogens, in particular, seem to reduce CVD risk through many pathways. On the other hand, SSRIs and SNRIs, although effective in reducing menopausal vasomotor symptoms, should be cautiously administered to women with known CVD (e.g. with cardiac arrhythmias, atherosclerotic disease or stroke). As clonidine has been associated with cardiovascular adverse effects, it should be administered only in cases where blood pressure regulation is mandatory. CONCLUSION: Further research is needed to produce definite conclusions regarding the cardiovascular safety of non-hormonal medications for menopausal symptoms relief.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Clonidina/uso terapêutico , Gabapentina/uso terapêutico , Menopausa/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Pregabalina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Clonidina/efeitos adversos , Feminino , Gabapentina/efeitos adversos , Humanos , Menopausa/metabolismo , Fitoestrógenos/efeitos adversos , Pregabalina/efeitos adversos , Medição de Risco , Fatores de Risco , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Resultado do Tratamento
17.
J Addict Med ; 13(3): 169-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531234

RESUMO

OBJECTIVES: To investigate the safety and efficacy of lofexidine for treating opioid withdrawal syndrome (OWS) and facilitating completion of opioid withdrawal. METHODS: A multicenter, double-blind, placebo-controlled study was conducted at 18 US centers from June 2013 to December 2014. Participants (n = 603) aged ≥18 years, dependent on short-acting opioids, and seeking withdrawal treatment, randomized 3:3:2 to receive lofexidine 2.88 mg/d (n = 222), lofexidine 2.16 mg/d (n = 230), or placebo (n = 151) for 7 days. Primary outcome was the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) scores rating withdrawal symptoms over days 1 to 7. RESULTS: Participants were of mean age, 35 years; 71% male. Pairwise differences in overall SOWS-Gossop log-transformed least squares means were statistically significant for lofexidine 2.16 mg (difference, -0.21; 95% CI, -0.37 to -0.04; P = 0.02) and 2.88 mg (-0.26; 95% CI, -0.44 to -0.09; P = 0.003) compared with placebo. Fewer than half of participants in both groups completed the study. Completion rates for lofexidine 2.16 mg (41.5%; odds ratio [OR], 1.85; P = 0.007) and 2.88 mg (39.6%; OR, 1.71; P = 0.02) were significantly better compared with placebo (27.8%). Overall adverse event (AE) rates were similar across groups. Common AEs for lofexidine included orthostatic hypotension, hypotension, and bradycardia, but resulted in few study discontinuations. CONCLUSIONS: Lofexidine 2.16 mg and 2.88 mg significantly reduced symptoms of OWS versus placebo, and increased absolute rates of completing the 7-day study by 14% and 12%, respectively (a relative increase of 85% and 71%). Data suggest that lofexidine is a generally safe and effective nonopioid treatment for opioid withdrawal. Lofexidine could serve as a withdrawal treatment option when a nonopioid agent is preferred or required, when agonist-assisted withdrawal is unavailable, when agonist discontinuation caused OWS, and during induction into maintenance treatment with opioid agonists or antagonists. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01863186.


Assuntos
Clonidina/análogos & derivados , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Idoso , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/efeitos adversos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
20.
Cochrane Database Syst Rev ; 6: CD007522, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29929212

RESUMO

BACKGROUND: Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. OBJECTIVES: To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. SEARCH METHODS: We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. SELECTION CRITERIA: Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence). AUTHORS' CONCLUSIONS: Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.


Assuntos
Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Ópio/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Amantadina/uso terapêutico , Aminas/uso terapêutico , Baclofeno/uso terapêutico , Buprenorfina/efeitos adversos , Buprenorfina/uso terapêutico , Clonidina/efeitos adversos , Clonidina/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Gabapentina , Humanos , Metadona/uso terapêutico , Ópio/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tramadol/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico
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