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1.
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
4.
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
5.
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
6.
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
8.
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
9.
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
11.
Pediatr Crit Care Med ; 19(8): e409-e416, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29912068

RESUMO

OBJECTIVES: Clonidine is an antihypertensive drug used for analgosedation in the PICU. Lack of reliable data on its hemodynamic tolerance limits its use. This study explores the hemodynamic tolerance of IV clonidine infusion in a broad population of children with high severity of disease. DESIGN: Retrospective analysis of prospectively collected data. SETTING: A tertiary and quaternary referral PICU. PATIENTS: Critically ill children age 0-18 years old who received an IV clonidine infusion for analgosedation of at least 1 hour. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were the prevalences of bradycardia and hypotension. Secondary endpoints were changes in heart rate, blood pressure, Vasoactive-Inotropic Score, COMFORT Behavior score (a sedation scoring scale), and body temperature during the infusion. The association of bradycardia with other hemodynamic variables was explored, as well as potential risk factors for severe bradycardia. One-hundred eighty-six children (median age, 12.9 mo [interquartile range, 3.5-60.6 mo]) receiving a maximum median clonidine infusion of 0.7 µg/kg/hr (interquartile range, 0.3-1.5) were included. Severe bradycardia and systolic hypotension occurred in 72 patients (40.2%) and 105 patients (58%), respectively. Clonidine-associated bradycardia was hemodynamically well tolerated, as it was not related with hypotension and the need for vasoactive drugs decreased in parallel with a sedation score guided clonidine infusion rate increase. Younger age was the only identified risk factor for clonidine-associated bradycardia. CONCLUSIONS: Although administration of clonidine is often associated with bradycardia and hypotension, these complications do not seem clinically significant in a mixed PICU population with a high degree of disease severity. Clonidine may have a vasoactive-inotropic sparing effect.


Assuntos
Bradicardia/induzido quimicamente , Clonidina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/induzido quimicamente , Administração Intravenosa , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Bradicardia/epidemiologia , Pré-Escolar , Clonidina/administração & dosagem , Clonidina/farmacologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Hipotensão/epidemiologia , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Países Baixos , Uso Off-Label , Estudos Retrospectivos
12.
J Subst Abuse Treat ; 91: 1-11, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29910009

RESUMO

BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS: Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.


Assuntos
Clonidina/análogos & derivados , Diazepam/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Adulto , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Fissura/efeitos dos fármacos , Diazepam/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pupila/efeitos dos fármacos , Singapura
13.
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
14.
Ophthalmic Plast Reconstr Surg ; 34(6): 547-551, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29634605

RESUMO

PURPOSE: To determine the relationship between the distribution of adrenergic receptors in the human eyelid and the eyelid elevation after topically instilling 0.5% apraclonidine in blepharoptosis patients. METHODS: A total of 26 blepharoptotic patients (30 eyelids) were included in the experimental study. Marginal reflex distance 1 was measured before and after topical instillation of 0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine were classified as group A and those that negatively responded to it were classified as group B. Müller's muscle was obtained during the blepharoptotic surgery, followed by immunohistochemical staining and scoring. This study was approved by the Institutional Review Board of Kim's Eye Hospital and the study protocol adhered to the tenets of the Declaration of Helsinki. RESULTS: α-1D staining intensity was significantly higher in group A than in B (p < 0.001) and α-2C and ß-1 staining intensities were significantly higher in group B than in A (p < 0.001 and p < 0.05, respectively). The difference in ß-2 staining intensity between groups A and B was not statistically significant. CONCLUSIONS: α-1D adrenoceptor was predominant in patients showing a positive response to topical 0.5% apraclonidine. Because apraclonidine has an α-1 agonistic effect, α-1D adrenoceptor may contribute to apraclonidine's elevating effect in patients with blepharoptosis.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Blefaroptose/tratamento farmacológico , Clonidina/análogos & derivados , Pálpebras/metabolismo , Receptores Adrenérgicos/metabolismo , Adolescente , Agonistas alfa-Adrenérgicos/efeitos adversos , Adulto , Idoso , Criança , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Pálpebras/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
J Int Med Res ; 46(6): 2466-2469, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29587554

RESUMO

A 37-year-old man suffered irreversible profound symptomatic bradycardia requiring a pacemaker 3 days after beginning tizanidine/loxoprofen combination therapy for neck pain. This combination therapy is prescribed frequently for joint pain; however, combining loxoprofen with tizanidine could increase the risk of symptomatic bradycardia that is both permanent and severe. Similar cases have not been reported. This case suggests that tizanidine should be used cautiously when combined with loxoprofen, and drug interaction screening should be performed.


Assuntos
Analgésicos/efeitos adversos , Bradicardia/terapia , Estimulação Cardíaca Artificial , Clonidina/análogos & derivados , Cervicalgia/tratamento farmacológico , Fenilpropionatos/efeitos adversos , Adulto , Analgésicos/uso terapêutico , Bloqueio Atrioventricular/induzido quimicamente , Bloqueio Atrioventricular/terapia , Bradicardia/induzido quimicamente , Clonidina/efeitos adversos , Clonidina/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Fenilpropionatos/uso terapêutico
16.
Anesth Analg ; 127(1): 165-170, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29596102

RESUMO

BACKGROUND: Intrathecal clonidine prolongs spinal anesthesia. We evaluated the effects of the addition of intrathecal or intravenous clonidine (75 µg) to standard cesarean delivery spinal anesthesia on postoperative pain and neonatal outcomes. METHODS: In a randomized, placebo-controlled, double-blind trial, 64 women scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated and compared among 3 groups: intrathecal clonidine 75 µg, intravenous clonidine 75 µg, and placebo. The primary outcome was acute postoperative pain. A sample size of 26 individuals per group (N = 78) was planned. RESULTS: From April 2015 to April 2016, 64 women were analyzed (14 excluded). No differences in postoperative pain scores were found (Numerical Verbal Scale for pain at movement at 24 hours of postcesarean delivery: 4.53 ± 3.0 vs 4.45 ± 2.73 vs 3.93 ± 3.07 for control, intrathecal, and intravenous, respectively, P = .771). Intrathecal and intravenous clonidine led to more sedation, in comparison to the control group, during the intraoperative period (Richmond Agitation and Sedation Scale: -0.3 ± 0.47 vs -1 ± 0.53 vs -0.73 ± 0.45 for control, intrathecal, and intravenous, respectively, overall P < .001; Dunn correction: P < .001 for intrathecal versus control; P = .021 for intravenous versus control; and P = .208 for intrathecal versus intravenous). CONCLUSIONS: Intrathecal or intravenous clonidine had no effect on postoperative pain after cesarean delivery. Both intrathecal and intravenous clonidine caused more sedation.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgesia Obstétrica/métodos , Anestesia Obstétrica/métodos , Raquianestesia/métodos , Cesárea/efeitos adversos , Clonidina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Adulto , Analgesia Obstétrica/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Brasil , Clonidina/efeitos adversos , Estado de Consciência/efeitos dos fármacos , Feminino , Humanos , Injeções Intravenosas , Injeções Espinhais , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Gravidez , Fatores de Tempo , Resultado do Tratamento
17.
Hypertension ; 71(4): 681-690, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29463627

RESUMO

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Clonidina , Hipertensão , Espironolactona , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/classificação , Monitorização Ambulatorial da Pressão Arterial/métodos , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Monitoramento de Medicamentos/métodos , Resistência a Medicamentos , Quimioterapia Combinada/métodos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Espironolactona/administração & dosagem , Espironolactona/efeitos adversos , Resultado do Tratamento
18.
BMC Pharmacol Toxicol ; 19(1): 6, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29433586

RESUMO

BACKGROUND: Clonidine is an imidazoline sympatholytic, acting on both α2-adrenergic and imidazoline receptors in the brainstem to induce antihypertensive and negative chronotropic effects in the vasculature and heart respectively. CASE PRESENTATION: A 69-year-old gentleman with hypertension presented to the emergency department after multiple syncopal episodes over the past 12 months. Electrocardiogram demonstrated sinus bradycardia with a heart rate of 42 beats per minute. It was hypothesized that the antihypertensive agent clonidine was responsible for inducing symptomatic bradycardia. Clonidine was thus gradually tapered and then discontinued over five days restoring normal sinus rhythm rates while avoiding hypertensive rebound related to sympathetic surge. His heart rate and blood pressure remained within normal limits after the clonidine taper and subsequent adjustments to his other hypertensive medications and he was discharged. CONCLUSIONS: While clonidine has fallen out of favor for its indication as an antihypertensive, it remains a viable option for the use of opioid withdrawal, chronic pain, and smoking cessation, necessitating the appropriate clinical and pharmacological competencies for a physician to prescribe. A discussion of the clinical effects of clonidine brainstem receptor activation follows.


Assuntos
Anti-Hipertensivos/efeitos adversos , Clonidina/efeitos adversos , Síncope/induzido quimicamente , Idoso , Humanos , Masculino
20.
Clin Pharmacol Ther ; 103(2): 287-295, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29052226

RESUMO

Polypharmacy increases the risk of drug-drug interactions (DDIs). Combining epidemiological studies with pharmacokinetic modeling, we detected and evaluated high-dimensional DDIs among 30 frequent drugs. Multidrug combinations that increased the risk of myopathy were identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) and electronic medical record (EMR) databases by a mixture drug-count response model. CYP450 inhibition was estimated among the 30 drugs in the presence of 1 to 4 inhibitors using in vitro / in vivo extrapolation. Twenty-eight three-way and 43 four-way DDIs had significant myopathy risk in both databases and predicted increases in the area under the concentration-time curve ratio (AUCR) >2-fold. The high-dimensional DDI of omeprazole, fluconazole, and clonidine was associated with a 6.41-fold (FAERS) and 18.46-fold (EMR) increased risk of myopathy local false discovery rate (<0.005); the AUCR of omeprazole in this combination was 9.35. The combination of health record informatics and pharmacokinetic modeling is a powerful translational approach to detect high-dimensional DDIs.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores do Citocromo P-450 CYP2C19/efeitos adversos , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Mineração de Dados/métodos , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Registros Eletrônicos de Saúde , Doenças Musculares/induzido quimicamente , Pesquisa Médica Translacional/métodos , Clonidina/efeitos adversos , Clonidina/farmacocinética , Inibidores do Citocromo P-450 CYP2C19/administração & dosagem , Inibidores do Citocromo P-450 CYP2C19/farmacocinética , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Bases de Dados Factuais , Interações de Medicamentos , Medicina Baseada em Evidências/métodos , Fluconazol/efeitos adversos , Fluconazol/farmacocinética , Humanos , Modelos Biológicos , Doenças Musculares/enzimologia , Doenças Musculares/epidemiologia , Omeprazol/efeitos adversos , Omeprazol/farmacocinética , Segurança do Paciente , Polimedicação , Reprodutibilidade dos Testes , Medição de Risco , Estados Unidos/epidemiologia
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