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1.
Cochrane Database Syst Rev ; 8: CD011786, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397100

RESUMO

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence). AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.


Assuntos
Hidrato de Cloral/administração & dosagem , Técnicas de Diagnóstico Neurológico , Hipnóticos e Sedativos/administração & dosagem , Criança , Hidrato de Cloral/efeitos adversos , Humanos , Hidroxizina/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Pentobarbital/administração & dosagem
2.
Clin Neurophysiol ; 132(9): 2054-2061, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34284240

RESUMO

OBJECTIVE: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia. METHODS: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics. RESULTS: Hydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011). CONCLUSIONS: Hydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms. SIGNIFICANCE: The findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.


Assuntos
Eletroencefalografia/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Hidroxizina/administração & dosagem , Propofol/administração & dosagem , Sevoflurano/administração & dosagem , Adulto , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Sinergismo Farmacológico , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
3.
Intern Med ; 60(20): 3257-3260, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33896871

RESUMO

An 82-year-old woman was admitted to our hospital because of dyspnea and bradycardia during exertion. Electrocardiography revealed complete atrioventricular block. During pacemaker implantation, a small dose (12.5 mg) of hydroxyzine was injected for sedation, and torsade de pointes (Tdp) occurred. The QT interval was prolonged after administration of hydroxyzine, and Tdp was observed after the R on T phenomenon occurred, indicating that hydroxyzine was capable of prolonging the QT interval and causing Tdp. Therefore, we must be cautious when administering hydroxyzine for sedation during surgery, especially in patients with bradycardia.


Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Torsades de Pointes , Idoso de 80 Anos ou mais , Bloqueio Atrioventricular/induzido quimicamente , Bloqueio Atrioventricular/diagnóstico , Eletrocardiografia , Feminino , Humanos , Hidroxizina/efeitos adversos , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico , Torsades de Pointes/terapia
4.
Am J Emerg Med ; 48: 375.e5-375.e6, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33836933

RESUMO

Priapism is a severe urologic condition requiring emergency management. Ischemic priapism is the most common subtype which is characterized by a long-lasting, painful, and rigid erection which can be caused by medications with alpha-adrenergic properties such as hydroxyzine. Typically, medication-induced priapism is reported at therapeutic doses and few case reports exist implicating medication overdose as the cause. We report a case of a patient taking hypercompliant doses of hydroxyzine hydrochloride for worsening insomnia (200-600 mg), including the night before admission. Blood-gas analysis of blood from the right corpora was completed and revealed a pH of 6.736, pCO2 of 147, HCO3 of 18.6 and a base excess of 17.7. The patient required aspiration and 560 µg of intracavernosal phenylephrine to achieve sustained detumescence. Emergency physicians should be aware of this risk as priapism is a medical emergency and this is the first report with hydroxyzine after an intentional overdose to our knowledge.


Assuntos
Antagonistas dos Receptores Histamínicos H1/envenenamento , Hidroxizina/envenenamento , Priapismo/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto , Humanos , Masculino , Priapismo/terapia
5.
Eur Arch Paediatr Dent ; 22(5): 801-811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33840073

RESUMO

PURPOSE: Management of a child's anxiety early in their treatment is essential in dentistry. Sedative medications are used to overcome increased anxiety from previous appointments and to promote the cooperation of children during treatment. Hydroxyzine is currently prescribed to young patients as part of the first level of conscious sedation. The main objective was to evaluate the professional practice of oral hydroxyzine, when prescribed for children presenting anxiety during dental treatment procedure performed by students and senior practitioners. METHODS: A retrospective study of dental records and questionnaires was conducted at the Dental Care Centre of the University Hospital of Rennes, France. Parameters related to the prescription of hydroxyzine in children were evaluated as potential predictors of the dental session success, with adjustments on potential confounders. RESULTS: The therapeutic outcome was very encouraging with 78.3% of success during dental sessions under sedation with oral hydroxyzine. Anxiety levels before the dental procedure and the medication compliance of the child were the main predictors of success. On the other hand, lower age (< 6 years old) and longer treatments (such as pulpotomy) worsened the outcome. CONCLUSIONS: Careful analysis of the literature and results of this work showed the safety of hydroxyzine within the maximum dose authorized without adverse effects, compared to other molecules described and commonly used in dentistry. No adverse effects during dental procedure were noted. This allows for minimal sedation with efficiency for the great majority of pediatric treatment. This solution should be the first step in sedation to help practicing clinicians.


Assuntos
Anestesia Dentária , Hidroxizina , Criança , Comportamento Infantil , Sedação Consciente , Hospitais , Humanos , Hipnóticos e Sedativos/efeitos adversos , Prática Profissional , Estudos Retrospectivos
6.
Pharmacoepidemiol Drug Saf ; 30(4): 482-491, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33386650

RESUMO

BACKGROUND: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. METHOD: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. RESULTS: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (-12.05, 95%CI -18.47 to -5.63) and Scotland (-19.01, 95%CI -26.99 to -11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (-1.72, 95%CI -2.69 to -0.75) and Scotland (-2.38, 95%CI -3.32 to -1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. CONCLUSION: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.


Assuntos
Hidroxizina , Dinamarca , Inglaterra , Humanos , Análise de Séries Temporais Interrompida , Países Baixos , Análise de Regressão , Escócia
7.
AAPS J ; 23(1): 20, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33415501

RESUMO

Alcohol dehydrogenases (ADHs) are most known for their roles in oxidation and elimination of ethanol. Although less known, ADHs also play a critical role in the metabolism of a number of drugs and metabolites that contain alcohol functional groups, such as abacavir (HIV/AIDS), hydroxyzine (antihistamine), and ethambutol (antituberculosis). ADHs consist of 7 gene family numbers and several genetic polymorphic forms. ADHs are cytosolic enzymes that are most abundantly found in the liver, although also present in other tissues including gastrointestinal tract and adipose. Marked species differences exist for ADHs including genes, proteins, enzymatic activity, and tissue distribution. The active site of ADHs is relatively small and cylindrical in shape. This results in somewhat narrow substrate specificity. Secondary alcohols are generally poor substrates for ADHs. In vitro-in vivo correlations for ADHs have not been established, partly due to insufficient clinical data. Fomepizole (4-methylpyrazole) is a nonspecific ADH inhibitor currently being used as an antidote for the treatment of methanol and ethylene glycol poisoning. Fomepizole also has the potential to treat intoxication of other substances of abuse by inhibiting ADHs to prevent formation of toxic metabolites. ADHs are inducible through farnesoid X receptor (FXR) and other transcription factors. Drug-drug interactions have been observed in the clinic for ADHs between ethanol and therapeutic drugs, and between fomepizole and ADH substrates. Future research in this area will provide additional insights about this class of complex, yet fascinating enzymes.


Assuntos
Álcool Desidrogenase/metabolismo , Fármacos Anti-HIV/farmacocinética , Antituberculosos/farmacocinética , Etanol/metabolismo , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Álcool Desidrogenase/antagonistas & inibidores , Álcool Desidrogenase/genética , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/química , Antituberculosos/administração & dosagem , Antituberculosos/química , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/química , Didesoxinucleosídeos/farmacocinética , Interações Medicamentosas , Etambutol/administração & dosagem , Etambutol/química , Etambutol/farmacocinética , Etanol/química , Fomepizol/farmacologia , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/química , Humanos , Hidroxizina/administração & dosagem , Hidroxizina/química , Hidroxizina/farmacocinética , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Oxirredução/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Especificidade da Espécie , Especificidade por Substrato
8.
BMJ Case Rep ; 13(12)2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33310825

RESUMO

Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement.


Assuntos
Histamina N-Metiltransferase/genética , Homozigoto , Deficiência Intelectual/genética , Mutação , Agressão/fisiologia , Encéfalo/metabolismo , Histamina/metabolismo , Histamina N-Metiltransferase/metabolismo , Humanos , Hidroxizina/uso terapêutico , Deficiência Intelectual/dietoterapia , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/metabolismo , Masculino , Sono/fisiologia , Resultado do Tratamento , Adulto Jovem
10.
Clin Exp Dermatol ; 45(7): 866-871, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32363638

RESUMO

BACKGROUND: Pruritus is one of the most common problems in patients with chronic renal failure. Of all patients with end-stage renal disease (ESRD), 60-80% report pruritus during their life. AIM: To compare the effect of gabapentin (GBP) and hydroxyzine (HYDZ) in treating pruritus in patients on dialysis. METHODS: In a double-blind, randomized, crossover clinical trial, 32 patients on dialysis who reported pruritus were assigned randomly to receive either GBP or HYDZ for 6 weeks; the first group received GBP 100 mg/day orally and the second group received HYDZ 25 mg/day orally for 6 weeks. After this 6-week period (Period 1) there was a washout period of 2 weeks then patients were crossed over to the other drug (the first group receiving HYDZ and second group receiving GBP) and followed up for a further 6 weeks (Period 2). A visual analogue scale was used to measure pruritus intensity in the groups before and after the first and second period. RESULTS: In Period 1, pruritus severity decreased from 7.1 ± 1.46 at baseline to 2.17 ± 1.82 at 6 weeks in the GBP group (P = 0.001) and from 6.83 ± 2.11 to 2.86 ± 1.67 in the HYDZ group (P = 0.001). In Period 2, pruritus severity decreased from 5.1 ± 1.61 at baseline to 1.56 ± 0.82 at 6 weeks in the GBP group (P < 0.01) and from 5.23 ± 2.11 to 2.1 ± 1.87 in the HYDZ group (P = 0.001). CONCLUSION: Results showed that both HYDZ and GBP significantly improved and controlled pruritus in patients on dialysis, with no significant difference observed between the two drugs.


Assuntos
Gabapentina/uso terapêutico , Hidroxizina/uso terapêutico , Prurido/tratamento farmacológico , Diálise Renal/efeitos adversos , Administração Oral , Adulto , Ansiolíticos/administração & dosagem , Ansiolíticos/uso terapêutico , Antipruriginosos/administração & dosagem , Antipruriginosos/uso terapêutico , Estudos de Casos e Controles , Estudos Cross-Over , Método Duplo-Cego , Feminino , Seguimentos , Gabapentina/administração & dosagem , Humanos , Hidroxizina/administração & dosagem , Irã (Geográfico)/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Prurido/epidemiologia , Prurido/etiologia , Diálise Renal/métodos , Índice de Gravidade de Doença , Escala Visual Analógica
11.
Int J Legal Med ; 134(4): 1339-1344, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32144480

RESUMO

It is difficult to carry out toxicological investigations in biological samples collected from extensively decomposed bodies and to interpret obtained results as several pitfalls should be considered: redistribution phenomena, degradation of xenobiotics during the postmortem period, contamination by putrefaction fluids, and external contamination. This work aims to present two cases in order to illustrate and discuss these difficulties in this tricky situation. Case#1: the body of a 30-year-old woman was found in a wooded area (1 month after she has been reported missing by her family): hair and a femur section were sampled. Case#2: the decomposed corpse of a 52-year-old man was found in a ditch: hair and nails were sampled. After decontamination steps, toxicological investigations were performed using liquid chromatography with high-resolution mass spectrometry and tandem mass spectrometry detection methods. In case#1, the same drugs or metabolites (benzodiazepines, propranolol, tramadol, acetaminophen, paroxetine, and oxetorone) were detected in hair and in bone specimens. This result combination strongly suggests intakes close to the time of death for three of them (oxazepam, lormetazepam, and propranolol). In case#2, results of toxicological investigations in hair and nails [(hair/nail concentration in ng/mg) nordiazepam (1.12/1.06), oxazepam (0.113/0.042), zolpidem (0.211/< 0.01), hydroxyzine (0.362/< 0.01), and cetirizine (0.872/1.110)] were both consistent with several drug intakes but were not contributory to cause of death determination. In case of positive toxicological results in biological samples collected from extensively decomposed bodies (such as hair, bones, or nails), it is challenging to determine the time, and even more, the level of the dose of exposure(s).


Assuntos
Restos Mortais , Toxicologia Forense , Mudanças Depois da Morte , Detecção do Abuso de Substâncias/métodos , Adulto , Benzodiazepinas/análise , Osso e Ossos/química , Feminino , Cabelo/química , Humanos , Hidroxizina/análise , Masculino , Pessoa de Meia-Idade , Unhas/química , Propranolol/análise , Manejo de Espécimes , Zolpidem/análise
13.
Trials ; 21(1): 1, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898511

RESUMO

BACKGROUND: Surgery can generate significant stress and anxiety in up to 70% of the paediatric population. There are several pharmacological and non-pharmacological strategies to reduce pre-operative anxiety in children, however, they have several side effects and the available information about them is contradictory. The role of clowns and hydroxyzine in the management of anxiety is controversial, with some studies supporting and others contraindicating both strategies. METHODS: We propose a randomised double-blind, controlled clinical trial that will evaluate the effectiveness of both interventions (hydroxyzine and clowns), alone or in combination, to reduce pre-operative anxiety (using the modified Yale scale of preoperative anxiety) in children aged 2-16 years undergoing outpatient surgery (n = 188). Subjects will be randomised into two groups - (1) standard procedure (parental accompaniment) combined with placebo or (2) standard procedure combined with preoperative hydroxyzine. After randomisation, they will be divided by chance into two further groups, depending on the presence of clowns on the patient's surgery day. Control of pre-operative anxiety will be determined in the four groups by a modified Yale scale of preoperative anxiety and cortisol levels. Compliance of children during induction of anaesthesia, time until anaesthesia recovery, presence of postoperative delirium and use of analgesia until discharge will be also assessed. For additional information, the children, parents and healthcare professionals involved in the study will complete a satisfaction survey. CONCLUSIONS: This study aims to gather evidence on which of these four therapeutic options achieves the highest reduction of pre-operative anxiety with the best safety profile to allow paediatricians and anaesthesiologists to use the most effective and safe option for their patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03324828. Registered 21 September 2017.


Assuntos
Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Hidroxizina/uso terapêutico , Cuidados Pré-Operatórios/métodos , Adolescente , Ansiedade/psicologia , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino
14.
J Pharm Pract ; 33(2): 206-212, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31030620

RESUMO

INTRODUCTION: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with several indications, one of which is for depression. We present a case of probable paroxetine-induced serotonin syndrome. CASE SUMMARY: A 21-year-old female with a history of generalized anxiety disorder and major depression presented with increased depressive symptoms over several months while taking fluoxetine 20 mg daily. Fluoxetine was discontinued without taper and replaced with paroxetine 10 mg daily, along with hydroxyzine 50 mg twice daily as needed for anxiety. Within a week of starting the paroxetine, the patient reported increased anxiety, insomnia, and constant shaking. The paroxetine continued to be uptitrated over a 3-week period to a dose 30 mg due to unremitting depressive symptoms. One month later, the patient presented with tachycardia, generalized body aches, extreme fatigue, weakness, uncontrollable twitching, tremor, and hyperreflexia. A widespread burning sensation accompanied by random hot flashes without diaphoresis was also noted. Serotonin syndrome was diagnosed using the Hunters criteria. Paroxetine was discontinued, and the patient's physical symptoms resolved within a week. DISCUSSION: To date, only 5 cases of serotonin syndrome have been reported in patients receiving SSRI monotherapy at recommended therapeutic doses.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Paroxetina/administração & dosagem , Paroxetina/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Ansiedade/tratamento farmacológico , Feminino , Fluoxetina/administração & dosagem , Humanos , Hidroxizina/administração & dosagem , Serotonina , Adulto Jovem
16.
J Nutr Health Aging ; 24(1): 20-27, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31886804

RESUMO

OBJECTIVES: The association between anticholinergic load-based Anticholinergic Risk Scale scores and nutritional status is unclear in Japanese patients. The aim of this study was to establish whether anticholinergic load affects the nutritional status of geriatric patients in convalescent stages. DESIGN: Retrospective longitudinal cohort study. SETTING: Convalescent rehabilitation wards. PARTICIPANTS: Of the 1490 patients aged ≥65 years who were discharged from convalescent rehabilitation wards between July 2010 and October 2018, 908 patients met the eligibility criteria. They were categorized according to the presence or absence of increased anticholinergic load from admission to discharge. MEASUREMENTS: Demographic data, laboratory data, the Functional Independence Measure were analyzed between the groups. The primary outcome was Geriatric Nutritional Risk Index (GNRI) at discharge. Multiple linear regression analysis was performed to analyze the relationship between anticholinergic load and GNRI at discharge. RESULTS: Multiple linear regression analysis after adjusting for confounding factors revealed that anticholinergic load was independently and negatively correlated with GNRI at discharge. Particularly, the use of chlorpromazine, hydroxyzine, haloperidol, metoclopramide, risperidone, etc. increased significantly from admission to discharge. CONCLUSION: Increased anticholinergic load during hospitalization may be a predictor of nutritional status in geriatric patients.


Assuntos
Antagonistas Colinérgicos/sangue , Antagonistas Colinérgicos/farmacocinética , Desnutrição/epidemiologia , Estado Nutricional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Clorpromazina/farmacocinética , Antagonistas Colinérgicos/uso terapêutico , Feminino , Avaliação Geriátrica , Haloperidol/farmacocinética , Hospitalização , Humanos , Hidroxizina/farmacocinética , Japão/epidemiologia , Modelos Lineares , Estudos Longitudinais , Masculino , Metoclopramida/farmacocinética , Análise Multivariada , Avaliação Nutricional , Alta do Paciente , Análise de Regressão , Estudos Retrospectivos , Risperidona/farmacocinética
17.
Mikrochim Acta ; 187(1): 51, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848718

RESUMO

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.


Assuntos
Etilenoglicóis/química , Estruturas Metalorgânicas/química , Metacrilatos/química , Anlodipino/análise , Eletrocromatografia Capilar , Cloroquina/análise , Clembuterol/análise , Hidroxicloroquina/análise , Hidroxizina/análise , Estrutura Molecular , Nefopam/análise , Tamanho da Partícula , Estereoisomerismo , Propriedades de Superfície
20.
J Vet Pharmacol Ther ; 42(6): 617-623, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490561

RESUMO

Hydroxyzine is a first-generation antihistamine and cetirizine, a second-generation antihistamine and active metabolite of hydroxyzine. Hydroxyzine is commonly used in performance horses and as such its use in closely regulated; however, there are no published studies suitable for establishing appropriate regulatory recommendations. In the current study, 12 exercised Thoroughbred research horses received a single oral administration of 500 mg of hydroxyzine. Blood and urine samples were collected prior to and up to 96 hr postdrug administration and concentrations of hydroxyzine and cetirizine determined using liquid chromatography-tandem mass spectrometry. A joint parent/metabolite population 2-compartment pharmacokinetic model with first-order absorption and elimination was utilized to describe the pharmacokinetics of both compounds. Serum hydroxyzine and cetirizine concentrations were above the limit of quantitation (0.1 ng/ml) of the assay at 96 hr (the last time point sampled). The terminal half-life was 7.41 and 7.13 hr for hydroxyzine and cetirizine, respectively. Findings from this study suggest that a prolonged withdrawal time should be observed if this compound is used in performance administered to performance horses and is classified as prohibited substance by the applicable regulatory body.


Assuntos
Cetirizina/farmacocinética , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Cavalos/metabolismo , Hidroxizina/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Cetirizina/administração & dosagem , Cetirizina/sangue , Cetirizina/metabolismo , Meia-Vida , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/sangue , Antagonistas dos Receptores Histamínicos H1/metabolismo , Cavalos/sangue , Hidroxizina/administração & dosagem , Hidroxizina/sangue , Hidroxizina/metabolismo
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