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1.
Expert Opin Pharmacother ; 21(5): 567-580, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32286097

RESUMO

Introduction: Though many unanswered questions about the pathophysiology of Tourette Syndrome remain, several pharmacotherapies for tics have been studied, with varying results in terms of efficacy and the strength of evidence.Areas covered: This literature review encompasses pharmacotherapies for tics. The pharmacotherapies discussed in this review include: alpha agonists, antipsychotics, topiramate, botulinum toxin, and dopamine depleters.Expert opinion: Once the presence of tics is confirmed and psychoeducation and support are provided to patients and caregivers, one must examine the degree of tic-related impairment and the presence of psychiatric comorbidities. These factors influence treatment decisions as the presence of comorbidity and related impairment may shift the treatment target. When selecting a medication for tics, the presence of ADHD (the most frequent comorbidity) strengthens the case for choosing an alpha agonist. The case for antipsychotic medications is strongest when tic-related impairment is severe and/or the tics are refractory to more conservative measures. All medications require drug safety monitoring procedures and reevaluation over time.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Tique/tratamento farmacológico , Tiques/tratamento farmacológico , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/efeitos adversos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Toxinas Botulínicas/uso terapêutico , Comorbidade , Humanos , Transtornos de Tique/epidemiologia , Transtornos de Tique/psicologia , Tiques/epidemiologia , Tiques/psicologia , Síndrome de Tourette/tratamento farmacológico , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/psicologia
2.
PLoS One ; 15(1): e0227595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929565

RESUMO

OBJECTIVE: To evaluate the prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017. METHODS: A descriptive analysis using pharmacy prescription data was conducted. Outpatient prescription data was extracted from the Hospital Prescription Analysis Cooperative Project. Prescribing patterns, trends of visits, and corresponding expenditures for glaucoma medications were analyzed. RESULTS: A total of 84297 ambulatory prescriptions were included in the current study. Visits by glaucoma patients increased from 13808 in 2013 to 20060 in 2017. Over the same period, the yearly expenditure for glaucoma drugs increased from 2.33 million to 3.95 million Chinese Yuan (CNY). Among all the six classes of glaucoma drugs (prostaglandin analogues, carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, cholinergic agonists and fixed combinations), ß-receptor antagonists were the most commonly prescribed in 2013, accounting for 34.3% of patients, but gradually decreased to 27.1% in 2017. Prostaglandin analogues became the most frequently prescribed drugs in 2017, accounting for 30.2% of the visits. Prostaglandin analogues are the most expensive and yielded a total expenditure of 2.34 million CNY in 2017, followed by carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, fixed combinations, and cholinergic agonists. Combination therapy became increasingly prescribed in 2017. CONCLUSION: Glaucoma prescribing practices exhibited substantial changes over the study period. The number of glaucoma prescriptions continuously increased from 2013 to 2017, leading to increased prescription costs. These findings implied a similar trend observed in previous studies, as well as recommendations in the appropriate guidelines.


Assuntos
Glaucoma/tratamento farmacológico , Padrões de Prática Médica/tendências , Adolescente , Agonistas alfa-Adrenérgicos/economia , Agonistas alfa-Adrenérgicos/uso terapêutico , Antagonistas Adrenérgicos beta/economia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Anidrase Carbônica/economia , Inibidores da Anidrase Carbônica/uso terapêutico , China , Agonistas Colinérgicos/economia , Agonistas Colinérgicos/uso terapêutico , Cidades , Quimioterapia Combinada/economia , Quimioterapia Combinada/tendências , Feminino , Glaucoma/economia , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/economia , Prostaglandinas Sintéticas/economia , Prostaglandinas Sintéticas/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
3.
Einstein (Sao Paulo) ; 18: eRW5055, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31994613

RESUMO

The objective of the present study was to assess the efficacy of different doses, times for infusion of the first dose, intervals of administration of subsequent doses, and number of epinephrine doses in the survival of children and adolescents who went into cardiorespiratory arrest. It is a review study with data from the PubMedⓇ/MEDLINEⓇdatabase. The search was for articles published from January 1st, 2000 to February 10, 2019, with a sample of patients aged under 18 years, published in English, Portuguese and Spanish. We found 222 articles, of which 16 met the inclusion criteria of the study. The first dose should be given as soon as possible. The standard dose (0.01mg/kg) has a better outcome when compared to the higher dose (0.1mg/kg). There is an iⓇverse relation between the number of epinephrine doses and survival. The interval currently recommended between doses has lower survival when compared to larger intervals. The dosage recommended by the American Heart Association presents a better outcome for survival, but the interval between doses and the maximum number of doses should be better assessed.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Epinefrina/administração & dosagem , Parada Cardíaca/tratamento farmacológico , Adolescente , Criança , Relação Dose-Resposta a Droga , Feminino , Parada Cardíaca/mortalidade , Humanos , Masculino , Fatores de Tempo
5.
Arch Med Res ; 50(6): 325-332, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31677537

RESUMO

BACKGROUND: The timing of initiation of Norepinephrine (NEP) in septic shock is controversial. AIM OF THE STUDY: We evaluated the impact of early NEP simultaneously with fluids in those patients. METHODS: We randomized 101 patients admitted to the emergency department with septic shock to early NEP simultaneously with IV fluids (early group) or after failed fluids trial (late group). The primary outcome was the in-hospital survival while the secondary outcomes were the time to target mean arterial pressure (MAP) of 65 mmHg, lactate clearance and resuscitation volumes. RESULTS: There was no significant difference between the two groups regarding the baseline characteristics. NEP infusion started after 25 (20-30) and 120 (120-180) min in the early and late groups (p = 0.000). MAP of 65 mmHg was achieved faster in the early group (2 [1-3.5] h vs. 3 [2-4.75] h, p = 0.003). Serum lactate was decreased by 37.8 (24-49%) and 22.2 (3.3-38%) in both groups respectively (p = 0.005). Patients with early NEP were resuscitated by significantly lower volume of fluids (25 [18.8-28.7] mL/kg vs. 32.5 [24.4-34.6] mL/kg) in the early and late groups (p = 0.000). The early group had survival rate of 71.9% compared to 45.5% in the late group (p = 0.007). NEP started after 30 (20-120 min) in survivors vs. 120 (30-165 min) in non-survivors (p = 0.013). CONCLUSIONS: We concluded that early Norepinephrine in septic shock might cause earlier restoration of blood pressure, better lactate clearance and improve in-hospital survival.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Norepinefrina/uso terapêutico , Ressuscitação/métodos , Choque Séptico/tratamento farmacológico , Idoso , Pressão Sanguínea/fisiologia , Feminino , Humanos , Infusões Intravenosas/métodos , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Vet Clin North Am Small Anim Pract ; 49(6): 1013-1027, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31481257

RESUMO

Alpha-2 agonists have potent analgesic effects, in addition to their sedative actions. Alpha-2 agonists provide analgesia through any of several routes of administration, including parenteral, oral, epidural or intrathecal and intraarticular, because of spinal and supraspinal actions. Systemic doses are short acting, whereas local administration at the site of action result in longer analgesic effects. The potent cardiovascular and respiratory effects of alpha-2 agonists should be considered when used as analgesics.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Dor/veterinária , Animais de Estimação , Analgesia/métodos , Analgesia/veterinária , Animais , Dor/tratamento farmacológico
7.
Vestn Oftalmol ; 135(3): 113-120, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31393455

RESUMO

Glaucoma is the main cause of irreversible blindness in the world. The selective α2 adrenergic receptor agonist brimonidine holds an important place among the hypotensive eye drops. The second part of this review focuses on some important effects of brimonidine that characterizes it as a medication with direct neuroprotective multifactorial action, discusses its influence on ocular blood flow and highlights its capability to maintain normal autoregulation of ocular blood flow.


Assuntos
Glaucoma , Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos , Tartarato de Brimonidina , Humanos , Pressão Intraocular , Quinoxalinas
8.
Anaesthesia ; 74(11): 1389-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389614

RESUMO

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio do Plexo Braquial/métodos , Epinefrina/farmacologia , Hemodinâmica/efeitos dos fármacos , Lidocaína/farmacologia , Microcirculação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Hemodinâmica/fisiologia , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Ultrassonografia de Intervenção/métodos , Adulto Jovem
9.
Fish Shellfish Immunol ; 92: 188-195, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176766

RESUMO

Octopamine (OA), a biogenic monoamine, is known to mediate several immune responses. This study analyzed the effects of OA on immunological regulation in the tiger shrimp Penaeus monodon. The immune parameters including total haemocyte count, differential haemocyte count, phenoloxidase activity, respiratory bursts, superoxide dismutase activity, and phagocytic activity and clearance efficiency in response to the pathogen, Photobacterium damselae, were determined when shrimp were individually injected with saline or OA at 100 or 1000 pmol shrimp-1. In addition, the intracellular second messengers in haemocyte such as Ca2+ and adenosine 3',5'-cyclic monophosphate (cAMP) were examined in shrimp receiving saline or OA at 1 or 10 nmol shrimp-1. Results showed that all of the immune parameters significantly increased at 2-4 h in OA-injected shrimp except hyaline cells in 100 pmol shrimp-1-injected shrimp at 4 h, but phenoloxidase activity per granulocyte significantly decreased at 2-4 h. However, these had returned to saline control levels after receiving OA for 8 h except differential haemocyte count and phenoloxidase activity per granulocyte for 16 h. An injection of OA also significantly increased the survival rate of shrimp challenged with Pho. damselae. Shrimp receiving OA at 1 and 10 nmol shrimp-1 significantly increased the intracellular Ca2+ concentration ([Ca2+]i) at 30-60 min and 30 min, and cAMP concentration [cAMP]i) at 5-15 min and 15 min, respectively. However, [Ca2+]i at 50-60 min, and [cAMP]i at 30-60 min returned to saline control when the shrimp received OA at 10 nmol shrimp-1, and at 1 and 10 nmol shrimp-1, respectively. These results suggest that OA administration by injection at ≤1000 pmol shrimp-1 mediates transient upregulation of immunity together with the increased resistance of P. monodon to Pho. damselae, which are modulated through intracellular Ca2+ and cAMP second messenger pathways.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/efeitos dos fármacos , Octopamina/metabolismo , Penaeidae/genética , Penaeidae/imunologia , Transdução de Sinais/imunologia , Adjuvantes Imunológicos/farmacologia , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/metabolismo , Animais , Cálcio/metabolismo , AMP Cíclico/metabolismo , Perfilação da Expressão Gênica , Octopamina/administração & dosagem , Photobacterium/fisiologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/imunologia
10.
Vestn Oftalmol ; 135(2): 144-150, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31215546

RESUMO

Glaucoma is the main cause of irreversible blindness in the world. Among the hypotensive eye drops, an important place belongs to the selective α2-adrenergic receptor antagonist brimonidine. This part of the review focuses on key pharmacological and therapeutic characteristics of brimonidine and its mode of action. The article also discusses the side effects of brimonidine and the methods of their prevention.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Glaucoma , Tartarato de Brimonidina , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Soluções Oftálmicas , Quinoxalinas
11.
Biol Pharm Bull ; 42(5): 736-743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061315

RESUMO

ß-Adrenoceptors are subclassified into 3 subtypes (ß1-ß3). Among these, ß3-adrenoceptors are present in various types of smooth muscle and are believed to play a role in relaxation responses of these muscles. ß3-Adrenoceptors are also present in urinary bladder smooth muscle (UBSM), although their expression varies depending on the animal species. To date, there has been little information available about the endogenous ligand that stimulates ß3-adrenoceptors to produce relaxation responses in UBSM. In this study, to determine whether noradrenaline is a ligand of UBSM ß3-adrenoceptors, noradrenaline-induced relaxation was analyzed pharmacologically using rat UBSM. We also assessed whether noradrenaline metabolites were ligands in UBSM. In isolated rat urinary bladder tissues, mRNAs for ß1-, ß2-, and ß3-adrenoceptors were detected using RT-PCR. In UBSM preparations contracted with methacholine (3 × 10-5 M), noradrenaline-induced relaxation was not inhibited by the following antagonists: atenolol (10-6 M; selective ß1-adrenoceptor antagonist), ICI-118,551 (3 × 10-8 M; selective ß2-adrenoceptor antagonist), propranolol (10-7 M; non-selective ß-adrenoceptor antagonist), and bupranolol (10-7 M; non-selective ß-adrenoceptor antagonist). In the presence of propranolol (10-6 M), noradrenaline-induced relaxation was competitively inhibited by bupranolol (3 × 10-7-3 × 10-6 M) or SR59230A (10-7-10-6 M; selective ß3-adrenoceptor antagonist), with their pA2 values calculated to be 6.64 and 7.27, respectively. None of the six noradrenaline metabolites produced significant relaxation of methacholine-contracted UBSM. These findings suggest that noradrenaline, but not its metabolites, is a ligand for ß3-adrenoceptors to produce relaxation responses of UBSM in rats.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Norepinefrina/farmacologia , Receptores Adrenérgicos beta 3/fisiologia , Bexiga Urinária/efeitos dos fármacos , Animais , Masculino , Relaxamento Muscular/fisiologia , Músculo Liso/fisiologia , Ratos Wistar , Bexiga Urinária/fisiologia
13.
BMJ Case Rep ; 12(4)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30996064

RESUMO

Pesticide self-poisoning is rare in developed countries. We report a suicide case after inhalation of a pyrethrins containing insecticide spray. The patient presented at the emergency department with respiratory failure. Despite mechanical ventilation, he developed severe pulmonary inflammation with a systemic inflammatory response syndrome and died 5 days later. Studies reporting on acute pyrethrins or pyrethroids insecticide poisoning in both occupational and non-occupational cases usually describe mild and self-limiting respiratory symptoms as the predominant symptom. Severe or fatal cases of pyrethrins or pyrethroids poisoning are very rare. Patients with asthma or allergies are apparently more at risk for severe symptoms. In these cases, early and aggressive treatment with bronchodilatators, steroids, antihistamines and epinephrine should be considered.


Assuntos
Cuidados Críticos/métodos , Inseticidas/administração & dosagem , Piretrinas/administração & dosagem , Suicídio , Administração por Inalação , Agonistas alfa-Adrenérgicos/uso terapêutico , Idoso , Hidratação , Humanos , Inseticidas/envenenamento , Masculino , Norepinefrina/uso terapêutico , Piretrinas/efeitos adversos , Respiração Artificial
14.
Kardiologiia ; 59(4): 52-63, 2019 Apr 17.
Artigo em Russo | MEDLINE | ID: mdl-31002040

RESUMO

AIM: to investigate the functional interaction of α2-adrenergic and imidazoline receptors recently identified on the sarcolemma of isolated cardiomyocytes for regulation of the intracellular calcium and the production of the signal molecule of nitric oxide (NO). MATERIALS AND METHODS: experiments were performed on isolated left ventricular cardiomyocytes of Wistar rats. Potential-dependent Ca2+-currents were measured from the whole-cell by the patch-clamp method in "perforated-patch" configuration. The intracellular calcium and the production of nitric oxide were estimated from the changes in fluorescence intensity of the Ca2+-specific and NO-sensitive dyes at fluorescent or confocal microscope. RESULTS: It has been shown that α2­adrenergic and imidazoline receptor agonists inhibit L-type Ca2+-currents by themselves, but their effects do not develop against each other's background. The blockade of key effector molecules: protein kinase B (Akt kinase) for α2­adrenergic receptors, and protein kinase C for imidazoline receptors causes the action of agonists to become additive. Both the selective α2­agonist, guanabenz, and the specific agonist of the first type imidazoline receptors, rilmenidine, show an additional inhibition of Ca2+-currents against the basal background already reduced by the activation of one of the two receptor systems. Wherein rilmenidine increases the level of free  Ca2+ in the cytosol, and guanabenz, on the contrary, decreases it. The action of guanabenz does not develop against the background of rilmenidine, although it, in turn, effectively increases the intracellular level of calcium in guanabenz-pretreated cardiac cells. Activation of α2­adrenergic receptors leads to significant stimulation of the endothelial isoform of NO-synthase, and as a result to an increase in the NO level. Activation of imidazoline receptors itself does not affect NO synthesis but it prevents the production of NO induced by α2­agonists. CONCLUSION: obtained data make it possible to formulate a number of useful recommendations for clinical practice, and also to clarify the non-central peripheral effects arising from the activation of α2­adrenergic or imidazoline systems under conditions of endogenous hyperactivation on of the two systems.


Assuntos
Imidazolinas/antagonistas & inibidores , Agonistas alfa-Adrenérgicos , Animais , Receptores de Imidazolinas , Ratos , Ratos Wistar
15.
Mov Disord ; 34(5): 637-656, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30919519

RESUMO

Movement disorders differ in children to adults. First, neurodevelopmental movement disorders such as tics and stereotypies are more prevalent than parkinsonism, and second, there is a genomic revolution which is now explaining many early-onset dystonic syndromes. We outline an approach to children with movement disorders starting with defining the movement phenomenology, determining the level of functional impairment due to abnormal movements, and screening for comorbid psychiatric conditions and cognitive impairments which often contribute more to disability than the movements themselves. The rapid improvement in our understanding of the etiology of movement disorders has resulted in an increasing focus on precision medicine, targeting treatable conditions and defining modifiable disease processes. We profile some of the key disease-modifying therapies in metabolic, neurotransmitter, inflammatory, and autoimmune conditions and the increasing focus on gene or cellular therapies. When no disease-modifying therapies are possible, symptomatic therapies are often all that is available. These classically target dopaminergic, cholinergic, alpha-adrenergic, or GABAergic neurochemistry. Increasing interest in neuromodulation has highlighted that some clinical syndromes respond better to DBS, and further highlights the importance of "disease-specific" therapies with a future focus on individualized therapies according to the genomic findings or disease pathways that are disrupted. We summarize some pragmatic applications of symptomatic therapies, neuromodulation techniques, and some rehabilitative interventions and provide a contemporary overview of treatment in childhood-onset movement disorders. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Doenças Autoimunes do Sistema Nervoso/terapia , Tomada de Decisão Clínica , Estimulação Encefálica Profunda , Dietoterapia , Terapia Genética , Fatores Imunológicos/uso terapêutico , Erros Inatos do Metabolismo/terapia , Transtornos dos Movimentos/terapia , Agonistas alfa-Adrenérgicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Doenças Autoimunes do Sistema Nervoso/complicações , Toxinas Botulínicas Tipo A/uso terapêutico , Canabinoides/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Quelantes/uso terapêutico , Ácido Quenodesoxicólico/uso terapêutico , Criança , Suplementos Nutricionais , Dopaminérgicos/uso terapêutico , Terapia de Reposição de Enzimas , GABAérgicos/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Erros Inatos do Metabolismo/complicações , Inibidores da Monoaminoxidase/uso terapêutico , Transtornos dos Movimentos/etiologia , Fármacos Neuromusculares/uso terapêutico , Compostos Organofosforados/uso terapêutico , Pterinas/uso terapêutico
16.
Laryngoscope ; 129(12): 2775-2781, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30786035

RESUMO

OBJECTIVES/HYPOTHESIS: Oxymetazoline is an α-adrenergic agonist that is commonly used as a topical hemostatic agent in the operating room during ear, nose, and throat surgery. There are limited data on oxymetazoline pharmacokinetics in children who undergo general anesthesia. We assessed the hemodynamic effects and systemic absorption of topically applied oxymetazoline in children undergoing various nasal procedures. STUDY DESIGN: Prospective trial. METHODS: Children ages 2 to 17 years undergoing functional endoscopic sinus surgery, turbinate resection, or adenoidectomy were enrolled. The surgeon placed oxymetazoline-soaked pledgets (1.5 mL of 0.05% solution) according to our usual clinical practice. Blood samples for oxymetazoline assay were drawn at 5, 10, 20, 45, 90, and 150 minutes, and hemodynamic data were recorded at 5-minute intervals. Data analysis included mixed-effects regression and population pharmacokinetic/pharmacodynamic modeling. RESULTS: The analysis included 27 patients, age 7 ± 4 years, who received between 2 and 12 pledgets (3-18 mL) of oxymetazoline. Relative bioavailability compared to the spray formulation was 2.3 (95% confidence interval [CI]: 1.6-3.2), with slow absorption from the mucosal surface (absorption half-life 64 minutes; 95% CI: 44-90). Mean arterial pressure did not increase with oxymetazoline instillation at the observed oxymetazoline serum concentrations (0.04-7.6 µg/L). CONCLUSIONS: Despite concerns regarding oxymetazoline administration to mucosal membranes, we found that hemodynamic changes were clinically negligible with our usual clinical use of pledgets soaked in oxymetazoline. Compared to data on oxymetazoline in spray formulation, bioavailability was increased twofold with pledgets, but systemic absorption was very slow, contributing to low serum concentrations and limited hemodynamic effects. LEVEL OF EVIDENCE: 1b. Laryngoscope, 129:2775-2781, 2019.


Assuntos
Hemodinâmica/fisiologia , Procedimentos Cirúrgicos Nasais/métodos , Doenças Nasais/cirurgia , Oximetazolina/farmacocinética , Administração Intranasal , Adolescente , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacocinética , Criança , Pré-Escolar , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Período Intraoperatório , Masculino , Doenças Nasais/metabolismo , Doenças Nasais/fisiopatologia , Oximetazolina/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
17.
Am J Physiol Endocrinol Metab ; 316(5): E729-E740, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807213

RESUMO

The attractive tenet that recruitment and activation of brown adipose tissue (BAT) and uncoupling protein 1 (UCP1) could counteract the development of obesity and its comorbidities in humans has been experimentally corroborated mainly by experiments demonstrating that UCP1-ablated mice on a C57Bl/6 background (exempt from thermal stress) become more obese when fed a high-fat diet. However, concerns may be raised that this outcome of UCP1 ablation is restricted to this very special inbred and particularly obesity-prone mouse strain. Therefore, we have examined to which degree UCP1 ablation has similar metabolic effects in a mouse strain known to be obesity resistant: the 129S strain. For this, male 129S2/sv or 129SV/Pas mice and corresponding UCP1-knockout mice were fed chow or a high-fat or a cafeteria diet for 4 wk. The absence of UCP1 augmented obesity (weight gain, body fat mass, %body fat, fat depot size) in high-fat diet- and cafeteria-fed mice, with a similar or lower food intake, indicating that, when present, UCP1 indeed decreases metabolic efficiency. The increased obesity was due to a decrease in energy expenditure. The consumption of a high-fat or cafeteria diet increased total BAT UCP1 protein levels in wild-type mice, and correspondingly, high-fat diet and cafeteria diet-fed mice demonstrated increased norepinephrine-induced oxygen consumption. There was a positive correlation between body fat and total BAT UCP1 protein content. No evidence for diet-induced adrenergic thermogenesis was found in UCP1-ablated mice. Thus, the obesity-reducing effect of UCP1 is not restricted to a particular, and perhaps not representative, mouse strain.


Assuntos
Dieta Hiperlipídica , Obesidade/genética , Termogênese/genética , Proteína Desacopladora 1/genética , Tecido Adiposo , Tecido Adiposo Marrom/metabolismo , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Ingestão de Alimentos , Metabolismo Energético/genética , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Norepinefrina/farmacologia , Obesidade/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo , Ganho de Peso
18.
Int J Obstet Anesth ; 38: 25-31, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30685301

RESUMO

BACKGROUND: Phenylephrine, although considered the vasopressor of choice, can cause reflex bradycardia and a fall in cardiac output. Norepinephrine, due to its direct positive chronotropic and reflex negative chronotropic actions, is expected to overcome this problem. However, limited information about its effective dose for management of post-spinal hypotension, and its potency compared to phenylephrine, is available. METHODS: One hundred consecutive patients who developed post-spinal hypotension were treated with a predetermined dose of either phenylephrine or norepinephrine. Correction of hypotension after one minute was considered 'success'. The starting dose for the first patient and testing interval (the incremental or decremental dosing) were 100 µg and 10 µg in the phenylephrine group, and 6 µg and 0.5 µg in the norepinephrine group. Doses for subsequent patients were determined by the responses of previous patients according to the Narayana rule for up-down sequential allocation. ED95 and ED50 of phenylephrine and norepinephrine boluses and their potency ratio were calculated. RESULTS: Using Probit analysis, ED95 and ED50 values were 43.1 µg (95% CI 39.5 to 65.0 µg) and 33.2 µg (95% CI 5.1 to 37.0 µg) for phenylephrine, and 3.7 µg (95% CI 3.5 to 4.7 µg) and 3.2 µg (95% CI 1.8 to 3.4 µg) for norepinephrine. The relative potency ratio of norepinephrine and phenylephrine was 11.3 (95% CI 8.1 to 16.9). CONCLUSION: Based on the results of this study, norepinephrine is about 11 times more potent than phenylephrine. When used as bolus doses for treatment of hypotension, 100 µg phenylephrine should be approximately equivalent to 9 µg norepinephrine.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/tratamento farmacológico , Norepinefrina/farmacologia , Fenilefrina/farmacologia , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Hipotensão/etiologia , Gravidez , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(4): e14128, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681574

RESUMO

To determine whether cataract or glaucoma and combined cataract and glaucoma surgery (CGS) affect glaucoma medication usage.We recruited patients who received new diagnoses of glaucoma, either primary open-angle glaucoma (POAG) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 365.1) or primary angle-closure glaucoma (PACG) (ICD-9-CM code 365.2), between 1998 and 2011 and had undergone cataract surgery alone (CS), glaucoma surgery alone (GS), or CGS under the National Health Insurance program in Taiwan. CS, GS, and CGS in all the patients were performed after the glaucoma diagnosis date. The patients were subdivided into CS, CGS, and GS groups. The number of glaucoma medications, including prostaglandin analogs, ß-blockers, carbonic anhydrase inhibitors, α-agonists, pilocarpine, and a combination of drugs, in each prescription, were compared before and after surgery.The mean number of glaucoma medications in each prescription before the surgery increased from approximately 0.5/1 (CS/CGS + GS) to a peak of 1.75/3 within 3 months before the index date. The mean number of glaucoma medications in each prescription reduced to 0 (CS group) and to approximately 0.5 (CGS and GS) at the end of the 3-year follow-up period. The mean number of glaucoma medications in each prescription significantly reduced at the time points within 6 months, between 6 months and 2 years, and during 2 to 3 years after surgery in each group. At the end of the 3-year period, the reduction effect was most evident in the CS group. Similar trends were also observed in the POAG and PACG group.CS, GS, and CGS significantly reduced the number of glaucoma medications used by the glaucoma patients.


Assuntos
Extração de Catarata/estatística & dados numéricos , Glaucoma de Ângulo Fechado/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Prescrições/estatística & dados numéricos , Trabeculectomia/estatística & dados numéricos , Agonistas alfa-Adrenérgicos/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Anti-Hipertensivos/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Estudos de Casos e Controles , Catarata/complicações , Bases de Dados Factuais , Feminino , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Pilocarpina , Prostaglandinas Sintéticas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
20.
Dis Colon Rectum ; 62(2): 234-240, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30451757

RESUMO

BACKGROUND: Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence. OBJECTIVES: The aim of this study was to investigate the effect of the α-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury. DESIGN: This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study. SETTINGS: The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary. PATIENTS: Nineteen patients were enrolled into a randomized double-blind, placebo-controlled clinical trial with 2 arms: placebo for 4 weeks followed by oxymetazoline for 4 weeks, or vice versa, with an interval 2-week washout period, in a crossover trial design. Treatment order was randomly assigned, and fecal incontinence was captured with daily diaries. MAIN OUTCOME MEASURES: The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration. RESULTS: Resting anal pressure increased in response to oxymetzoline (25.2%). The change in the mean fecal incontinence episodes per month (12 hours post drug application) favored oxymetazoline over placebo: 26.3 (SD ±28.4) versus 36 (SD ±39.8) (p = 0.021). When only nongas episodes were included, the mean number of episodes decreased from 10.1 (+4.3) to 6.3 (±2.1) fecal incontinence episodes per month (p = 0.022). No difference was observed in adverse events between treatment and placebo periods. All pharmacokinetic samples were below the detection limit. LIMITATIONS: The study was limited by the small number of participants. CONCLUSIONS: In this study, oxymetazoline gel presented a clear clinical beneficial effect accompanied by a favorable safety and tolerability profile. Results of the pharmacokinetic analysis indicate that the clinical benefit was mainly due to a local effect of oxymetazoline. Future studies are planned to investigate higher doses of oxymetazoline for this indication. See Video Abstract at http://links.lww.com/DCR/A797.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Incontinência Fecal/tratamento farmacológico , Oximetazolina/uso terapêutico , Pressão , Administração Retal , Administração Tópica , Adulto , Estudos Cross-Over , Método Duplo-Cego , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/complicações , Resultado do Tratamento , Adulto Jovem
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