RESUMO
OBJECTIVE: To investigate the efficacy and safety of different dosage regimens of zuranolone in the treatment of patients with major depressive disorder (MDD). METHODS: PubMed, Embase, The Cochrane Library and other databases were searched from inception until July 2019. Randomized controlled trials (RCTs) related to the efficacy and safety of zuranolone in the treatment of MDD were included. The data were extracted independently by 2 investigators and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcome includes the 17-item HAMILTON total score (HAMD-17) and the incidence of adverse events (AEs). RESULTS: Six high-quality RCTs with 1593 patients were finally included in our analysis. Zuranolone group achieve a notable treatment effect at day15 in HAMD-17 compared with placebo group (MD = -2.69, 95 % CI: -4.45 to -0.94, P < 0.05). For safety, no significant differences existed in the proportion of patients with AEs between zuranolone with placebo (RR = 1.25, 95 % CI: 0.99 to 1.58, P = 0.06). CONCLUSION: Zuranolone has a significant efficacy in improving depressive symptoms in the short term and is positively correlated with the dosage administered. However, the efficacy of zuranolone decreased significantly when the time of administration was extended. Zuranolone demonstrated a controllable safety issue. But adverse effects increased as the dose of zuranolone was gradually increased to 50 mg.
Assuntos
Transtorno Depressivo Maior , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Resultado do Tratamento , Relação Dose-Resposta a Droga , Adulto , Feminino , Pregnanos/administração & dosagem , Pregnanos/uso terapêutico , Pregnanos/efeitos adversos , Pregnanolona , PirazóisRESUMO
OBJECTIVE: This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy. LITERATURE SEARCH: A literature search was conducted utilizing PubMed, clinicaltrials.gov, and the manufacturer's website. DATA SYNTHESIS: One phase II trial and two phase III trials evaluating the efficacy and safety of brexanolone were identified. Brexanolone demonstrated efficacy through significantly reduced Hamilton Depression Rating Scale (HAM-D) scores compared to placebo in the treatment of postpartum depression (PPD). Noted adverse effects were somnolence and dizziness, excessive sedation, and loss of consciousness. One published phase II study and the interim results of two phase III trials and one phase II trial on zuranolone were included in this review. Zuranolone, an oral allopregnanolone agonist, is given as a single, 14-day course. A significant reduction in HAM-D scores was demonstrated in patients with major depressive disorder (MDD) at 15 and 28 days compared to placebo. Interim results for zuranolone in PPD and bipolar disorder (BPD) show promising reductions in HAM-D scores. Adverse effects included sedation, dizziness, and headache. PLACE IN THERAPY: Allopregnanolone agonists seem to have a role in PPD when weighing the quick onset of action and potential risks of untreated PPD. The class of medications is limited by the single course for this indication and may fit as a bridge to maintenance therapy with selective serotonin reuptake inhibitors (SSRIs). Brexanolone, specifically, is hindered by the long infusion time, hospitalization associated with administration, and risk evaluation and mitigation strategy program. Zuranolone may also have a role in MDD or BPD, but more data are needed. CONCLUSION: Allopregnanolone agonists present a novel mechanism of action in the treatment of depressive disorders. Clinical trials and interim results support significant reductions in depression scores for brexanolone in PPD, and for zuranolone in PPD, MDD, and BPD.
Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/tratamento farmacológico , Pregnanolona/agonistas , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Depressão Pós-Parto/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Combinação de Medicamentos , Feminino , Humanos , Gravidez , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pregnanos/farmacologia , Pregnanolona/administração & dosagem , Pregnanolona/efeitos adversos , Pregnanolona/farmacologia , Escalas de Graduação Psiquiátrica , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/farmacologia , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversos , beta-Ciclodextrinas/farmacologiaRESUMO
Importance: Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy, negatively affecting both mother and child. Objective: To demonstrate the efficacy and safety of zuranolone, a neuroactive steroid γ-aminobutyric acid receptor-positive allosteric modulator, in PPD. Design, Setting, and Participants: This phase 3, double-blind, randomized, outpatient, placebo-controlled clinical trial was conducted between January 2017 and December 2018 in 27 enrolling US sites. Participant were women aged 18 to 45 years, 6 months or fewer post partum, with PPD (major depressive episode beginning third trimester or ≤4 weeks postdelivery), and baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) score of 26 or higher. Analysis was intention to treat and began December 2018 and ended March 2019. Interventions: Randomization 1:1 to placebo:zuranolone, 30 mg, administered orally each evening for 2 weeks. Main Outcomes and Measures: Primary end point was change from baseline in HAMD-17 score for zuranolone vs placebo at day 15. Secondary end points included changes from baseline in HAMD-17 total score at other time points, HAMD-17 response (≥50% score reduction) and remission (score ≤7) rates, Montgomery-Åsberg Depression Rating Scale score, and Hamilton Rating Scale for Anxiety score. Safety was assessed by adverse events and clinical assessments. Results: Of 153 randomized patients, the efficacy set comprised 150 patients (mean [SD] age, 28.3 [5.4] years), and 148 (98.7%) completed treatment. A total of 76 patients were randomized to placebo, and 77 were randomized to zuranolone, 30 mg. Zuranolone demonstrated significant day 15 HAMD-17 score improvements from baseline vs placebo (-17.8 vs -13.6; difference, -4.2; 95% CI, -6.9 to -1.5; P = .003). Sustained differences in HAMD-17 scores favoring zuranolone were observed from day 3 (difference, -2.7; 95% CI, -5.1 to -0.3; P = .03) through day 45 (difference, -4.1; 95% CI, -6.7 to -1.4; P = .003). Sustained differences at day 15 favoring zuranolone were observed in HAMD-17 response (odds ratio, 2.63; 95% CI, 1.34-5.16; P = .005), HAMD-17 score remission (odds ratio, 2.53; 95% CI, 1.24-5.17; P = .01), change from baseline for Montgomery-Åsberg Depression Rating Scale score (difference, -4.6; 95% CI, -8.3 to -0.8; P = .02), and Hamilton Rating Scale for Anxiety score (difference, -3.9; 95% CI, -6.7 to -1.1; P = .006). One patient per group experienced a serious adverse event (confusional state in the zuranolone group and pancreatitis in the placebo group). One patient in the zuranolone group discontinued because of an adverse event vs none for placebo. Conclusions and Relevance: In this randomized clinical trial, zuranolone improved the core symptoms of depression as measured by HAMD-17 scores in women with PPD and was generally well tolerated, supporting further development of zuranolone in the treatment of PPD. Trial Registration: ClinicalTrials.gov Identifier: NCT02978326.
Assuntos
Depressão Pós-Parto/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Moduladores GABAérgicos/farmacologia , Pregnanos/farmacologia , Pirazóis/farmacologia , Adolescente , Adulto , Método Duplo-Cego , Feminino , Moduladores GABAérgicos/administração & dosagem , Moduladores GABAérgicos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Parto , Gravidez , Terceiro Trimestre da Gravidez , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).
Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Moduladores GABAérgicos/uso terapêutico , Pregnanos/uso terapêutico , Pirazóis/uso terapêutico , Receptores de GABA-A/metabolismo , Administração Oral , Adulto , Regulação Alostérica , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/classificação , Tontura/induzido quimicamente , Método Duplo-Cego , Feminino , Moduladores GABAérgicos/efeitos adversos , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pregnanos/efeitos adversos , Escalas de Graduação Psiquiátrica , Pirazóis/efeitos adversosRESUMO
Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation, and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples, and the lack of long-term follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides, and neuroactive steroids. Evidence supporting the role of neuroactive steroids and γ-aminobutyric acid (GABA) in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble proprietary intravenous preparation of synthetic allopregnanolone, has been developed. A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3ß-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.
Assuntos
Depressão Pós-Parto/tratamento farmacológico , Desenvolvimento de Medicamentos , Moduladores GABAérgicos/uso terapêutico , Neuroesteroides/uso terapêutico , Pregnanos/uso terapêutico , Pregnanolona/uso terapêutico , Pirazóis/uso terapêutico , beta-Ciclodextrinas/uso terapêutico , Animais , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/metabolismo , Combinação de Medicamentos , Feminino , Moduladores GABAérgicos/administração & dosagem , Moduladores GABAérgicos/efeitos adversos , Humanos , Neuroesteroides/administração & dosagem , Neuroesteroides/efeitos adversos , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pregnanolona/administração & dosagem , Pregnanolona/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos , United States Food and Drug Administration , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversosRESUMO
The aim of this work was to compare different chemical substances used in the treatment of ganglions located in the hand and wrist region. Their basic properties and mechanisms of action have been described. Moreover, the risks associated with the use of particular substances have been highlighted and potential complications connected with their administration have been discussed. On the basis of the available literature, the results of ganglion aspiration treatment followed by an injection of a chemical substance into the cyst cavity have been assessed. In the authors' opinion, due to the existing risk of complications associated with this treatment, as well as the relatively high rate of ganglion recurrence, this procedure should only be performed by qualified medical personnel. The authors recommend observation in cases of asymptomatic ganglions of the hand and wrist, and operative treatment in cases in which pain, restriction of limb mobility and weakening of handgrip strength are observed.
Assuntos
Cistos Glanglionares/tratamento farmacológico , Mãos , Hialuronoglucosaminidase/uso terapêutico , Pregnanos/uso terapêutico , Tetradecilsulfato de Sódio/uso terapêutico , Punho , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Humanos , Hialuronoglucosaminidase/administração & dosagem , Hialuronoglucosaminidase/efeitos adversos , Pregnanos/efeitos adversos , Recidiva , Tetradecilsulfato de Sódio/efeitos adversos , Resultado do TratamentoAssuntos
Terapia de Reposição Hormonal/efeitos adversos , Menopausa , Trombose Venosa/induzido quimicamente , Resistência à Proteína C Ativada/induzido quimicamente , Administração Cutânea , Administração Oral , Idoso , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Feminino , Hemostasia/fisiologia , Terapia de Reposição Hormonal/métodos , Humanos , Fígado/metabolismo , Pessoa de Meia-Idade , Norpregnanos/administração & dosagem , Norpregnanos/efeitos adversos , Norpregnanos/uso terapêutico , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pregnanos/uso terapêutico , Progesterona/administração & dosagem , Progesterona/efeitos adversos , Progesterona/uso terapêutico , Risco , Trombose Venosa/epidemiologiaRESUMO
PURPOSE: To study the corneal topographic response to IOP reduction in vernal keratoconjunctivitis (VKC) with steroid-induced glaucoma. METHODS: A total of 42 eyes of 21 patients with VKC and steroid-induced glaucoma (Group I) and 66 eyes of 33 patients with VKC without glaucoma (Group II) underwent an evaluation by Orbscan topography. In eyes with glaucoma, the IOP was controlled medically and the corneal topography was repeated at 3 months to evaluate effect on corneal parameters. RESULTS: The mean baseline IOP was 36.40+/-13.08 mmHg in Group I, 14.67+/-4.62 mmHg in Group II (P<0.0001). The IOP after treatment at 3 months follow-up was 15.00+/-5.41 mmHg in Group I (P<0.0001). In Group I, the mean maximum Sim K decreased from 44.86+/-3.21 D to 43.87+/-2.62 D (P=0.031) and mean posterior corneal elevation decreased from 64.9+/-22.36 microm to 35.7+/-28.91 microm at 3 months after reduction of IOP (P=0.001). There was a significant positive correlation between the reduction in the IOP and the decrease in the posterior corneal elevation (r=0.664, P=0.001). CONCLUSION: Eyes with VKC with and without glaucoma have similar corneal topography. Increased IOP associated with steroid-induced glaucoma and VKC may contribute to an increase in the corneal curvature and posterior corneal elevation. These changes may be reversed by a reduction in the IOP with medical therapy.
Assuntos
Anti-Inflamatórios/efeitos adversos , Conjuntivite Alérgica/tratamento farmacológico , Topografia da Córnea/métodos , Glaucoma/induzido quimicamente , Pressão Intraocular/fisiologia , Ceratoconjuntivite/tratamento farmacológico , Pregnanos/efeitos adversos , Administração Tópica , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Criança , Pré-Escolar , Conjuntivite Alérgica/complicações , Conjuntivite Alérgica/fisiopatologia , Córnea/efeitos dos fármacos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Glaucoma/complicações , Glaucoma/fisiopatologia , Humanos , Hidrocarbonetos Fluorados/administração & dosagem , Hidrocarbonetos Fluorados/efeitos adversos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Ceratoconjuntivite/complicações , Ceratoconjuntivite/fisiopatologia , Masculino , Pregnanos/administração & dosagem , Estudos ProspectivosRESUMO
Neuroactive steroids are a large group of substances having effect in the brain and on brain function. The steroids most studied are allopregnanolone (ALLO), tetrahydrodesoxycorticosterone (THDOC), pregnenolone sulfate (PS) dihydroepiandrosteronesulfate (DHEAS), and estradiol (E2). ALLO and THDOC are called gamma-aminobutyric acid (GABA) steroids as they are positive modulators of the GABAA receptor in a similar way as benzodiazepines, barbiturates, and alcohol. GABA steroids not only have similar behavioral effects as benzodiazepines and barbiturates but, possibly, also similar adverse effects as well. This review aims to elucidate the possible role that neuroactive steroids play in the development of mood disorders in women. One of the most clear-cut examples of the interaction between mood, neuroactive steroids, and the GABA system is premenstrual dysphoric disorder (PMDD), which is a cluster of negative mood symptoms occurring during the luteal phase of the menstrual cycle in 2-6% of reproductive women. Furthermore, certain women also experience adverse mood effects during sequential progestin addition to postmenopausal estrogen treatment, which is why the role of neuroactive steroids in postmenopausal women is also addressed in this review.
Assuntos
Transtornos do Humor/etiologia , Pregnanos/metabolismo , Encéfalo/metabolismo , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/metabolismo , Estrogênios/uso terapêutico , Feminino , Moduladores GABAérgicos/efeitos adversos , Moduladores GABAérgicos/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Menopausa/metabolismo , Transtornos do Humor/metabolismo , Ovário/metabolismo , Pregnanos/efeitos adversos , Pregnanos/uso terapêutico , Síndrome Pré-Menstrual/etiologia , Síndrome Pré-Menstrual/metabolismo , Receptores de GABA-A/metabolismoRESUMO
PURPOSE: Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment. RESULTS: Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly. CONCLUSION: Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Pregnanos/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Antagonistas de Androgênios/efeitos adversos , Estradiol/sangue , Ginecomastia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pregnanos/efeitos adversos , Próstata/efeitos dos fármacos , Próstata/patologia , Antígeno Prostático Específico/análise , Pirazóis/efeitos adversos , Testosterona/sangue , Urodinâmica/efeitos dos fármacosRESUMO
The third generation of combination estrogen/progestogen oral contraceptives (OCs) first became available in the early 1980s. The gonanes (e.g., norgestimate, desogestrel, and gestodene) are alternatives to the long-standing progestogens, norethindrone and norgestrel/levonorgestrel. While the newer compounds are related to levonorgestrel, their biochemical structure differs. All, however, are strongly progestogenic with respect to ovulation inhibition and are very selective in their affinity for endometrial progesterone receptors. At present, experience with the third-generation combined OCs is relatively limited, and extensive comparative data have yet to be accrued. Nevertheless, these ultra-low-dose compounds appear to be as efficacious as the traditional OCs, while their cycle control may be slightly superior. In addition, the incidence of minor side effects, such as nausea, weight gain, and mastalgia, compares favorably with that of the earlier OCs. In combination with estrogen, these new progestogens have revealed a neutral or possibly beneficial effect on lipid/lipoprotein metabolism. Thus, the newer progestogens do not appear to have adverse effects on the cardiovascular system and offer a range of noncontraceptive health benefits.
PIP: A study using data from the United Kingdom (UK), Denmark, and Sweden and an ongoing study in the UK found a significant association between estrogen content of high dose combined oral contraceptives (OCs) and all thromboses except venous thrombosis of lower limb. In fact, the ongoing study and another study both found a distinct association between progestogen dose and arterial disease. These association prompted formulators to decrease OC estrogen and progestogen (norethindrone and levonorgestrel) content. These new formulations entered the market after 1975. The early 1980s witnessed the introduction of yet another generation of genane progestogens which were developed in hoped of reducing the incidence of thrombosis. Clinical trials found their contraceptive effectiveness to be comparable to those of the older demonstrated that their effect on associated incidence of bleeding is similar to the older OCs and falls over time. Moreover, even though the 3rd generation OCs have brought on the same side effects (weight gain, mastalgia, and nausea) as the others, the frequency has been at least, and often less, than the others. So far data have not implicated the 3rd generation OCs in impairing glucose tolerance. In addition, research has demonstrated that 3rd generation formulations cause a small increase in high density lipoprotein and either did not change or reduced low density lipoprotein and total cholesterol levels. Thus the new combined OCs do not promote atherosclerotic changes in lipid metabolism. Even though more research is needed, the data have indicated that physicians should continue to prescribe the 3rd generation OCs.
Assuntos
Anticoncepcionais Orais Combinados , Estranos , Gonanos , Pregnanos , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/química , Anticoncepcionais Orais Combinados/metabolismo , Estranos/efeitos adversos , Estranos/metabolismo , Feminino , Gonanos/efeitos adversos , Gonanos/metabolismo , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Aceitação pelo Paciente de Cuidados de Saúde , Pregnanos/efeitos adversos , Pregnanos/metabolismo , Trombose/induzido quimicamente , Trombose/metabolismoRESUMO
Minaxolone, a water-soluble steroid intravenous anaesthetic, has been used in clinical trials for induction and maintenance in patients presenting for minor operations. A standard induction dose of 0.5 mg/kg was given. There was a low incidence of pain on injection and venous sequelae. Excitatory effects occurred commonly at induction but these were reduced by opiate premedication. The frequency of uneventful induction was significantly greater when the 5 mg/ml solution of minaxolone was given at a rate of 6 ml/minute than at a rate of 24 ml/minute. Minaxolone has been withdrawn from clinical trials following equivocal toxicological findings in rats which require further investigation.
Assuntos
Anestesia Intravenosa , Anestésicos , Pregnanos , Pregnanolona , Adulto , Acatisia Induzida por Medicamentos , Anestésicos/efeitos adversos , Feminino , Doenças dos Genitais Femininos/cirurgia , Humanos , Medicação Pré-Anestésica , Pregnanos/efeitos adversos , Pregnanolona/efeitos adversos , Pregnanolona/análogos & derivados , Transtornos Respiratórios/induzido quimicamenteRESUMO
Minaxolone, a new water-soluble steroid anaesthetic, was studied in combination with nitrous oxide in 30 healthy female patients. The objective of the study was to assess induction dosage, clinical efficacy, recovery characteristics, and frequency of side effects. It proved to be an effective anaesthetic causing only minimal cardiovascular and respiratory depression. Those side effects which occurred during operation were felt to be due in part to light anaesthesia and lack of analgeia. Excitatory movements and hypertonus occurred in seven patients during operation and in ten patients in the early recovery phase. Late recovery was impressive, both in quality and lack of side effects, and all patients were considered fit for discharge from hospital within four hours of the operation. Minaxolone appears to be a promising new anaesthetic worthy of further study.
Assuntos
Anestesia Intravenosa , Anestésicos , Pregnanos , Pregnanolona , Adulto , Análise Química do Sangue , Pressão Sanguínea , Avaliação de Medicamentos , Feminino , Humanos , Período Pós-Operatório , Pregnanos/administração & dosagem , Pregnanos/efeitos adversos , Pregnanos/análogos & derivados , Pregnanolona/administração & dosagem , Pregnanolona/efeitos adversos , Pregnanolona/análogos & derivadosRESUMO
Minaxolone has been used for the induction and maintenance of anaesthesia in 60 patients undergoing minor surgical procedures. With nitrous oxide as the only supplement, satisfactory conditions were obtained in 56 patients. Patient acceptance was high.