The effects of phentolamine and propranolol on contractural responses of guinea-pig superior mesenteric-portal vein to adrenaline and isoprenaline were investigated. Phentolamine was capable of completely abolishing the response to adrenaline and to isoprenaline while propranolol had no effect on responses to either agonist. It is suggested that Alpha receptors are the only type of adrenoceptor involved in adrenergic control of contraction of this vein and that isoprenaline is capable of stimulating these receptors.
A 27-year-old male of Malaysian descent presented to the Emergency Department (ED) with rapidly progressive flaccid paralysis that quickly compromised his respiratory effort. The patient was found to have a serum potassium of 1.9 meq/L, and was diagnosed as having an acute paralytic episode secondary to thyrotoxic periodic paralysis. The paralytic attack was aborted with a combination of potassium replacement and parenteral propranolol in large doses. We report the use of a rarely described, yet possibly more effective, therapy for an acute attack of thyrotoxic periodic paralysis.
Twenty eight patients with hyperthyroidism complicating their pregnancies were seen at the Obstetrics and Gynaecology Department, University Hospital, Kuala Lumpur, Malaysia in a six-year period. All patients were treated with antithyroid drugs, carbimazole being the mainstay of treatment. The incidence of the disease was 0.9 per 1000 births and was similar with other series. No cases of fetal goitre were noted. The mean birth weight was 2952 g; there was no significant difference in the birth weight of term live births in patients treated with carbimazole alone or carbimazole combined with propranolol.
This study investigated the reaction kinetics and the transformation by-products of acebutolol during aqueous chlorination. Acebutolol is one of the commonly used β-blockers for the treatment of cardiovascular diseases. It has been frequently detected in the aquatic environment. In the kinetics study, the second-order rate constant for the reaction between acebutolol and chlorine (k app) was determined at 25 ± 0.1 °C. The degradation of acebutolol by free available chlorine was highly pH dependence. When the pH increased from 6 to 8, it was found that the k app for the reaction between acebutolol and free available chlorine was increased from 1.68 to 11.2 M(-1) min(-1). By comparing with the reported k app values, the reactivity of acebutolol toward free available chlorine was found to be higher than atenolol and metoprolol but lower than nadolol and propranolol. Characterization of the transformation by-products formed during the chlorination of acebutolol was carried out using liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. Seven major transformation by-products were identified. These transformation by-products were mainly formed through dealkylation, hydroxylation, chlorination, and oxidation reactions.
The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12 h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer.
The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.
This article describes the dataset for the elucidation of the possible mechanisms of antidiarrhoeal actions of methanol leaves extract of Combretum hypopilinum (Diels) Combretaceae in mice. The plant has been used in traditional medicine to treat diarrhoea in Nigeria and other African countries. We introduce the data for the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum at 1,000 mg/kg investigated using charcoal meal test in mice with loperamide (5 mg/kg) as the standard antidiarrhoeal agent. To elucidate the possible mechanisms of its antidiarrhoeal action, naloxone (2 mg/kg), prazosin (1 mg/kg), yohimbine (2 mg/kg), propranolol (1 mg/kg), pilocarpine (1 mg/kg) and isosorbide dinitrate (150 mg/kg) were separately administered to different groups of mice 30 minutes before administration of the extract. Each mouse was dissected using dissecting set, and the small intestine was immediately removed from pylorus to caecum, placed lengthwise on moist filter paper and measured the distance travelled by charcoal relative to the length of the intestine using a calibrated ruler in centimetre. Besides, the peristaltic index and inhibition of charcoal movement of each animal were calculated and recorded. The methods for the data collection is similar to the one used to investigate the possible pathways involved in the antidiarrhoeal action of Combretum hypopilinum in mice in the research article by Ahmad et al. (2020) "Mechanisms of Antidiarrhoeal Activity of Methanol Leaf Extract of Combretum hypopilinum Diels (Combretaceae): Involvement of Opioidergic and (α1 and β)-Adrenergic Pathways" (https://doi.org/10.1016/j.jep.2020.113750) [1]. Therefore, this datasets could form a basis for in-depth research to elucidate further the pharmacological properties of the plant Combretum hypopilinum and its bioactive compounds to develop standardized herbal product and novel compound for management of diarrhoea. It could also be instrumental for evaluating the plant's pharmacological potentials using other computational-based and artificial intelligence approaches, including predictive modelling and simulation.
Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S. polyanthum leaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion and α -adrenergic receptors using hexamethonium and phentolamine (n = 5 for each group) partially attenuated AESP-induced hypotension, suggesting involvement of α -adrenergic receptors. Blockages of autonomic ganglion, β -adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N- ω -nitro-l arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement of β -adrenergic and cholinergic receptors via nitric oxide production.
A 45-year-old woman with poorly controlled hypertension and diabetes mellitus presented with left iliac fossa pain, constipation alternating with diarrhea, and weight loss. She had been diagnosed with idiopathic cardiomyopathy five years previously. Echocardiogram had shown a left ventricular ejection fraction (LVEF) of 35%; coronary angiogram was normal. Colonoscopy revealed sigmoid colitis with stenosis. Abdominal computed tomography revealed a 5 cm right adrenal tumor. Twenty-four hour urinary free catecholamines and fractionated metanephrine excretion values were elevated, confirming pheochromocytoma. Her colitis resolved after one month of adrenergic blockade. Repeat echocardiogram showed improvement of LVEF to 65%. After laparoscopic right adrenalectomy, the patient's hypertension resolved, and diabetic control improved. Timely management avoided further morbidity and potential mortality in our patient.
Hypokalemic thyrotoxic periodic paralysis is a potentially life-threatening complication of hyperthyroidism, defined by 3 characteristic features: thyrotoxicosis, hypokalemia, and acute painless muscle weakness. In this case, a 25-year-old Malaysian man presented with acute, painless lower extremity weakness immediately after a meal. His associated symptoms included palpitations, tremor, and anxiety. He also reported a 30-pound unintentional weight loss over the previous 18 months, dyspnea on exertion, and insomnia.