SciCombinator

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Concept: Beta blocker

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TY-0201 (TY) is a new drug absorbed by the transdermal delivery system developed for the treatment of hypertension, which contains the free base of bisoprolol fumarate that is widely used. An 8-week randomized, double-blind, placebo-controlled study was conducted in hypertensive patients to evaluate the superiority of TY 8 mg to placebo and the noninferiority of TY 8 mg to bisoprolol fumarate oral formulation (BO) 5 mg. Changes in diastolic blood pressure (BP) (primary endpoint) from baseline in the TY 8 mg group, the BO 5 mg group, and the placebo group were -12.2 mm Hg, -11.8 mm Hg, and -3.7 mm Hg, respectively, with TY 8 mg demonstrating superiority to placebo and noninferiority to BO 5 mg. Changes from baseline for systolic BP and pulse rate produced significant reductions compared with placebo. TY is expected to serve as a new treatment approach for hypertensive patients.

Concepts: Myocardial infarction, Hypertension, Cardiology, Blood pressure, Pulse, Orthostatic hypotension, Prehypertension, Beta blocker

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Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Treatment with losartan, an angiotensin-II receptor-1 blocker, may reduce aortic dilatation rate in Marfan patients.

Concepts: Randomized controlled trial, Syndromes, Aortic dissection, Aorta, Marfan syndrome, Beta blocker, Losartan

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OBJECTIVE: To test whether long-term anti-hypertensive treatment with metoprolol succinate (a β1 -adrenoceptor blocker) or olmesartan medoxomil (an angiotensin II AT1 -receptor blocker) reverses microvascular dysfunction in hypertensive patients. METHODS: This study included 44 hypertensive outpatients and 20 age and sex-matched healthy controls. We used skin capillaroscopy to measure capillary density and recruitment at rest and during postocclusive reactive hyperemia (PORH). Endothelium-dependent vasodilation of skin microcirculation was evaluated with a laser Doppler perfusion monitoring system in combination with acetylcholine iontophoresis, PORH and local thermal hyperemia (LTH). RESULTS: Pretreatment capillary density in hypertensive patients was significantly reduced compared to controls (71.3±1.5 vs 80.6±1.8 cap/mm(2) ; p<0.001), as was PORH (71.7±1.5 vs 79.5±2.6 cap/mm(2) ; p<0.05). After treatment for six months, capillary density increased to 75.4±1.1 cap/mm(2) (p<0.01) at rest and 76.8±1.1 cap/mm(2) during PORH. During LTH, cutaneous vascular conductance (CVC) in perfusion units (PU)/mm Hg was similar in patients (1.71 [1.31-2.12]) and controls (1.60 [1.12-1.91]) and increased significantly (1.82 [1.30-2.20]) after treatment. Maximal CVC during PORH was reduced in hypertensive patients (0.30 [0.22-0.39]) compared to controls (0.39 [0.31-0.49], p<0.001) and increased (0.41 [0.29-0.51], p<0.001) after treatment. CONCLUSIONS: Capillary rarefaction and microvascular endothelial dysfunction in hypertensive patients responded favorably to long-term pharmacological treatment. This article is protected by copyright. All rights reserved.

Concepts: Hypertension, Endothelium, Angiotensin II receptor antagonist, Angiotensin receptor, Beta blocker, Copyright, Microcirculation, Metoprolol

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Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (-37.5 ± 48.7 vs -24.7 ± 29.4 ml), and LV end-systolic volume (-41.9 ± 43.0 vs -29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.

Concepts: Myocardial infarction, Cardiology, Heart failure, Ejection fraction, Heart, Beta blocker, Frank-Starling law of the heart, Beta blockers

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BACKGROUND: Carvedilol has been shown to be more effective than propranolol in decreasing portal pressure. Sufficient data from controlled trials remains limited. This trial compared the relative safety and efficacy between carvedilol and nadolol plus isosorbide mononitrate in preventing variceal rebleeding. METHODS: After successful control of acute esophageal variceal bleeding, eligible patients were randomized to Carvedilol group, 61 patients, using carvedilol 6.25-12.5 mg daily or N+ I group, 60 patients, using nadolol 40-80 mg plus isorsorbide-5-mononitrate 20mg daily. The end points were rebleeding from varices, adverse events or death. RESULTS: After a median follow up of 30 months, recurrent upper gastrointestinal bleeding developed in 37 patients (61%) in the Carvedilol group and 37 patients (62%) in the N+I group (p=0.90). Recurrent bleeding from esophageal varices occurred in 31 patients (51%) in the Carvedilol group and in 26 patients (43%) in the N+I group (p=0.46). Recurrent bleeding from gastric varices occurred in 2 patients (3%) in the Carvedilol group and in 8 patients (13%) in the N+I group (p=0.05). Severe adverse events occurred in 1 patient in Carvedilol group and 17 patients in N+I group (p<0.0001). Fifteen patients of the Carvedilol group and 17 patients in the N+I group died (p=0.83). Two patients in the Carvedilol group and 3 patients in N+I group died of variceal bleeding. CONCLUSIONS: Carvedilol was as effective as nadolol plus isorsorbide-5 -mononitrate mononitrate in the prevention of gastroesophageal variceal rebleeding with fewer severe adverse events and similar survival.

Concepts: Clinical trial, Gastroenterology, Esophageal varices, Gastric varices, Portal hypertension, Beta blocker, Propranolol, Isosorbide mononitrate

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Infantile haemangioma (IH) are vascular tumours with a unique growth dynamic, mostly absent at birth, growth in the first months followed by involution over several years, often resulting in residual skin changes. Immune-histologically, IH cells are exclusively glucose transporter protein-1 positive.The incidence of IH is increasing with decreasing gestational age, from 1-4% in term infants to 23% in those of <1000 g birth weight, with a female and Caucasian predominance. Discovery of systemic and topical beta blockers as an effective treatment option resulted in a rapid shift away from systemic steroids towards these drugs. For preterm infants, however, data on efficacy, pharmacokinetics and long-term safety are sparse or absent. Topical treatment without systemic side effects like cryotherapy may thus be an attractive alternative at an early growth stage (<10 mm). Indications for treatment with beta blockers, mostly propranolol systemically and timolol maleat 0.5% topically, are currently extrapolated from studies in older infants. Both seem effective, but adverse effects on sleep, circulation and metabolism are well described for propranolol. Long-term outcome data for either drug are missing. In conclusion, evidence on optimal IH treatment in preterms is lacking despite their high incidence; pharmacokinetic and clinical studies are warranted.

Concepts: Immune system, Pharmacology, Clinical trial, Effectiveness, Obstetrics, Antibiotic, Order theory, Beta blocker

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Adrenergic urticaria (AU) is a rare type of stress-induced physical urticaria characterized by widespread pruritic urticarial papules. Diagnosis can be made by i.d. injection of adrenaline or noradrenaline, which produces the characteristic rash. Although the lesions of AU typically respond to beta-blockers such as propranolol, the therapeutic options for AU are limited. Here, we report a case of AU that was resistant to beta-blockers and successfully treated with clotiazepam. The clinical picture of AU resembles that of cholinergic urticaria (CU), however, positive noradrenaline test and negative acetylcholine skin test were useful for the differential diagnosis of AU and CU. Although his symptoms were resistant to several therapeutic methods including olopatadine (H1 antagonist), lafutidine (H2 antagonist) and propranolol, the severity and frequency of his attacks and his subjective symptoms were reduced by oral clotiazepam, an anxiolytic benzodiazepine. Dermatologists should be aware that anxiolytic benzodiazepines may be a therapeutic option in AU.

Concepts: Neurotransmitter, Norepinephrine, Differential diagnosis, Adrenergic receptor, Beta blocker, Urticaria, Cholinergic urticaria, Pruritic urticarial papules and plaques of pregnancy

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It has been over half a century since propranolol, the first beta-blocker, was developed for medical treatment. Since that time a large number of compounds from this group have been synthesised and many are now in clinical use. The structure, function, pharmacokinetics, and mechanism of beta-blockers have been established. The possibilities for their use in treating different conditions continue to evolve. Since the discovery of later generation beta-blockers, such as carvedilol and nebivolol, the search for new compounds continues, and may include known substances with beta-blocking properties which could extend their therapeutic potential.

Concepts: Medicine, Hypertension, Beta blocker, Propranolol, Beta blockers, Carvedilol, Bisoprolol, Nebivolol

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 To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction.

Concepts: Myocardial infarction, Atherosclerosis, Cardiology, Heart failure, Percutaneous coronary intervention, Beta blocker

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Noradrenaline (NA) is released from the locus coeruleus in the brainstem to almost the whole brain depending on the physiological state or behavioral context. NA modulates various brain functions including vision, but many questions about the functional role of its effects and mechanisms remain unclear. To explore these matters, we focused on three questions, 1) whether NA improves detectability of a behavior-relevant visual stimulus, 2) which receptor subtypes contribute to the NA effects, and 3) whether the NA effects are specific for visual features such as spatial frequency (SF). We measured contrast sensitivity in rats by a two-alternative forced choice visual detection task and tested the effects of NA receptor blockers in three SF conditions. Propranolol, a β-adrenergic receptor inhibitor, significantly decreased contrast sensitivity, but neither prazosin nor idazoxan, α1- and α2-adrenergic receptor inhibitors, respectively, had an effect. This β blocker effect was observed only at optimal SF. These results indicate that endogenous NA enhances visual detectability depending on stimulus spatial properties via mainly β-adrenergic receptors.

Concepts: Effect, Receptor, Visual perception, Inhibitor, Locus coeruleus, Adrenergic receptor, Applied behavior analysis, Beta blocker