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Carvedilol versus propranolol effect on hepatic venous pressure gradient at 1 month in patients with index variceal bleed: RCT.
Gupta, V, Rawat, R, Shalimar, , Saraya, A
Hepatology international. 2017;(2):181-187
Abstract
BACKGROUND AND AIMS Endoscopic variceal ligation (EVL) plus beta blocker is the mainstay treatment after index bleed to prevent rebleed. Primary objective of this study was to compare EVL plus propranolol versus EVL plus carvedilol on reduction of HVPG after 1 month of therapy. METHODS Patients of cirrhosis presenting with index esophageal variceal bleed received standard treatment (Somatostatin therapy f/b EVL) following which HVPG was measured and patients were randomized to propranolol or carvedilol group if HVPG was >12 mmHg. Standard endotherapy protocol was continued in both groups. HVPG was again measured at 1 month of treatment. RESULTS Out of 129 patients of index esophageal variceal bleed, 59 patients were eligible and randomized into carvedilol (n = 30) and propranolol (n = 29). At 1 month of treatment, decrease in heart rate, mean arterial blood pressure (MAP) and HVPG was significant within each group (p = 0.001). Percentage decrease in MAP was significantly more in carvedilol group as compared to propranolol group (p = 0.04). Number of HVPG responders (HVPG decrease >20 % or below 12 mmHg) was significantly more in carvedilol group (22/29) as compared to propranolol group (14/28), p = 0.04. CONCLUSION Carvedilol is more effective in reducing portal pressure in patients with cirrhosis with esophageal bleed. Though a larger study is required to substantiate this, the results in this study are promising for carvedilol. Clinical trials online government registry (CTRI/2013/10/004119). Trial registration number CTRI/2013/10/004119.
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Efficacy and safety of cinnarizine in the prophylaxis of migraine headaches in children: an open, randomized comparative trial with propranolol.
Togha, M, Malamiri, RA, Rashidi-Ranjbar, N, Asa, S, Mahvelati, F, Ashrafi, MR
Acta neurologica Belgica. 2012;(1):51-5
Abstract
Migraine headaches are common in children. Early diagnosis and appropriate interventions are mandatory to prevent decades of suffering and diminished quality of life. There is need for data regarding the efficacy and safety of prophylactic agents in children with migraine; therefore, we designed a randomized clinical trial to compare the efficacy and safety of cinnarizine with that of a well-known prophylactic agent (propranolol) in the prophylaxis of pediatric migraine headache. A total of 120 patients aged between 6 and 17 years were recruited and 113 patients succeeded in completing all phases of the trial. Of them, 57 patients were given cinnarizine, and propranolol was administered in 56 patients. Reduction in headache frequency was the main response to treatment. Cinnarizine reduced the baseline headache frequency by more than 50% in 74.6% of patients and the mean headache frequency per month was reduced from 11.851 ± 0.739 (mean ± SEM) to 3.358 ± 0.739 (mean ± SEM) attacks per month (P < 0.001). In the propranolol group, more than 50% reduction of the baseline headache frequency was seen in 72.5% of patients and the mean headache frequency per month was reduced from 10.264 ± 0.830 (mean ± SEM) to 2.774 ± 0.830 (mean ± SEM) attacks per month (P < 0.001). No significant difference was seen in 50% reduction of the baseline headache frequency between treatment groups (P = 0.358). No significant adverse effects were reported. In this open study, cinnarizine appeared thus as effective as propranolol and safe for the prophylaxis of migraine in children, but this remains to be confirmed in a double-blind placebo-controlled trial.
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Variation in almotriptan effectiveness according to different prophylactic treatments.
Bermejo, PE, Dorado, R, Gomez-Arguelles, JM
Headache. 2009;(9):1277-82
Abstract
OBJECTIVE To evaluate the effect of different migraine prophylaxis medications on subject responsiveness to almotriptan. BACKGROUND There is evidence supporting an increase of responsiveness of symptomatic medications for migraine attacks by some prophylactic treatments although this has not been probed. METHODS A total of 345 patients (230 women, mean age 37.3) with episodic or chronic migraine were classified according to the prophylaxis they were taking in the following groups: (1) no prophylactic medication; (2) propranolol; (3) topiramate; (4) flunarizine. Decrease in Analogical Visual Scale and pain-free at 2 hours after almotriptan intake was assessed at 2 months. Side effects and discontinuation or treatment were also assessed. RESULTS Headache severity was reduced 4.2 in control group, 5.3 in propranolol group, 4.1 in topiramate group, and 4.0 in flunarizine group, whereas pain-free status was achieved in 37.3%, 48.7%, 36.1%, and 38.1% respectively. These two parameters were statistically significative between propranolol and control groups. Side effects were similar in all groups. CONCLUSIONS Our results displayed a higher efficacy of almotriptan in propranolol group and we hypothesized it may be due to a common mechanism of action at serotoninergic receptors.
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Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study.
Schepke, M, Wiest, R, Flacke, S, Heller, J, Stoffel-Wagner, B, Herold, T, Ghauri, M, Sauerbruch, T
The American journal of gastroenterology. 2008;(5):1152-8
Abstract
OBJECTIVES Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis. METHODS Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 +/- 1.1 mg/dL, creatinine 0.86 +/- 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 +/- 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk. RESULTS One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 +/- 1.5 mmHg to 16.6 +/- 1.2 mmHg, P= 0.037, propranolol/placebo group 17.8 +/- 1.1 mmHg to 15.1 +/- 1.2 mmHg, P= 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 +/- 20 mmol/d to 230 +/- 23 mmol/d, P= 0.045), but not in the propranolol/placebo group. CONCLUSIONS Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.
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Modulation by cationic amphiphilic drugs of serine base-exchange, phosholipase d and intracellular calcium homeostasis in glioma C6 cells.
Bobeszko, M, Czajkowski, R, Wójcik, M, Sabała, P, Lei, L, Nalepa, I, Barańska, J
Polish journal of pharmacology. 2002;(5):483-93
Abstract
We aimed to assess the effect of three drugs belonging to amphiphilic cations, imipramine, amitriptyline and propranolol, on lipid synthesis and intracellular calcium homeostasis in glioma C6 cells. Antidepressants, imipramine and amitriptyline, had a stimulatory effect on [14C]serine incorporation into phosphatidylserine. Similar effect was induced by propranolol, antidysrhythmic drug and an antagonist of beta-adrenergic receptor, but not by isoproterenol, a selective agonist of this receptor. Stimulation of serine base-exchange activity by amphiphilic cations occured at concentration as low as 5-25 microM that may be reached during clinical treatment. At much higher concentration (250 microM), those drugs also stimulated phospholipase D-mediated synthesis of [14C]phosphatidylethanol and blocked phorbol ester-induced, protein kinase C-dependent phospholipase D activity. The latter effect already occurred at low (25 microM) concentration of drugs. We have also shown that treatment of the cells with amphiphilic cations (1 mM) produced only a weak increase in the intracellular Ca2+ concentration and did not affect Ca2+ release from the intracellular stores evoked by nucleotide receptor agonists, ATP and ADP. In contrast, this treatment strongly diminished an unspecific leak of Ca2+ from the endoplasmic reticulum caused by thapsigargin and ionomycin. Mianserin, which is not cationic amphiphilic drug, did not affect phosphatidylserine synthesis and phospholipase D activity and produced heterogenous and chaotic Ca2+ responses. Our results suggest that imipramine, amitriptyline and propranolol may modulate lipid synthesis and intracellular calcium signaling independently of their action on membrane receptors, most probably by modification of the physicochemical properties of cell membranes.
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Comparison of the effect of verapamil and propranolol on response of coronary vasomotion to cold pressor test in symptomatic patients with hypertrophic cardiomyopathy.
Dimitrow, PP, Krzanowski, M, Nizankowski, R, Szczeklik, A, Dubiel, JS
Cardiovascular drugs and therapy. 2000;(6):643-50
Abstract
Impaired endothelium-dependent vasodilatation of coronary resistance vessels has been demonstrated in patients with hypertrophic cardiomyopathy (HC). The aim of this study was to compare the effect of verapamil and propranolol on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to the cold pressor test (CPT) in symptomatic HC patients. In 15 patients with HC, the CBFV was measured in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV and coronary vascular resistance index (calculated as ratio of mean aortic pressure/CBFV ratio) were measured at baseline and after CPT. Changes of these parameters induced by the CPT (expressed as percentage of baseline values) were compared after verapamil and propranolol treatment in a crossover study. The same measurements were obtained in nine healthy control subjects. CPT induced an increasing pattern of CBFV during verapamil therapy, which was absent in CPT after propranolol administration (10.1 +/- 5.6% vs. -0.9 +/- 4.1%, P < 0.01). In healthy controls CBFV increased in response to CPT more than in HC patients receiving verapamil or propranolol (23.1+/- 12.8% P < 0.01 and P < 0.05, respectively). The coronary vascular resistance index increased during the CPT significantly less on verapamil than on propranolol treatment (3.5 +/- 9.2% vs. 18.1 +/- 13.5%, P < 0.01). In healthy controls the coronary vascular resistance index decreased during CPT -4.5 +/- 8.5% (P < 0.05 vs. verapamil and P < 0.01 vs. propranolol). Verapamil improved the coronary vasomotor response to CPT in relation to propranolol. Verapamil blunted the increase of the coronary vascular resistance index to the CPT in comparison with its change at CPT after propranolol. Thus, coronary endothelial dysfunction in symptomatic HC patients may be partially reduced by verapamil in comparison with propranolol treatment.
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A comparative study of the elective treatment of variceal hemorrhage with beta-blockers, transendoscopic sclerotherapy, and surgery: a prospective, controlled, and randomized trial during 10 years.
Orozco, H, Mercado, MA, Chan, C, Guillén-Navarro, E, López-Martínez, LM
Annals of surgery. 2000;(2):216-9
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Abstract
OBJECTIVE To compare three options for the elective treatment of portal hypertension during a 10-year period. METHODS Patients included in the trial were 18 to 76 years old, had a history of bleeding portal hypertension, and had undergone no prior treatment. Treatment options were beta-blockers (propranolol), sclerotherapy, and portal blood flow-preserving procedures (selective shunts and the Sugiura-Futagawa operation). RESULTS A total of 119 patients were included: 40 in the pharmacology group, 46 in the sclerotherapy group,and 33 in the surgical group. The three groups showed no differences in terms of age, Child-Pugh classification, and cause of liver disease. The rebleeding rate was significantly lower in the surgical group than in the other two groups. The rebleeding rate was only 5% in the Child A surgical group, compared with 71% and 68% for the sclerotherapy and pharmacotherapy groups, respectively. Survival was better for the low-risk patients (Child A) in the three groups, but when the three options were compared, no significant difference was found. CONCLUSIONS Portal blood flow-preserving procedures offer the lowest rebleeding rate in low-risk patients undergoing elective surgery.