Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propranolol HCl (7.5 mg X kg-1), timolol maleate (7.0 mg X kg-1), and sotalol HCl (10 mg X kg-1) were administered intracerebroventricularly (icv) to spontaneously breathing (SB) rats. The respiratory rate declined until the rats all died from respiratory arrest. Artificial ventilation resulted in survival of the rats for a 3-hr observation period. Intravenous (iv) administration of the same doses of the three beta blockers to SB rats did not result in either respiratory depression or death. Except for a decrease in heart rate (HR) the hemodynamic and respiratory parameters remained almost constant during the 3-hr observation period after iv administration to SB rats. After icv administration to SB as well as to ventilated rats no significant differences could be observed in the initial decrease in HR in comparison with iv administration. In SB rats at the end of the experiments a further decrease in HR was observed which might be ascribed to hypoxia since it did not occur in ventilated rats. After icv administration of each drug to the ventilated rats, mean arterial blood pressure showed a significantly greater decrease at the end of the 3-hr observation period than after iv administration. Plasma concentrations of the three drugs were determined just before death after icv administration in SB rats. In the other two groups they were measured at mean survival time and at the end of the experimental period. The plasma concentrations showed that the route of administration rather than the concentration of the beta blocker in plasma determines the occurrence of respiratory arrest. It was concluded that an overdose of propranolol, timolol, or sotalol can cause a centrally mediated respiratory arrest. Furthermore, a central mechanism appears to be implicated in the decrease in blood pressure.
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PMID:Central origin of respiratory arrest in beta-blocker intoxication in rats. 360 68

The effects of nine calcium ion antagonists on exercise tolerance, heart rate and ST-segment changes were compared with those of propranolol in two hundred and eighty patients with established chronic stable angina pectoris. These patients participated in clinical trials for anti-anginal efficacy against placebo, using identical methods and similar protocols, but the comparison reported here was retrospective. The trials were all fixed dose, and the dose was determined by previous upward titration to arrive at an average maximal tolerance level. All the drugs except prenylamine increased the exercise tolerance significantly when compared with placebo. Maximal ST-segment depression on exercise was reduced during treatment with propranolol while treatment with the calcium ion antagonists had no significant effect. The time to the development of 1 mm ST-segment depression was prolonged by all the drugs. Nifedipine, PY-108-068 and nicardipine increased the resting heart rate whereas verapamil, diltiazem, gallopamil, KB-944, prenylamine and tiapamil produced a slight reduction. Propranolol produced a highly significant reduction in the resting and maximal heart rates and the rate-pressure product, whereas gallopamil increased the rate-pressure product by +8% and prenylamine reduced it by -10%. At the doses used, diltiazem, gallopamil and verapamil produced a greater increase in exercise tolerance than did propranolol, while the other drugs were inferior. None of the calcium ion antagonists matched the increase in the time taken to develop 1 mm ST-segment depression with propranolol, although the results with verapamil and gallopamil were close. The calcium ion antagonists are effective antianginal agents which produce their effects by mechanisms which are very different to the beta-adrenoreceptor blocking agents.
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PMID:A comparison of nine calcium ion antagonists and propranolol: exercise tolerance, heart rate and ST-segment changes in patients with chronic stable angina pectoris. 365 22

In 14 patients with obstructive hypertrophic cardiomyopathy and angiographically normal coronary arteries, 8 with angina (group B) and 6 without (group A), the effects of intravenous isoproterenol, 2 to 4 micrograms/min, followed by intravenous propranolol, 0.2 mg/kg, were studied. An intraventricular systolic gradient less than 50 mm Hg, high-quality echocardiograms and cineangiograms and high-fidelity pressure tracings were selection criteria. Hemodynamic and metabolic variables were assessed during basal conditions, after 5 minutes of isoproterenol infusion or at angina and ST-segment depression, and 5 and 10 minutes after intravenous propranolol infusion. Isoproterenol increased the intraventricular systolic gradient more significantly in group B than in group A (102.4 +/- 8.3 vs 52.2 +/- 8.2, p less than 0.0001). Group B also had higher left ventricular end-diastolic pressure (32.5 +/- 3.9 vs 20.2 +/- 5.7), lower mean arterial pressure (69.7 +/- 3.5 vs 84.7 +/- 4.8) and a smaller increase in coronary sinus flow (176.1 +/- 9.2 vs 261.5 +/- 33.9, all p less than 0.0001), concomitant with lactate release and ST-segment depression. Propranolol promptly reversed hemodynamic and metabolic changes caused by isoproterenol, except for a further coronary sinus flow increase (from 176.1 +/- 9.2 to 219 +/- 14.2 ml/min, p less than 0.001), and heart rate decrease below basal values (57.8 +/- 7.5 vs 79.9 +/- 9.8 beats/min, p less than 0.001) in group B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of isoproterenol-induced angina pectoris in patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries. 366 32

Seventy three patients (63 males and 10 females) aged 41-75 years with established stable exertional angina pectoris were studied in a double-blind fashion to confirm the efficacy of 80 mg propranolol administered three times daily and also to examine its effect on ST-segment changes in the electrocardiogram by ambulatory ST-segment monitoring and exercise testing using on-line computer analysis. During ambulatory monitoring, episodes of ST-segment depression in lead CM5 were significantly reduced from 6.5 +/- 0.7 during placebo to 3.4 +/- 0.6 during propranolol therapy (p less than 0.001). The total duration of ST-segment depression was also significantly reduced and the maximal depth of ST-segment depression improved from 2.6 +/- 0.2 mm during placebo to 1.7 +/- 0.2 mm during propranolol therapy (p less than 0.001). The mean +/- SEM exercise time of 5.5 +/- 0.2 minutes on placebo increased to 8.6 +/- 0.4 minutes on propranolol 240 mg daily (p less than 0.001). The 1 mm ST-segment depression time of 3.5 +/- 0.2 minutes on placebo in lead CM5 was prolonged to 6.2 +/- 0.3 minutes during propranolol therapy (p less than 0.001). Propranolol treatment significantly reduced the resting and maximal heart rates (p less than 0.001). The maximal ST-segment depression during exercise in lead CM5 was reduced from 2.3 +/- 0.1 mm on placebo to 1.9 +/- 0.1 mm with propranolol (p less than 0.01). Similarly, the rate-pressure product at peak exercise of 188 +/- 5 units on placebo was reduced to 144 +/- 3 units with propranolol (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of propranolol on indices of intermittent myocardial ischemia, assessed by exercise testing and ambulatory ST-segment monitoring. 373 66

Adrenochrome uptake and its subcellular distribution were examined using isolated perfused rat heart preparation. The heart was perfused for 30 min with a medium containing 1 to 50 mg/l of 14C-adrenochrome and the subcellular fractions were isolated to measure their radioactivities. A decline in contractile force, a rise in resting tension and an increase in adrenochrome uptake by the heart were seen to depend upon the time of perfusion and the concentration of adrenochrome in the medium. The sarcolemmal fraction had the highest uptake of adrenochrome and this was followed by the microsomal fraction; some accumulation of adrenochrome was also observed in the myofibrillar and mitochondrial fractions. Either 10 or 20 min reperfusion of the heart previously exposed to 25 mg/l of adrenochrome, resulted in approximately 50 or 37% of the radioactivity remaining in the heart; this indicates irreversible binding of adrenochrome to the tissue. Reperfusion of the heart showed restoration of the resting tension but the contractile force did not show any recovery. Propranolol and iproniazid, which have been shown to inhibit the adrenochrome induced cardiotoxicity, reduced adrenochrome uptake by the heart, and prevented adrenochrome-induced depression in contractile force and rise in resting tension. These results indicate that adrenochrome is taken up by the heart and induces cardiac disturbances through its action on different subcellular organelles in the myocardium.
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PMID:Adrenochrome uptake and subcellular distribution in the isolated perfused rat heart. 385 Jul 68

The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p less than 0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 +/- 1.2 minutes from a baseline of 7.3 +/- 2.2 with bepridil plus propranolol compared with an increase of 0.02 +/- 1.3 minutes from a baseline of 7.6 +/- 2.9 with placebo plus propranolol (p less than 0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p less than 0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p less than 0.06) and total work (p less than 0.03) compared with placebo plus propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combination propranolol and bepridil therapy in stable angina pectoris. 388 41

The comparative efficacy and safety of oxyfedrine and propranolol in the management of angina pectoris was evaluated in a double-blind randomized cross-over study. Out of 21 patients registered, 14 completed the study. Three patients dropped out due to poor response and 4 were lost to follow up. Both the drugs i.e. oxyfedrine (8-24 mg three times a day) and propranolol (40-80 mg three times a day) produced a significant reduction in the incidence of anginal attacks and the consumption of nitroglycerine tablets. Propranolol produced a better response than oxyfedrine although the difference was not significant. This may be due to the small sample size. No change in heart rate and rate-pressure product was observed with oxyfedrine, in contrast to that seen with propranolol. The beneficial effect of treatment on exercise tolerance and ST-segment depression was more marked with propranolol. No significant change in laboratory parameters was observed with either drug.
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PMID:Double-blind crossover clinical trial of oxyfedrine and propranolol in angina pectoris. 388 57

Episodes of depression and acute psychosis in two patients receiving propranolol hydrochloride are described, and the literature on propranolol-induced depression and psychosis is reviewed. A 42-year-old woman developed severe depression, marked apathy, social withdrawal, and anorexia after taking propranolol hydrochloride (80 mg/day) for three months to control her hypertension. Five days after the dose was reduced to 40 mg/day, there was a major improvement in her depressive symptoms, with a complete resolution in eight days. Upon rechallenge with 80 mg/day of propranolol, she again experienced depressive symptoms. Atenolol 50 mg/day was substituted for the propranolol therapy, and she exhibited a complete remission of her depression. The second patient was a 63-year-old man who had been taking propranolol hydrochloride 160 mg/day for three months without incident. Because of an increased frequency of anginal attacks, the dosage was increased to 240 mg/day. Within two days, he demonstrated such agitation, excitement, and combativeness that he had to be controlled with a 25-mg dose of methotrimeprazine. When the propranolol dose was reduced to 160 mg/day, his psychotic symptoms rapidly cleared. However, when the dose was subsequently increased to 200 mg/day, he again showed increased agitation. After substituting atenolol 100 mg/day for propranolol, the patient's mental status returned to normal. Both of these patients experienced symptoms that were temporarily associated with propranolol. Both patients were subsequently controlled without symptoms with atenolol therapy. Propranolol is a highly lipophilic beta blocker that achieves high concentrations in the brain. When continued beta-blocking therapy is necessary or beta blockade is indicated, a weakly lipophilic agent such as atenolol is indicated.
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PMID:Propranolol-induced depression and psychosis. 398 22

Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.
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PMID:The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. 404 15

Effects of caffeine on the action potential and contractile force of human atrial fibres obtained at cardiac surgery were studied with standard microelectrode technique. In 4 mmol . litre-1 [K]o, the only significant action produced by 0.3 to 3 mmol . litre-1 caffeine on the electro-mechanical activity of relatively normal atrial fibres was a slight shortening of the action potential duration at 50% repolarisation. When the fibres were depolarised in 27 mmol . litre-1 [K]o or in atrial fibres showing slow responses in 4 mmol . litre-1 [K]o, however, caffeine could increase the upstroke of slow response and the force. In 18% of atrial fibres showing slow responses in 4 mmol . litre-1 [K]o, caffeine induced spontaneous discharges and potentiated afterdepolarisations. The positive inotropic and the arrhythmogenic effects of caffeine could be diminished by pretreating the fibres with propranolol or Ca antagonists (diltiazem and verapamil). In fibres beating spontaneously in normal [K]o, caffeine accelerated spontaneous rhythms initially and then depressed them. Propranolol potentiated the later depression but did not block the initial acceleration. The results suggest that caffeine increases the transmembrane Ca influx and enhances the release of Ca from the intracellular stores in human atrial fibres. As a consequence, caffeine could induce arrhythmias in atria from certain individuals.
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PMID:Electromechanical effects of caffeine in isolated human atrial fibres. 408 29


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