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American Heart Journal Nov 1971
Review
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bretylium Compounds; Dogs; Heart; Heart Conduction System; Heart Rate; Humans; Myocardial Infarction; Rabbits; Vascular Resistance; Ventricular Fibrillation
PubMed: 4940224
DOI: 10.1016/0002-8703(71)90341-3 -
American Journal of Hospital Pharmacy Sep 1979The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic agent, are reviewed. Bretylium tosylate is used to treat life-threatening ventricular arrhythmias, principally ventricular fibrillation and ventricular tachycardia, that have not responded to treatment with first-line antiarrhythmic agents. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission. The drug is poorly absorbed orally, requiring either i.m. or i.v. administration. Drug excretion occurs primarily through the kidney, necessitating dosage modification in renal disease. Hypotension is the most commonly observed adverse reaction to bretylium tosylate. Rapid i.v. administration may cause severe nausea and vomiting, and i.m. injection at the same site may cause atrophy and necrosis of muscle tissue. Quinidine and procainamide may potentiate the hypotensive effects of bretylium. Bretylium will aggravate digitalis-induced arrhythmias. Bretylium's use in resistant ventricular tachyarrhythmias requires close clinical monitoring.
Topics: Arrhythmias, Cardiac; Bretylium Compounds; Bretylium Tosylate; Drug Interactions; Humans; Kinetics; Monitoring, Physiologic
PubMed: 386786
DOI: No ID Found -
Annals of Internal Medicine Aug 1979Bretylium tosylate (Bretylol) has recently been approved for parenteral use against resistant ventricular arrhythmias. The pharmacologic action of bretylium is complex,... (Review)
Review
Bretylium tosylate (Bretylol) has recently been approved for parenteral use against resistant ventricular arrhythmias. The pharmacologic action of bretylium is complex, and its antiarrhythmic action differs significantly from other drugs. Bretylium is an adrenergic neuronal blocking agent taken up selectively at peripheral adrenergic nerve terminals, where it initially releases norepinephrine (sympathomimetic effect) and then produces adrenergic neuronal blockade. It has direct cardiac membrane effect to prolong action potential duration and effective refractory period but, unlike other membrane active antiarrhythmic agents, does not depress conduction velocity or automaticity. Bretylium increases ventricular fibrillation threshold and prevents the decrease in ventricular fibrillation threshold associated with myocardial ischemia. It does not depress myocardial contractility. Clinical studies have shown parenteral bretylium to be effective in suppressing ventricular arrhythmias, particularly recurrent, drug resistant ventricular tachycardia or ventricular fibrillation.
Topics: Action Potentials; Adrenergic Fibers; Animals; Arrhythmias, Cardiac; Bretylium Compounds; Bretylium Tosylate; Drug Evaluation; Drug Interactions; Drug Resistance; Heart Conduction System; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Myocardial Contraction; Myocardial Infarction; Pharmaceutical Vehicles; Purkinje Fibers; Quinidine; Sympathetic Nervous System; Tachycardia; Ventricular Fibrillation
PubMed: 380436
DOI: 10.7326/0003-4819-91-2-229 -
Clinical Therapeutics 1985Bretylium tosylate, the only approved class III antiarrhythmic agent, is a unique quaternary ammonium compound with prominent experimental and clinical antifibrillatory... (Review)
Review
Bretylium tosylate, the only approved class III antiarrhythmic agent, is a unique quaternary ammonium compound with prominent experimental and clinical antifibrillatory effects. Intravenous bretylium causes a biphasic hemodynamic response; initial norepinephrine release is followed by sympathetic ganglionic blockade. Cardiac output is well maintained. Electrocardiographic intervals are unchanged, and global conduction unchanged or facilitated. With long-term experimental use, proportionate lengthening of ventricular action potential and refractory period occurs. Bretylium is largely eliminated unchanged in the urine, with a long terminal half-life of about 13 hours. Bretylium demonstrates substantial activity in several animal models and clinical circumstances of ventricular fibrillation, including those in which standard antiarrhythmic therapy is ineffective. Bretylium is thus currently approved as a first-line agent for prophylaxis and treatment of ventricular fibrillation, and as a second-line agent for ventricular tachycardia and other prefibrillatory ventricular arrhythmias. In contrast, bretylium's weak antiectopic activity and limited oral absorption make it a poor choice for management of simple ventricular ectopy. Side effects of bretylium are generally limited to its hemodynamic actions (eg, postural hypotension). Nausea may occur with rapid intravenous administration. Emerging clinical concepts emphasize the clinical importance of antifibrillatory action over antiectopic effects alone. Bretylium is thus likely to continue to find increasing usage in the acute management of malignant ventricular arrhythmia.
Topics: Administration, Oral; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bretylium Compounds; Bretylium Tosylate; Chemical Phenomena; Chemistry; Coronary Disease; Dogs; Drug Implants; Electrophysiology; Heart Arrest; Hemodynamics; Humans; Injections, Intramuscular; Injections, Intravenous; Kinetics; Myocardial Infarction; Postoperative Complications; Tachycardia
PubMed: 3886143
DOI: No ID Found -
The American Journal of Emergency... Jul 1983
Topics: Bretylium Compounds; Bretylium Tosylate; Humans; Ventricular Fibrillation
PubMed: 6680600
DOI: 10.1016/0735-6757(83)90045-1 -
The American Journal of Emergency... Nov 1990Bretylium tosylate has been shown effective in the treatment of ventricular fibrillation and in the prevention of its recurrence. However, lidocaine is generally... (Comparative Study)
Comparative Study
Bretylium tosylate has been shown effective in the treatment of ventricular fibrillation and in the prevention of its recurrence. However, lidocaine is generally preferred because bretylium could have adverse hemodynamic effects related to its antiadrenergic action. To explore further the differences between these two antiarrhythmic agents, the authors compared the effects of bretylium, lidocaine, and saline on a standardized dog model of ventricular fibrillation followed by electromechanical dissociation (EMD). The protocol included three successive episodes of cardiac arrest in each animal. Three minutes before each episode of ventricular fibrillation, 5 mg/kg of bretylium tosylate (n = 11), 1 mg/kg of lidocaine (n = 9) or saline (n = 12) were administered blindly. There was no difference in the duration of cardiac arrest (bretylium, 8 min 18 sec; lidocaine, 7 min 54 sec; saline, 8 min 20 sec) or the total doses of epinephrine required to resuscitate the animals. Both bretylium and lidocaine appeared to preserve cardiac function 5 minutes after recovery, as stroke volume increased from 17.8 +/- 6.7 to 18.7 +/- 6.7 mL (NS) after bretylium and from 17.7 +/- 7.7 to 19.0 +/- 7.0 mL (NS) after lidocaine, but decreased from 19.0 +/- 5.3 to 14.6 +/- 6.0 mL (P less than .05) after saline. During the first 10 minutes of EMD, ventricular fibrillation or ventricular tachycardia recurred in 4 dogs treated with lidocaine, 3 dogs treated with saline, but no dog treated with bretylium (P less than .05 between bretylium and saline).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Bretylium Tosylate; Disease Models, Animal; Dogs; Electric Countershock; Heart Arrest; Hemodynamics; Lidocaine; Sodium Chloride; Stroke Volume; Ventricular Fibrillation
PubMed: 2222590
DOI: 10.1016/0735-6757(90)90148-s -
Experimental Physiology Oct 2020What is the central question of this study? Does the administration of the adrenergic presynaptic release inhibitor bretylium tosylate modulate sweating during exercise...
NEW FINDINGS
What is the central question of this study? Does the administration of the adrenergic presynaptic release inhibitor bretylium tosylate modulate sweating during exercise in the heat, and does this response differ between habitually trained and untrained men? What is the main finding and its importance? Iontophoretic administration of bretylium tosylate attenuates sweating during exercise in the heat in habitually trained and untrained men. However, a greater reduction occurred in trained men. The findings demonstrate a role for cutaneous adrenergic nerves in the regulation of eccrine sweating during exercise in the heat and highlight a need to advance our understanding of neural control of human eccrine sweat gland activity.
ABSTRACT
We recently reported an influence of cutaneous adrenergic nerves on eccrine sweat production in habitually trained men performing an incremental exercise bout in non-heat stress conditions. Based on an assumption that increasing heat stress induces cholinergic modulation of sweating, we evaluated the hypothesis that the contribution of cutaneous adrenergic nerves on sweating would be attenuated during exercise in the heat. Twenty young habitually trained and untrained men (n = 10/group) underwent three successive bouts of 15 min of light-, moderate- and vigorous-intensity cycling (equivalent to 30, 50, and 70% of peak oxygen uptake ( ) respectively), each separated by a 15 min recovery while wearing a perfusion suit perfused with warm water (43°C). Sweat rate (ventilated capsule) was measured continuously at two bilateral forearm skin sites treated with 10 mm bretylium tosylate (an inhibitor of neurotransmitter release from adrenergic nerve terminals) and saline (control) via transdermal iontophoresis. A greater sweat rate was measured during vigorous exercise only in trained as compared to untrained men (P = 0.014). In both groups, sweating was reduced at the bretylium tosylate versus control sites, albeit the magnitude of reduction was greater in the trained men (P ≤ 0.024). These results suggest that cutaneous adrenergic nerves modulate sweating during exercise performed under a whole-body heat stress, albeit a more robust response occurs in trained men. While it is accepted that a cholinergic mechanism plays a primary role in the regulation of sweating during an exercise-heat stress, our findings highlight the need for additional studies aimed at understanding the neural control of human eccrine sweating.
Topics: Adult; Bretylium Tosylate; Eccrine Glands; Exercise; Forearm; Hot Temperature; Humans; Iontophoresis; Male; Oxygen; Skin; Sweat; Sweating; Young Adult
PubMed: 32776611
DOI: 10.1113/EP088797 -
Annals of Emergency Medicine Aug 1981To evaluate the therapeutic effectiveness of intravenous bretylium tosylate as a first-line drug for patients in cardiopulmonary arrest, a randomized, double-blind study... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
To evaluate the therapeutic effectiveness of intravenous bretylium tosylate as a first-line drug for patients in cardiopulmonary arrest, a randomized, double-blind study was conducted, comparing bretylium with a normal saline placebo. Fifty-nine patients presenting to the emergency department with cardiopulmonary arrest due mainly to ventricular fibrillation or asystole initially received either bretylium (10 mg/kg) or placebo in a rapid intravenous bolus and were then otherwise treated according to standard American Heart Association guidelines. If ventricular fibrillation or asystole persisted, a second bolus of bretylium or normal saline was given after 20 minutes. Thirty-five percent of patients presenting with ventricular fibrillation or asystole who received bretylium were successfully resuscitated, whereas 6% of patients who received placebo survived (P less than 0.05). These findings serve to suggest that the early use of bretylium tosylate in cardiopulmonary arrest improves survival.
Topics: Anti-Arrhythmia Agents; Bretylium Compounds; Bretylium Tosylate; Double-Blind Method; Drug Evaluation; Female; Heart Arrest; Humans; Injections, Intravenous; Male; Middle Aged; Placebos; Random Allocation; Resuscitation
PubMed: 7258754
DOI: 10.1016/s0196-0644(81)80306-x -
The American Journal of Cardiology Jul 1984Experience with bretylium tosylate accumulated during a period of over 10 years, during which time greater than 1,500 patients with acute myocardial infarction were...
Experience with bretylium tosylate accumulated during a period of over 10 years, during which time greater than 1,500 patients with acute myocardial infarction were treated, is summarized. On the diagnosis of acute infarction, the agent was given by continuous intravenous drip at a rate of 10 mg/kg/24 hours for 5 to 7 days for prophylaxis of ventricular fibrillation. Bretylium administration prevented primary ventricular fibrillation in about 99% of these patients. No undesirable side effects were observed with this protocol, which lessens the initial sympathomimetic effect of the drug while allowing sufficient time for the adrenergic neuronal blocking effect to develop. The beneficial effects of the drug are believed to be due, in part, to a direct electrophysiologic effect on both normal and ischemic myocardium. This effect equalizes the duration of both the effective refractory periods and the ventricular action potentials, and it creates conditions capable of blocking reentrant pathways. Bretylium stabilizes the duration of electrical systole in patients with acute myocardial infarction. Hemodynamic studies during bretylium treatment further confirm the effectiveness of this drug and have prompted additional studies to evaluate its potential as an agent capable of decreasing impedance in acute myocardial infarction.
Topics: Animals; Arrhythmias, Cardiac; Bretylium Compounds; Bretylium Tosylate; Hemodynamics; Humans; Hypotension; Myocardial Contraction; Myocardial Infarction; Ventricular Fibrillation
PubMed: 6464996
DOI: 10.1016/0002-9149(84)90813-0 -
Annals of Emergency Medicine Oct 1981
Topics: Bretylium Compounds; Bretylium Tosylate; Heart Arrest; Humans
PubMed: 7283224
DOI: 10.1016/s0196-0644(81)80016-9