Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although many cases of beta-adrenoceptor antagonist (beta-blocker) poisoning are uneventful, a proportion develop serious and sometimes fatal cardiovascular system depression with severe hypotension. As beta-adrenergic tone is not essential for cardiovascular function in health, there is no physiological reason why total beta-adrenoceptor blockade should have serious consequences in the resting individual. The toxic actions of beta-blockers appear to be related to properties such as membrane depressant activity and possibly due to actions on beta-adrenoceptors distinct from those in the cardiovascular system. Most reports of serious adverse effects following overdosage concern beta-blockers with significant membrane depressant activity, and in particular propranolol and oxprenolol, with which progressive heart block and bradycardia are features. Sotalol toxicity, with its unique electrophysiological action, is a special case. Animal experiments confirm that beta-blockers with membrane depressant activity are more toxic than the newer more selective ones, such as atenolol and nadolol. However, experimental models also reveal that artificial ventilation markedly reduces the toxicity of all beta-blockers tested, suggesting a respiratory depressant action with very high doses. Treatment of serious overdosage in man should include maintenance of adequate ventilation. High dose intravenous glucagon is recommended, because its inotropic action depends on direct stimulation of adenylate cyclase. beta-Agonists such as isoprenaline (isoproterenol) or prenalterol may be effective, but the nature of agonist-competitive antagonist interactions may necessitate the use of unrealistically large doses to overcome very high tissue beta-blocker concentrations.
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PMID:The management of acute poisoning due to beta-adrenoceptor antagonists. 256 23

Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).
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PMID:Class III antiarrhythmics in overdose. Presenting features and management principles. 812 65

Sotalol overdose has special features because this beta-blocker has the potential to lengthen the Q-T interval and to initiate severe arrhythmias such as ventricular tachycardia or fibrillation. We describe the case of a 70-year-old woman who ingested 6.72 g sotalol with suicide attempt. Despite administration of activated charcoal, glucagon, atropine and isoprenaline, two episodes of asystole occurred, requiring cardiopulmonary resuscitation. Further treatment included ventricular pacing and dopamine. The patient recovered without neurologic nor cardiac sequelae.
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PMID:Sotalol poisoning associated with asystole. 844 Aug 1

Calcium channel blockers (CCB) and beta-blockers (BB) account for approximately 40% of cardiovascular drug exposures reported to the American Association of Poison Centers. However, these drugs represent >65% of deaths from cardiovascular medications. Yet, caring for patients poisoned with these medications can be extremely difficult. Severely poisoned patients may have profound bradycardia and hypotension that is refractory to standard medications used for circulatory support.Calcium plays a pivotal role in cardiovascular function. The flow of calcium across cell membranes is necessary for cardiac automaticity, conduction and contraction, as well as maintenance of vascular tone. Through differing mechanisms, CCB and BB interfere with calcium fluxes across cell membranes. CCB directly block calcium flow through L-type calcium channels found in the heart, vasculature and pancreas, whereas BB decrease calcium flow by modifying the channels via second messenger systems. Interruption of calcium fluxes leads to decreased intracellular calcium producing cardiovascular dysfunction that, in the most severe situations, results in cardiovascular collapse.Although, CCB and BB have different mechanisms of action, their physiological and toxic effects are similar. However, differences exist between these drug classes and between drugs in each class. Diltiazem and especially verapamil tend to produce the most hypotension, bradycardia, conduction disturbances and deaths of the CCB. Nifedipine and other dihydropyridines are generally less lethal and tend to produce sinus tachycardia instead of bradycardia with fewer conduction disturbances.BB have a wider array of properties influencing their toxicity compared with CCB. BB possessing membrane stabilising activity are associated with the largest proportion of fatalities from BB overdose. Sotalol overdoses, in addition to bradycardia and hypotension, can cause torsade de pointes. Although BB and CCB poisoning can present in a similar fashion with hypotension and bradycardia, CCB toxicity is often associated with significant hyperglycaemia and acidosis because of complex metabolic derangements related to these medications. Despite differences, treatment of poisoning is nearly identical for BB and CCB, with some additional considerations given to specific BB. Initial management of critically ill patients consists of supporting airway, breathing and circulation. However, maintenance of adequate circulation in poisoned patients often requires a multitude of simultaneous therapies including intravenous fluids, vasopressors, calcium, glucagon, phosphodiesterase inhibitors, high-dose insulin, a relatively new therapy, and mechanical devices. This article provides a detailed review of the pharmacology, pathophysiology, clinical presentation and treatment strategies for CCB and BB overdoses.
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PMID:Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. 1589 28