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β2-agonists
POISONOUS SUBSTANCES
β2-agonists
Benzodiazepines
Allister Vale
D Nicholas Bateman
Poisoning with β2-agonists (e.g. fenoterol, pirbuterol, reproterol, rimiterol, salbutamol (albuterol), terbutaline) may occur as a result of deliberate or accidental ingestion or by therapeutic intravenous infusion. Intoxication may also result from confusion about the difference between oral and parenteral doses.
Many benzodiazepine compounds are available; the main differences between them relate to their duration of action. Benzodiazepines are often taken in overdose with CNS depressants or ethanol, potentiating their respiratory depressant effects. This may be particularly hazardous with opioids. However, coingestion of benzodiazepines may be beneficial if the other agent causes convulsions. For this reason, routine use of benzodiazepine antagonists as a ‘diagnostic test’ in poisoning is absolutely contraindicated.
Clinical features: patients who have taken an overdose of β2agonist have a feeling of excitement, often accompanied by tremor and palpitations, which may be followed by agitation and convulsions. Electrolyte and acid–base disturbances are common in severe poisoning. Hypokalaemia, caused by β2-receptor-mediated activation of Na+/K+-ATPase, may precipitate supraventricular and ventricular arrhythmias and must be corrected promptly. Hyperglycaemia and lactic acidosis may occur. Myocardial ischaemia, with ST segment depression and T wave inversion, and pulmonary oedema are also reported.
Clinical features: when taken alone in overdose, benzodiazepines produce clinical features of drowsiness, dizziness, ataxia, dysarthria and nystagmus; less commonly, coma and hypotension develop. Respiratory depression is a potential complication, particularly when opioids, ethanol and other CNS depressants have also been ingested. It may require special attention in patients with pre-existing chronic obstructive pulmonary disease.
Management: when a substantial dose of a β2-agonist has been ingested less than 1 hour previously, gastric lavage may be considered or activated charcoal, 50–100 g, may be administered, though no clinical trial has been performed to confirm the efficacy of these treatments. Symptomatic and supportive measures should then be implemented. Hypokalaemia should be corrected as soon as possible, by administration of potassium, 40–60 mmol/hour, diluted with 5% dextrose or normal saline. Patients given potassium may develop significant hyperkalaemia during recovery; potassium concentrations should be monitored closely. A non-selective β-blocker (e.g. propranolol, 1–5 mg) administered by slow intravenous injection also reverses hypokalaemia, but may exacerbate pre-existing obstructive airways disease. If myocardial ischaemia occurs as a result of the tachyarrhythmia, propranolol, 1–5 mg i.v., should be administered. Convulsions are usually single and short-lived but, if necessary, diazepam, 5–10 mg i.v., may be given.
Management: generally, only careful nursing and supportive care are required. A specific benzodiazepine antagonist (flumazenil) may be given in carefully selected patients, usually to avoid ventilation. Its efficacy is determined clinically from the improvement in consciousness level and respiration. Flumazenil is used more often than is justified by the severity of the poisoning and should be reserved for patients with coma, hypotension or respiratory depression who are known not to be benzodiazepine dependant, not to have epilepsy, and not to have ingested proconvulsants concurrently. It may precipitate convulsions and cardiac arrhythmias when tricyclic antidepressants have been taken, and normal ECG is mandatory (i.e. no QRS or QT abnormality). Flumazenil has a short half-life (about 1 hour), so patients with severe poisoning may need repeated doses (0.5 mg i.v. over 1 minute, repeated if there is no or only partial response) or an intravenous infusion (0.1–0.5 mg/hour). Most patients poisoned with benzodiazepines respond to flumazenil, 1 mg. Many benzodiazepines have long half-lives (e.g. diazepam, 36 hours) or active metabolites with long half-lives (e.g. nordiazepam, about 100 hours). Major functions return rapidly, but it may be several days before the patient can perform skilled tasks safely. FURTHER READING Gaudreault P, Guay J, Thivierge R L et al. Benzodiazepine Poisoning. Clinical and Pharmacological Considerations and Treatment. Drug Saf 1991; 6: 247–65. Kulka PJ, Lauven P M. Benzodiazepine Antagonists – an Update of their Role in the Emergency Care of Overdose Patients. Drug Saf 1992; 7: 381–6.
FURTHER READING Leikin J B, Linowiecki K A, Soglin D F et al. Hypokalaemia after Pediatric Albuterol Overdose: A Case Series. Am J Emerg Med 1994; 12: 64–6. Lewis L D, Essex E, Volans G N et al. A Study of Self-poisoning with Oral Salbutamol – Laboratory and Clinical Features. Hum Exp Toxicol 1993; 12: 397–401.
MEDICINE
36
© 2003 The Medicine Publishing Company Ltd
β2-agonists
Benzodiazepines
Allister Vale
D Nicholas Bateman
Poisoning with β2-agonists (e.g. fenoterol, pirbuterol, reproterol, rimiterol, salbutamol (albuterol), terbutaline) may occur as a result of deliberate or accidental ingestion or by therapeutic intravenous infusion. Intoxication may also result from confusion about the difference between oral and parenteral doses.
Many benzodiazepine compounds are available; the main differences between them relate to their duration of action. Benzodiazepines are often taken in overdose with CNS depressants or ethanol, potentiating their respiratory depressant effects. This may be particularly hazardous with opioids. However, coingestion of benzodiazepines may be beneficial if the other agent causes convulsions. For this reason, routine use of benzodiazepine antagonists as a ‘diagnostic test’ in poisoning is absolutely contraindicated.
Clinical features: patients who have taken an overdose of β2agonist have a feeling of excitement, often accompanied by tremor and palpitations, which may be followed by agitation and convulsions. Electrolyte and acid–base disturbances are common in severe poisoning. Hypokalaemia, caused by β2-receptor-mediated activation of Na+/K+-ATPase, may precipitate supraventricular and ventricular arrhythmias and must be corrected promptly. Hyperglycaemia and lactic acidosis may occur. Myocardial ischaemia, with ST segment depression and T wave inversion, and pulmonary oedema are also reported.
Clinical features: when taken alone in overdose, benzodiazepines produce clinical features of drowsiness, dizziness, ataxia, dysarthria and nystagmus; less commonly, coma and hypotension develop. Respiratory depression is a potential complication, particularly when opioids, ethanol and other CNS depressants have also been ingested. It may require special attention in patients with pre-existing chronic obstructive pulmonary disease.
Management: when a substantial dose of a β2-agonist has been ingested less than 1 hour previously, gastric lavage may be considered or activated charcoal, 50–100 g, may be administered, though no clinical trial has been performed to confirm the efficacy of these treatments. Symptomatic and supportive measures should then be implemented. Hypokalaemia should be corrected as soon as possible, by administration of potassium, 40–60 mmol/hour, diluted with 5% dextrose or normal saline. Patients given potassium may develop significant hyperkalaemia during recovery; potassium concentrations should be monitored closely. A non-selective β-blocker (e.g. propranolol, 1–5 mg) administered by slow intravenous injection also reverses hypokalaemia, but may exacerbate pre-existing obstructive airways disease. If myocardial ischaemia occurs as a result of the tachyarrhythmia, propranolol, 1–5 mg i.v., should be administered. Convulsions are usually single and short-lived but, if necessary, diazepam, 5–10 mg i.v., may be given.
Management: generally, only careful nursing and supportive care are required. A specific benzodiazepine antagonist (flumazenil) may be given in carefully selected patients, usually to avoid ventilation. Its efficacy is determined clinically from the improvement in consciousness level and respiration. Flumazenil is used more often than is justified by the severity of the poisoning and should be reserved for patients with coma, hypotension or respiratory depression who are known not to be benzodiazepine dependant, not to have epilepsy, and not to have ingested proconvulsants concurrently. It may precipitate convulsions and cardiac arrhythmias when tricyclic antidepressants have been taken, and normal ECG is mandatory (i.e. no QRS or QT abnormality). Flumazenil has a short half-life (about 1 hour), so patients with severe poisoning may need repeated doses (0.5 mg i.v. over 1 minute, repeated if there is no or only partial response) or an intravenous infusion (0.1–0.5 mg/hour). Most patients poisoned with benzodiazepines respond to flumazenil, 1 mg. Many benzodiazepines have long half-lives (e.g. diazepam, 36 hours) or active metabolites with long half-lives (e.g. nordiazepam, about 100 hours). Major functions return rapidly, but it may be several days before the patient can perform skilled tasks safely. FURTHER READING Gaudreault P, Guay J, Thivierge R L et al. Benzodiazepine Poisoning. Clinical and Pharmacological Considerations and Treatment. Drug Saf 1991; 6: 247–65. Kulka PJ, Lauven P M. Benzodiazepine Antagonists – an Update of their Role in the Emergency Care of Overdose Patients. Drug Saf 1992; 7: 381–6.
FURTHER READING Leikin J B, Linowiecki K A, Soglin D F et al. Hypokalaemia after Pediatric Albuterol Overdose: A Case Series. Am J Emerg Med 1994; 12: 64–6. Lewis L D, Essex E, Volans G N et al. A Study of Self-poisoning with Oral Salbutamol – Laboratory and Clinical Features. Hum Exp Toxicol 1993; 12: 397–401.
MEDICINE
36
© 2003 The Medicine Publishing Company Ltd