Medical Pharmacology Chapter 5:  Autonomic Pharmacology:  Adrenergic Drugs

 
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Asthma

Interaction of Sympathomimetic Drugs with Some Agents Used in Anesthesia61
  • β- adrenergic agonists used in management of asthma, drugs that include terbutaline, aminophylline, and theophylline. Sympathomimetic agents can interact with volatile anesthetics.61 

    • A consequence of this interaction may be induction of cardiac arrhythmias. 

    • Halothane is one example of a volatile anesthetic that sensitizes the heart to exogenous catecholamines.

      •  In this context, sensitization means that a reduced amount of epinephrine (IV) would be required to induce a premature ventricular contraction (PVC) in the presence of halothane compared to that in a normal, unanesthetized individual. 

      • If halothane is used, a dosage of 0.15 ml/kg of a 1:100000 epinephrine solution over a 10 minute. (Not to exceed 0.45 ml/kg of a 1:100000) is thought to be safe. Furthermore, lidocaine given in combination with epinephrine provides additional safety margin. 

      • Enflurane and isoflurane appear to cause less myocardial sensitization compared to halothane. 

      • Halothane is a potent bronchodilator and accordingly may be the best choice for anesthetizing asthmatic patients. However, if the asthmatic patient is already taking exogenous catecholamines or xanthines, halothane might not be most appropriate.

  • The mechanism of action by which xanthines promote bronchodilation appear to include xanthine-mediated endogenous norepinephrine release as well as possible inhibition of phosphodiesterase, which breaks down cAMP. This latter mechanism may be questionable because of the high concentrations required for xanthine-mediated phosphodiesterase inhibition.61 

    • However perhaps 40% of aminophylline's positive inotropic effect may be due to promotion of endogenous norepinephrine release.

  • Plasma theophylline concentrations of 5 mg/L is required to decrease the high airway resistance; furthermore, if levels exceed 20 mg/L, toxicity may occur.61 

    • Theophylline is metabolized by the liver, exhibiting a half-life of about four h in adults with a clearance of 1.2 ml/min./kg. [Aminophylline is composed of 85% theophylline and 15% ethylenediamine]. 

    • Because of toxicity concerns, factors that reduce clearance become important. 

    • Such factors include liver disease or pulmonary edema which can reduce theophylline clearance by 50% (liver) and 33% (pulmonary edema). 

    • In the laboratory setting, aminophylline and halothane interaction has been documented. The administration of 1% halothane with high dose, bolus aminophylline resulted in a significant number of ventricular arrhythmias in dogs (12/16) with 8/16 exhibiting ventricular tachycardia fibrillation.

    • Based on this analysis, it would appear reasonable to wait three drug half-lives following the last aminophylline dose prior to administering anesthesia to an asthmatic patient. An alternative to halothane for those patients who require aminophylline or other sympathomimetic agents might be the substitution of halothane by enflurane or isoflurane which either of which is less likely to sensitize myocardium to catecholamines.

 

 

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