Dear Editor,
I read with interest the study performed by Oransay et al. published in your journal (CitationOransay et al., 2011). Based on this experimental study, the investigators concluded that bolus doses followed by a continuous infusion of theophylline were effective in reversing the hypotension and QRS prolongation in amitriptyline toxicity and might be an alternative antidote in the management of amitriptyline poisoning. There are some concerns about their study and suggestions. In human beings, as you know, the most common dysrhythmia observed after cyclic antidepressant (CA) overdoses (including amitriptyline) is sinus tachycardia, and this finding is present in most patients with clinically significant tricyclic antidepressant poisoning (CitationMarshall and Forker, 1982; CitationLiebelt, 2011). This is the result of the antimuscarinic, vasodilatory (i.e., reflex tachycardia), and sympathomimetic effects of CAs (CitationLiebelt, 2011). Interestingly, the rats in this study developed hypotension and QRS widening without sinus tachycardia, the cause of which was not clear. Methylxanthines (including theophylline) cause the release of endogenous catecholamines, which result in the stimulation of β1 and β2 receptors (CitationHoffman, 2011). Pharmacologically, they function as adenosine antagonists. Antagonism of adenosine results in the release of norepinephrine and, to a lesser extent, epinephrine (CitationHoffman, 2011). Thus, it seems that administration of theophylline in amitriptyline toxicity aggravates tachycardia. Theophylline is also a phosphodiesterase inhibitor, the enzyme responsible for degradation of intracellular cyclic AMP (cAMP). Therefore, elevated cAMP levels cause clinical effects similar to adrenergic stimulation, including peripheral vasodilation, myocardial stimulation, smooth muscle relaxation, skeletal muscle contractility, and central nervous system excitation (CitationHoffman, 2011). It should not be forgotten that, usually, CA-poisoned patients have degrees of agitation and delirium, which are caused by the central anticholinergic and -histaminergic effects (CitationLiebelt, 2011). It seems that administration of theophylline may aggravate these effects as well.
Declaration of interest
The author reports no conflicts of interest. The author alone is responsible for the content and writing of this paper.
References
- Hoffman, R. J. (2011). Methylxanthines and selective β2 adrenergic agonists. In: Nelson, L. S., Lewin, N. A., Howland, M. A., Hoffman, R. S., Goldfrank, L. R., Flomenbaum, N. E. (Eds.), Goldfrank’s toxicologic emergencies, 9th ed. (pp. 952–964). New York: McGraw-Hill.
- Liebelt, E. L. (2011). Cyclic antidepressants. In: Nelson, L. S., Lewin, N. A., Howland, M. A., Hoffman, R. S., Goldfrank, L. R., Flomenbaum, N. E. (Eds.), Goldfrank’s toxicologic emergencies, 9th ed. (pp. 1049–1049). New York: McGraw-Hill.
- Marshall, J. B., Forker, A. D. (1982). Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 103:401–414.
- Oransay, K., Kalkan, S., Hocaoglu, N., Arici, A., Tuncok Y. (2011). An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline. Drug Chem Toxicol 34:53–60.