ACUTE LUNG FAILURE INDUCED BY TRICYCLIC ANTIDEPRESSANTS

Overdosing of several drugs, such as tricyclic antidepressants, salicy lates, and opiates, is known to induce effects like those seen in pati ents with adult respiratory distress syndrome. By exposing isolated pe rfused and ventilated rat lungs via the perfusate to six different tri cyclic antidepressants (amitriptyline, nortriptyline, imipramine, desi pramine, mianserine, and maprotiline), we investigated possible effect s on ventilation (conductance and dynamic compliance), lung perfusion flow, and edema formation. The effects of these substances were pronou nced and appeared within 15 min after exposure. Amitriptyline was stud ied in greater detail and caused a dose-related (0.01-1.0 mM) reductio n in ventilation and perfusion flow. At the highest drug concentration pronounced lung edema was observed. Morphological studies were conduc ted with a transmission electron microscope. The microscopic preparati ons showed dose-related edema (amitriptyline 0.1 and 1.0 mM). The effe cts noted in our experimental studies are similar to those described i n patients who have taken an overdose of tricyclic antidepressants. Th is emphasizes the possibility of a noncardiogenic edema component in t hese patients. (C) 1997 Academic Press.