Treatment of Pediatric Life Threatening Amitriptilin Intoxication with Plasma Exchange

Tricyclic antidepressant (TCA) overdose is one of the most common causes of serious drug poisoning in children. Amitriptyline is a major TCA drug that is used widely. Tricyclic antidepressant intoxications are very important because of their severe adverse effects and probable fatal outcomes. It may cause cardiovascular, respiratory and neurological side effects. Poisoning results in hypotension, cardiac dysrhythmia, depression of the central nervous system (CNS) and seizures. The most common effects on the central nervous system are agitation, lethargy, seizures, and coma. Cardiovascular toxicities manifest itself especially with electrocardiographic (ECG) abnormalities, arrhythmias, and refractory hypotension and they are the leading cause of fatal outcome. Treatments in TCA overdose are mainly conservative including gastric lavage, activated charcoal and vasopressors for hypotension, sodium bicarbonate for dysrhythmias, and benzodiazepines for seizures. Magnesium sulfate (MgSO4) also has an effective role in the treatment of fatal cardiac arrhythmias occurring in high-dose amitriptyline intoxication. Intravenous lipid emulsions have been increasingly studied as antidotes to reverse acute, life-threatening drug toxicity. Unpredictable and poor results with hemoperfusion (HP) and hemodialysis (HD) should be expected, as the drug binds rapidly to tissues and has a large volume of distribution. But beside it, in the last few years, HP has been successfully used in severe TCA overdose, especially in patients with persistent respiratory, cardiac, and neurologic symptoms. Besides all these, recently, plasma exchange, have been increasingly used. A reduction of plasma levels by 63% after plasmapheresis in TCA poisoning has been reported. Here, we report a successful treatment of plasma exchange 3 year patient with amitriptyline overdose who had arrhythmias and seizures that wasn't respond all to conservative therapies.

Inhibition of Neutrophil Secretion Upon Adhesion as a Basis for the Anti-Inflammatory Effect of the Tricyclic Antidepressant Imipramine

Recent studies demonstrate the involvement of inflammatory processes in the development of depression and the anti-inflammatory effects of antidepressants. Infiltration and adhesion of neutrophils to nerve tissues and their aggressive secretion are considered as possible causes of inflammatory processes in depression. We studied the effect of the antidepressant imipramine on the adhesion and accompanied secretion of neutrophils under control conditions and in the presence of lipopolysaccharides (LPS). As a model of integrin-dependent neutrophil infiltration into tissues, we used integrin-dependent adhesion of neutrophils to the fibronectin-coated substrate. Imipramine inhibited neutrophil adhesion and concomitant secretion of proteins, including matrix metalloproteinase 9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL), which modify the extracellular matrix and basement membranes required for cell migration. Imipramine also significantly and selectively blocked the release of the free amino acid hydroxylysine, a product of lysyl hydroxylase, an enzyme that affects the organization of the extracellular matrix by modifying collagen lysine residues. In contrast, imipramine enhanced the release of ROS by neutrophils during adhesion to fibronectin and stimulated apoptosis. The anti-inflammatory effect of imipramine may be associated with the suppression of neutrophil infiltration and their adhesion to nerve tissues by inhibiting the secretion of neutrophils, which provides these processes.

Science

There was a strong desire within psychopharmacology to find a firm scientific basis for the field, hoping to ensure that it was regarded as a science. This chapter explains how the pseudo-scientific proposition on drug efficacy has become the notion that patients are suffering from “chemical imbalances.” It also emphasizes the industry’s leaping on chemical imbalance from the very beginning, because it sounded so plausible and so scientific that patients could easily grasp it. The chapter refers to a 1976 ad for USV’s tricyclic antidepressant Pertofrane that promised higher norepinephrine levels through reuptake blockade. It explains how depressions are associated with an absolute or relative deficiency of catecholamines, particularly norepinephrine.