al depression, quinidine-like effects on fast sodium channel blockade, inhibition of neurotransmitter re-uptake and generalized blockade of musarinic acetycholine, histamine and alpha-adrenergic receptors. The main systems involved are the cardiovascular system, central nervous system (CNS), and parasympathetic nervous system (PNS)
             TCAs so called because of the characteristic three-ring nucleus have been used clinical for the past thirty years. They closely resemble the phenothiazines chemically, and somewhat resemble them pharmacologially. They were first thought to be usful antihistamines and later as antipsychotics. The discovery of their antidepressent properties was fortuitous clinical observation.
             All TCAs have similar prpperties. They are highly lipophilic, readly cross the blood-brain barrier, and reach peak plasma levels between two and six hours at therapeutic doses. Gastrointestinal absorption can be prolonged due to their anticholinergic eff on the gastronintestinal tract. Tissue TCA levels are commonly 10 to 1000 times greater than plasma levels. Only 1 to 2% of total body burden of TCAs are found in the blood. These properties help explain why attemps at removing TCAs by hemodialysis, hemoperfusion, peritoneal dialysis, or forced diuresis are generally unproductive.
             The TCAs are eliminated alost entirely by hepatic oxidation, which consists of N-demethylation of the amine side chain groups and hydroxylation of ring structures. Some TCAs undergo enterohepatic circulation prior to their eventual oxidation, conjugation, andrenal elimination, but this does not sighificantly contribute to their toxicity. Tertiary amines such as amitriptyline, imipramine, doxepin, clomipramine, and trimipramine are demethylated to active metabolites (secondary amines) before their elimination. Although secondary amines such as desipramine, nortriptyline, and protriptyline are effective antidepressants, their metabolites are...