Amitriptyline elimination

The metabolism and elimination of TCAs takes several days to occur, the elimination half-life ranging from 20 hours for amitriptyline to 80 hours for protriptyline. The half-life values for the desmethylated metabolites such as desmethylimipramine and nortriptyline are approximately twice those of the parent compounds imipramine and amitriptyline. It is also well established that the half-life values of the TCAs are considerably greater in the elderly, which predisposes such patients to a greater possibility of severe side effects. 

Maprotiline has relatively minor anticholinergic properties compared to amitriptyline. It has a very large elimination half-life of 36 to 48 h and in large doses produces convulsions. 

Molnar et al. [69] studied antibacterial effect and plasmid curing property of several phenothaizines and tried to correlate these functions with respect to their chemical structure. They observed that diethazine, amitriptyline, and impipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulfoxide and fluorescein were ineffective even at 1000 Ag/ml. The antibacterial compounds deleted at 40-70% frequency the F lac-t- plasmid of Escherichia coli K12 Le-140. Similar plasmid elimination potentiality by phenothiazines was reported by the same group of authors in 1982 [72],... 

If, following absorption, medications were undisturbed by the body, we would need to take only one dose for an eternal effect. Of course, this is not the case. As soon as drugs enter the bloodstream, the process of metabolism ensues. The body recognizes the drug as a foreign substance and eliminates it outright (say, via the kidneys, as in the case of lithium) or transforms it chemically, using a complex enzyme mechanism located in the liver. This chemical transformation enables the medication to be eliminated from the body. In some cases, the chemical transformation produces a new compound that may also have therapeutic effects (or, in some rare instances, a toxic effect). For example, fluoxetine (trade name Prozac) is transformed into norfluoxetine, which is also an antidepressant. A similar situation occurs with the old tricyclic antidepressants (amitriptyline—trade name Elavil—to nortriptyline the latter, in fact, is... 

Prototypical agent amitriptyline Inhibits norepinephrine and serotonin reuptake Hepatic metabolism with renal elimination High anticholinergic and antihistamine effects imipramine has high orthostasis profile 2nd degree amines (nortriptyline, desipramine) and doxepin have moderate anticholinergic effects... 

Nortriptyline Hydrochloride, USP. Pertinent biological and chemical properties for nortriptyline. 3-(IO.II-di-hydro-5//-dibenzu(a.d cyclohepten-S-ylidcne)fV-mcthyl-1 -propanamine hydrochloride. 5-(3-methyl-aminoprupyli-denc)-IO.t l-hydro-S//-dibcnzo a.Metabolic inactivation and elimination are like tho.se of amitriptyline. Nortriptyline is a selective NE transporter (NET) inhibitor. ... 

Nortriptyline is a secondary amine dibenzocycloheptene TCA (Fig. 21.8) as well as the major metabolite of amitriptyline. Similar to desipramine, nortriptyline appears in mother s milk and is metabolized by CYP2D6 to the primary amine and by ring hydroxylation to its E-10-hydroxy metabolite (Table 21.2). Approximately one-third of a dose of nortriptyline is excreted in urine as metabolites within 24 hours, and small amounts are excreted in feces via biliary elimination. 

Other studies have shown that nortriptyline 75 mg daily had an insignificant effect on the serum phenytoin levels of 5 patients, and that amitriptyline had no effect on the elimination of phenytoin in 3 subjects. ... 

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