Increase synaptiside effects can be reduced by starting with low dosages c concentration of serotonin and or norepinephrine in the CNS.
Inhibit serotonin and norepinephrine reuptake by the presynaptic neuronal membrane resulting in availability of more drug to bind postsynaptic neuronal receptors.
Used to treat chronic pain, major depression, and anxiety disorders.
The TCAs include the following agents which are predominantly serotonin and/or norepinephrine reuptake inhibitors:
Amitriptyline (Tryptomer, Elavil, Endep)
Amitriptylinoxide (Amioxid, Ambivalon, Equilibrin)
Demexiptiline (Deparon, Tinoran)
Desipramine (Norpramin, Pertofrane)
Dibenzepin (Noveril, Victoril)
Dimetacrine (Istonil, Istonyl, Miroistonil)
Doxepin (Adapin, Sinequan)
Imipramine (Tofranil, Janimine, Praminil)
Imipraminoxide (Imiprex, Elepsin)
Lofepramine (Lomont, Gamanil)
Melitracen (Deanxit, Dixeran, Melixeran, Trausabun)
Nortriptyline (Pamelor, Aventyl, Norpress)
Noxiptiline (Agedal, Elronon, Nogedal)
Propizepine (Depressin, Vagran)
Quinupramine (Kevopril, Kinupril, Adeprim, Quinuprine)
Amineptine (Survector, Maneon, Directim) – Norepinephrine-dopamine reuptake inhibitor
Iprindole (Prondol, Galatur, Tetran) – 5-HT2 receptor antagonist
Opipramol (Insidon, Pramolan, Ensidon, Oprimol) – σ receptor agonist
Tianeptine (Stablon, Coaxil, Tatinol) – Selective serotonin reuptake enhancer
Trimipramine (Surmontil) – 5-HT2 receptor antagonist and moderate-potency norepinephrine reuptake inhibitor.
Tricyclic antidepressants-overdose remains a common cause of fatal poisoning accounting for the second highest number of fatal poisonings in the U.S. in 1999.
Toxicity secondary to anticholinergic effects, alpha-adrenergic blockade and sodium channel blocking effects.
Overdose causes CNS toxicity manifested by coma, seizures, cardiovascular complications of dysarrhythmias and hypotension.
Cardiotoxicity caused by sodium channel blockade of the Purkinje system with impaired myocardial conduction and impaired inotropy.
Management of tricyclic antidepressant overdose includes airway control, fluid resuscitation, vasopressors therapy and alkalinization of the serum.
Effective agents in the management of headache and neuropathic pain.
Tricyclic antidepressants have painkilling effect thought to do so by indirectly activating the endogenous opioid system.
The potential for analgesic effects with the TCAs needs to be weighed against their adverse-effect profile of anticholinergic effects, with dry mouth, constipation, and difficulty urinating and may be associated with problems with cognition, and sedation.
Dose limiting effects include dry mouth, urine retention, sedation, weight gain, constipation and cardiac arrhythmias.
Anticholinergic side effects can be reduced by starting with low dosages at bedtime, with slow titration to higher doses and by the use of secondary amine tricyclic agents nortriptyline or desipramine.
Associated with the risk of impaired cardiac conduction.
Adverse effects limit use of TCAs in the geriatric population.
Should be used with caution with patients with ischemic cardiac disease or ventricular conduction abnormalities and doses should be limited to less than 100 mg, if possible.
Patients older than 40 years of age should have a screening electrocardiogram.
An adequate trial of such drugs may take 6-8 weeks, with 2 weeks at the highest doses.