Norepinephrine tricyclic antidepressants affecting

Tricyclic antidepressants are used for treatment of chronic pain. The mechanism of action supposedly is related to their activity at the sodium channel. It also is hypothesized that tricyclic antidepressants affect norepinephrine release and, possibly, serotonin release, thereby altering spinothalamic transmission of pain. However patients who require higher doses often find that the pain relief obtained is not adequate to justify the adverse effects. 

Norepinephrine Noradrenergic neuron cell bodies are mainly located in the brain stem and the lateral tegmental area of the pons. These neurons fan out broadly to provide most regions of the CNS with diffuse noradrenergic input. Excitatory effects are produced by activation of alpha and beta, receptors. Inhibitory effects are caused by activation of alphaj and beta, receptors. CNS stimulants, monoamine oxidase inhibitors, and tricyclic antidepressants affect the activity of noradrenergic pathways. 

Mechanism of Action A tricyclic antidepressant that blocks the reuptake of neu-rotransmitters, such as norepinephrine and serotonin, at presynaptic membranes, in-creasing their concentration at postsynaptic receptor sites. Therapeutic Effect Results in antidepressant effect. Anticholinergic effect controls nocturnal enuresis, Pharmacohinetics Rapidly, completely absorbed after PO administration, and not affected by food. Protein binding 95%, Metabolized in liver (significant first-pass effect), Primarily excreted in urine. Not removed by hemodialysis. Half-life 16-40 hr. 

Chronic pain patients tend to have concurrent depression however, the antidepressants chosen may not have any pain-relieving properties. Antidepressants that affect one neurotransmitter in the brain, such as selective serotonin reuptake inhibitors have not appeared to be effective in the management of pain in clinical trials. Antidepressants that affect multiple neurotransmitters— namely, serotonin and norepinephrine—have been shown to be effective pain relievers.Two published metaanalyses have shown that tricyclic antidepressants amitriptyline, desipramine, imipramine, and nortriptyline are the most effective treatment for the management of neuropathic pain. ° These publications review the published clinical trial data for all agents available for the management of neuropathic pain. 

MAOI monoamine oxidase inhibitor NE norepinephrine REM rapid eye movement SAD seasonal affective disorder TCA tricyclic antidepressant... 

Tricyclics modify peripheral sympathetic effects in two ways through blockade of norepinephrine reuptake at neuroeffector junctions and through alpha adrenoceptor blockade. Sedation and atropine-like side effects are common with tricyclics, especially amitriptyline. In contrast to sedative-hypnotics, tricyclics lower the threshold to seizures. The answer is (B). Selective serotonin reuptake inhibitors cause sexual dysfunction in some patients, with changes in libido, erectile dysfunction, and anorgasmia. Tricyclic antidepressants may also decrease libido or prevent ejaculation. Of the heterocyclic antidepressants bupropion is the least likely to affect sexual performance. The drug is also used in withdrawal from nicotine dependence. The answer is (B). 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

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