Tofranil action

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Some antidepressants—specifically, tricyclics like imipramine (trade name Tofranil) and amitryptiline (trade name Elavil)—are thought to exert their antidepressant effect through inhibition of a reuptake mechanism that sucks back the neurotransmitters from the synapse into the neuron for storage and future use, a process mentioned in Chapter 1. The resulting net effect is an increase of these molecules at the synapse and thus a more robust neurotransmission. A different category of antidepressants—monoamine oxidase inhibitors (MAOIs)—display a different mechanism of action but with the same net effect of increasing norepinephrine and serotonin neurotransmission they inhibit the metabolism (breakdown) of the molecules stored in the neurons, thus creating more abundant supplies for neurotransmission. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Fortunately, most patients will not experience all of these side effects. Each type of TCA acts somewhat differently on different people, depending on lifestyle, genetic makeup, and the kind of depression that is being treated. Each TCA also has slightly varying actions, too. For instance, a number of clinical studies report that over 60 percent of patients taking Tofranil (imipramine), a TCA that has a dual action on norepinephrine and serotonin, experience two or more... 

Imipramine (e.g., Tofranil) Original TCAD. Prescribed less often because of side effects. Less sedating than amitryptiline. Significant anticholinergic effects. Has quinidine-like action that may induce arrhythmias. 

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