Tricyclic antidepressants anticholinergic effects

Clinical signs of toxicity most frequently seen include sedation, coma, seizures, extrapyramidal effects, and rarely hypotension and cardiac arrhythmias. Coma and seizures may develop rapidly following an exposure to loxapine. Cardiac effects include prolonged QRS, Q-T intervals, and mild hypotension however, the cardiac effects are less pronounced than those associated with tricyclic antidepressants. Anticholinergic effects, including dry mouth, blurred vision, and tachycardia, have been seen. Neuroleptic malignant syndrome has been reported after therapeutic use and acute intoxication. Hypokalemia has also been noted. 

The very slow onset of action and side effects which follow from the anticholinergic side effects characteristic of the tricyclic antidepressants has led to a continuing effort to find replacements from other structural classes which might thus be devoid of this defect. A series of alkoxy phenylpropylamines has been investigated extensively in this search for non-tricyclic antidepressants. The most recent analogue, tomoxetine (69), is accessible by the same route [15] used to prepare the earlier analogue, nisoxetine, in which methoxyl replaces the ortho methyl group. 

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

Administration of atropine with meperidine (Demerol), flurazepam (Dalmane), diphenhydramine (Benadryl), phenothiazines, and the tricyclic antidepressants may increase the effects of atropine. There is a decreased effectiveness of haloperidol when administered with the anticholinergic dragp. 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

Although probably equally effective, the tricyclic antidepressants are usually avoided because of anticholinergic side effects. 

Common side effects of the SSRIs are somnolence, nausea, ejaculation disorders, decreased libido, dry mouth, insomnia, and fatigue. Tricyclic antidepressants (TCAs) commonly cause sedation, orthostatic hypotension, anticholinergic effects, and weight gain. TCAs are very toxic on overdose. 

Antidepressants, tricyclic Anticholinergic effects, a-antagonist effects... 

Anticholinergic effect is an important adverse effect that is frequent in the elderly taking tricyclic antidepressants... 

When treating insomnia without depression, doxepin and amitriptyline (both tricyclic antidepressants) can be administered in low doses (25-100 mg) at bedtime. These antidepressants, however, do have troublesome anticholinergic side effects (dry mouth, constipation, blurred vision, dizziness) and adverse effects on the heart, and they can be lethal if taken in overdose. Because of their effect on heart function, these antidepressants should be avoided in patients with heart problems and administered cautiously, if at all, to those who are already receiving one of any number of newer antidepressants that inhibit the metabolism of the TCAs. 

Before the arrival of the new antidepressants, the older tricyclic antidepressants were widely used to treat depression and agitation in demented patients. They have now largely been abandoned in these patients as their prominent anticholinergic effects tend to worsen dementia and the increased risk for cardiac toxicity can be especially dangerous in geriatric patients. 

Antidepressants. Depression after TBl is routinely treated with antidepressant medicines. Although all antidepressants are potentially helpful, antidepressants prone to burdensome side effects, particularly sedative and anticholinergic side effects, should generally be avoided, as they are likely to be tolerated poorly by these patients. In addition, antidepressants that may increase the risk for seizure, such as many of the older tricyclic antidepressants (TCAs) and bupropion (Well-butrin), should be avoided because post-TBl patients as a rule are already more vulnerable to seizures. 

The efficacy of fluoxetine in treating patients with moderate depression is comparable to the efficacy of tricyclic antidepressants. It is capable of elevating mood and removing feelings of fear and stress. It does not have a sedative effect. Fluoxetine is used in depression as well as in bulemic neuroses. Use of fluoxetine is preferred in cases when sedative, hypotensive, and anticholinergic side effects caused by other antidepressants are con-traindicative to patients. Prozac is a synonym for fluoxetine. 

Tricyclic antidepressants are notorious for their risk to be involved in drug-drug interactions. Additive anticholinergic effects can be expected in combination with antihistamines, antipsychotics and anticholinergic-type anti-Parkinson agents. Hepatic enzyme-inducing agents increase their hepatic metabolism while enzyme inhibitors may potentiate the effects of tricyclics. Concomitant use with monoamine oxidase inhibitors will produce hypertension, hyperpyrexia and convulsions. 

Agents from this class of antidepressants are selective blockers of the re-uptake of serotonin at presynaptic neurones and have little if any effects on muscarinic, histaminergic, adrenergic or serotonergic receptors. They are as effective as the tricyclic antidepressants in the management of depressive disorders, but have less cardiovascular effects. They have less anticholinergic activity and because of their lower risk of cardiotoxicity in overdose they... 

A number of drugs in addition to atropine and scopolamine have antimuscarinic properties. Tbese include tricyclic antidepressants, phenothiazines, and antihistamines. Physostigmine has been used in the treatment of acute toxicity produced by these compounds. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects of its own, and therefore, it should be considered as an antidote only in life-threatening cases of anticholinergic drug overdose. 

With the introduction of the SSRIs, the safety and tolerability of antidepressants improved remarkably. As a class, these medications have little or no affinity for cholinergic, (3-adrenergic or histamine receptors and do not interfere with cardiac conduction. They are well tolerated by patients with heart disease and by the elderly, who are especially sensitive to the anticholinergic and orthostatic effects of the tricyclic antidepressant agents (TCAs) and monoamine oxidase inhibitors (MAOIs). 

Mechanism of Action A tricyclic antidepressant that blocks the reuptake of neu-retransmitters, including norepinephrine and serotonin, at presynaptic membranes, thus increasing their availability at postsynaptic receptor sites. Also has strong anticholinergic activity. Therapeutic Effect Relieves depression. 

Equal efficacy as tricyclic antidepressants advantages include minimal anticholinergic effects, lack of orthostatic hypotension, no cardiac conduction problems, absence of weight gain, no sedation... 

Geriatric Considerations - Summary Bupropion has several advantages as an antidepressant agent for use in older adults. It has neither the anticholinergic or cardiac toxicities of the tricyclic antidepressants, and has fewer sexual side effects than selective serotonin reuptake inhibitors. Because this drug may lower seizure threshold, it should be used with caution in older adults with increased risk of seizures (e.g., previous stroke, early-onset Alzheimer s disease). 

Equally effective as other tricyclic antidepressants for depression fewer anticholinergic effects than tertiary amines, less orthostasis, and mild stimulatory property... 

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. 

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