Tricyclic antidepressants urinary retention

The classic anticholinergic (technically, "antimuscarinic") syndrome is remembered as "red as a beet" (skin flushed), "hot as a hare" (hyperthermia), "dry as a bone" (dry mucous membranes, no sweating), "blind as a bat" (blurred vision, cycloplegia), and "mad as a hatter" (confusion, delirium). Patients usually have sinus tachycardia, and the pupils are usually dilated (see Chapter 8). Agitated delirium or coma may be present. Muscle twitching is common, but seizures are unusual unless the patient has ingested an antihistamine or a tricyclic antidepressant. Urinary retention is common, especially in older men. 

Older men with prostatic enlargement are at increased risk for urinary retention when they take the tricyclic antidepressants. 

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Trimipramine is a tricyclic antidepressant with sedative properties that is used in the management of depression. As with other tricyclic antidepressants, trimipramine has antimuscarinic activity and therefore side-effects include dry mouth, blurred vision, constipation and urinary retention. 

Because of the multiple receptor sites that TCAs bind to, there are a variety of possible side effects that can be seen in treatment. The blockade of muscarinic receptors leads to increased anticholinergic tone and subsequent anti-cholinergic side effects, especially in the gastrointestinal system. These include delirium, dry mouth, tachycardia, constipation, and urinary retention in adults. In children, anticholinergic side effects are often not seen with treatment (Geller et ah, 1992). Tricyclic antidepressant blockade of the presynaptic a 2 receptors leads to increased autonomic tone throughout the body, causing elevations in heart rate and blood pressure. 

In terms of side effects of the tricyclic antidepressants (Table 6—5), blockade of alpha 1 adrenergic receptors causes orthostatic hypotension and dizziness (Fig. 6—30). Anticholinergic actions at muscarinic cholinergic receptors cause dry mouth, blurred vision, urinary retention, and constipation and memory disturbances (Fig. 

The tricyclic antidepressants increase bladder sphincter tone and the volume of fluid necessary to trigger detrusor contraction (80). Such effects may account for their efficacy in nocturnal enuresis, in which the benefit occurs early and at a low dosage, consistent with anticholinergic activity. However, this pharmacological action can cause hesitancy and urinary retention, especially in predisposed men who have prostatic hyperplasia. 

Antimuscarinic syndromes consist of tachycardia, dilated pupils, dry, flushed skin, urinary retention, decreased bowel sounds, mild elevation of body temperature, confusion, cardiac arrhythmias and seizures. They are commonly caused by antipsych-otics, tricyclic antidepressants, antihistamines, anti-spasmodics and many plants (see p. 160). 

The antimuscarimc actions of tricyclic antidepressants are responsible for side effects frequently experienced even at therapeutic doses and are therefore commonly present in overdose. These effects include tachycardia, hyperpyrexia, dilated pupds, dry skin and mouth, flushing, decreased GI motility, and urinary retention. 

The main side effects of tricyclic antidepressants are sedation, anti-cholinergic effects (dry mouth, constipation and urinary retention) and postural hypotension. Some patients may experience mania, seizures or impotence. Tricyclic antidepressants should be used with caution in patients with liver disease. 

Tricyclic antidepressants resemble the phenothiazine antipsychotics such as chlorpromazine in structure and function. Like the phenothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., amitriptyline) may reduce the seizure threshold and precipitate seizures in epileptic patients, cause cholestatic jaundice, movement disorders, and hematologic side effects. Unlike the phenothiazine derivatives, the tricyclic antidepressants may increase motor activity, have a very slow onset and long duration of action, a relatively narrow margin of safety, and a strong anticholinergic effect. In fact, dry mouth is the most common side effect, and other anticholinergic effects such as tachycardia, loss of accommodation, constipation, urinary retention, and paralytic ileus have been reported following amitriptyline. 

Cyclobenzaprine (10 mg t.i.d.) is a centrally acting skeletal muscle relaxant and is indicated as an adjunct to rest and physical therapy for relief of muscular spasm associated with injury related to painful musculoskeletal conditions. However, cyclobenzaprine is not effective in spasticity associated with cerebral or spinal cord injury. Cyclobenzaprine is structurally related to tricyclic antidepressants possessing sedative and anticholinergic properties. Therefore, cyclobenzaprine should be used cautiously in individuals with angle-closure glaucoma and urinary retention due to obstruction or prostatic hypertrophy. Because it causes drowsiness and blurred vision, it should be used carefully when alermess is required. 

Bethanechol may be used to treat urinary retention and stimulate GI motility. It is also used in the treatment of postpartum and postoperative nonobstructive urinary retention, and to counteract the antimuscarinic effects of phenothiazines and tricyclic antidepressants (e.g., bladder dysfunction). 

ADVERSE EEEECTS Tricyclic antidepressants routinely produce adverse autonomic responses, in part related to their relatively potent antimuscarinic effects, including dry mouth and a sour or metallic taste, epigastric distress, constipation, dizziness, tachycardia, palpitations, blurred vision (poor accommodation and increased risk of glaucoma), and urinary retention. Cardiovascular effects include orthostatic hypotension, sinus tachycardia, and variable prolongation of cardiac conduction times with the potential for arrhythmias, particularly with overdoses. 

Detailed information about adverse interactions between nefopam and other drugs does not seem to be available. The manufacturer advises caution if nefopam is given with a tricyclic antidepressant because they lower the convulsive threshold convulsions have been seen in some patients taking nefopam. In addition, the antimuscarinic adverse effects of nefopam may be additive with those of tricyclics and other drugs with antimuscarinic effects. For example, the CSM in the UK has a number of reports of urinary retention caused by nefopam, which would be expected to be worsened by drugs with antimuscarinic activity. Nefopam appears to have sympathomimetic activity and the manufacturer therefore says it should not be given with the MAOIs (see MAOIs or RIMAs + Sym-pathomimetics Indirectly-acting , p.l 147). 

Information is limited. Some therapeutic improvement including accelerated response is seen in some patients. This may be partially because of the very marked rise in the blood levels of the antidepressant due to methylphenidate, but may also be due to an additional effect on mood attributable to methylphenidate. Concurrent use may cause adverse effects sufficiently severe to necessitate withdrawal of methylphenidate, but it is not certain whether this can solely be attributed to increases in serum levels of tricyclic antidepressants. Information about other tricyclic antidepressants is lacking. However, it has been suggested that concurrent use in children and adolescents may be undesirable, due to case reports of adverse behavioural effects. If concurrent use is deemed necessary it would seem prudent to monitor concurrent use for adverse tricyclic effects (e.g. dry mouth, blurred vision, urinary retention) and adjust the dose as necessary. 

Information seems to be limited to these reports. It would seem prudent to monitor for trieyolie adverse effeets (sueh as dry mouth, blurred vision and urinary retention) in patients given valproate and amitriptyline, clomipramine, or nortriptyline and to reduee the dosage of the tricyclic if necessary. Where possible eonsider monitoring tricyclic levels. Information about other trieyelie antidepressants seems to be lacking. The occurrence of status epileptieus in another patient reinforces the fact that the tricyclics can lower the eonvulsive threshold and should therefore be used with caution in patients with epilepsy. 

Information seems to be limited to these two studies. The clinical importance of this interaction is uncertain, but it would now be prudent to monitor the outcome if propranolol or labetalol is added to treatment with imipramine. Tricyclic adverse effects include dry mouth, blurred vision and urinary retention. Where possible consider monitoring the plasma imipramine levels. There seems to be no information as yet about other beta blockers or tricyclic antidepressants. 

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