Anticholinergic activity antidepressants

The antiemetics and antivertigo drug may have additive effects when used with alcohol and other CNS depressants such as sedatives, hypnotics, antianxiety drugp, opiates, and antidepressants. There may be additive anticholinergic effects (see Chap. 25) when administered with drag s that have anticholinergic activity such as the antihistamines, antidepressants, pheno-thiazines, and disopyramide The antacids decrease absorption of the antiemetics. 

The antidiarrheal drugs cause an additive CNS depression when administered with alcohol, antihistamines, narcotics, and sedatives or hypnotics. There are additive cholinergic effects when administered with other drugp having anticholinergic activity, such as antidepressants or antihistamines. Concurrent use of the antidiarrheals witii a monoamine oxidase inhibitor increases the risk of a hypertensive crisis. 

DIBENZOCYCLOHEPTANES AND DIBENZOCYCLOHEPTENES Drugs in this structural class have effected a revolution in the treatment of severely depressed patients such that deinstitutionalization is a feasible public policy. The compounds often show other CNS activities which depend on the length of the side chain. One-carbon chains generally lead to anticonvulsant activity amines separated from the nucleus by three carbons usually donvey antidepressant activity. Selected examples possess significant anticholinergic activity. 

Many tricyclic tranquilizers and antidepressants exhibit some measure of anticholinergic activity. 

Evidence that central muscarinic receptors are supersensitive in depressed patients and that chronic antidepressant treatments normalize the supersensitivity of these receptors. This effect does not depend on any intrinsic anticholinergic activity of the antidepressant (i.e. it is an indirect, adaptive effect). 

Mianserin was the first of the second-generation antidepressants to be developed. It lacked the amine reuptake inhibitory and MAOI actions of the first-generation drugs and also lacked the cardiotoxicity and anticholinergic activity of the TCAs. However, it was sedative (antihistaminic), caused postural hypotension (alpha-1 blockade) and also caused blood dyscrasias and agranulocytosis in a small number of patients. This has limited the use of mianserin in recent years. 

Bupropion is an a-aminoketone that is structurally related to amphetamines, and it exhibits unique activity comparable to that of other antidepressants. It is believed that bupropion restores the total amount of norepinephrine in the body. This compound is a poor reuptake inhibitor of dopamine, and does not exhibit anticholinergic activity or inhibit MAO. Its efficacy as an antidepressant is comparable to that of tricyclic antidepressants, and as a serotonin uptake inhibitor it is comparable to fluoxetine. It is preferable to use amoxapine. Synonyms of bupropion are amphebutamon and wellbutrin. 

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... 

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. 

Mechanism of Action A tetracyclic compound that blocks reuptake norepi nephri ne by CNS presynaptic neuronal membranes, increasing availability at postsynaptic neuronal receptor sites, and enhances synaptic activity. Therapeutic Effect Produces antidepressant effect, with prominent sedative effects and low anticholinergic activity. Pharmacokinetics Slowly and completely absorbed after PO administration. Protein binding 88%. Metabolized in liver by hydroxylation and oxidative modification. Excreted in urine. Unknown if removed by hemodialysis. Half-life 27-58 hr. 

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. 

Mild anticholinergic activity (less than some other tricyclic antidepressants) could possibly lead to sedative effects, dry mouth, constipation, and blurred vision... 

Some systemic agents may possess sufficient anticholinergic activity to produce mydriasis and a weak cycloplegic effect.These medications include antimuscarinic drugs, antihistamines, phenothiazines, and tricyclic antidepressants (Table 35-9). 

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