Anticholinergics gastrointestinal effects

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

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. 

The major advantages of SSRIs over the tricyclic antidepressants are their less pronounced anticholinergic adverse effects and lack of severe cardiotoxicity. However, some studies have shown some degree of nervousness or agitation, sleep disturbances, gastrointestinal symptoms, and perhaps sexual adverse effects more commonly in patients treated with SSRIs than in those treated with tricyclic antidepressants. SSRIs may also be associated with an increased risk of suicide, particularly in children under 16 (9). 

The 25-mg dose of the anticholinergic drug mepenzolate bromide, often given several times a day for gastrointestinal disorders, is sufficient to cause anticholinergic adverse effects, but the compound may itself be a cause... 

Emerging evidence suggests that the high incidence of adverse effects, especially dry mouth, of oxybutynin IR, and to a lesser extent oxybutynin extended-release (XL) and oxybutynin transder-mal system (TDS), may be largely due to the active metabolite, A-desethyloxybutynin (DEO). This metabofite is generated by extensive first-pass metabolism in the liver and upper gastrointestinal tract. ° Since many of the adverse effects seen with oxybutynin are felt to be related to the primary hepatic metabolite DEO, the lower DEO plasma concentrations seen with oxybutynin TDS and oxybutynin XL (which are due to reduced first-pass metabolism) compared to those of oxybutynin IR may explain their lesser propensity to cause dry mouth and other anticholinergic adverse effects. 

The flavonoids and pipecolic derivatives could assist in modulating gastrointestinal motility with reduced anticholinergic side effects. Their effects in patients with carcinoid syndrome can be particularly beneficial, since in this condition an excess production of 5-HT is responsible of peristalsis and hypersecretion. In addition, some triterpenes from B. crassifolia have reported anti-inflammatory effect [28]. Gallic phenols and flavonoids are antiseptic, antioxidant and immunomodulators [28], activities that can explain, in part, the beneficial effects of B. crassifolia in diarrhea. Moreover, olygomeric proanthocyanidines (OPC s, 44) are... 

Mechanism of Action A peripheral anticholinergic agent that has limited ability to cross the blood-brain barrier and provides a peripheral blockade of muscarinic receptors. Therapeutic Effect Reduces the volume and the total acid content of gastric secretions, inhibits salivation, and reduces gastrointestinal motility. 

Bupropion is an aminoketone that exerts its therapeutic effect through the inhibition of norepinephrine and dopamine reuptake. Bupropion s receptor occupancy profile shows an absence of anticholinergic and antihista-minic effects (Cusack et ah, 1994). Bupropion is absorbed rapidly from the gastrointestinal tract, and peak blood levels are achieved within 2 hours for regular release and 3 hours for sustained-release preparations = 10 hours). Bupropion undergoes extensive first-pass metabolism in the liver, yielding three active metabolites hydrobupropion, threohydroxybu-propion, and erythrohydrobupropion. The half-lives of the active metabolites are approximately 20 + hours (Preskorn, 1993). 

Metoclopramide Anticholinergic drugs such as atropine, benzhexol, propantheline, narcotic analgesics Antagonism - they have opposing effects on gastrointestinal activity. 

For chronic abdominal pain, low doses of tricyclic antidepressants (eg, amitriptyline or desipramine, 10-50 mg/d) appear to be helpful (see Chapter 30). At these doses, these agents have no effect on mood but may alter central processing of visceral afferent information. The anticholinergic properties of these agents also may have effects on gastrointestinal motility and secretion, reducing stool frequency and liquidity. Finally, tricyclic antidepressants may alter receptors for enteric neurotransmitters such as serotonin, affecting visceral afferent sensation. 

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