145 Anticholinergics
Key Points• Antimuscarinic poisoning syndrome is a more appropriate description than anticholinergic overdose because only the muscarinic receptors, not the nicotinic acetylcholine receptors, are involved. In this chapter the term anticholinergic will be used for consistency and is specifically meant to indicate antimuscarinic.
• Anticholinergic agents antagonize the neurotransmitter acetylcholine at both central and peripheral muscarinic acetylcholine receptors, which leads to altered mental status, mydriasis, tachycardia, urinary retention, ileus, and dry, flushed skin.
• The diagnosis of anticholinergic syndrome is largely clinical and should include physical examination, fingerstick serum glucose measurement, and an electrocardiogram.
• Anticholinergic syndrome is a key clinical finding leading to the diagnosis of poisoning by tricyclic antidepressants (a subset of antimuscarinic agents).
• Basic treatment involves supportive care of the vital signs, activated charcoal, benzodiazepines for agitation, sodium bicarbonate for a QRS complex longer than 100 msec or wide-complex tachycardia, and physostigmine for consequential central and peripheral anticholinergic (antimuscarinic) manifestations, if appropriate.
Epidemiology
Because anticholinergic toxicologic syndrome (toxidrome) is common, recognition of its associated signs and symptoms is a necessary clinical skill. It occurs following exposure to many seemingly unrelated agents, many of which are available without prescription or used in patients with a propensity toward self-harm (Box 145.1). For example, according to data from the American Association of Poison Control Centers, 25,788 single exposures to diphenhydramine alone occurred in 2008, with 201 major outcomes and 3 deaths.1
Pathophysiology and Pharmacology
Muscarinic acetylcholine receptors are linked to G proteins to execute their postreceptor effects. They are found primarily in the CNS (most abundantly in the brain). They are also present at effector organs innervated by postganglionic parasympathetic neurons. Stimulation of these end-organs, either pharmacologically or through enhanced neuronal output, results in miosis, lacrimation, salivation, bronchospasm, bronchorrhea, bradydysrhythmia, urination, and increased gastrointestinal motility (Table 145.1). Finally, muscarinic receptors are located in sweat glands innervated by postsynaptic sympathetic neurons and cause diaphoresis when stimulated.
Table 145.1 Pathophysiology of Anticholinergic (Antimuscarinic Poisoning Syndrome) Symptoms
| ANTICHOLINERGIC EFFECT | SYMPTOMS |
|---|---|
| Central inhibition of muscarinic acetylcholine receptors | Confusion, disorientation, psychomotor agitation, ataxia, myoclonus, tremor, picking movements, abnormal speech, visual and auditory hallucinations, psychosis, seizures, cardiovascular collapse, coma |
| Inhibition of postsynaptic sympathetic muscarinic acetylcholine receptors in the sweat glands, as well as vasodilation of peripheral blood vessels | Dry, flushed skin |
| Inhibition of postsynaptic parasympathetic muscarinic acetylcholine receptors in the: | |
| Salivary glands | Dry mucous membranes |
| Eye | Paralysis of the sphincter muscle of the iris and the ciliary muscle of the lens resulting in mydriasis, cycloplegia, and blurred vision |
| Heart (vagus nerve) | Tachycardia |
| Bladder | Urinary retention and overflow incontinence |
| Bowel | Adynamic ileus |
Tricyclic antidepressants are a unique subset of antimuscarinic agents that deserve special attention. Their antidepressant effect is achieved pharmacologically through blockade of the reuptake of norepinephrine, dopamine, and serotonin in the CNS. Additionally, tricyclic antidepressants interact with other channels and receptors and cause considerably more profound clinical toxicity in overdose than occurs with most other agents that exhibit anticholinergic effects. Adverse effects of a tricyclic antidepressant overdose include competitive inhibition at both central and peripheral muscarinic acetylcholine receptors (antimuscarinic poisoning syndrome); histamine receptor antagonism (sedation); sodium channel blockade in the myocardium (widening of the QRS complex or wide-complex dysrhythmias, atrioventricular block, QT prolongation, and rightward shift of the terminal 40-msec QRS axis on an electrocardiogram [ECG], as well as negative inotropy leading to hypotension); α-adrenergic receptor antagonism on vascular smooth muscle (vasodilation leading to hypotension); and although the mechanism of this effect is unclear, γ-aminobutyric acid (GABA) antagonism (seizures). In the right clinical setting, anticholinergic syndrome is a key clinical finding leading to the diagnosis of tricyclic antidepressant poisoning (Table 145.2).
Table 145.2 Pathophysiology of Tricyclic Antidepressants and Associated Symptoms
| EFFECT | SYMPTOMS |
|---|
