Anticholinergic intoxication can occur with a wide variety of prescription and over-the-counter medications and with numerous plants. Common drugs that have anticholinergic activity include antihistamines, antipsychotics, antispasmodics, skeletal muscle relaxants, and tricyclic antidepressants. Common anticholinergic medications are described in Table II-5. Plants containing anticholinergic alkaloids include jimsonweed (Datura stramonium), deadly nightshade (Atropa belladonna), and henbane (Hyoscyamus niger).

1. Anticholinergic agents competitively antagonize the effects of acetylcholine at peripheral and central muscarinic receptors. Exocrine glands, such as those responsible for sweating and salivation, and smooth muscle are primarily affected. The inhibition of muscarinic activity in the heart leads to a rapid heartbeat.
2. Tertiary amines (eg, atropine) have better CNS penetration compared with quaternary amines (eg, glycopyrrolate) and therefore more profound effects on mental status.
3. Pharmacokinetics. Absorption may be delayed because of the pharmacologic effects of these drugs on GI motility. The duration of toxic effects can be quite prolonged (eg, benztropine intoxication may persist for 2-3 days; see also Table II-63).

The range of toxicity is highly variable and unpredictable. The potentially lethal dose of atropine has been estimated to be greater than 10 mg in adults. Ingestion of 30-50 jimsonweed seeds has been reported to cause significant toxicity. Doses up to 360 mg of trospium chloride produced increased heart rate and dry mouth but no other significant toxicity in healthy adults.

The anticholinergic syndrome is characterized by warm, dry, flushed skin; dry mouth; mydriasis; agitated delirium; tachycardia; ileus; and urinary retention. Myoclonic movements and choreoathetosis are common, and in conjunction with agitation may lead to rhabdomyolysis. Hyperthermia, coma, and respiratory arrest may occur. Seizures are rare with pure antimuscarinic agents, although they may result from other pharmacologic properties of the drug (eg, tricyclic antidepressants and antihistamines).

Is based on a history of exposure and the presence of typical features, such as dilated pupils and flushed skin. A trial dose of physostigmine (see below) can be used to confirm the presence of anticholinergic toxicity; rapid reversal of signs and symptoms is consistent with the diagnosis.

1. Specific levels. Concentrations in body fluids are not generally available. Common over-the-counter (OTC) agents are usually detectable on comprehensive urine toxicology screening but are not found on drugs of abuse panels.
2. Other useful studies include electrolytes, glucose, creatine kinase (CK), arterial or venous blood gases or pulse oximetry, and ECG monitoring.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if needed.
   2. Treat hyperthermia, coma, rhabdomyolysis, and seizures.
2. Specific drugs and antidotes.
   1. A small dose of physostigmine, 0.5-2 mg IV in an adult, can be given to patients with severe toxicity (eg, hyperthermia, severe delirium, or tachycardia). If an initial response is seen, but delirium recurs, a continuous infusion of physostigmine may be useful. Caution: Physostigmine can cause atrioventricular (AV) block, asystole, and seizures, especially in patients with tricyclic antidepressant overdose.
   2. Neostigmine, a peripherally acting cholinesterase inhibitor, may be useful in treating anticholinergic-induced ileus.
3. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly. Because of slowed GI motility, gut decontamination procedures may be helpful, even in late-presenting patients.
4. Enhanced elimination. Hemodialysis, hemoperfusion, peritoneal dialysis, and repeat-dose charcoal are not effective in removing anticholinergic agents.