M. M. Ciammaichella, A. Galanti, C. Rossi
Dirigenti Medici I livello
U.o.c. Medicina I per l’Urgenza
A.C.O. S. Giovanni - Addolorata - Roma, Italia
(Direttore: Dott. G. Cerqua)


anticholinergic toxicity




The Authors examined anticholinergic toxicity




Because of the frequent use of tricyclic antidepressants, phenothiazines, antihistamines, and antiparkinsonian drugs, anticholinergic toxicity is commonly seen in the emergency department. Anticholinergic medications are commonly prescribed for elderly patients, often resulting in drug-induced delirium. Many drugs have anticholinergic properties (Table 1) that may be mild at therapeutic doses but are life-threatening in overdose. The use and abuse of some plants and mushrooms may also result in anticholinergic toxicity.




Drug absorption can occur after ingestion, smoking, or ocular use. The rate of absorption varies depending on the drug and the route of exposure. Because cholinergic blockade delays gastric emptying and decreases intestinal motility, absorption and peak clinical effects are often delayed.

The signs and symptoms of anticholinergic toxicity are a result of both central and peripheral cholinergic blockade. Muscarinic acetylcholine receptors predominate in the brain, while nicotinic receptors predominate in the spinal cord. Depending on the drug involved, antagonism of muscarinic, nicotinic, or both receptors may occur. The central effects of cholinergic blockade include agitation, amnesia, anxiety, ataxia, coma, confusion, delirium, disorientation, dysarthria, hallucinations, hyperactivity, lethargy, somnolence, seizures, circulatory collapse, mydriasis, and respiratory failure. The peripheral effects include arrhythmias, tachycardia, decreased bronchial secretions, dysphagia, decreased gastrointestinal motility, hyperthermia, hypo- or hypertension, decreased salivation, decreased sweating, urinary retention, and vasodilation.




The classic presentation of patients with anticholinergic toxicity can be remembered as:

Hot as Hades

Blind as a Bat

Dry as a Bone

Red as a Beet

Mad as a Hatter

Clinical characteristics include unreactive mydriasis, hypo- or hypertension, absent bowel sounds, tachycardia, flushed skin, disorientation, urinary retention, hyperthermia, dry skin and mucous membranes, and auditory and visual hallucinations. Patients can also present with seizures or coma. Cardiogenic pulmonary edema may occur secondary to depression of myocardial contraction.

The diagnosis of anticholinergic toxicity must be based on clinical presentation. The diagnosis may be confused with delirium tremens or an acute psychiatric disorder. Anticholinergic toxicity can be differentiated from delirium tremens and sympathomimetic toxicity by the presence of dry skin and the absence of bowel sounds. Acute psychiatric disorders may have associated tachycardia and tachypnea, but usually the physical examination is normal. Complications from anticholinergic toxicity occur secondary to hyperthermia, arrhythmias, seizures, and circulatory collapse.

Electrocardiographic abnormalities may include QRS prolongation, abnormal conduction, bundle branch block, AV dissociation, and atrial and ventricular tachycardias. Sinus tachycardia is the most common abnormality. Routine laboratory evaluations, including measurement of electrolytes, glucose, and arterial blood gases, should be checked in the presence of abnormal mental status but should be normal in isolated anticholinergic toxicity. Comprehensive toxicologic screens are of little value in the acute setting, and some anticholinergic agents (e.g., scopolamine) may not be detected. The screen can be used for confirmation, but the diagnosis should be based on clinical findings.




Conservative, supportive therapy is the mainstay of treatment of anticholinergic toxicity. Evaluation of the airway, breathing, and circulation is a priority. An intravenous line should be established and an ECG monitor placed in any patient with significant symptoms. Because gastrointestinal motility is delayed, gastric emptying may be effective after several hours. Activated charcoal may be useful to decrease drug absorption, particularly with agents that undergo enterohepatic circulation or when the agents ingested are unknown. A cathartic should also be administered.

Hyperthermia should be controlled with conventional therapy. Seizures can be treated with benzodiazepines and barbiturates. Hypertension usually does not require treatment, but conventional therapy should be used if necessary. The treatment of arrhythmias depends on the type and on the causative agent. Standard antiarrhythmics are usually effective, but class Ia agents should be avoided due to the quinidine-like effect of many anticholinergic drugs. Agitation can be treated with benzodiazepines. Because of their anticholinergic effects, phenothiazines should be avoided.

The most controversial topic surrounding anticholinergic toxicity is the use of physostigmine. Physostigmine is a tertiary ammonium compound which is a reversible acetylcholinesterase inhibitor that crosses the blood-brain barrier and reverses both central and peripheral anticholinergic effects. Physostigmine may aggravate arrhythmias and seizures and must be used with extreme caution. The indications for its use include the presence of peripheral anticholinergic signs and seizures unresponsive to conventional therapy, uncontrollable agitation, hemodynamically unstable arrhythmias unresponsive to conventional therapy, coma with respiratory depression, malignant hypertension, or refractory hypotension. Physostigmine should be avoided in cyclic antidepressant overdose as it may potentiate toxicity and increase mortality. The initial dose of physostigmine is 0.5 to 2.0 mg IV over 5 min. Improvement of central signs usually occurs within 5 to 15 min. The minimal effective dose should be used. Due to rapid elimination, repeat doses may be necessary every 30 to 60 min. Physostigmine use is contraindicated in patients with cardiovascular disease, bronchospasm, intestinal obstruction, heart block, peripheral vascular disease, and bladder obstruction. Patients receiving physostigmine should be on a monitor and observed for cholinergic symptoms (salivation, lacrimation, urination, and defecation).

Patients with mild symptoms of anticholinergic toxicity can be discharged after 6 h of observation, if their symptoms are improving. Patients receiving physostigmine usually require admission for at least 24 h.




Many plants have anticholinergic effects, including deadly nightshade, henbane, mandrake, burdock root, Jimsonweed, and others. They are often used for medicinal purposes or brewed in teas. Datura stramonium, also known as Jimsonweed, is a member of the Solanaceae family. It is a common weed that grows to be 3 to 6 ft high and can be found throughout the United States. Its leaves are large, jagged, and have a bitter taste and foul odor. The plant has large white or purple trumpet-shaped flowers that bloom in the late spring and become thorny quadripartite capsules in the fall, filled with black seeds. The entire plant is toxic and contains atropine, hyoscyamine, and scopolamine in various amounts. In the past, Jimsonweed was marketed and sold in health food stores in a preparation for the treatment of asthma. Many accidental childhood poisonings from Jimsonweed have been reported. Over the past 20 to 30 years, Jimsonweed has been involved in inadvertent overdoses in persons experimenting with mind-altering drugs. The plant can be smoked or ingested. Fifty to one hundred seeds contain the equivalent of 3 to 6 mg atropine.

Symptoms of anticholinergic toxicity occur within 2 to 6 h after the ingestion of Jimsonweed. As with other agents causing anticholinergic toxicity, patients present with fever, erythema, mydriasis, delirium, hallucinations, tachycardia, and amnesia. The treatment is the same as that described above. Because the seeds may remain in the stomach for prolonged periods, gastric emptying is recommended up to 12 to 24 h after the ingestion of seeds. The most persistent symptom of Jimsonweed toxicity is blurred vision, as mydriasis can persist for up to 1 week. Mydriasis can also occur from isolated local contact of Jimsonweed with the eye (cornpicker's pupil).




Anticholinergic Substances

  • Antihistamines
    • Ethanolamines
      • Dimenhydrinate
      • Diphenhydramine
    • Ethylenediamines
      • Tripelennamine
    • Alkylamines
      • Chlorpheniramine
    • Piperazines
      • Astemizole
      • Terfenadine
      • Loratadine
      • Cyclizine
      • Meclizine
    • Phenothiazines
      • Promethazine
  • Antiparkinsonian drugs
    • Benztropine mesylate
    • Biperiden
    • Ethopropazine
    • Trihexyphenidyl
    • Procyclidine
  • Antipsychotics
    • Phenothiazines
      • Chlorpromazine
      • Thioridazine
      • Perphenazine
    • Nonphenothiazines
      • Molindone
      • Loxapine
  • Antispasmodics
    • Clidinium bromide
    • Dicyclomine
    • Methantheline bromide
    • Propantheline bromide
    • Tridihexethyl chloride
  • Plants
    • Deadly nightshade
    • Mandrake
    • Jimsonweed
  • Belladonna alkaloids, synthetic cogeners
    • Atropine
    • Belladonna alkaloid mixtures
    • Glycopyrrolate
    • Homatropine
    • Methscopolamine bromide
    • Scopolamine hydrobromide
  • Cyclic antidepressants
    • Amitryptyline hydrochloride
    • Desipramine hydrochloride
    • Doxepin hydrochloride
    • Imipramine hydrochloride
    • Nortriptyline hydrochloride
    • Protriptyline hydrochloride
    • Trimipramine
    • Maprotiline hydrochloride
    • Zimelidine hydrochloride
    • Fluoxetine
    • Amoxapine
  • Ophthalmic products
    • Atropine and scopolamine solutions
    • Cyclopentolate hydrochloride
    • Tropicamide
  • OTC medications (including antihistamines and belladonna alkaloids)
    • Analgesics: Excedrin PM, Percogesic
    • Cold remedies: Actifed, Allerest, Coricidin, Dristan, Flavihist, Romex, Sine-Off
    • Hypnotics: Compoz, Sleep-Eze, Sominex
    • Menstrual products: Pamprin, Premesyn PMS
  • Skeletal muscle relaxants
    • Orphenadrine citrate
    • Cyclobenzaprine hydrochloride
  • Mushrooms
    • Amanita muscaria
    • Amanita pantherina



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