A 78-year-old man was found to have a perihilar mass on screening CT scan. The patient's medical history is remarkable for chronic obstructive pulmonary disease, for which he takes albuterol inhalers as needed. He has smoked a pack of cigarettes daily for the last 50 years and does not drink alcohol or use illicit drugs. The patient is admitted for bronchoscopy and is premedicated with intramuscular atropine and becomes acutely restless, disoriented, and combative. Temperature is 38.1 C (100.5 F), blood pressure is 116/72 mm Hg, pulse is 110/min, and respirations are 15/min. Oxygen saturation is 99% on room air. On physical examination, his pupils are widely dilated and nonreactive to light. ECG shows sinus tachycardia. Which of the following agents will reverse all of this patient's signs and symptoms?
Anticholinergic toxicity | |
Symptom | Mechanism |
"Hot as a hare" |
|
"Dry as a bone" |
|
"Red as a beet" |
|
"Blind as a bat" |
|
"Mad as a hatter" |
|
"Full as a flask" |
|
"Fast as a fiddle" Tachycardia |
|
Atropine is an anticholinergic medication that can be administered prior to bronchoscopy to decrease respiratory mucus secretions and promote bronchodilation. Anticholinergic drugs competitively inhibit the muscarinic acetylcholine receptor both centrally (leading to delirium, coma, and respiratory failure) and peripherally (see toxidrome in table). The elderly are at particularly high risk of developing anticholinergic toxicity, likely due to decreased renal and hepatic clearance.
Cholinesterase inhibitors overcome this toxicity by inhibiting the degradation of acetylcholine, thereby increasing the concentration of acetylcholine at the synaptic cleft. Central nervous system (CNS) penetration and reversal of central symptoms are dependent on chemical structure:
Tertiary amines (eg, physostigmine, galantamine, donepezil, rivastigmine) are lipophilic (nonpolar) and can easily cross the blood-brain barrier to reverse both central and peripheral symptoms.
Quaternary amines (eg, neostigmine, edrophonium, pyridostigmine) are hydrophilic (polarized) and do not readily cross the blood-brain barrier. These drugs reverse peripheral symptoms only (Choices B and D).
(Choices A and C) Both diazepam and haloperidol can be used for sedation or cases of severe agitation. Haloperidol is an antipsychotic that blocks dopamine receptors in the CNS, and diazepam is a long-acting benzodiazepine that positively modulates GABA-A activity. Neither medication reverses the peripheral anticholinergic manifestations (eg, mydriasis, tachycardia).
Educational objective:
Physostigmine is a cholinesterase inhibitor with a tertiary ammonium structure that can reverse both the central and peripheral nervous system symptoms of anticholinergic toxicity. Neostigmine, edrophonium, and pyridostigmine have a quaternary ammonium structure that limits central nervous system penetration.