Toxicology 3: Anticholinergic and Cholinergic Drugs, Other Common Offenders

Question-and-answer flashcards covering mechanisms, clinical manifestations, and antidote/management strategies for cholinergic, anticholinergic, iron, methotrexate, TCA toxicities, and other commonly encountered poisonings mentioned in the lecture.

What mnemonic summarizes muscarinic cholinergic toxicity symptoms?

DUMBBELLS (Diaphoresis/diarrhea, Urination, Miosis, Bradycardia, Bronchospasm/secretions, Emesis, Lacrimation, Lethargy, Salivation) or SLUDGE (Salivation, Lacrimation, Urinary incontinence, Diarrhea, GI cramps, Emesis).

Which mnemonic is commonly used to remember anticholinergic toxicity signs?

"Hot as a hare, dry as a bone, blind as a bat, red as a beet, mad as a hatter" (also summarized as “can’t see, can’t pee, can’t spit, can’t sh*t”).

Organophosphate insecticides exert toxicity through what mechanism of action?

Irreversible inhibition of acetylcholinesterase, leading to excess acetylcholine.

List three examples of organophosphate insecticides.

Dichlorvos, malathion, parathion (others: disulfoton, mevinphos, phosmet).

What are the "Killer Bs" of cholinergic crisis?

Bronchorrhea, bronchospasm, and bradycardia.

Initial management steps for suspected organophosphate poisoning include ___ and ___.

Decontamination (remove clothing, wash skin, consider gastric lavage) and supportive therapy (maintain airway, ventilate, secure IV access).

Nerve agents (e.g., sarin) differ from typical organophosphates chiefly by what clinical feature?

Hyper-acute onset with fulminant respiratory failure within seconds to minutes.

Antidote of choice to dry secretions and relieve bronchospasm in cholinergic toxicity

Atropine (2–5 mg IV, repeat every 5–10 min until secretions/rales resolve).

Drug that reactivates acetylcholinesterase after organophosphate exposure

Pralidoxime (25–50 mg/kg up to 2 g IV over 5–20 min; repeat as needed).

Why must pralidoxime be co-administered with atropine?

It has little effect on muscarinic symptoms; atropine controls secretions and bronchospasm while pralidoxime regenerates the enzyme.

Name two centrally acting anticholinergic (antimuscarinic) drugs used for Parkinsonism.

Benztropine and trihexyphenidyl.

Which inhaled bronchodilators are classified as antimuscarinic agents?

SAMAs/LAMAs such as ipratropium, tiotropium, umeclidinium, glycopyrrolate.

Give three non-antimuscarinic drug classes that commonly have anticholinergic side effects.

Tricyclic antidepressants, first-generation antihistamines, antipsychotics (e.g., chlorpromazine, clozapine).

Peripheral manifestations of anticholinergic toxicity include ____, ____, and ____.

Elevated body temperature, dry mucous membranes/skin, tachycardia (others: blurred vision, urinary retention, decreased bowel sounds).

First-line agent for agitation or seizures caused by severe anticholinergic poisoning (before antidote)

Benzodiazepines.

Specific antidote for moderate-to-severe anticholinergic toxicity

Physostigmine (0.5–2 mg IV over ≥5 min; repeat q10–15 min prn).

When is physostigmine contraindicated?

In known or suspected tricyclic antidepressant (TCA) overdose because of risk of cardiac asystole/seizures.

Two hallmark cardiovascular findings in TCA toxicity

Refractory hypotension from myocardial depression and QRS prolongation (ventricular dysrhythmias/tachycardias).

Primary pharmacologic therapy to narrow QRS and treat hypotension in TCA overdose

IV hypertonic sodium bicarbonate (serum alkalinization).

Which antiarrhythmic class is preferred for TCA-induced dysrhythmias unresponsive to bicarbonate?

Class IB agent lidocaine.

What minimum elemental iron dose (mg/kg) is associated with serious pediatric toxicity?

≥ 60 mg/kg of elemental iron.

List the three classic phases of iron poisoning.

Early GI phase (30 min–6 h), shock/metabolic acidosis phase (6–72 h), delayed hepatotoxicity phase (12–96 h).

Why is activated charcoal ineffective in iron overdose?

Iron does not bind to activated charcoal.

Name the chelating antidote for iron toxicity and briefly describe its mechanism.

Deferoxamine; chelates ferric iron to form water-soluble ferrioxamine excreted renally.

Common medication error leading to methotrexate toxicity

Dispensing or taking weekly methotrexate doses on a daily schedule.

Systems most affected by methotrexate toxicity and why

Bone marrow, GI tract, skin—these have rapidly dividing cells requiring folate for DNA synthesis.

First-line rescue therapy for methotrexate overdose and ideal timing

IV leucovorin (folinic acid) or levoleucovorin within 1 hour of exposure.

Enzyme antidote for severe methotrexate toxicity unresponsive to leucovorin

Glucarpidase (rapidly catabolizes methotrexate to inactive metabolites).

What reversal agent is used for dabigatran (Pradaxa) anticoagulation?

Idarucizumab (Praxbind).

Which agent reverses factor Xa inhibitors (e.g., apixaban, rivaroxaban)?

Andexanet alfa (Andexxa).

Antidote for isoniazid-induced seizures and neurotoxicity

Pyridoxine (vitamin B6).

Why is thiamine administered to patients with chronic ethanol use before glucose?

To prevent Wernicke’s encephalopathy (thiamine depletion can precipitate neurologic damage when glucose is given first).