STEPTRACKERPHARMACOLOGY + TOXICOLOGY | AUTONOMIC | HIGH-YIELD REVIEW

Muscarinic Antagonists & Organophosphate Poisoning

Blocking muscarinic receptors dries, speeds up and dilates — useful organ by organ, dangerous in excess. Organophosphates are the mirror image.

FOCUS ON
Atropine: bradycardia, organophosphate poisoning (large doses), pupil dilation; glycopyrrolate (quaternary): ↓ secretions, paired with neostigmine; scopolamine: motion sickness (CNS); ipratropium/tiotropium: COPD, asthma; oxybutynin, tolterodine, solifenacin: overactive bladder; benztropine, trihexyphenidyl: Parkinson tremor, antipsychotic dystonia; tropicamide, cyclopentolate: eye exams (mydriasis + cycloplegia); hyoscyamine, dicyclomine: GI spasm. Anticholinergic toxidrome: hyperthermia, dry flushed skin, mydriasis, delirium, tachycardia, urinary retention, ileus. Precipitates acute angle-closure glaucoma; worsens BPH retention and dementia. Organophosphates (insecticides, nerve agents) irreversibly inhibit AChE → muscarinic excess (diarrhea, urination, miosis, bronchorrhea, bradycardia, vomiting, tears, salivation, sweating) plus nicotinic weakness and respiratory failure → atropine (muscarinic) + pralidoxime (regenerates AChE before "aging").
DRUG
TARGET · FEATURE
USE
NOTES
Atropine
Nonselective muscarinic antagonist, tertiary
Symptomatic bradycardia, organophosphate poisoning, ↓ secretions
Endpoint in poisoning: drying of bronchial secretions, not pupil size
Glycopyrrolate
Quaternary — no CNS
Preoperative ↓ secretions, with neostigmine, drooling
No delirium
Scopolamine
Tertiary, strong CNS action
Motion sickness (transdermal patch)
Sedation, confusion in elderly
Ipratropium · tiotropium
Inhaled, quaternary; M3 blockade in airways
COPD (tiotropium long-acting), acute asthma add-on
Dry mouth; little systemic effect
Oxybutynin · tolterodine · solifenacin · darifenacin
M3 antagonists at detrusor
Urge incontinence, overactive bladder
Dry mouth, constipation, cognitive effects (oxybutynin worst)
Benztropine · trihexyphenidyl
Central muscarinic antagonists
Parkinson tremor, acute dystonia from antipsychotics
Avoid in elderly (confusion)
Tropicamide · cyclopentolate
Topical eye drops
Mydriasis and cycloplegia for exams
Can trigger angle closure
Hyoscyamine · dicyclomine
GI antispasmodics
IBS cramping
Anticholinergic effects
Drugs with hidden anticholinergic effects
First-generation antihistamines, TCAs, low-potency antipsychotics, cyclobenzaprine
—
Cumulative burden → delirium, retention in elderly
Organophosphates
Irreversible AChE phosphorylation; lipophilic, absorbed through skin
Parathion, malathion, sarin
Farmworker with pinpoint pupils, wheeze, secretions, fasciculations
Pralidoxime
Regenerates AChE (cleaves phosphate) — must be given before "aging"
Organophosphate poisoning (with atropine)
Reverses nicotinic (muscle) and muscarinic effects; acts peripherally
Carbamate insecticides
Reversible AChE inhibitors
Similar picture, shorter
Pralidoxime less needed

Mechanism — anticholinergic toxidrome

M3 block on sweat glands
→
No sweating → hyperthermia, flushed skin
M3 block on iris and ciliary muscle
→
Mydriasis, blurred near vision
M2 block on SA node
→
Tachycardia

Anticholinergic vs sympathomimetic

FINDING
ANTICHOLINERGIC
SYMPATHOMIMETIC
Pupils
Dilated
Dilated
Skin
Dry, hot
Sweaty
Bowel sounds
Absent
Normal or ↑
Bladder
Retention
Normal

How it's tested

COMMON CONFUSIONDilated pupils + tachycardia fits both cocaine and atropine-like drugs — the skin (dry vs sweaty) tells them apart.
THE TRAPIn organophosphate poisoning, atropine does nothing for muscle weakness or paralysis (nicotinic) — pralidoxime and ventilation are needed.
YOUR APPROACHPick the organ → choose a selective agent (inhaled, quaternary, topical) to avoid CNS and systemic effects.

If you see… think…

Fever, dry flushed skin, dilated pupils, delirium, urinary retention → anticholinergic toxicity
Farmer with salivation, miosis, wheeze, fasciculations → organophosphate
Antidote that restores AChE → pralidoxime
Treatment for motion sickness patch → scopolamine
Long-acting inhaled antimuscarinic for COPD → tiotropium
Acute dystonia on haloperidol → benztropine or diphenhydramine
Eye pain and halos after dilating drops → acute angle-closure glaucoma
Confusion in elderly on oxybutynin → central anticholinergic effect
Atropine endpoint in poisoning → clear bronchial secretions
Quaternary antimuscarinic paired with neostigmine → glycopyrrolate