Cholinergic and Anticholinergic Drugs for NEET PG Pharmacology: Neostigmine, Atropine, Pralidoxime and Organophosphate Poisoning

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🎯 Exam priority: High. Organophosphate poisoning is one of the most asked toxicology topics, and autonomic drugs underpin cardiology, anaesthesia and ophthalmology questions. Learn the signs, the two antidotes, and which drugs enter the brain.

CBME mapping: PH 2.1 (cholinergic and anticholinergic drugs) and PH 9 (poisoning).

The Autonomic Layout

• Acetylcholine is released by all preganglionic fibres (sympathetic and parasympathetic), all postganglionic parasympathetic fibres, and the sympathetic fibres to sweat glands and piloerector muscles.

• Noradrenaline is released by most postganglionic sympathetic fibres.

• The vagus carries about 75% of all parasympathetic fibres. Sympathetic is catabolic (fight or flight); parasympathetic is anabolic (rest and restore).

• Acetylcholine acts on two receptor families, muscarinic and nicotinic; which signs appear depends on which are stimulated or blocked.

Direct Cholinergic Agonists

• Bethanechol: post-operative and post-partum non-obstructive urinary retention and neurogenic bladder atony. Contraindicated in hyperthyroidism, peptic ulcer and asthma, among others.

• Pilocarpine (oral): dry mouth after head-and-neck radiotherapy and in Sjögren syndrome. Avoid when miosis is undesirable, as in acute iritis and angle-closure glaucoma, and in uncontrolled asthma.

Anticholinesterases

These block cholinesterase, so acetylcholine accumulates at both muscarinic and nicotinic sites.

Myasthenic vs cholinergic crisis: sudden weakness in a treated myasthenic can be worsening disease (myasthenic crisis) or overtreatment with anticholinesterases (cholinergic crisis); edrophonium is used to evaluate this, only once breathing is secured.

Antimuscarinics

• Quaternary vs tertiary: glycopyrrolate (quaternary) barely crosses the blood-brain barrier; atropine and scopolamine (tertiary amines) cross easily, so they cause central effects. Atropine or glycopyrrolate is given with neostigmine, and physostigmine is the anticholinesterase used for central anticholinergic toxicity.

• Atropine's block is competitive (surmountable): enough acetylcholine overcomes it.

• Atropine overdose: palpitations, dilated pupils, difficulty swallowing, hot dry skin, thirst; toxic doses cause excitement, hallucinations, delirium and coma.

Organophosphate and Carbamate Poisoning

Organophosphate poisoning: muscarinic signs are treated with atropine, nicotinic weakness with pralidoxime. Drawn by TrackNation from the MSD Manual and the pralidoxime label.

• Mechanism: both inhibit cholinesterase. Carbamates clear spontaneously within about 48 hours; organophosphates can bind irreversibly.

• Muscarinic: salivation, lacrimation, urination, defecation, vomiting, miosis, bronchorrhoea and wheeze, bradycardia. Nicotinic: fasciculations and weakness (typical), sometimes mydriasis, tachycardia and sweating. CNS toxicity is common. Many organophosphates smell of garlic or petroleum.

• Diagnosis is clinical; if unclear, improvement after 1 mg atropine supports it. RBC cholinesterase activity reflects severity.

• Atropine: 2–3 mg IV, doubled every 3–5 minutes, titrated to dry the chest (bronchorrhoea and bronchospasm), not to normalise pupils or heart rate. Severe cases may need grams.

• Pralidoxime: reactivates phosphorylated cholinesterase (mainly outside the brain) and slows its "ageing" into a form that cannot be reactivated. Its key effect is relieving respiratory muscle paralysis; it does not fix central respiratory depression, so atropine is always needed with it. MSD gives 1–2 g IV over 15–30 minutes after atropine.

• Carbamates: MSD advises giving pralidoxime when the agent is unknown, but the pralidoxime label says it is not indicated for carbamate poisoning because it may increase carbaryl toxicity.

• Decontaminate (remove clothes, wash skin; activated charcoal within 1 hour of ingestion); benzodiazepines for seizures.

• Late effects: intermediate syndrome — proximal, cranial and respiratory weakness 1–3 days after exposure, resolving in 2–3 weeks; delayed axonal neuropathy 1–3 weeks after some agents (chlorpyrifos, triorthocresyl phosphate).

Traps the Examiner Sets

• Atropine endpoint = dry chest, not pupil size.

• Pralidoxime treats nicotinic (muscle) weakness; atropine treats muscarinic signs. Both are needed.

• Sweat glands are sympathetic but cholinergic.

• Glycopyrrolate (quaternary) stays out of the brain; atropine and scopolamine enter it.

• Physostigmine, not neostigmine, reverses central anticholinergic toxicity.

• Intermediate syndrome (1–3 days) ≠ delayed neuropathy (1–3 weeks).

• Tiotropium is for maintenance, not acute bronchospasm.

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 SLUDGE + 3 Bs — Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis + Bronchorrhoea, Bronchospasm, Bradycardia — muscarinic OP signs

• 🧠 Dry the chest, not the eyes — atropine is titrated to bronchial secretions, not pupils

• 🧠 Pralidoxime Pulls the Phosphate — 2-PAM reactivates phosphorylated cholinesterase before ageing

• 🧠 Quaternary stays Quiet — quaternary drugs (glycopyrrolate, neostigmine) stay out of the brain

• 🧠 Physo goes to the Head — physostigmine reverses central anticholinergic toxicity

• 🧠 Three days, three weeks — intermediate syndrome at 1–3 days; delayed neuropathy at 1–3 weeks

Rapid-Revision Cards

• Cholinergic fibres

  All preganglionic, all postganglionic parasympathetic, sympathetic to sweat glands and piloerectors.

• Vagus share

  About 75% of parasympathetic fibres.

• OP muscarinic signs

  Salivation, lacrimation, urination, defecation, vomiting, miosis, bronchorrhoea, bradycardia.

• OP nicotinic signs

  Fasciculations, weakness; sometimes mydriasis, tachycardia, sweating.

• OP odour

  Garlic or petroleum.

• Atropine in OP

  2–3 mg IV, double every 3–5 min; target dry chest.

• Pralidoxime

  Reactivates phosphorylated cholinesterase; slows ageing; relieves respiratory muscle paralysis.

• 2-PAM + atropine

  Atropine always needed too (respiratory centre).

• 2-PAM in carbamates

  Label: not indicated (may worsen carbaryl); MSD: give if agent unknown.

• Intermediate syndrome

  1–3 days; proximal, cranial, respiratory weakness; resolves 2–3 weeks.

• Delayed OP neuropathy

  1–3 weeks; chlorpyrifos, triorthocresyl phosphate.

• Carbamate vs OP

  Carbamate clears in ~48 h; OP can bind irreversibly.

• Neostigmine

  Reverses non-depolarising block; no CNS entry; give with atropine/glycopyrrolate.

• Pyridostigmine

  Oral, myasthenia gravis.

• Edrophonium

  Diagnosis of MG; crisis evaluation; too brief for maintenance.

• Physostigmine

  Reverses central anticholinergic syndrome (datura, atropine).

• Glycopyrrolate

  Quaternary; no CNS entry; drying secretions.

• Atropine and scopolamine

  Tertiary amines; enter the CNS.

• Atropine uses

  Antisialagogue, bradycardia, OP and mushroom poisoning.

• Atropine toxicity

  Dilated pupils, hot dry skin, thirst, delirium.

• Tiotropium

  M3 block in airways; maintenance COPD; not acute.

• Oxybutynin

  Detrusor relaxant for urge incontinence.

• Bethanechol

  Non-obstructive urinary retention; avoid in asthma, peptic ulcer, hyperthyroidism.

• Pilocarpine oral

  Dry mouth (radiotherapy, Sjögren); avoid in angle closure.

Sources

Facts in this article were checked against these documents.

• MSD Manual Professional Edition: Organophosphate Poisoning and Carbamate Poisoning; Overview of the Autonomic Nervous System — Merck & Co. (MSD Manuals), 2025 (link)

• Prescribing labels: Protopam (pralidoxime), atropine sulfate injection, Bloxiverz (neostigmine), Mestinon (pyridostigmine), Anticholium (physostigmine), Enlon (edrophonium), Salagen (pilocarpine), bethanechol, glycopyrrolate injection, Transderm Scop, ipratropium HFA, Spiriva Respimat (tiotropium), oxybutynin — DailyMed, US National Library of Medicine, current labels, accessed November 2026 (link)

• Competency Based Undergraduate Curriculum, Pharmacology (PH 2.1, PH 9) — National Medical Commission, 2024

Test Yourself: Practice Questions

Twenty-five questions in NEET PG style, including clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. Sympathetic postganglionic fibres to sweat glands release

• (a) acetylcholine

• (b) adrenaline

• (c) dopamine

• (d) noradrenaline

Q2. Which nerve carries about 75% of all parasympathetic fibres?

• (a) Vagus

• (b) Glossopharyngeal

• (c) Pelvic splanchnic

• (d) Oculomotor

Q3. A farmer has pinpoint pupils, profuse salivation, wheeze and bradycardia after spraying a pesticide. These are

• (a) adrenergic effects

• (b) muscarinic effects

• (c) nicotinic effects

• (d) dopaminergic effects

Q4. In organophosphate poisoning, fasciculations and muscle weakness are

• (a) muscarinic effects

• (b) nicotinic effects

• (c) a sign of atropine toxicity

• (d) due to central depression only

Q5. The end point for atropine in organophosphate poisoning is

• (a) drying of bronchial secretions and relief of bronchospasm

• (b) full dilatation of the pupils

• (c) a heart rate above 120

• (d) return of muscle power

Q6. The initial adult atropine dose in organophosphate poisoning, per the MSD Manual, is

• (a) 10 mg IV once

• (b) 1 mg orally

• (c) 2 to 3 mg IV, doubled every 3 to 5 minutes as needed

• (d) 0.6 mg once

Q7. Pralidoxime acts by

• (a) reactivating phosphorylated cholinesterase before it ages

• (b) blocking muscarinic receptors

• (c) stimulating nicotinic receptors

• (d) binding the organophosphate in the gut

Q8. Why must atropine be given along with pralidoxime?

• (a) Atropine activates pralidoxime

• (b) Pralidoxime is a muscarinic agonist

• (c) Pralidoxime causes bradycardia

• (d) Pralidoxime is less effective on the respiratory centre, where acetylcholine must still be blocked

Q9. According to its US label, pralidoxime is not indicated for poisoning by

• (a) parathion

• (b) anticholinesterase overdose in myasthenia

• (c) carbamates such as carbaryl

• (d) organophosphate nerve agents

Q10. Proximal and respiratory muscle weakness 1–3 days after organophosphate poisoning, despite treatment, is

• (a) atropine toxicity

• (b) myasthenic crisis

• (c) the intermediate syndrome

• (d) organophosphate-induced delayed neuropathy

Q11. Carbamate inhibition of cholinesterase differs from organophosphate inhibition because carbamates

• (a) only affect nicotinic receptors

• (b) cannot be absorbed through skin

• (c) bind irreversibly

• (d) clear spontaneously within about 48 hours

Q12. Neostigmine is used after surgery to

• (a) reverse opioid overdose

• (b) reverse non-depolarising neuromuscular blockade

• (c) treat malignant hyperthermia

• (d) reverse benzodiazepines

Q13. Atropine or glycopyrrolate is given with neostigmine to

• (a) prolong neostigmine's action

• (b) reverse the neuromuscular block itself

• (c) cause sedation

• (d) prevent muscarinic effects such as bradycardia

Q14. Which anticholinesterase is used to reverse the central effects of datura (atropine/scopolamine) poisoning?

• (a) Edrophonium

• (b) Physostigmine

• (c) Neostigmine

• (d) Pyridostigmine

Q15. Glycopyrrolate causes fewer central side effects than atropine because it

• (a) is a nicotinic antagonist

• (b) is a tertiary amine

• (c) is shorter acting

• (d) is a quaternary ammonium compound that barely crosses the blood-brain barrier

Q16. Edrophonium is not used for maintenance in myasthenia gravis because

• (a) it is not a cholinesterase inhibitor

• (b) it is too toxic

• (c) it crosses into the CNS

• (d) its action is very brief

Q17. Oral maintenance treatment of myasthenia gravis uses

• (a) pyridostigmine

• (b) pralidoxime

• (c) physostigmine

• (d) edrophonium

Q18. Bethanechol is indicated for

• (a) motion sickness

• (b) post-operative non-obstructive urinary retention

• (c) urge incontinence

• (d) glaucoma surgery

Q19. Oral pilocarpine is contraindicated in

• (a) open-angle glaucoma

• (b) Sjögren syndrome

• (c) post-radiotherapy dry mouth

• (d) angle-closure glaucoma and acute iritis

Q20. Tiotropium produces bronchodilation mainly by blocking

• (a) nicotinic receptors

• (b) H1 receptors

• (c) M3 receptors on airway smooth muscle

• (d) beta-2 receptors

Q21. A transdermal scopolamine patch is indicated for

• (a) urinary retention

• (b) bradycardia

• (c) motion sickness

• (d) myasthenia gravis

Q22. Hot dry skin, dilated pupils, thirst and delirium after an overdose suggest toxicity from

• (a) neostigmine

• (b) an organophosphate

• (c) pilocarpine

• (d) atropine

Q23. Atropine should be used cautiously because it may precipitate

• (a) bradycardia at normal doses

• (b) acute angle-closure glaucoma

• (c) miosis

• (d) bronchospasm

Q24. A woman with myasthenia gravis on pyridostigmine becomes acutely weak after her dose was raised. Once breathing is secured, edrophonium is used to

• (a) reverse pyridostigmine

• (b) test for organophosphate poisoning

• (c) treat the crisis long term

• (d) tell a myasthenic crisis from a cholinergic crisis

Q25. Two weeks after organophosphate ingestion, treated successfully, a man develops a new peripheral neuropathy. The likely cause is

• (a) atropine toxicity

• (b) intermediate syndrome

• (c) delayed axonal neuropathy from the organophosphate

• (d) pralidoxime toxicity

Active Recall

From memory: list which fibres are cholinergic; give the muscarinic and nicotinic signs of organophosphate poisoning; explain how atropine and pralidoxime are used and what each treats; list the anticholinesterases with one use each; compare glycopyrrolate with atropine; and describe the intermediate syndrome and delayed neuropathy.