Cholinergic (parasympathomimetic) drugs increase the effect of acetylcholine (ACh). They work in two ways.

• Direct-acting muscarinic agonists bind muscarinic receptors themselves (bethanechol, pilocarpine, cevimeline).
• Indirect-acting drugs (cholinesterase inhibitors) block acetylcholinesterase, the enzyme that breaks down ACh, so ACh builds up at both muscarinic and nicotinic sites.
  • Reversible (therapeutic): neostigmine, pyridostigmine, physostigmine, donepezil, rivastigmine, galantamine
  • Irreversible (toxic): organophosphate insecticides and nerve agents — covered in Section 7

Receptor map — what "more ACh" does

Key idea: the therapeutic effect and the adverse effects are the same actions in different degrees. A drug given to empty the bladder can also slow the heart and tighten the airways.

CNS penetration: physostigmine, donepezil, rivastigmine, and galantamine enter the brain (tertiary amines). Neostigmine and pyridostigmine are quaternary amines and act mainly in the periphery.

Edrophonium (the old "Tensilon test") is no longer marketed; myasthenia gravis is diagnosed with antibody and electrodiagnostic tests.

Adverse effects are excess muscarinic and nicotinic stimulation. Use the memory aid SLUDGE-BBB (or DUMBELS):

• Salivation, Lacrimation, Urination, Diarrhea/defecation, GI cramping, Emesis
• Bradycardia, Bronchospasm, Bronchorrhea (excess airway secretions)
• Plus miosis, sweating, hypotension, and blurred near vision (accommodation spasm)
• Nicotinic excess: muscle fasciculations, cramps, weakness, and eventually respiratory muscle paralysis

Drug-specific points

• Cholinesterase inhibitors for dementia: nausea, vomiting, diarrhea, anorexia and weight loss, bradycardia, heart block, syncope (fall risk), insomnia and vivid dreams (donepezil is usually given at bedtime; give it in the morning if this occurs), increased gastric acid (GI bleeding risk, especially with NSAIDs); rivastigmine patch — skin reactions
• Pyridostigmine/neostigmine in excess → cholinergic crisis: increasing weakness plus muscarinic signs. It must be told apart from myasthenic crisis (too little drug or a trigger such as infection):

Contraindications (direct agonists and cholinesterase inhibitors)

• Mechanical obstruction of the GI or urinary tract — increased contraction against a blockage can rupture the bladder or bowel
• Recent bladder or bowel surgery with a fresh anastomosis (bethanechol)
• Asthma and active bronchospasm (bronchoconstriction and secretions); caution in COPD
• Bradycardia, hypotension, AV block, recent myocardial infarction or coronary artery disease
• Peptic ulcer disease (increased acid), hyperthyroidism (risk of atrial fibrillation), seizure disorders, parkinsonism
• Pilocarpine eye drops: acute iritis; caution with history of retinal detachment
• Physostigmine: tricyclic antidepressant overdose or a wide QRS on ECG (risk of asystole and seizures)

Pregnancy and lactation

• Pyridostigmine is continued in pregnancy for myasthenia gravis under specialist care — stopping it is more dangerous than continuing it
• In a pregnant client with myasthenia gravis, IV magnesium sulfate (used for preeclampsia) is avoided because it can precipitate a myasthenic crisis
• IV cholinesterase inhibitors near term can increase uterine irritability; use only when clearly indicated
• Limited lactation data for most drugs; infants of mothers with myasthenia gravis need monitoring for transient neonatal myasthenia (a disease effect, not a drug effect)

Major interactions

• Anticholinergic drugs (oxybutynin, diphenhydramine, tricyclics) oppose the effect — a common "prescribing cascade" is donepezil causing urinary urgency, then an anticholinergic being added, which worsens cognition
• Beta blockers, digoxin, non-dihydropyridine calcium channel blockers, amiodarone — additive bradycardia and AV block
• Succinylcholine — effect prolonged by cholinesterase inhibitors (including donepezil); tell anesthesia
• Drugs that worsen myasthenia gravis: aminoglycosides, fluoroquinolones, macrolides, magnesium, beta blockers, and some others — check every new drug
• NSAIDs + cholinesterase inhibitors — increased GI bleeding risk

Listed in priority order.

1. Airway and breathing
   • Before and after doses, assess respiratory rate, lung sounds (wheezes, secretions), and SpO₂; keep suction available for clients receiving IV neostigmine or physostigmine
   • Myasthenia gravis: monitor vital capacity or negative inspiratory force, cough strength, and swallowing; report falling values or difficulty handling secretions at once
2. Circulation
   • Check apical pulse and blood pressure before doses; report heart rate < 60/min or new dizziness or syncope (common hold threshold; follow the order and facility policy)
   • Keep atropine available when giving IV cholinesterase inhibitors
3. Drug-specific checks
   • Bethanechol: confirm there is no obstruction before the first dose; measure intake and output and post-void residual (bladder scanner); expect voiding within about 1.5 hours
   • Pyridostigmine: give on a strict schedule; if the client is NPO or has trouble swallowing, notify the provider promptly (an alternative route may be needed); assess strength at peak effect (about 1–2 hours) and before the next dose to detect under- or over-dosing
   • Dementia drugs: weigh weekly (anorexia, weight loss), assess pulse and falls, and assess GI bleeding signs (black stools)
4. Safety — orthostatic precautions for hypotension and dizziness; assist with ambulation for older adults

• Myasthenia gravis: take pyridostigmine on time, 30–60 minutes before meals; do not double or skip doses. Report increasing weakness, trouble swallowing or breathing, drooling, sweating, cramps, or diarrhea at once. Wear medical identification and tell every prescriber and pharmacist about the diagnosis before any new drug
• Bethanechol: take on an empty stomach; stay near a toilet; rise slowly; report wheezing, slow pulse, or no urine output
• Pilocarpine eye drops: vision may be dim or blurred, especially in poor light — avoid night driving until you know how it affects you; press the inner corner of the eye for 1–2 minutes after instilling to reduce systemic absorption
• Donepezil and similar drugs: take with food if nausea occurs; donepezil is usually taken at bedtime — take it in the morning instead if dreams disturb sleep; report fainting, a slow pulse, black stools, or weight loss. Improvement is modest and gradual — do not stop suddenly without advice
• Caregivers should keep a list of medicines and avoid over-the-counter sleep aids and allergy pills with strong anticholinergic effects (e.g., diphenhydramine), which cancel the benefit
• Store agricultural chemicals in labeled original containers, locked away from children; never reuse pesticide containers for food or water

Organophosphate and carbamate poisoning (insecticides, nerve agents) is the classic cholinergic toxidrome. Organophosphates bind acetylcholinesterase irreversibly over time ("aging").

Recognize: SLUDGE signs, bronchorrhea and bronchospasm (the main cause of death with respiratory muscle weakness), miosis, sweating, fasciculations, weakness, confusion, seizures. Heart rate can be slow or fast (nicotinic and hypoxic effects), so tachycardia does not rule out poisoning.

Management (priority order)

1. Protect staff — personal protective equipment; remove contaminated clothing and wash the skin with soap and water (decontamination)
2. Airway and breathing — suction, oxygen, early intubation if needed. Avoid succinylcholine for intubation (prolonged paralysis)
3. Atropine — IV, repeated and escalated per protocol until bronchial secretions dry and lungs clear, with adequate heart rate and blood pressure. Dry lung sounds are the end point, not pupil size; large total doses may be needed
4. Pralidoxime — reactivates acetylcholinesterase and treats nicotinic effects (weakness); give early, before aging. Rapid IV injection can cause hypertension, muscle rigidity, and laryngospasm
5. Benzodiazepine for seizures
6. Watch for the intermediate syndrome 1–4 days after exposure: weakness of neck flexors, proximal limbs, and respiratory muscles — can cause delayed respiratory failure even after cholinergic signs settle

Therapeutic drug overdose (neostigmine, pyridostigmine, bethanechol, donepezil): hold the drug, support airway and circulation, and give atropine for muscarinic effects as ordered. Atropine does not reverse nicotinic muscle weakness — ventilation may be required.

• Cholinergic = "rest and digest": slow heart, wet secretions, active gut and bladder, small pupils
• Toxicity memory aid: SLUDGE + bradycardia, bronchospasm, bronchorrhea
• Bethanechol is for nonobstructive retention only — rule out obstruction first; give on an empty stomach
• Pyridostigmine 30–60 minutes before meals, exactly on time
• Myasthenic vs. cholinergic crisis: both cause weakness; muscarinic signs point to cholinergic crisis; airway first in both
• Neostigmine reversal is given with glycopyrrolate or atropine
• Donepezil and similar drugs: bradycardia, syncope, weight loss; morning dosing if vivid dreams
• Contraindicated with GI/urinary obstruction, asthma, bradycardia
• Atropine is the antidote for muscarinic excess — titrate to dry lung secretions; add pralidoxime early for organophosphates
• Physostigmine treats anticholinergic delirium; avoid with tricyclic overdose or wide QRS