Parkinson disease (PD) — loss of dopamine-producing neurons in the substantia nigra leaves a relative excess of acetylcholine in the striatum. Drugs either increase dopamine activity or reduce cholinergic activity.

Alzheimer disease (AD) — loss of cholinergic neurons and amyloid and tau deposits.

• Cholinesterase inhibitors block the enzyme that breaks down acetylcholine, raising acetylcholine in the brain.
• Memantine blocks NMDA receptors, limiting glutamate excitotoxicity.
• Anti-amyloid monoclonal antibodies remove amyloid plaques and modestly slow decline in early disease.

None cure the disease.

Myasthenia gravis (MG) — antibodies attack acetylcholine receptors at the neuromuscular junction. Acetylcholinesterase inhibitors (pyridostigmine) raise acetylcholine at the junction so the remaining receptors are stimulated more; immunotherapies reduce the antibody attack.

Parkinson disease

Alzheimer disease

Myasthenia gravis

Levodopa — nausea, orthostatic hypotension, hallucinations and confusion (older adults), dyskinesias (involuntary writhing at peak dose), wearing-off and on-off fluctuations, harmless darkening of urine and sweat.

Dopamine agonists — impulse-control disorders (gambling, shopping, binge eating, hypersexuality), sudden sleep attacks (driving risk), hallucinations, orthostasis, leg edema, nausea. Abrupt stopping can cause dopamine agonist withdrawal syndrome (anxiety, depression, pain) — taper.

MAO-B inhibitors — insomnia (selegiline), nausea, dyskinesia with levodopa, hypertensive or serotonin reactions with interacting drugs.

Anticholinergics — dry mouth, constipation, urinary retention, blurred vision, confusion, reduced sweating.

Cholinesterase inhibitors (AD) — nausea, vomiting, diarrhea, anorexia, weight loss; bradycardia and syncope; vivid dreams or insomnia; muscle cramps; increased gastric acid (GI bleeding risk with NSAIDs).

Anti-amyloid antibodies — ARIA (brain edema or microhemorrhage): headache, confusion, visual change, dizziness, seizures; usually early in treatment. Infusion reactions.

Pyridostigmine and neostigmine — muscarinic effects: abdominal cramps, diarrhea, sweating, increased saliva and bronchial secretions, bradycardia, miosis; muscle fasciculations.

Levodopa

• Nonselective MAOIs (phenelzine, tranylcypromine) — hypertensive crisis; stop at least 2 weeks before starting
• Dopamine blockers (haloperidol, most first-generation antipsychotics, metoclopramide, prochlorperazine) oppose the effect and worsen PD — avoid
• High-protein meals reduce absorption and brain entry; iron supplements reduce absorption
• Caution in narrow-angle glaucoma, melanoma history, severe cardiovascular disease, psychosis
• Pyridoxine (vitamin B6) does not reduce effect when carbidopa is included

MAO-B inhibitors — avoid meperidine, tramadol, methadone, dextromethorphan; caution with SSRIs, SNRIs, TCAs; tyramine restriction may be needed at higher selegiline doses.

Anticholinergics — avoid in older adults, narrow-angle glaucoma, prostatic hyperplasia, urinary retention, dementia.

Cholinesterase inhibitors — caution with bradycardia, heart block, sick sinus syndrome, peptic ulcer, asthma or COPD, seizures, urinary obstruction. Beta blockers, digoxin, diltiazem, verapamil add to bradycardia. Anticholinergic drugs cancel the benefit — review the medication list.

Anti-amyloid antibodies — highest ARIA risk in APOE e4 homozygotes (genotype testing before treatment); caution with anticoagulants and thrombolytics (hemorrhage risk).

Pyridostigmine/neostigmine — contraindicated in mechanical intestinal or urinary obstruction; caution in asthma, bradycardia, recent MI, peptic ulcer.

Drugs that can worsen MG — aminoglycosides, fluoroquinolones (boxed warning), macrolides, IV magnesium, beta blockers, some calcium channel blockers, procainamide, quinine, neuromuscular blocking agents, botulinum toxin, immune checkpoint inhibitors, D-penicillamine.

Pregnancy — carbidopa-levodopa is used when needed; pyridostigmine is generally continued in pregnancy (IV magnesium for preeclampsia is avoided in MG); mycophenolate is contraindicated.

Listed in priority order.

1. MG: airway and breathing first — weak cough, dysphagia, rising respiratory rate, falling FVC or NIF signal crisis. Keep suction and a bag-valve mask available; prepare for ventilatory support.
2. Distinguish crises — myasthenic crisis (too little drug or a trigger such as infection) versus cholinergic crisis (too much drug: increased secretions, cramps, diarrhea, bradycardia, miosis, fasciculations). Both cause weakness; support ventilation first.
3. Give MG and PD drugs on time — delays cause swallowing and mobility decline. Time pyridostigmine 30–60 minutes before meals; check swallowing before oral intake.
4. Fall prevention — orthostatic BP with levodopa and dopamine agonists; bradycardia and syncope with cholinesterase inhibitors (check apical pulse; report HR below 60/min or syncope).
5. Monitor response and adverse effects — dyskinesia and wearing-off timing (a symptom diary helps); hallucinations; impulse-control behaviors; weight and nutrition in AD.
6. Anti-amyloid therapy — MRI before treatment and before specific infusions per the label; hold and report new headache, confusion, visual change, or seizures.
7. Medication review — remove dopamine blockers in PD; remove anticholinergics in AD; flag drugs that worsen MG before procedures.
8. Aspiration precautions — upright positioning, dysphagia screening in PD and MG.

Parkinson disease

• Take carbidopa-levodopa on a consistent schedule; if nausea occurs, take with a small non-protein snack. Take it 30–60 minutes before meals, and spread protein across the day.
• Never stop levodopa suddenly — severe rigidity, fever, and confusion (a syndrome resembling NMS) can result.
• Rise slowly; report hallucinations, confusion, or new urges to gamble, shop, or eat.
• Dopamine agonists: do not drive if you fall asleep suddenly during daily activities.
• Urine or sweat may darken (levodopa, COMT inhibitors) — harmless.
• MAO-B inhibitors: check with the pharmacist before cough or cold medicines and pain medicines.

Alzheimer disease

• Caregivers give doses and keep them consistent; the benefit is modest and gradual.
• Take donepezil at bedtime; move it to the morning if dreams disturb sleep. Take with food if nausea occurs.
• Report slow pulse, fainting, black stools, or weight loss.
• Rivastigmine patch: apply one patch daily to clean, dry skin, rotate sites, remove the old patch — a double patch can cause overdose.
• Anti-amyloid therapy: carry a card showing the treatment; report headache, confusion, or vision change right away.

Myasthenia gravis

• Take pyridostigmine exactly on time, 30–60 minutes before meals; do not double doses.
• Report increased weakness, trouble swallowing or breathing, or signs of overdose (cramps, diarrhea, drooling, excess sweating, slow pulse).
• Tell every provider and dentist you have MG; carry medical identification.
• Do not stop prednisone suddenly; get meningococcal vaccination before complement inhibitors and carry the patient safety card.

Cholinergic crisis (pyridostigmine or neostigmine excess) — increased weakness with muscarinic signs: salivation, lacrimation, sweating, bronchorrhea, diarrhea, cramps, bradycardia, miosis, fasciculations → respiratory failure.

• Hold the cholinesterase inhibitor, support ventilation, suction, and give atropine (the muscarinic antidote) as ordered.
• The edrophonium test once used to separate the crises is rarely available now.

Myasthenic crisis — respiratory muscle weakness from under-treatment or triggers: ventilation, plasmapheresis or IVIG; cholinesterase inhibitors are often held while ventilated.

Cholinesterase inhibitor overdose (AD drugs) — nausea, vomiting, bradycardia, hypotension, seizures, weakness → supportive care; atropine for symptomatic bradycardia.

Levodopa excess — dyskinesias, agitation, hallucinations, hypertension or hypotension → lower the dose. Abrupt withdrawal → parkinsonism-hyperpyrexia syndrome (NMS-like) → restart dopaminergic therapy, cooling, fluids.

Anticholinergic toxicity — hot, dry, flushed skin; dilated pupils; tachycardia; urinary retention; delirium → supportive care; physostigmine only in selected cases under specialist guidance.

ARIA — hold infusions, MRI, corticosteroids for symptomatic cases per specialist.

• Carbidopa blocks peripheral conversion so more levodopa reaches the brain
• Levodopa: protein competes for absorption; long-term dyskinesia and wearing-off; never stop abruptly
• Avoid dopamine blockers in PD: haloperidol, metoclopramide, prochlorperazine
• Dopamine agonists: impulse-control disorders, sleep attacks
• MAO-B inhibitors + meperidine/tramadol/dextromethorphan → serotonin syndrome; nonselective MAOIs with levodopa → hypertensive crisis
• Anticholinergics: avoid in older adults and AD
• Cholinesterase inhibitors (donepezil): bradycardia, syncope, GI effects — check pulse
• Memantine for moderate to severe AD; renal dose adjustment
• Anti-amyloid antibodies: early AD only; ARIA — MRI monitoring; APOE e4 risk
• Pyridostigmine 30–60 min before meals, on a strict schedule
• Cholinergic crisis → hold drug, atropine; myasthenic crisis → ventilation, plasmapheresis or IVIG
• Drugs that worsen MG: aminoglycosides, fluoroquinolones, magnesium, neuromuscular blockers