Autonomic drugs — cholinergic, anticholinergic, sympathomimetic

◆Direct muscarinic (cholinergic) agonists

• •Bethanechol — urinary retention (post-op, neurogenic bladder); resistant to AChE so longer acting
• •Pilocarpine — open-angle glaucoma drops; oral for Sjögren xerostomia (stimulates salivation)
• •Carbachol — glaucoma; α & muscarinic
• •Methacholine — bronchoprovocation testing in asthma
• •Side effects (DUMBELS): Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, Emesis, Lacrimation, Salivation
• •Avoid in: asthma/COPD (bronchospasm), peptic ulcer (↑ acid), bradyarrhythmias

◆Cholinesterase inhibitors (indirect cholinergic)

• •Edrophonium — historic 'Tensilon test' for myasthenia; rapid onset, short duration
• •Neostigmine — myasthenia treatment; reversal of non-depolarizing NMB (with glycopyrrolate)
• •Pyridostigmine — chronic myasthenia gravis maintenance; longer acting
• •Physostigmine — CROSSES BBB; antidote for ANTICHOLINERGIC toxicity (only one for CNS effects); CONTRAINDICATED in TCA overdose (asystole)
• •Donepezil, rivastigmine, galantamine — Alzheimer dementia (cognitive slowing helps mildly)
• •Toxicity: cholinergic crisis (DUMBELS); ANTIDOTE = atropine + pralidoxime (if organophosphate)

◆Anticholinergics (muscarinic antagonists)

• •Atropine — bradycardia (1st line ACLS), pre-op antisialagogue, mushroom toxicity, organophosphate poisoning (titrate to dry secretions)
• •Scopolamine — motion sickness (transdermal); antiemetic
• •Ipratropium / tiotropium — COPD bronchodilator (no systemic anticholinergic effects with inhalation)
• •Oxybutynin, tolterodine, solifenacin — overactive bladder; cause dry mouth, urinary retention (paradoxical!)
• •Glycopyrrolate — antisialagogue (does NOT cross BBB so no CNS effects)
• •Benztropine, trihexyphenidyl — Parkinson tremor; drug-induced EPS (esp acute dystonia)
• •Diphenhydramine, hydroxyzine — antihistamines with anticholinergic effects
• •TCAs, antipsychotics — significant anticholinergic SE
• •Toxicity (anticholinergic): 'hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter, full as a flask' — fever, dry skin, flushing, mydriasis, delirium, urinary retention
• •Antidote: PHYSOSTIGMINE (crosses BBB; AVOID in TCA overdose — sodium bicarb is the answer there)

◆Sympathomimetics — by receptor

• •α1 selective (phenylephrine): nasal decongestant, ↑ BP in shock; reflex bradycardia
• •α1 + α2 (clonidine, methyldopa): central α2 agonists ↓ sympathetic outflow → HTN, ADHD, withdrawal; rebound HTN if stopped abruptly
• •β1 selective (dobutamine): cardiogenic shock — ↑ contractility, mild ↑ HR
• •β2 selective (albuterol, terbutaline, salmeterol): bronchodilator; terbutaline tocolytic
• •Mixed α+β (epinephrine): anaphylaxis (first line), cardiac arrest, severe asthma
• •Mixed α+β (norepinephrine): septic shock first line — predominantly α1
• •Dopamine: low doses D1 (renal), medium β1 (inotropy), high α1 (vasoconstriction)
• •Isoproterenol: pure β-agonist; rarely used (refractory bradycardia, torsades)
• •Vasopressin (V1): refractory septic shock add-on
• •Cocaine, amphetamines: indirect sympathomimetics (release stored catecholamines)

◆α-blockers

• •α1 selective (-osin: prazosin, doxazosin, terazosin, tamsulosin, alfuzosin, silodosin)
• •BPH: tamsulosin (most α1A-selective, less orthostatic hypotension)
• •HTN: doxazosin/terazosin (not first-line — ALLHAT showed worse outcomes); useful in BPH + HTN combo
• •PTSD nightmares: prazosin
• •Pheochromocytoma pre-op: PHENOXYBENZAMINE (irreversible non-selective α) — must be given BEFORE β-blocker
• •Side effects: first-dose orthostatic hypotension (give at bedtime), reflex tachycardia, dizziness
• •Floppy iris syndrome: tamsulosin — alert ophtho before cataract surgery

◆Vasopressors quick reference (shock)

• •Septic shock: norepinephrine 1st line → add vasopressin → add epinephrine; add hydrocortisone if refractory
• •Cardiogenic shock: norepinephrine ± dobutamine (inotrope) ± milrinone
• •Anaphylactic shock: IM epinephrine 0.3–0.5 mg
• •Neurogenic shock (spinal): norepinephrine; may also need atropine for bradycardia
• •Hypovolemic shock: FLUIDS first, then norepinephrine if persistent hypotension

Toxidromes side by side