Pharmacology · ANS Introduction

Autonomic Drug Classes, Integration, and Clinical Applications

Cholinergic and adrenergic agonists and antagonists — mechanisms, indications, and prediction framework

Cholinergic drugs span direct muscarinic agonists (bethanechol for urinary retention, pilocarpine for glaucoma), reversible anticholinesterases (neostigmine for myasthenia gravis and NMB reversal; physostigmine for anticholinergic toxidrome because it crosses the blood-brain barrier), and muscarinic antagonists (atropine, inhaled ipratropium/tiotropium for COPD, scopolamine for motion sickness).
The cholinergic toxidrome (organophosphate/nerve agent poisoning) presents as SLUDGE (salivation, lacrimation, urination, defecation, GI cramps, emesis) plus bradycardia, bronchospasm, and miosis from muscarinic excess, and fasciculations → paralysis from nicotinic excess; treatment is atropine in large doses plus early pralidoxime before acetylcholinesterase aging.
The anticholinergic toxidrome is the mirror image — hot, blind, dry, red, and mad (hyperthermia, mydriasis, anhidrosis, flushing, delirium) plus tachycardia and urinary retention; physostigmine is the antidote because it penetrates the CNS to reverse both central and peripheral effects.
Adrenergic drug selectivity maps directly onto receptor subtypes: epinephrine is non-selective (drug of choice for anaphylaxis); norepinephrine is alpha-dominant + beta-1 (vasopressor in septic shock); phenylephrine is pure alpha-1 (raises BP without tachycardia); dobutamine is beta-1 selective (acute heart failure); albuterol/salmeterol are beta-2 selective (asthma).
The three-step prediction framework — where does the drug act, which receptor and where, and agonist or antagonist — allows prediction of any autonomic drug's effects without memorization; antagonists remove dominant tone, unmasking the opposing division (atropine removes vagal tone → tachycardia; prazosin removes sympathetic vascular tone → vasodilation).

Abbreviations: COPD = chronic obstructive pulmonary disease · NMB = neuromuscular blockade · CNS = central nervous system · SLUDGE = salivation, lacrimation, urination, defecation, GI cramps, emesis · BPH = benign prostatic hyperplasia · ADHD = attention-deficit/hyperactivity disorder

Cholinergic Drug Classes

Drug / Class	Mechanism	Primary Uses	Key Points
Bethanechol Direct muscarinic agonist	Activates M3	Urinary retention, paralytic ileus	Resistant to acetylcholinesterase; no nicotinic activity
Pilocarpine Direct muscarinic agonist	Activates M3	Open-angle glaucoma, Sjogren syndrome	Miosis + ciliary contraction; increases aqueous outflow
Neostigmine / Pyridostigmine Reversible anticholinesterase (carbamate)	Inhibits acetylcholinesterase	Myasthenia gravis; reversal of NMB	Does not cross blood-brain barrier; quaternary amine
Physostigmine Reversible anticholinesterase (carbamate)	Inhibits acetylcholinesterase	Anticholinergic toxidrome reversal	Crosses blood-brain barrier; tertiary amine
Donepezil / Rivastigmine Central anticholinesterase	Inhibits acetylcholinesterase (CNS)	Alzheimer disease	Improves cognition; does not alter disease progression
Organophosphates Irreversible anticholinesterase	Covalent acetylcholinesterase inhibition	Toxin (nerve agents, insecticides)	Treatment: atropine + pralidoxime (before aging)
Atropine Muscarinic antagonist	Blocks M1–M5	Bradycardia, organophosphate poisoning, pre-anesthetic	Tachycardia, mydriasis, dry secretions, urinary retention
Ipratropium / Tiotropium Inhaled muscarinic antagonist	Blocks M3 in airways	COPD, asthma	Quaternary amine — minimal systemic absorption
Scopolamine Muscarinic antagonist	Blocks M1–M5 (central > peripheral)	Motion sickness, postoperative nausea and vomiting	Greater CNS penetration than atropine

Adrenergic Drug Classes

Drug / Class	Receptor	Primary Uses	Key Points
Epinephrine Non-selective agonist	α1, α2, β1, β2	Anaphylaxis, cardiac arrest, local anesthetic adjunct	Drug of choice for anaphylaxis; dose-dependent receptor shift
Norepinephrine Mostly alpha + beta-1	α1, α2, β1	Septic shock (vasopressor)	Reflex bradycardia from vasoconstriction; minimal beta-2
Phenylephrine Selective alpha-1 agonist	α1	Nasal decongestion, hypotension	Raises blood pressure without increasing heart rate
Clonidine Alpha-2 agonist	α2 (central)	Hypertension, opioid/alcohol withdrawal, ADHD	Central sympatholysis; rebound hypertension on abrupt withdrawal
Dobutamine Beta-1 selective agonist	β1	Acute heart failure, stress echocardiography	Increases contractility; less tachycardia than isoproterenol
Albuterol / Salmeterol Beta-2 selective agonist	β2	Asthma, COPD	Albuterol: short-acting rescue; salmeterol: long-acting maintenance
Prazosin / Tamsulosin Alpha-1 antagonist	α1	Hypertension, BPH	First-dose orthostatic hypotension; take at bedtime
Propranolol Non-selective beta antagonist	β1 + β2	Hypertension, arrhythmia, migraine prophylaxis, thyroid storm	Avoid in asthma; avoid abrupt withdrawal
Metoprolol / Atenolol Cardioselective beta antagonist	β1 (selective)	Hypertension, heart failure, post-MI	Safer in asthma at therapeutic doses; taper on discontinuation
Carvedilol Combined antagonist	α1 + β1 + β2	Heart failure, hypertension	Reduces mortality in systolic heart failure

Autonomic Toxidromes

Excess Acetylcholine

Cholinergic Toxidrome

Cause: Organophosphates, carbamates, nerve agents

Muscarinic: SLUDGE — salivation, lacrimation, urination, defecation, GI cramps, emesis; also bradycardia, bronchospasm, miosis

Nicotinic: Fasciculations → paralysis

Treatment: Atropine (large doses) + pralidoxime (early)

Excess Antimuscarinic

Anticholinergic Toxidrome

Cause: Atropine overdose, jimsonweed, tricyclic antidepressants

Signs: Hot as a hare (hyperthermia), blind as a bat (mydriasis), dry as a bone (anhidrosis), red as a beet (flushing), mad as a hatter (delirium); tachycardia; urinary retention

Treatment: Physostigmine (reverses central + peripheral effects)

Three-Step Prediction Framework

Step 1

Where Does the Drug Act?

Ganglionic (blocks both divisions) vs. neuroeffector junction (division-specific) vs. CNS. Ganglionic blockers always affect both divisions simultaneously.

Step 2

Which Receptor and Where?

Identify subtype and its dominant organ locations. Know which division holds resting tone at each organ: parasympathetic at heart and bronchi; sympathetic at blood vessels.

Step 3

Agonist or Antagonist?

Agonist amplifies the dominant tone. Antagonist removes it, unmasking the opposing division or intrinsic organ rate (~100 bpm for sinoatrial node without autonomic input).

Suggested References

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