Autonomic Nervous System Series · Module 4
Cholinergic and adrenergic agonists and antagonists — mechanisms, indications, and prediction framework
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 neuromuscular blockade | 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 | Chronic obstructive pulmonary disease, asthma | Quaternary — minimal systemic absorption |
| Scopolamine Muscarinic antagonist | Blocks M1-M5 (central > peripheral) | Motion sickness, postoperative nausea and vomiting | Greater central nervous system 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, attention-deficit/hyperactivity disorder | Central sympatholysis; rebound hypertension on abrupt withdrawal |
| Dobutamine Beta-1 selective agonist | β1 | Acute heart failure, stress echocardiography | Increases contractility; less effect on heart rate than isoproterenol |
| Albuterol / Salmeterol Beta-2 selective agonist | β2 | Asthma, chronic obstructive pulmonary disease | Albuterol: short-acting rescue; salmeterol: long-acting maintenance |
| Prazosin / Tamsulosin Alpha-1 antagonist | α1 | Hypertension, benign prostatic hyperplasia | 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-myocardial infarction | Safer in asthma at therapeutic doses; still 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, gastrointestinal 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. central nervous system. 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).