Alpha-1 vs Alpha-2
Alpha-1 = Gq → IP3/DAG → Vasoconstriction; Alpha-2 = Gi → ↓ cAMP → ↓ NE release
Beta-1 vs Beta-2
Beta-1 = Heart (↑ Inotropy/Chronotropy); Beta-2 = Lungs/Vessels (Broncho/Vasodilation)
SLUDGE Mnemonic
Salivation, Lacrimation, Urination, Defecation, GI cramping, Emesis
Organophosphate Antidote
Atropine (blocks muscarinic excess) + Pralidoxime (2-PAM) (regenerates AChE)
Autonomic Receptors, G-Protein Coupling & Second Messengers
Master the exact signaling pathways tested on pharmacology vignettes (Mnemonic: "HAVe 1 M&M" for Gq, "MAD 2s" for Gi):
| Receptor Type | G-Protein Class | Intracellular Second Messenger | Primary Clinical Target & Physiologic Effect |
|---|---|---|---|
| α1 Adrenergic | Gq | ↑ Phospholipase C → ↑ IP3 & DAG → ↑ Intracellular Ca2+ | Vascular smooth muscle: Vasoconstriction, pupil dilation (mydriasis), bladder sphincter contraction |
| α2 Adrenergic | Gi | ↓ Adenylyl Cyclase → ↓ cAMP | Presynaptic nerve terminals: Decreased sympathetic outflow (Clonidine, Methyldopa); ↓ insulin |
| β1 Adrenergic | Gs | ↑ Adenylyl Cyclase → ↑ cAMP → PKA | Heart: ↑ Heart rate, contractility, AV conduction; Juxtaglomerular cells: ↑ Renin release |
| β2 Adrenergic | Gs | ↑ Adenylyl Cyclase → ↑ cAMP → PKA (smooth muscle) | Bronchioles: Bronchodilation; Vascular: Vasodilation; Uterus: Tocolysis; ↑ Glycogenolysis, ↑ K+ cell uptake |
| β3 Adrenergic | Gs | ↑ Adenylyl Cyclase → ↑ cAMP | Adipose tissue: Lipolysis; Bladder detrusor: Relaxation (Mirabegron) |
| M1 Muscarinic | Gq | ↑ IP3 & DAG | CNS, enteric nervous system |
| M2 Muscarinic | Gi | ↓ cAMP, opens K+ channels | Heart: ↓ Heart rate and AV node conduction velocity |
| M3 Muscarinic | Gq | ↑ IP3 & DAG | Exocrine glands: ↑ Secretions; Eye: Miosis & accommodation; Bronchioles: Bronchoconstriction; Bladder: Detrusor contraction |
Cholinergic Crisis vs. Anticholinergic Toxicity
Board questions constantly contrast cholinergic toxicity (organophosphates) with anticholinergic poisoning (atropine, diphenhydramine, TCAs):
| Clinical Sign | Cholinergic Excess (Organophosphates) | Anticholinergic Toxicity (Atropine/TCAs) |
|---|---|---|
| Pupil Size | Miosis (pinpoint pupils) | Mydriasis (dilated, non-reactive) ("Blind as a bat") |
| Heart Rate | Bradycardia ± AV block | Tachycardia ("Mad as a hatter") |
| Skin & Sweating | Diaphoretic / soaked skin | Dry, flushed, hot skin ("Hot as a hare, Dry as a bone, Red as a beet") |
| Bowel Sounds | Hyperactive / diarrhea | Hypoactive or absent / ileus |
| Urinary System | Incontinence | Urinary retention / distended bladder |
| Antidote | Atropine + Pralidoxime (2-PAM) | Physostigmine (crosses BBB; contraindicated if TCA overdose due to QRS widening) |
COMLEX / OMM Integration
NBOME High-Yield Correlate
Autonomic Balancing Techniques
- Rib Raising: Rhythmic articulation of the ribs engages sympathetic chain ganglia, directly modulating thoracic and abdominal autonomic outflow.
- OA Decompression: Alleviates impingement on the vagus nerve (CN X) at the jugular foramen, restoring parasympathetic tone in hyperadrenergic states.
Board Traps & Common Distractors
- Trap: Administering beta-blockers before alpha-blockers in pheochromocytoma. Unopposed alpha-1 receptor activation causes catastrophic life-threatening hypertensive crisis. Always give Phenoxybenzamine (alpha-blocker) FIRST, followed by a beta-blocker.
- Trap: Giving Physostigmine for TCA overdose. Although TCAs have anticholinergic features, physostigmine can cause fatal asystole in TCA toxicity. Treat TCA cardiotoxicity with IV Sodium Bicarbonate!