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🧠 ANS Pharmacology - Exam Notes

As per KD Tripathi (Essentials of Medical Pharmacology) & Shankar Bhag (Pharmacology for Medical Graduates)

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UNIT 1: OVERVIEW OF AUTONOMIC NERVOUS SYSTEM

Organization of ANS

Exam Tip: Both sympathetic and parasympathetic preganglionic fibers release ACh acting on Nicotinic (NN) receptors. Only the postganglionic fibers differ.

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UNIT 2: NEUROHUMORAL TRANSMISSION

Cholinergic Transmission (ACh)

1. Choline enters nerve terminal via Na+-dependent choline transporter (CHT) - blocked by hemicholinium
2. ACh synthesized by choline acetyltransferase (ChAT) from choline + Acetyl-CoA
3. ACh stored in vesicles via vesicular ACh transporter (VAT) - blocked by vesamicol
4. Ca2+ influx triggers vesicle fusion and ACh release - blocked by botulinum toxin
5. ACh broken down in synapse by acetylcholinesterase (AChE)
6. Choline recycled back into presynaptic terminal

Mnemonic for ACh blockers: "He Visits Beautiful Girls" = Hemicholinium (CHT) → Vesamicol (VAT) → Botulinum toxin (release)

Adrenergic Transmission (NA/Adrenaline)

1. Tyrosine → DOPA (by tyrosine hydroxylase - rate-limiting step)
2. DOPA → Dopamine (by DOPA decarboxylase)
3. Dopamine → Noradrenaline in vesicles (by dopamine-β-hydroxylase)
4. Noradrenaline → Adrenaline in adrenal medulla (by PNMT - phenylethanolamine-N-methyl transferase)
5. NA release into synapse
6. Termination: mainly by reuptake (Uptake-1) into presynaptic terminal; also by MAO (monoamine oxidase) and COMT (catechol-O-methyl transferase)

Exam Tip: Reuptake (Uptake-1) is the main mechanism of NA termination (unlike ACh which is enzymatically destroyed).

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UNIT 3: CHOLINERGIC RECEPTORS

Muscarinic Receptors (M1-M5) - G-protein coupled

Nicotinic Receptors - Ion channel (Na+/K+)

Exam Tip: Muscarinic = Metabotropic (G-protein). Nicotinic = Ionotropic (ion channel).

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UNIT 4: CHOLINOMIMETIC DRUGS (Parasympathomimetics)

Classification (KD Tripathi style):

Mnemonic: "Can Bill Please Make Music" = Carbachol, Bethanechol, Pilocarpine, Muscarine, (Methacholine)

Exam Tip (Frequently asked): Edrophonium = Tensilon Test for MG diagnosis. Pyridostigmine = treatment of MG. Atropine + Pralidoxime = treatment of organophosphate poisoning.

Organophosphate Poisoning - SLUDGE mnemonic

• Also: Miosis, bradycardia, bronchospasm, bronchorrhea
• Treatment: Atropine (for muscarinic effects) + Pralidoxime/2-PAM (reactivates AChE - must be given early before "aging")

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UNIT 5: ANTICHOLINERGIC DRUGS (Parasympatholytics)

Classification:

Atropine - Pharmacological Effects

Mnemonic for Atropine toxicity: "Dry as a bone, Blind as a bat, Mad as a hatter, Red as a beet, Hot as a hare"

Uses of Atropine:

1. Premedication (↓secretions before anesthesia)
2. Organophosphate poisoning (antidote)
3. Bradycardia (cardiac emergencies)
4. Ophthalmology (mydriasis, cycloplegia)
5. Peptic ulcer (pirenzepine preferred)
6. Motion sickness (scopolamine preferred)

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UNIT 6: ADRENERGIC RECEPTORS

Alpha (α) Receptors

Beta (β) Receptors

Exam Tip: β1 = mainly heart (1 heart). β2 = mainly lungs/bronchi (2 lungs).

Dopamine Receptors (D1, D2):

• D1: renal/mesenteric vasodilation (low dose dopamine effect)
• D2: presynaptic inhibition of NA release

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UNIT 7: SYMPATHOMIMETIC DRUGS (Adrenergic Agonists)

Classification:

• Amphetamine - releases NA from nerve terminals; CNS stimulant
• Tyramine - found in cheese, red wine; releases NA (cheese reaction with MAO inhibitors)

• Ephedrine - direct + indirect; used in hypotension under anesthesia, nasal decongestant

Dopamine - Dose-Dependent Effects (Exam Favourite!):

Adrenaline vs Noradrenaline (Classic Comparison):

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UNIT 8: ADRENERGIC BLOCKERS

Alpha Blockers (α-Blockers)

Exam Tip: Phenoxybenzamine = irreversible (can only be overcome by synthesis of new receptors). "Pheno-never-blocks-amine"

• Normally adrenaline → ↑BP (α1 effect)
• After phentolamine/phenoxybenzamine → adrenaline causes ↓BP (because α1 is blocked, only β2 vasodilation acts)
• Exam tip: This is called adrenaline reversal or Dale's phenomenon

Beta Blockers (β-Blockers)

Pharmacological Effects of Beta Blockers:

Uses of Beta Blockers:

1. Hypertension
2. Angina pectoris
3. Myocardial infarction (post-MI - ↓mortality)
4. Heart failure (carvedilol, metoprolol, bisoprolol)
5. Arrhythmias
6. Glaucoma (timolol eye drops)
7. Thyrotoxicosis (propranolol - controls symptoms)
8. Anxiety/tremor (propranolol)
9. Migraine prophylaxis (propranolol)
10. Phaeochromocytoma (only AFTER alpha blockade!)

Contraindications of Beta Blockers:

1. Asthma/COPD (bronchoconstriction)
2. Heart block (worsens AV conduction)
3. Cardiogenic shock (↓HR and contractility)
4. Peripheral vascular disease (Raynaud's - β2 block causes vasoconstriction)
5. Diabetes on insulin (masks hypoglycemia)

Exam Tip: In phaeochromocytoma, NEVER give beta blocker alone (causes unopposed α vasoconstriction → hypertensive crisis). Always give alpha blocker first, then beta blocker.

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UNIT 9: HIGH-YIELD EXAM POINTS (One-Liners)

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UNIT 10: IMPORTANT COMPARISONS (Short Answer / SAQ Type)

Muscarinic vs Nicotinic effects of ACh:

Reversible vs Irreversible Anticholinesterases:

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UNIT 11: NEUROMUSCULAR BLOCKING DRUGS (NMBDs)

Classification:

• Malignant hyperthermia (with halothane)
• Hyperkalemia (contraindicated in burns, crush injury, denervation)
• Muscle pains (fasciculations → post-op myalgia)
• Prolonged apnea in pseudocholinesterase deficiency

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SUMMARY DIAGRAM - ANS Drug Classification

ANS Pharmacology
├── CHOLINERGIC DRUGS
│   ├── Agonists (Parasympathomimetics)
│   │   ├── Direct: ACh, Carbachol, Bethanechol, Pilocarpine
│   │   └── Indirect (AChE inhibitors): Neostigmine, Physostigmine, Pyridostigmine, 
│   │       Edrophonium, Organophosphates
│   └── Antagonists (Parasympatholytics/Anticholinergics)
│       ├── Non-selective: Atropine, Scopolamine
│       └── Selective: Pirenzepine (M1), Ipratropium, Tiotropium
│
└── ADRENERGIC DRUGS
    ├── Agonists (Sympathomimetics)
    │   ├── Non-selective: Adrenaline, Noradrenaline, Isoprenaline
    │   ├── α selective: Phenylephrine (α1), Clonidine (α2)
    │   └── β selective: Salbutamol, Salmeterol (β2), Dobutamine (β1)
    └── Antagonists (Sympatholytics)
        ├── α blockers: Phentolamine, Phenoxybenzamine, Prazosin, Tamsulosin
        └── β blockers: Propranolol, Atenolol, Metoprolol, Carvedilol, Labetalol

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QUICK REVISION MNEMONICS

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Sources: Ganong's Review of Medical Physiology (Cholinergic/Adrenergic receptor details), Katzung's Basic & Clinical Pharmacology (receptor pharmacology, drug classification), Goodman & Gilman (anticholinesterase poisoning, adrenergic mechanisms) - cross-referenced with KD Tripathi and Shankar Bhag structure.