Autonomic Nervous System Drugs

Overview

The Autonomic Nervous System (ANS) controls involuntary bodily functions and is divided into the Sympathetic (SNS) and Parasympathetic (PNS) nervous systems. Drugs acting on the ANS are among the most frequently tested topics in NEET PG Pharmacology, appearing almost every year. Questions often involve mechanism of action, receptor specificity, indications, and side effects of cholinergic and adrenergic drugs.

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Functional Organization of ANS

Sympathetic vs Parasympathetic

Feature	Sympathetic	Parasympathetic
Origin	T1-L2 (thoracolumbar)	CN III, VII, IX, X, S2-S4 (craniosacral)
Neurotransmitter	Norepinephrine (at effector)	Acetylcholine (at effector)
Receptors	Alpha (α), Beta (β) adrenergic	Muscarinic (M), Nicotinic (N) cholinergic
Dominant effects	Fight or flight	Rest and digest
Heart rate	Increases	Decreases
Bronchi	Dilates	Constricts
Pupil	Dilates (mydriasis)	Constricts (miosis)
GI motility	Decreases	Increases
Bladder	Relaxes	Contracts

Receptors of ANS

Adrenergic Receptors

Receptor	Location	Effect when Activated
α1	Vascular smooth muscle, GU smooth muscle, eye	Vasoconstriction, bladder relaxation, mydriasis
α2	Presynaptic nerve terminals, CNS	Decreases NE release (autoreceptor)
β1	Heart	↑ Heart rate, ↑ contractility, ↑ conduction
β2	Bronchi, blood vessels, uterus	Bronchodilation, vasodilation, uterine relaxation
β3	Adipose tissue	Lipolysis

Cholinergic Receptors

Receptor	Location	Mechanism
Muscarinic M1	CNS, gastric parietal cells	Gq → ↑IP3/DAG
Muscarinic M2	Heart, smooth muscle	Gi → ↓cAMP
Muscarinic M3	Exocrine glands, smooth muscle	Gq → ↑IP3/DAG
Nicotinic Nn	Autonomic ganglia	Ligand-gated Na+/K+ channel
Nicotinic Nm	Neuromuscular junction	Ligand-gated Na+/K+ channel

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Cholinergic Drugs (Parasympathomimetics)

Cholinergic drugs mimic the action of Acetylcholine (ACh). They are classified as direct-acting (muscarinic agonists) or indirect-acting (acetylcholinesterase inhibitors).

Direct-Acting Cholinergic Agonists

Muscarinic Agonists

Drug	Selectivity	Clinical Use	Key Points
Bethanechol	M3 > M2	Urinary retention (post-operative, neurogenic bladder), gastroparesis	Does NOT cross BBB; selective for bladder and GI tract
Methacholine	M3	Used in methacholine challenge test for asthma diagnosis	Also called Mecholyl
Oxotremorine	M1, M2, M3	Experimental; Parkinson’s research	Not used clinically

Muscarinic Effects (SLUDGE/DUMBBELS):

Effect	Manifestation
Salivation	Excessive drooling
Lacrimation	Tearing
Urination	Involuntary urination
Defecation	Loose stools, defecation
GI distress	Cramping, nausea
Emesis	Vomiting

Or DUMBBELS for anti-cholinesterase toxicity: Diarrhea, Urination, Miosis, Bronchospasm/Bronchorrhea, Bradycardia, Emesis, Lacrimation, Sweating

Nicotinic Agonists

Drug	Mechanism	Clinical Use
Nicotine	Agonist at NN and Nm receptors	Not used therapeutically (used in nicotine replacement therapy as agonist — paradoxical)
Succinylcholine	Depolarizing Nm blocker (agonist at Nm → initial fasciculations then sustained paralysis)	Neuromuscular blockade for intubation (short-acting)

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Indirect-Acting Cholinergic Drugs (Acetylcholinesterase Inhibitors)

These drugs inhibit acetylcholinesterase, preventing breakdown of ACh, thereby increasing its concentration at synapses.

Reversible AChE Inhibitors

Drug	Selectivity	Clinical Use	Key Points
Physostigmine	CNS-penetrating (crosses BBB)	Anticholinergic toxicity (especially with CNS symptoms), glaucoma	Natural alkaloid from calabar bean
Neostigmine	Peripheral mainly (doesn’t cross BBB)	Myasthenia gravis, reversal of neuromuscular blockade, post-operative ileus	Also has direct Nm agonist activity
Edrophonium	Peripheral (short-acting)	Diagnosis of myasthenia gravis (Tensilon test)	Very short duration (minutes)
Donepezil, Rivastigmine, Galantamine	CNS-penetrating	Alzheimer’s disease	↑ ACh in brain → cognitive improvement
Pyridostigmine	Peripheral	Myasthenia gravis (long-acting)	Used for chronic management
Rivastigmine	Both central + peripheral	Alzheimer’s disease, Lewy body dementia

Irreversible AChE Inhibitors

Drug	Mechanism	Clinical Use	Key Points
Echothiophate	Irreversible (organophosphate)	Glaucoma (topical)	Long-acting; watch for systemic toxicity
Malathion, Parathion	Irreversible (organophosphates)	Insecticides (not clinical use)	Toxic in humans; causes cholinergic crisis

Treatment of Organophosphate Poisoning

Mnemonic: Atropine + Pralidoxime (2-PAM)

• Atropine — blocks muscarinic effects (given in large doses)
• Pralidoxime (2-PAM) — reactivates AChE by removing phosphate group (must be given early before “aging”)

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Anticholinergic Drugs (Muscarinic Antagonists)

These drugs block muscarinic receptors, preventing ACh from binding.

Non-Selective Muscarinic Blockers

Drug	Selectivity	Clinical Use	Key Side Effects
Atropine	Non-selective M blocker	Bradycardia (by blocking vagus), mydriasis/cycloplegia, premedication (reduces secretions), anticholinesterase poisoning, organophosphate poisoning	Dry mouth, flushing, tachycardia, urinary retention, constipation, confusion (elderly), hot as a hare (hyperthermia due to ↓sweating)
Scopolamine	Non-selective M blocker (crosses BBB)	Motion sickness (antiemetic), preoperative sedation, ophthalmology	More CNS effects than atropine; causes drowsiness, amnesia
Hyoscyamine	Non-selective M blocker	IBS, peptic ulcer, renal colic	Similar to atropine but more potent peripherally
Tropicamide	M1, M3 (short-acting)	Ophthalmic: mydriasis/cycloplegia for eye examination	Short duration (~4 hours)
Cyclopentolate	M blocker	Ophthalmic: mydriasis/cycloplegia	Longer acting than tropicamide

Selective Muscarinic Antagonists

Drug	Selectivity	Clinical Use	Key Points
Pirenzepine	M1 selective	Peptic ulcer (reduces gastric acid)	Fewer CNS side effects
Telenzepine	M1 selective	Peptic ulcer	Similar to pirenzepine
Darifenacin	M3 selective	Overactive bladder, urge incontinence	Bladder selective
Solifenacin	M3 selective	Overactive bladder	Long-acting
Trospium	Non-selective quaternary amine	Overactive bladder	Does NOT cross BBB (fewer CNS effects)

Atropine — Complete Profile

Feature	Details
Mechanism	Competitive antagonist at muscarinic receptors (M1-M5)
Pharmacokinetics	Crosses BBB; systemic absorption from eye, skin; metabolized in liver; half-life ~4 hours
Cardiovascular	Blocks M2 in heart → tachycardia (dose-dependent)
Eye	Blocks M3 in iris sphincter → mydriasis (pupil dilation); blocks ciliary muscle → cycloplegia (loss of accommodation)
Respiratory	Blocks M3 in bronchial smooth muscle → bronchodilation
GI	↓ motility, ↓ secretions → constipation
Urinary	Bladder detrusor relaxation → urinary retention
CNS	Delirium, confusion (especially elderly) at high doses
Skin	Dry, warm, flushed (“dry as a bone, blind as a bat, red as a beet, mad as a hatter”)

Memory Aid: Atropine effects: “Hot as a hare, dry as a bone, blind as a bat, mad as a hatter”

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Adrenergic Drugs (Sympathomimetics)

Adrenergic drugs act on adrenergic receptors (α or β) to produce effects similar to sympathetic activation.

Catecholamines

Catecholamines have a catechol ring + amine group. They are NOT effective orally (destroyed by MAO and COMT) and do not cross BBB (except dopamine).

Drug	α	β1	β2	Clinical Use
Epinephrine	+++	++	++	Cardiac arrest, anaphylaxis, glaucoma, local anesthetic adjunct
Norepinephrine	+++	++	-	Septic shock (vasopressor), hypotension
Dopamine	+ (low), +++ (high)	++	-	Shock, heart failure, acute renal failure
Isoproterenol	-	+++	+++	Bradycardia, heart block, bronchospasm (rare)
Dobutamine	+	+++	+	Acute heart failure, cardiogenic shock (inotrope)

Dopamine Receptors

Dose	Receptor	Effect
Low (<2 μg/kg/min)	D1	Renal, mesenteric, coronary vasodilation
Medium (2-10 μg/kg/min)	D1 + β1	↑ Cardiac contractility, ↑ renal blood flow
High (>10 μg/kg/min)	α1	Vasoconstriction, ↑ blood pressure

Dobutamine vs Dopamine

Feature	Dobutamine	Dopamine
Primary action	β1 agonist (inotrope)	Dose-dependent multiple receptors
Effect	↑ Contractility, ↑ CO	↑ CO at low-medium dose, ↑ BP at high dose
Use	Acute heart failure, cardiogenic shock	Shock, acute renal failure (low dose)

Non-Catecholamine Sympathomimetics

Drug	Selectivity	Mechanism	Clinical Use
Phenylephrine	α1 agonist	Vasoconstriction	Hypotension (not first-line), nasal decongestion, ophthalmic (mydriasis)
Methoxamine	α1 agonist	Vasoconstriction	Hypotension, paroxysmal SVT
Clonidine	α2 agonist	↓ Sympathetic outflow (central)	Hypertension, opioid withdrawal, pain management
α-Methyldopa	α2 agonist (prodrug → α-methyl NE)	↓ Sympathetic outflow	Hypertension in pregnancy (first-line)
Salbutamol/Albuterol	β2 agonist	Bronchodilation	Asthma, COPD, preterm labor (tocolysis)
Terbutaline	β2 agonist	Bronchodilation, uterine relaxation	Asthma, preterm labor
Ritodrine	β2 agonist	Uterine relaxation	Preterm labor
Ephedrine	Indirect + direct (α, β agonist)	↑ NE release, direct agonist	Hypotension during anesthesia, nasal congestion
Pseudoephedrine	Indirect sympathomimetic	↑ NE release	Nasal decongestant
Amphetamine	Indirect (↑ NE, DA, 5-HT release)	CNS stimulant	ADHD, narcolepsy, obesity

NEET PG Memory Aid: Ephedrine = Enters CNS, Pressor, Pseudoephedrine (used for Nasal Decongestion) = Enters CNS Poorly (doesn’t cross BBB well)

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Adrenergic Antagonists (Sympatholytics)

Alpha Blockers

Non-Selective α Blockers (α1 + α2)

Drug	Mechanism	Clinical Use	Key Points
Phenoxybenzamine	Irreversible (covalent binding) α blocker	Pheochromocytoma (preoperative), hypertensive crises	Blocks α2 presynaptic → ↑ NE release → reflex tachycardia; causes orthostatic hypotension
Phentolamine	Reversible α blocker (competitive)	Pheochromocytoma surgery, hypertensive crises, extravasation of vasopressors	Shorter acting; also blocks 5-HT

Selective α1 Blockers

Drug	Selectivity	Clinical Use	Key Points
Prazosin	α1 selective	Hypertension, BPH (benign prostatic hyperplasia)	First-dose phenomenon — severe orthostatic hypotension with first dose; given at bedtime
Terazosin	α1 selective	BPH, hypertension	Longer acting than prazosin
Doxazosin	α1 selective	BPH, hypertension	Once daily; fewer cardiovascular effects
Tamsulosin	α1A selective (uroselective)	BPH only	Does NOT cause significant orthostatic hypotension — uroselective for prostate

Selective α2 Blockers

Drug	Mechanism	Clinical Use
Mirtazapine	α2 antagonist + 5-HT blocker	Depression (antidepressant)

NEET PG Memory Aid: α1 blockers cause orthostatic hypotension — warn patients to rise slowly
First-dose phenomenon → Prazosin → Take bedtime dose

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Beta Blockers

Non-Selective β Blockers (β1 + β2)

Drug	Selectivity	Clinical Use	Key Points
Propranolol	Non-selective (β1=β2)	Hypertension, angina, arrhythmias, migraine prophylaxis, hyperthyroidism, anxiety, portal hypertension	Does NOT cause vasodilation
Nadolol	Non-selective	Hypertension, angina, arrhythmias, migraine prophylaxis	Long-acting; once daily
Timolol	Non-selective	Glaucoma (topical eye drops), hypertension, migraine	First-line for glaucoma (↓ aqueous humor production)
Sotalol	Non-selective + K+ channel blocker	Arrhythmias	Class III antiarrhythmic effect

β1-Selective (Cardioselective) Blockers

Drug	Selectivity	Clinical Use	Key Points
Metoprolol	β1 selective	Hypertension, angina, MI, heart failure	Short-acting (BID) or extended (once daily)
Atenolol	β1 selective	Hypertension, angina	Long-acting; renally excreted (caution in renal impairment)
Bisoprolol	β1 selective	Heart failure (second-line)	Combined with amlodipine in single pill
Nebivolol	β1 selective + NO-mediated vasodilation	Hypertension	Vasodilatory beta blocker; causes less peripheral vasoconstriction

Beta Blockers with Additional Actions

Drug	Additional Action	Clinical Use
Carvedilol	α1 + β blocker + antioxidant	Heart failure, hypertension
Labetalol	α1 + β blocker	Hypertension in pregnancy (IV), hypertensive emergencies
Celiprolol	β blocker + β2 agonist	Hypertension (vasodilatory)

NEET PG Memory Aid: “Olol” drugs — majority are beta blockers (propranolol, metoprolol, atenolol, bisoprolol, carvedilol, labetalol, timolol, nadolol, betaxolol, etc.)

Side Effects of Beta Blockers

System	Effect
Cardiovascular	Bradycardia, AV block, hypotension, cold extremities, worsening heart failure
Respiratory	Bronchospasm (β2 blockade — contraindicated in asthma/COPD)
Metabolic	Masking of hypoglycemia symptoms, impaired glycogenolysis (caution in diabetics)
Sexual	Erectile dysfunction, decreased libido
CNS	Fatigue, depression, insomnia, nightmares
Withdrawal	Abrupt withdrawal dangerous — rebound hypertension, angina, MI

Contraindications: Asthma/COPD (β2 blockade), severe bradycardia, AV block, decompensated heart failure, Prinzmetal angina

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NEET PG Drug Tables and Memory Aids

Summary: ANS Drug Classification

Category	Subcategory	Example Drugs
Cholinergic	Direct (Muscarinic)	Bethanechol, Methacholine
Cholinergic	Indirect (AChE inhibitors)	Physostigmine, Neostigmine, Donepezil
Anticholinergic	Non-selective M blocker	Atropine, Scopolamine
Anticholinergic	Selective M blocker	Pirenzepine, Darifenacin, Trospium
Adrenergic	α agonists	Phenylephrine, Clonidine
Adrenergic	β agonists	Isoproterenol, Salbutamol, Dobutamine
Adrenergic	α blockers	Prazosin, Phenoxybenzamine
Adrenergic	β blockers	Propranolol, Metoprolol, Carvedilol

Key Mnemonics for NEET PG

Atropine poisoning: “Dry as a bone, blind as a bat, red as a beet, hot as a hare, mad as a hatter”

Cholinergic excess (SLUDGE/DUMBBELS): Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis

Pheochromocytoma alpha-blockade FIRST: “Alpha before beta” — must block α1 first before β blockade to prevent unopposed α-mediated vasoconstriction

Beta blocker selectivity: “The heart has only β1; the lung has only β2” — cardioselective drugs mainly affect heart

Atropine ophthalmic: Mydriasis + Cycloplegia → contraindicated in glaucoma (can precipitate acute attack)

Scopolamine vs Atropine: Scopolamine = Sleep/CNS effects, Antiemetic for Motion sickness

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NEET PG Exam Tips

High-Yield Points

1. Atropine — MOA, uses (bradycardia, mydriasis, premedication), side effects — extremely high-yield
2. Neostigmine — MOA, use in myasthenia gravis, reversal of neuromuscular blockade
3. β blockers — selectivity (β1 vs non-selective), uses, contraindications
4. Prazosin — first-dose phenomenon; should be taken at bedtime
5. Salbutamol — β2 agonist for acute asthma; side effect: tremor, tachycardia
6. Dopamine — dose-dependent receptor effects (D1 → β1 → α1)
7. Organophosphate poisoning — treatment = Atropine + Pralidoxime
8. Physostigmine — crosses BBB (vs neostigmine doesn’t) → used in anticholinergic toxicity with CNS effects
9. β blockers in glaucoma — Timolol is first-line (topical, doesn’t affect pupils/accommodation)
10. Carvedilol/Labetalol — have both α and β blocking activity

Common NEET PG Question Patterns

• “Which drug is used to diagnose myasthenia gravis?” → Edrophonium (Tensilon test)
• “Which AChE inhibitor does NOT cross BBB?” → Neostigmine (vs Physostigmine does cross)
• “Which β blocker is uroselective (α1A)?” → Tamsulosin (for BPH)
• “Which drug causes first-dose syncope?” → Prazosin (α1 blocker)
• “Reversal of neuromuscular blockade by succinylcholine?” → Neostigmine (indirect cholinomimetic)
• “Treatment of organophosphate poisoning?” → Atropine + Pralidoxime

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Summary Table

Drug	Class	Mechanism	Key Use
Atropine	M blocker	Competitive antagonist at M receptors	Bradycardia, mydriasis, premedication
Scopolamine	M blocker	Blocks M receptors (CNS effects)	Motion sickness, sedation
Physostigmine	AChE inhibitor	Inhibits AChE (crosses BBB)	Anticholinergic toxicity (CNS)
Neostigmine	AChE inhibitor	Inhibits AChE (peripheral)	Myasthenia gravis, reversal of NMB
Propranolol	β blocker	β1 + β2 antagonist	Hypertension, angina, arrhythmia, migraine
Metoprolol	β1 blocker	Selective β1 antagonist	Hypertension, angina, MI
Carvedilol	α + β blocker	α1 + β1 + β2 antagonist	Heart failure, hypertension
Prazosin	α1 blocker	Selective α1 antagonist	Hypertension, BPH
Ephedrine	Sympathomimetic	↑ NE release + direct agonist	Hypotension during anesthesia
Salbutamol	β2 agonist	β2 receptor agonist	Acute asthma, bronchospasm

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Chapter: Autonomic Nervous System Drugs | Subject: Pharmacology | Exam: NEET PG