HA Pharmacology & Pharmacy – Unit 2

Drugs Acting on Autonomic Nervous System

CTEVT Second Year Health Science (PCL) | According to Syllabus 2024

Introduction to Autonomic Nervous System (ANS)

The Autonomic Nervous System regulates involuntary bodily functions through two main divisions: Sympathetic (SNS) “fight or flight” and Parasympathetic (PNS) “rest and digest”. Drugs acting on ANS either mimic or block neurotransmitters (acetylcholine, norepinephrine) at their receptors, allowing precise control of heart rate, blood pressure, bronchial tone, gastrointestinal motility, and glandular secretions.

Clinical Importance: Mastery of ANS pharmacology is crucial for managing conditions like hypertension, asthma, glaucoma, arrhythmias, shock, and myasthenia gravis. These drugs are frequently used in emergency and critical care settings.

1. Pharmacological Action of Acetylcholine (ACh)

Definition & Role

Acetylcholine is the primary neurotransmitter of:

Parasympathetic nervous system (PNS)
Somatic motor neurons (neuromuscular junction)
Autonomic ganglia (both SNS & PNS)
Central nervous system (CNS)

Metabolism: Rapidly hydrolyzed by acetylcholinesterase (AChE) at synapses.

Organ System Effects

Heart: ↓ Heart rate (negative chronotropic), ↓ Force of contraction (negative inotropic)
Smooth Muscle: Contraction (GI, bronchial, bladder)
Glands: ↑ Secretion (salivary, sweat, lacrimal, gastric)
Eye: Miosis (pupil constriction), accommodation for near vision
CNS: Learning, memory, arousal (affected in Alzheimer’s)

📌 Clinical Applications:

Diagnosis: Edrophonium test for myasthenia gravis (temporary improvement)
Surgery: Acetylcholine used in ophthalmic surgery to induce miosis
Therapeutic Limitation: Not used systemically due to rapid degradation and diffuse effects

2. Autonomic Receptors

Cholinergic Receptors

Muscarinic Receptors (M1-M5)

G-protein coupled receptors activated by ACh and muscarine

M1: CNS, gastric parietal cells (↑ acid secretion)
M2: Heart (↓ HR, ↓ AV conduction, ↓ contractility)
M3: Smooth muscle (contraction), glands (secretion), endothelium (NO release → vasodilation)
M4 & M5: Primarily in CNS (modulation)

Drug Relevance: Target for parasympathomimetics (stimulate) and anticholinergics (block)

Nicotinic Receptors (N_N & N_M)

Ligand-gated ion channels activated by ACh and nicotine

N_N (Neuronal): Autonomic ganglia (both SNS & PNS), adrenal medulla
N_M (Muscle): Neuromuscular junction (skeletal muscle contraction)

Clinical Note: Blocked by neuromuscular blockers (e.g., succinylcholine) during surgery

Adrenergic Receptors (Respond to Epinephrine/Norepinephrine)

Receptor Type	Primary Locations	Major Actions	Clinical Drug Examples
Alpha-1 (α₁)	Vascular smooth muscle, eye radial muscle, bladder sphincter, prostate	Vasoconstriction (↑BP), mydriasis, urinary retention	Phenylephrine (agonist), Prazosin (antagonist)
Alpha-2 (α₂)	Presynaptic nerve terminals, CNS, platelets	Inhibits NE release (↓BP), sedation, platelet aggregation	Clonidine (agonist), Yohimbine (antagonist)
Beta-1 (β₁)	Heart, kidney JG cells	↑HR, ↑contractility, ↑AV conduction, renin release	Dobutamine (agonist), Metoprolol (antagonist)
Beta-2 (β₂)	Bronchial smooth muscle, uterine muscle, liver, skeletal muscle vessels	Bronchodilation, uterine relaxation, glycogenolysis, vasodilation	Salbutamol (agonist), Propranolol (antagonist)

Memory Aid:
α₁ = Arteries, α₂ = Auto-inhibit, β₁ = Beats (heart), β₂ = Breathing (lungs)

3. ANS Drug Classes: Comparison & Applications

Autonomic Nervous System Drug Classification

PARASYMPATHETIC

Mimetics (Cholinergics)
Stimulate PNS

↓

Lytics (Anticholinergics)
Block PNS

SYMPATHETIC

Mimetics (Adrenergics)
Stimulate SNS

↓

Lytics (Antiadrenergics)
Block SNS

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A. Parasympathomimetics (Cholinergic Agonists)

Direct-acting (Muscarinic Agonists)

Examples: Pilocarpine, Bethanechol, Carbachol

Mechanism: Directly bind & activate muscarinic receptors

Key Uses:

Glaucoma (↓ intraocular pressure)
Xerostomia (↑ salivary secretion)
Post-operative ileus (↑ GI motility)
Neurogenic bladder (↑ bladder contraction)

Indirect-acting (AChE Inhibitors)

Examples: Neostigmine, Pyridostigmine, Physostigmine, Edrophonium

Mechanism: Inhibit acetylcholinesterase → ↑ ACh levels

Key Uses:

Myasthenia gravis (improves muscle strength)
Alzheimer’s disease (cognitive symptoms)
Reversal of neuromuscular blockade
Glaucoma (chronic)

Side Effects & Contraindications

Side Effects (SLUDGE syndrome):

Salivation, Lacrimation
Urination, Diarrhea
GI cramps, Emesis
Bronchoconstriction, Bradycardia

Contraindications: Asthma, COPD, peptic ulcer, bradycardia, hypotension

B. Parasympatholytics (Anticholinergics)

Major Drugs & Uses

Atropine: Bradycardia, pre-anesthetic, organophosphate poisoning
Ipratropium/Tiotropium: Asthma/COPD (bronchodilation)
Hyoscine (Scopolamine): Motion sickness, pre-op sedation
Oxybutynin, Tolterodine: Overactive bladder (↓ urgency)
Pralidoxime: Cholinesterase reactivator (OP poisoning)

Pharmacological Actions

↑ Heart rate (blocks M2)
↓ Glandular secretions (dry mouth, dry eyes)
Bronchodilation (relaxes smooth muscle)
↓ GI motility & secretion
Mydriasis & cycloplegia (eye)
Urinary retention (relaxes bladder)

Adverse Effects & Contraindications

Side Effects (Dry as a bone, blind as a bat, red as a beet, mad as a hatter):

Dry mouth, blurred vision
Urinary retention, constipation
Tachycardia, palpitations
Confusion, hallucinations (elderly)

Contraindications: Glaucoma (angle-closure), BPH, GI obstruction, myasthenia gravis

D. Sympatholytics (Adrenergic Antagonists)

Alpha Blockers (α-antagonists)

Non-selective (α1+α2): Phentolamine, Phenoxybenzamine

α1 selective: Prazosin, Terazosin, Tamsulosin

Uses:

Hypertension (α1 blockers)
Pheochromocytoma (pre-op)
BPH (improves urinary flow)
Raynaud’s phenomenon

Side Effects: First-dose syncope, orthostatic hypotension, nasal congestion, reflex tachycardia

Beta Blockers (β-antagonists)

Non-selective (β1+β2): Propranolol, Nadolol, Timolol

β1 selective (cardioselective): Atenolol, Metoprolol, Bisoprolol

Uses:

Hypertension, angina, MI
Arrhythmias (supraventricular)
Heart failure (selected β-blockers)
Glaucoma (timolol eye drops)
Migraine prophylaxis, anxiety

Side Effects: Bradycardia, fatigue, bronchospasm (non-selective), masking hypoglycemia, erectile dysfunction

Contraindications & Withdrawal

Beta Blocker Contraindications:

Asthma/COPD (non-selective)
Severe bradycardia/AV block
Decompensated heart failure
Peripheral vascular disease

Abrupt Withdrawal: Can cause rebound hypertension, tachycardia, angina exacerbation (taper slowly over 1-2 weeks)

Clinical Pearl: “Beta blockers should not be stopped suddenly” – always taper.

One Page Summary: ANS Drugs

ACETYLCHOLINE (ACh)
• Neurotransmitter of PNS, ganglia, NMJ
• Effects: ↓HR, ↑secretions, ↑GI motility, miosis
• Rapidly degraded by AChERECEPTORS
• Muscarinic (M1-M5): G-protein, PNS effects
• Nicotinic (N_N, N_M): Ion channels, ganglia & NMJ
• Adrenergic: α1 (vasoconstrict), α2 (inhibit), β1 (heart), β2 (lungs)PARASYMPATHOMIMETICS
• Direct: Pilocarpine (glaucoma, dry mouth)
• Indirect: Neostigmine (myasthenia gravis)
• SE: SLUDGE syndrome
• Contra: Asthma, bradycardiaSYMPATHOMIMETICS
• α1: Phenylephrine (decongestant, hypotension)
• β1: Dobutamine (cardiogenic shock)
• β2: Salbutamol (asthma)
• Mixed: Adrenaline (anaphylaxis, cardiac arrest)

PARASYMPATHOLYTICS
• Atropine: Bradycardia, pre-anesthetic, OP poisoning
• Ipratropium: Asthma/COPD
• Oxybutynin: Overactive bladder
• SE: Dry mouth, blurred vision, urinary retention, tachycardia
• Contra: Glaucoma, BPH, GI obstructionSYMPATHOLYTICS
• α-blockers: Prazosin (HTN, BPH), SE: first-dose syncope
• β-blockers: Propranolol (non-selective), Metoprolol (β1 selective)
• Uses: HTN, angina, arrhythmias, migraine
• SE: Bradycardia, fatigue, bronchospasm
• Contra: Asthma, severe bradycardia, heart failureMNEMONICS
• SLUDGE: Salivation, Lacrimation, Urination, Diarrhea, GI cramps, Emesis
• α1 = Arteries, β1 = Beats, β2 = Breathing
• Anticholinergic: “Dry as a bone, blind as a bat, red as a beet, mad as a hatter”

Key Clinical Points:
Atropine for bradycardia, Adrenaline for anaphylaxis, Salbutamol for asthma, Pilocarpine for glaucoma

Clinical Application Scenarios

Scenario 1: Myasthenia Gravis

Presentation: Ptosis, diplopia, muscle weakness worsening through day.

Drug Choice: Pyridostigmine (AChE inhibitor)

Mechanism: ↑ ACh at NMJ → improves muscle strength

Monitoring: Muscle strength, respiratory function, cholinergic crisis vs myasthenic crisis

Scenario 2: Anaphylactic Shock

Presentation: Hypotension, bronchospasm, urticaria after bee sting.

Drug Choice: Adrenaline (Epinephrine) IM

Mechanism: α1 → vasoconstriction (↑BP), β2 → bronchodilation, β1 → cardiac support

Key: First-line, life-saving; administer immediately.

Scenario 3: Organophosphate Poisoning

Presentation: SLUDGE + muscle fasciculations, confusion, respiratory distress.

Drug Choice: Atropine + Pralidoxime

Mechanism: Atropine blocks muscarinic effects; Pralidoxime reactivates AChE

Priority: Airway management, atropine until secretions dry.

Visual Aid: ANS Receptor Actions

Key Clinical Takeaways

ANS drugs work by mimicking or blocking neurotransmitters (ACh, NE/E) at specific receptors.
Parasympathomimetics cause SLUDGE; Parasympatholytics cause dry mouth, blurred vision, tachycardia.
Adrenaline is first-line for anaphylaxis (α1, β1, β2 effects).
Beta-blockers must be tapered to avoid rebound hypertension/angina.
Atropine is antidote for organophosphate poisoning and bradycardia.
Receptor selectivity determines drug’s therapeutic use and side effect profile.

Quick Self-Check

Question 1: Which drug class would you choose for acute bronchospasm in asthma?

Question 2: Match the drug to its primary use:

1. Pilocarpine

2. Atropine

3. Adrenaline

Download Notes

Get a printable PDF version of these comprehensive ANS pharmacology notes. HA Pharmacology and Pharmacy Unit 2 Drugs Acting on Autonomic Nervous System Notes

Includes all drug classes, receptors, clinical uses, and one-page summary. HA Pharmacology and Pharmacy Unit 2 Drugs Acting on Autonomic Nervous System Notes