SNS

Sympathetic Nervous System (SNS)

1. Overview

• Part of the autonomic nervous system (ANS) → works involuntarily.

• Responsible for “fight or flight” responses.

• Opposes the parasympathetic nervous system (PNS), which controls “rest and digest” functions.

2. Anatomical Location

Component	Description
Origin	Thoracolumbar region (T1–L2) of spinal cord
Preganglionic neurons	Cell bodies in intermediolateral horn of spinal cord
Preganglionic fibers	Exit spinal cord → synapse in sympathetic ganglia (paravertebral or prevertebral)
Postganglionic neurons	From ganglia → innervate target organs (heart, lungs, vessels, glands, etc.)
Neurotransmitters	- Preganglionic: Acetylcholine (ACh) → nicotinic receptors

• Postganglionic: Norepinephrine (NE) → adrenergic receptors (α, β)

• Exception: Sweat glands use ACh (muscarinic) instead of NE |

3. Neurotransmitters

Fiber Type	Neurotransmitter	Receptor Type
Preganglionic	ACh	Nicotinic (Nn)
Postganglionic (most)	Norepinephrine (NE)	α, β adrenergic
Postganglionic (sweat glands)**	ACh	Muscarinic (M3)
Adrenal medulla	ACh → Nicotinic receptor → releases Epinephrine + Norepinephrine into blood

4. Adrenergic Receptors (Targets of SNS)

Receptor	Location	Function (Activation)
α₁	Vascular smooth muscle, eye (radial muscle), bladder sphincter	Vasoconstriction ↑BP, mydriasis (dilation), bladder contraction
α₂	Presynaptic neurons, CNS	↓NE release (negative feedback), ↓insulin
β₁	Heart (SA node, AV node), kidney (juxtaglomerular cells)	↑HR, ↑contractility, ↑renin → ↑BP
β₂	Lungs (bronchioles), uterus, skeletal muscle vasculature	Bronchodilation, vasodilation, uterine relaxation
β₃	Adipose tissue, bladder detrusor	Lipolysis, bladder relaxation

5. Mechanisms of Action (MOA)

Receptor	Coupled G-Protein	Second Messenger	Effect
α₁	Gq	↑IP₃, ↑Ca²⁺	Smooth muscle contraction
α₂	Gi	↓cAMP	↓NE release
β₁, β₂, β₃	Gs	↑cAMP	β₁: ↑cardiac activity, β₂: relaxation (bronchial, uterine), β₃: lipolysis

6. Effects on Organ Systems

System	Sympathetic Effect
Heart	↑Rate (chronotropy), ↑Force (inotropy), ↑Conduction (dromotropy)
Blood vessels	Vasoconstriction (α₁), Vasodilation in skeletal muscle (β₂)
Lungs	Bronchodilation (β₂)
Eyes	Pupil dilation (α₁)
GI tract	↓Motility, constrict sphincters (α₁)
Bladder	Relax detrusor (β₃), contract sphincter (α₁)
Liver	↑Glycogenolysis, ↑Gluconeogenesis (β₂)
Adipose	Lipolysis (β₃)
Skin	Sweating (M₃) via ACh
Kidney	↑Renin secretion (β₁)

7. Adrenergic Agonists (Sympathomimetics)

🔹 Direct-acting

Drug	Receptor	Clinical Use
Epinephrine	α₁, α₂, β₁, β₂	Anaphylaxis, cardiac arrest, asthma (severe)
Norepinephrine	α₁, α₂, β₁	Hypotension, shock
Dopamine	D₁ (low dose), β₁ (medium), α₁ (high)	Shock, heart failure
Phenylephrine	α₁	Nasal decongestant, mydriatic
Clonidine / Methyldopa	α₂	Hypertension (central)
Dobutamine	β₁	Heart failure, stress testing
Albuterol / Salbutamol	β₂	Asthma, COPD
Mirabegron	β₃	Overactive bladder

🔹 Indirect-acting

Drug	Mechanism	Use
Amphetamine	↑NE release	ADHD, narcolepsy
Cocaine	Blocks NE reuptake	Local anesthesia (ENT)
Ephedrine	↑NE release, direct β agonist	Hypotension, nasal decongestant

8. Adrenergic Antagonists (Sympatholytics)

🔹 α-blockers

Drug	Receptor	Use	Adverse
Prazosin, Doxazosin	α₁	Hypertension, BPH	Orthostatic hypotension
Phentolamine, Phenoxybenzamine	α₁, α₂	Pheochromocytoma	Reflex tachycardia

🔹 β-blockers

Drug	Selectivity	Use	Adverse
Propranolol	β₁, β₂ (nonselective)	HTN, anxiety, migraine	Bronchospasm
Metoprolol, Atenolol, Bisoprolol	β₁ selective	HTN, angina, heart failure	Bradycardia
Carvedilol, Labetalol	α₁ + β	HTN, heart failure	Hypotension
Esmolol	β₁ (short-acting)	Acute arrhythmias	Bradycardia
Timolol	β (nonselective)	Glaucoma	↓IOP

9. Clinical Correlations

Condition	Mechanism	Drug
Anaphylaxis	Systemic vasodilation + bronchospasm	Epinephrine
Heart failure	↓Cardiac output	Dobutamine (acute), β-blockers (chronic)
Asthma/COPD	Bronchoconstriction	Albuterol (β₂ agonist)
Hypertension	↑Sympathetic tone	Clonidine (α₂ agonist), β-blockers, α₁-blockers
Benign prostatic hyperplasia	Smooth muscle constriction	Tamsulosin (α₁A blocker)
Pheochromocytoma	Catecholamine-secreting tumor	Phenoxybenzamine (α-blocker) pre-op
Glaucoma	↑Aqueous humor production	Timolol (β-blocker)

10. Summary Table

Aspect	Key Points
Origin	Thoracolumbar (T1–L2)
Neurotransmitters	ACh (preganglionic), NE (postganglionic)
Main Receptors	α₁, α₂, β₁, β₂, β₃
Functions	Fight or flight: ↑HR, ↑BP, bronchodilation, ↓digestion
Agonists	Epi, NE, Albuterol, Phenylephrine, Clonidine
Antagonists	Propranolol, Prazosin, Labetalol
Special exceptions	Sweat glands (ACh → M₃), Adrenal medulla (Epi + NE release)