ANS Pharmacology

25th April, 2013

Important Things to Remember about ANS

• ANS/Visceral/Vegetative System involuntarily regulates smooth muscles and glands

» heart, respiratory system, GI tract, peristalsis (digestion), bladder, and eyes

• Has two divisions i.e. PANS & SANS (homeostasis)

• Both have relay stations (ganglia) b/w CNS & end organ.

• Use the neurotransmitters Ach & NE

Anatomy of ANS•Pre & Post-ganglionic Neuron•Afferent Neurons•Sympathetic & Parasympathetic Divisions•Enteric Neurons

• Innervate• motility,

exocrine and endocrine, microcirculation of GI

Parasympathetic Ganglionic Synapse

Action Potential

Na+

Ca 2+

aa

b

ACH

Acetylcholinesterase

Na+

Preganglionic neuron

Nicotinic

Receptor

Parasympathetic Organ Synapse

Action Potential

Ca 2+

Na+

ACH

Acetylcholinesterase

K+

G

Postganglionic neuron

Muscarinic

Receptor

Sympathetic Ganglionic Synapse

Action Potential

Na+

Ca 2+

aa

b

ACH

Acetylcholinesterase

Na+

Preganglionic neuron

Nicotinic

Receptor

Sympathetic Organ Synapse

Action Potential

Ca 2+

Na+

NE

G

Postganglionic neuron

Adrenergic

Receptor

SummarySummary of parasympathetic neurons

and synapses

Preganglionic neurons• Long• Synapse with postganglionic neurons at

or near organ• Release acetylcholine (ACH) to activate

nicotinic receptors on postganglionic neurons

Postganglionic neurons• Short• Synapse on the target organ• Release acetylcholine (ACH) to activate

muscarinic receptors on the target organ

Summary of sympathetic neurons and synapses

Preganglionic neurons• Short• Synapse with postganglionic neurons

near spinal cord• Release acetylcholine (ACH) to activate

nicotinic receptors on postganglionic neurons

Postganglionic neurons• Long• Synapse on the target organ• Release norepinephrine to activate

adrenergic receptors on target organs

Summary

Exceptions in the sympathetic nervous system:

• Sweat glands:» Postganglionic neurons

involved with stress-related excretion release norepinephrine (“sweaty palms”)

» Postganglionic neurons involved with thermoregulation release acetylcholine

Exceptions in the sympathetic nervous system:

• Kidneys:» Postganglionic neurons to the

smooth muscle of the renal vascular bed release dopamine

• Adrenal gland:» Preganglionic neurons do not

synapse in the paraverterbral sympathetic ganglion

» Preganglionic neurons synapse directly on the adrenal gland, release acetylcholine, and activate nicotinic receptors on the adrenal gland

» Adrenal glands release epinephrine into systemic circulation

Functions

• Sympathetic Stimulation (Fight or Flight)– ↑HR, BP, blood flow– Diffuse distribution (more than one organ innervated)

• Parasympathetic Stimulation (Rest & Digest)– Maintaining homeostasis– Discrete distribution/activation

• Role of CNS– Reflex Arcs : Afferent input ~ hypothalamus, medulla oblongata, and spinal

cord ~ efferent reflex impulse via ANS– Emotions:

• Innervation by ANS– Dual – Only sympathetic (adrenal medulla, kidney, pilomotor muscles, and sweat

glands)

 Branch  Type  Location Typical Agonist

Drugs Typical Antagonist

Drugs

 Sympathetic

(adrenergic)

 α1 Most vascular arterioles, Sphincters of bladder & GI tract, Iris dilator

 NorepinephrineEpinephrine

 PhenoxybenzaminePhentolaminePrazosin

α2  GI tract, presynaptic sympathetic neurons ClonidineEpinephrine

 Yohimbine

 β1  Heart muscle, Salivary glands, Fat cells

 NorepinephrineIsoproteronolDobutamineEpinephrine

 "Beta blockers"PropranololMetoprolol

β 2 Bronchioles of lung, Arterioles of skeletal muscles, brain and lungs, Bladder wall, GIT

 EpinephrineIsoproteronolAlbuterol

 

"Beta blockers"PropranololButoxamine

  Parasympathetic

(cholinergic)

M Heart muscle, Sphincters of bladder & GI tractBronchioles of lung, Sweat glands Iris constrictor

 AcetylcholineMuscarineCarbachol

 AtropineScopolamine

  N  Neuromuscular junctions, Autonomic ganglia  AcetylcholineNicotineCarbachol

 Curare

Dual Innervation of the Iris

Without Dual Innervation• Some effectors receive only sympathetic

– adrenal medulla, arrector pili muscles, sweat glands and many blood vessels

• Sympathetic tone – a baseline firing frequency– vasomotor tone provides partial constriction

• increase in firing frequency = vasoconstriction• decrease in firing frequency = vasodilation• can shift blood flow from one organ to another as needed

– sympathetic stimulation increases blood to skeletal and cardiac muscles -- reduced blood to skin

Classification of drugs affecting the ANS

• Parasympathetic nervous systemMimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic

Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic

• Sympathetic nervous systemMimic norepinephrine = adrenergic = adrenergic agonist = sympathomimetic

Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic