physiology of autonomic nervous system

1Maninder Kaur M.Pharm (Pharmacology)

The autonomic nervous system is the subdivision of the peripheral nervous system that regulates body activities that are generally not under conscious control

Visceral motor innervates non-skeletal (non-somatic) muscles

Visceral sensory will be covered later


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Diagram of Autonomic nervous system

Diagram contrasts somatic (lower) and autonomic:

autonomic

somatic

this dorsal root ganglion is sensory

Maninder Kaur M.Pharm (Pharmacology)

Neurotransmission in ANS occurs in 5 steps:

• Impulse conduction.• Neurotransmitter release.• Activity on preganglionic neurons.• Activity on postganglionic neurons.• Termination of neurotransmitter

release.


Parasympathetic division Sympathetic division

Parasympathetic: routine maintenance.

“rest &digest”Sympathetic: mobilization &

increased metabolism. “fight, flight or fright”


2 divisions: Sympathetic ▪ “Fight or flight”▪ “E” division▪ Exercise, excitement, emergency, and embarrassment

Parasympathetic ▪ “Rest and digest”▪ “D” division▪ Digestion, defecation, and diuresis 7Maninder Kaur M.Pharm (Pharmacology)

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Also called the craniosacral system because all its preganglionic neurons are in the brain stem or sacral levels of the spinal cord. Cranial nerves III,VII, IX and X In lateral horn of gray matter from S2-S4

Only innervate internal organs (not skin).

Acetylcholine is neurotransmitter at end organ as well as at preganglionic synapse: “cholinergic”.


Works to save energy, aids in digestion, and supports restorative, resting body functions. Decrease in heart rate Increased gastro intestinal tract tone

and peristalsis Urinary sphincter relaxation Vasodilation – decrease in blood

pressure


Location of cholinergic receptors-1. Postganglionic parasympathetic neuroeffector

junctions. 2. All autonomic ganglia.3. At the neuromuscular endplate.


Two types of receptors are present- Muscarinic receptor.Nicotinic receptor.


M-cholinoceptors can be classified into subtypes

according to their molecular structure, signal transduction, and ligand affinity in the M1, M2, M3 subtypes etc.

• M1-receptors are present on nerve cells, e.g., in ganglia, where they mediate a facilitation of impulse transmission from preganglionic axon terminals to ganglion cells.

• M2-receptors mediate acetylcholine effects on the heart. Opening of K+ channels leads to slowing of diastolic depolarization in sinoatrial pacemaker cells and a decrease in heart rate. 16Maninder Kaur M.Pharm (Pharmacology)

M3-receptors are found in the glandular epithelia (which respond with activation of phospholipase C and increases secretory activity) and in smooth muscle.


Muscarinic receptor (G protein-linked: 7 subunits)18


NM -cholinoceptors Location: neuromuscular junction. Function: depolarization of muscle end plate and contraction of skeletal muscle.

NN -cholinoceptors Location: autonomic ganglia. Function: depolarization postganglionic membrane (in adrenal medulla – catecholamine release).


(1) Choline ester (stimulants of M- and N- receptors): Acetylcholine, Carbachol, etc.

(2) Alkaloids a) stimulants of M-receptors:▪ Pilocarpine, Cevimeline (dry mouth),▪ Bethanechole, Musacarine, Phalloidin

b) stimulants of N-receptors:▪ Nicotine, Cytisine (Tabex®), Lobeline


(1) Reversible drugs (most are carbamates)

a) With N3+ (cross BBB) Alkaloids: Galantamine, Physostigmine Synthetic drugs: Donepezil,

Rivastigmine, Tacrine.

b) With N4+ (do not cross BBB)- Demecarium, Edrophonium (Tensilon®),Neostigmine, Pyridostigmine.


(2) Irreversible anticholinesterase agents (most of them are organophosphates)-

a) Thiophosphate insecticides Parathion Malathion (Pedilin® – in pediculosis)

b) Nerve paralytic gases for chemical warfare Tabun Sarin Soman 23Maninder Kaur M.Pharm (Pharmacology)

cardiac output M2: decreases SA node: heart rate (chronotropic) M2: decreases cardiac muscle: contractility (inotropic) M2: decreases (

atria only) conduction at AV node M2: decreases smooth muscles of bronchioles M3: contracts pupil of eye M3: contracts ciliary muscle M3: contracts salivary glands: secretions stimulates watery secretions GI tract motility M1, M3: increases smooth muscles of GI tract M3: contracts sphincters of GI tract M3: relaxes glands of GI tract M3: secretes


Myasthenia gravis.Belladonna poisoning. In glucoma


These are drugs which oppose the acetylcholine actions or block the cholinergic receptors.

Anti- cholinergics mainly block the muscarinic receptor.


Atropine, the prototype drug of this class, is a highly selective blocking agent for pre and post muscarinic receptors, but some of its synthetic derivatives have significant nicotinic blocking property as well.


1. Natural alkaloids: Atropine (spasmolytic, mydriatic), Hyoscine (Scopolamine), Scopoderm® TTS

(antiemetic)

2. Semisynthetic derivatives• Mydriatics: Homatropine• GI spasmolytics: Hyoscine butyl bromide

(Buscolysin®)


3. Synthetic compounds

• GI spasmolytics: Oxyphenonium • Antiulcus drugs: Pirenzepine (M1-blockers)

• Antiasthmatics: Ipratropium and Tiotropium• Antidisurics: Flavoxate, Oxybutynyne, Trospium• Mydriatics: Tropicamide• Antiparkinsonian (central M-cholinolytics): ▪ Benztropine, Biperiden, Trihexyphenidyl


Atropine

(-)


• CNS. Atropine has an overall stimulant action. Its stimulant effects are not appreciable at low doses which produce peripheral effects because of restricted entry into the brain.

• Atropine stimulates many medullar centers- vagal, respiratory, and vasоmotor.

• By blocking the relative cholinergic overactivity in basal ganglia, it suppresses tremor and rigidity in parkinsonism.

• High doses cause cortical excitation, rest- lessness, disorientation, hallucinations.


CVS. Atropine causes tachycardia, due to blockade of M2-receptors on SA node through which vagal tone decreases HR.

Atropine does not influence BP. It blocks the vasodepressor action of cholinergic agonists.

Eye. Topical instillation of atropine (0.1%) causes mydriasis, abolition of light reflex, and cycloplegia, lasting 7–10 days. This results in photophobia and blurring of near vision. The intraocular tension rises, specially in narrow angle glaucoma, but conventional systemic doses produce minor ocular effects. 33Maninder Kaur M.Pharm (Pharmacology)

Smooth muscles. All visceral smooth muscles with parasympathetic inervation are relaxed (M3 blokade).Tone and amplitude of GIT are reduced. Spasm may be reduced, constipation may occur. Peristalsis is only incompletely suppressed because it is primarily regulated by local reflexes and other neurotransmitters (serotonin, encephalin, etc.).

Atropine causes bronchodilation and reduced airway resistance, especially in asthma patients.


Glands. Atropine decreases sweat, salivary, tracheo-bronchial, and lacrimal secretion (M3-blockade). Skin and eyes become dry, talking, and swallowing my be very difficult. Atropine decreases less the secretion of acid and pep-sin and more of the mucus in the stomach.

Body temperature. Rise in body temperature occurs at higher doses, and is due to both inhibition of sweating as well as stimulation of the temperature regulating centre in the hypothalamus.


saliva, sweat, bronchial secretion > eye > bronchial muscles > heart > intestinal and bladder smooth muscles > gastric glandsand gastric smooth muscles


NEUROMUSCULAR BLOCKING AGENTS:Skeletal muscle relaxants act peripherally at neuromuscular

junction. According to their action they are divided into the following groups.

•Nondepolarizing (competitive) agents or curare-like drugs •Depolarizing (hyperdepolarazing) agents


Also called thoracolumbar system: all its neurons are in lateral horn of gray matter from T1-L2

Lead to every part of the body Easy to remember that when nervous, you sweat; when

afraid, hair stands on end; when excited blood pressure rises (vasoconstriction): these sympathetic only

Also causes: dry mouth, pupils to dilate, increased heart & respiratory rates to increase O2 to skeletal muscles, and liver to release glucose

Norepinephrine (noradrenaline) is neurotransmitter released by most postganglionic fibers (acetylcholine in preganglionic): “adrenergic”


Helps the body cope with external stimuli and functions during stress (triggers the flight or fight response) Vasoconstriction – increase in blood

pressure Increased heart rate Increased respiratory rate Cold, sweaty palms Pupil dilation


Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. Consider sympathetic as "fight or flight" and parasympathetic as "rest and digest".


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physiology of autonomic nervous system

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