Autonomic Nervous System

Physiology of neurons (synaptic structure & function)

 Stimulation of nerve fibers liberate a substance at the nerve ending which activate a receptor in the organ supplied or another nerve cell This substance known as neurotransmitter

Overview of Nervous System

Nervous system
Includes neurons and ganglia outside of the brain and spinal cord
Peripheral Nervous System

*Either fight and flight mode or rest and digest

*Autonomic Nervous System (involuntary)

Somatic Nervous System (voluntary)

With neurotransmitters norepinephrine and acetylcholine

Sympathetic Nervous System (adrenergic)

Parasympathetic Nervous System (cholinergic)

 Autonomic Nervous System (ANS) Its function involuntarily to regulate the everyday needs & requirements of the body without the conscious participation of the mind

Basic (2-neurons) pattern of these systems

 Preganglionic neurons with cell bodies in CNS Postganglionic neurons with cell bodies in autonomic ganglia transmission from autonomic postganglionic neurons to effector organs in:
Parasympathetic system involve release of Ach Sympathetic system involve release of E & NE

Cholinergic Receptors
Two types, determined by:
Location Action once stimulated

Nicotinic receptors and Muscarinic receptors

 1. Nicotinic Receptors

Located in the ganglia of both the PSNS and SNS Affects the skeletal muscle Named nicotinic because can be stimulated by nicotine

2.Muscarinic Receptors
Located mainly postsynaptically:
Smooth muscle Cardiac muscle Glands of parasympathetic fibers Effector organs of cholinergic sympathetic fibers

Named muscarinic because can be stimulated by the alkaloid muscarine

Adrenergic receptors
A receptor that binds, and activated by one of the catecholamine transmitters norepinephrine, epinephrine, dopamine. Adrenoceptors are classified as or receptors.

The differences between sympathetic & parasympathetic nervous system Sympathetic parasympathetic

Anatomy

The preganglionic The preganglionic neurons arises neurons come from cranial from thoracic & nerves (III. VII, lumbar regions of IX, X)& sacral spinal cord regions Adjusting response to stressful situations Maintain essential body functions

Function

The differences between sympathetic & parasympathetic nervous system

Sympathetic parasympathetic

Neurotransmitter

Epinephrine (E) Norepinephrine (NE)

Adrenergic receptors receptors

Acetylcholine (Ach)

Receptors
Action on the effector organ

Muscarinic receptors (cholinergic)

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Action of sympathetic & parasympathetic nervous system on effector organs

Body Tissue/Organ Eye Lungs

Sympathetic Response Dilates pupils Dilates bronchioles

Parasympathetic Response Constricts pupils Constricts bronchioles and increase secretions Decreases heart rate Dilates Increases peristalsis

Heart Blood vessels GI

Increases heart rate Constricts(skin) Dilates(skeletal muscles) Relaxes smooth muscles of GIT Relaxes bladder muscle Relaxes uterine muscles Decreases salivation

Bladder Uterus Salivary gland

Constricts bladder

Increases salivation

 Most visceral organs are innervated by both sympathetic and parasympathetic fibers This results in dynamic antagonisms that precisely control visceral activity

Interactions of the Autonomic Divisions

Dual Innervation
Antagonistic effects oppose each other Example:

 Sympathetic fibers increase heart and respiratory rates, and inhibit digestion and elimination Parasympathetic fibers decrease heart and respiratory rates, and allow for digestion and the discarding of wastes

Role of the Parasympathetic Division

Concerned with keeping body energy use low Involves the D activities digestion, defecation, and diuresis Its activity is illustrated in a person who relaxes after a meal
Blood pressure, heart rate, and respiratory rates are low Gastrointestinal tract activity is high the pupils is constricted

Role of the Sympathetic Division

The sympathetic division is the fight-or-flight system Involves E activities exercise, excitement, emergency, and embarrassment Promotes adjustments during exercise blood flow to organs is reduced, flow to muscles is increased Its activity is illustrated by a person who is threatened
Heart rate increases, and breathing is rapid and deep the pupils dilate

How do drugs influence the ANS?

Mimic or block the effects of the two primary neurotransmitters, Acetylcholine and Norepinephrine/Epinephrine Drugs that mimic neurotransmitters are referred to as receptor agonists
These drugs activate receptors

Drugs that block neurotransmitters are referred to as receptor antagonists

These drugs block the endogenous neurotransmitters from activating receptors

 Classification of drugs affecting the ANS Parasympathetic nervous system

Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic

Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic

 Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist = sympathomimetic

Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic

Parasympathetic system Acetylcholine (Ach) is rapidly broken down by cholinesterase so not used therapeutically

Ach

acetylcholinesterase

choline + acetate

To mimic the action of Ach:

Giving Ach-like drugs (cholinergic agonists) Using drug that inhibit the action of acetylcholinesterase

The major groups of cholinoceptor-activating drugs

 Direct acting cholinergic agonists:

1. Bethanechol
Directly stimulate muscarinic receptors & causing: intestinal motility stimulates the detrusor muscles of the bladder while the sphincter is relaxed, causing expulsion of urine Uses(indications): Stimulates atonic bladder, particularly in non obstructive urinary retention

Some adverse effects observed with cholinergic agonists

2. Pilocarpine Used only as eye drops & causes miosis Uses: The drug of choice in the emergency lowering of intraocular pressure of glaucoma

Indirect-acting agonists: The Anticholinesterases

MOA: prevents the break down of Ach by cholinesterase The actions of Ach are thus intensified at 2 sites of action: The parasympathetic nerve endings The nerve ending in voluntary muscles

 Reversible Anticholinesterases Examples: 1. Neostigmine Its effect on NMJ of voluntary muscles & less to the eye & CVS Can be given orally, I.M., S.C. Uses: Treatment of disorders in NMJ of voluntary muscles (myasthenia gravis) Paralytic ileus Bladder atony

2. Physotigmine Has a wide range of action because it stimulates not only muscarinic & nicotinic receptors of ANS but also nicotinic receptors at NMJ Therapeutic uses: As eye drops to produce miosis & accommodation for near vision Atony bladder Antidote of anticholinergic drugs toxicity as Atropine

3.Rivastigmine Used in patients with Alzheimer's disease for the loss of cognitive function.

Anticholinesterase with irreversible inhibition Organophospahte anticholinesterases

E.g. Insecticides, War gas, Isoflurophate, Parathion Actions: Generalized cholinergic stimulation (sweating, HR, miosis, salivation, diarrhea, urination, colic, , paralysis of motor function (causing breathing difficulties))

 Atropine in doses can reverse many actions of Insecticides Pralidoxime (PAM) can reactivate the inhibited cholinesterase.

Action of anticholinesterase drugs & PAM

Cholinergic Antagonists
1. 2. 3. 4. 5. 1. Muscarinic antagonists: Atropine Given orally, I.M., S.C. Actions: HR Relaxation of bronchial muscles bronchial secretions Dilatation of the pupil (Mydriasis) with an inability to see near object clearly GIT motility & secretion

 Therapeutic uses

1. Relief intestinal, biliary or renal colic (given I.V. or S.C.) 2. Locally to the eye to dilate the pupil but homatropine is often used 3. Preoperative medication 4. relief bronchial spasm (ipratropium is given by inhalation to treat asthma)

5.Antidote for cholinergic agonists. 6. Treatment of Parkinson's disease. (benztropine)

 S/Es: Dry mouth Constipation Urinary retention With doses: Restlessness, Hallucination

2. Hyoscine (Scopolamine)
Similar to atropine but in smaller doses it causes CNS depression

Uses:
Preoperative medication Antiemetic & prevention of motion sickness

Atropine or similar drugs should not be given to patients with ?

2. Neuromuscular Blockers
Agents that block cholinergic transmission between nicotinic receptors & motor nerve endings on the NMJ

 2 types: Non-Depolarizing (Competitive) Blockers E.g. Tubocurarine MOA: They block nicotinic receptors & prevent Ach from binding Uses: Therapeutically in anesthesia during surgery as adjuvant drugs to relax skeletal muscles

Depolarizing Agents E.g. Succinylcholine (Suxamethonium) Suxamethonium has a rapid onset & short duration of action & mainly used for rapid endotrachial intubation at the beginning of anesthesia

 MOA; The drug attach to the nicotinic receptor & act like Ach to depolarize the junction, but it is not destroyed by cholinesterase, so the continued binding of depolarizing agent renders the receptor incapable of transmitting further impulses, with time membrane repolarizes but receptor is desensitized to effect of Ach

Therapeutic uses 1. Endotracheal intubation. 2. Electroconvulsive therapy (ECT).

S/Es: Apnea in patients who are genetically defect of plasma cholinesterase (because the enzyme metabolize the above drug) duration of drug paralysis of diaphragm