autonomic parasymp print

7/31/2019 Autonomic Parasymp Print

1/28

Parasympathetic nervous system

Dr.asaad

1


2/28


3/28

Classification of neurons (nervecells) by transmitter released

1. Adrenergic: release

1. norepinephrine (NE)

2. epinephrine (EPI)

3. dopamine (DA)

2. Cholinergic: release acetylcholine (ACh)

3. Other (non-adrenergic, non-cholinergic,NANC)

3


4/28

Cholinergic - release acetylcholine

1. pre-ganglionic (SNS and PSNS)

2. post-ganglionic (PSNS)

3. post-ganglionic SNS to sweat glands4. neuromuscular junction (NMJ)

5. CNS (99% muscarinic)

4


5/28

Cholinergic transmission

(terminal of the cholinergic neuron)

5


6/28

Synthesis, Storage, Release, and

Removal of Acetylcholine

Synthesis and storage:

Acetylcholine is synthesized in the cholinergic nerve terminal fromacetyl CoA and choline. The formed acetylcholine is stored intovesicles.

Release:

Conduction of an action potential through the terminal branches ofan axon causes entry of calcium into the nerve terminal resulting inthe release of acetylcholine

molecules outside the nerve terminal.

Interaction with cholinergic receptors:

Once in the junctional extracellular space , acetylcholine interactsreversibly with cholinoreceptors.

6


7/28

Termination of action of acetylcholine:

The length of time that the molecules of acetylcholine interactwith receptors is short because acetylcholinesterase, anenzyme that rapidly hydrolyzes acetylcholine, is highly

concentrated on the outer surfaces of both the prejunctional(neuronal) and postjunctional (effector cell) membranes. Arapid hydrolysis of acetylcholine by the enzyme results in alowering of the concentration of free acetylcholine and a rapiddissociation of receptor-bound acetylcholine from its

receptors.Little or no acetylcholine escapes into the circulation.

Any acetylcholine that reaches the circulation is immediatelyinactivated by plasma esterases.

7


8/28

Cholinergic receptors

8


9/28

Action of acetylcholine at cholinergic receptorsOrgan Receptor Action

Eye

Circular muscle of

the iris

M3 Contracts

Ciliary muscle M3 Contracts

Heart

Sino-atrial node M2 Slows

Myocardium M2 Negative inotropic action (more in

atria) and negative chronotropic action

Blood vessels Endothelium M3 Vasodilatation

Bronchioles M3 Contraction

GIT

Smooth muscle

walls

M3 Contraction

Sphincters M3 Relax

Glands M3 Secretion

Urinary bladderWall M3 Contracts

Sphincter M3 Relax

Pregnant uterus M3 Contracts

Glands M3 Secretion

9


10/28

10


11/28

Parasympathomimetics = Cholinoceptor stimulants:bind to acetylcholine receptors and stimulatesthem.

Parasympatholytics (cholinergic antagonistsanticholinergic drugs): bind to acetylcholinereceptors and reduce the effects of parasympathetic

stimulation by preventing endogenous acetylcholinefrom binding to them.

Modifying Autonomic Nervous System

Function

11


12/28

Parasympathomimetics

(Cholinoceptor stimulants)

Cholinoceptor

stimulants

Direct

Esters of choline

Alkaloids

Indirect Cholinesterase inhibitors

12


13/28

Cholinoceptor stimulants

13


14/28

Direct cholinoceptor stimulants

Alkaloids

Nicotine

Lobeline

Muscarine

Pilocarpine

Esters of choline

Acetylcholine

Methacholine

Bethanechol

Carbachol

14


15/28

NicotineSite of action:

A) nicotinic receptors (small doses stimulate and large doses

inhibit)1- NN at autonomic ganglia and adrenal medulla

2- NM at the motor end plate (Affinity is greater for NNsitesthan NM sites)

B) CNS 15

Acetylcholine (ACh) has no therapeutic

applications because of its diffuse action and its

rapid hydrolysis by both AChE and plasma

butyrylcholinesterase.


16/28

Actions of nicotine

Action at autonomic ganglia (both sympatheticand parasympathetic):

1. Small doses stimulate autonomic ganglia

leading to:

a) sympathetic effect on the cardiovascularsystem with tachycardia and hypertension

b)parasympathetic effect on the GIT - withnausea, vomiting and diarrhoea and urinary

bladder with voiding of urine2. Large doses or prolonged occupancy at

nicotinic receptors inhibit autonomic ganglia

16


17/28

Actions of nicotine

Action at the neuromuscularjunction:

1. Small doses stimulate leading toeither fasciculation or strongmuscle contraction

2. Large doses inhibit leading todepolarization blockade.

17


18/28

Actions of nicotine

Action at the CNS:

Used as an insecticide

18

Small doses (tobacco smoke) Mild alerting action

Larger doses Tremors

Very large doses Convulsions and death


19/28

Indirect cholinoceptor stimulants

(agents that inhibit acetylcholinesterase)

19


20/28

Cholinesterase inhibitors

Types of cholinesterases:

1- Acetylcholinesterase (true cholinesterase): Found at:

I. Cholinergic neurons

II. Cholinergic synapses

III. Neuromuscular junction

IV. Red blood cells

2- Butyrylcholinesterase (pseudocholinesterase):

- Found at:

Plasma and liver

20


21/28

Acetylcholinesterase inhibitors

Three chemical groups:

21

Alcohols Esters Organophosphates

1- Edrophonium 1- Neostigmine

2- Physostigmine

1- Echothiophate

Neostigmine is not absorbed

and does not enter CNS

Physostigmine is absorbed

from all sites including

conjunctiva and enters CNS

All organophosphorous

compounds are well

absorbed from all sites of

administration and enter the

CNS except echothiophate

Reversible inhibition after 2-10 min.

Reversible inhibition after 30min to 6 hours

Irreversible inhibition (can bereversed by pralidoxime)


22/28

Action of acetylcholinesterase

inhibitors:

Inhibit acetylcholinesterase and to a lesser

extent butyrylcholinesterase leading to

increase the concentration of endogenous

acetylcholine at cholinergic receptors

22


23/28

Organ system effects of acetylcholinesterase

inhibitors

CNS Low concentrations cause alertness

High concentrations cause convulsions followed by coma

Eye, GIT,

Bronchioles and

urinary bladder

Similar to acetylcholine (increase the effect of acetylcholine at

muscarinic receptor)

Cardiovascular

system

Effect is due to :

1- Stimulation of sympathetic and parasympathetic autonomic ganglia

2- Stimulation of cholinergic receptors at the heart and blood vessels

Effect on the heart:

Similar to acetylcholine leading to decreased cardiac output

Effect on the blood vessels:

Vasodilatation (less than direct cholinoceptor stimulants) with only

little hypotension

Neuromuscular

junction

Therapeutic doses increases strengh of contraction

Higher concentrations cause muscle fibrillation

Higher concentration cause neuromuscular blockade and paralysis

23


24/28

Therapeutic uses of cholinoceptor

stimulantsDisease Mechanism of action Drug

1- Glaucoma Contraction of the ciliary

muscle and increasing the

outflow of the aqueous

humor

Pilocarpine

Physostigmine

echothiophate

2- Postoperative ileusBethanechol or

neostigmine3- Reflux esophagitis

4- Urinary retention

5- Myasthenia gravis neostigmine,

pyridostigmine, or

ambenonium.

24


25/28

Myasthenia gravis

Definition:

Myasthenia gravis is a disease affecting skeletalmuscle neuromuscular junctions. An autoimmune

process causes production of antibodies thatdecrease the number of functional nicotinicreceptors on the motor end plates.

Frequent findings are ptosis, diplopia, difficulty in

speaking and swallowing, and extremity weakness.Severe disease may affect all the muscles, includingthose necessary for respiration.

25


26/28

Myasthenia gravis

Diagnosis: Edrophonium test:

A dose is injected intravenously. If the patient has myastheniagravis, an improvement in muscle strength that lasts about 5minutes will usually be observed.

Edrophonium is also used to assess the adequacy of treatment with

the longer-acting cholinesterase nhibitors in patients withmyasthenia gravis. If excessive amounts of cholinesterase inhibitorhave been used, patients may become paradoxically weak becauseof nicotinic depolarizing blockade of the motor end plate. Smalldoses of edrophonium (12 mg intravenously) will produce

no relief or even worsen weakness if the patient is receiving

excessive cholinesterase inhibitor therapy. On the other hand, if thepatient improves with edrophonium, an increase in cholinesteraseinhibitor dosage may be indicated.

26


27/28

Myasthenia gravis

Treatment:

Long-term therapy for myasthenia gravis is

usually accomplished with neostigmine,

pyridostigmine, or ambenonium.

If muscarinic effects of such therapy are

prominent, they can be controlled by the

administration of antimuscarinic drugs such as

atropine.

27


28/28

Toxicity of cholinoceptor stimulantsDirect acting muscarinic

stimulants (ex. Pilocarpine)

meiosis, nausea, vomiting, diarrhea, salivation,

sweating, cutaneous vasodilation, and bronchialconstriction. These effects are all blocked by

atropine.

Direct-Acting Nicotinic

Stimulants

Acute toxicity (treatment symptomatic)

(1) central stimulation, which cause convulsions and

may progress to coma and respiratory arrest;

(2) skeletal muscle paralysis

(3) hypertension and cardiac arrhythmias.

Cholinesterase inhibitors Acute toxicity: Treated by atropine and pralidoxime)

1- meiosis, nausea, vomiting, diarrhea, salivation,

sweating, cutaneous vasodilation, and bronchial

constriction2- These manifestations are followed by:

(1) central stimulation, which cause convulsions and

may progress to coma and respiratory arrest;

(2) skeletal muscle paralysis

(3) hypertension and cardiac arrhythmias.

28

autonomic parasymp print

Documents