DRUGS ACTING ON

AUTONOMIC NERVOUS SYSTEM

INTRODUCTION:-NERVOUS SYSTEM

CENTRAL NERVOUS SYSTEM (C.N.S)

PERIPHERAL NERVOUS SYSTEM

CENTRAL NERVOUS SYSTEM(C.N.S)

PERIPHERAL NERVOUS SYSTEM

AUTONOMIC NERVOUS

SYSTEM(A.N.S)

SOMATIC NURVOUS

SYSTEM

SYMPATHETIC PARASYMPATHETIC

PARASYMPATHETIC NERVOUS SYSTEM

It is also called as cholinergic system because the neurotransmitter is acetyl choline(ACH)

NEUROTRANSMITTER : (ACH)

It is also called as REST and DIGEST system

Effect : 1. Increasing secretion

2. Contraction of smooth muscleACH

ach

SYNOPSEGANGLIA POSTGANGLIONIC NERVE

ORGANPREGANGLIONIC NERVE

SYMPATHETIC NERVOUS SYSTEM

It is also called as adrenergic system because the neurotransmitter is adrenaline or noradrenaline

NEUROTRANSMITTER : (Adrenaline)

It is also called as FIGHT or FLIGHT system

Effect :1. Decreasing secretion.

2. Relaxation of smooth muscleACH

adrenaline

SYNOPSE PREGANGLIONIC NERVE POSTGANGLIONIC NERVEGANGLIA ORGAN

SYMPATHETIC RECEPTORS CLASSIFICATION

RECEPTORS

1 2

1 2 3

LOCATION OF RECEPTORS(SYMPATHETIC)

1:- These are present in smooth muscle,blood vessels,GI,Uterus,radius muscle of Eye, salivary glands and liver.

2:-These are present in pancreatic islets, nerve terminals (inhibitory type).

1:- These are located at only Heart(Cardiac muscle).

2:-These are present in Blood vessel ,GI,Urinary tract,iris,bronchi smooth muscle,liver.

3:-These are present in Adipose tissue.

PARASYMPATHETIC RECEPTORS CLASSIFICATION

Receptors

Nicotinic(N)

NN NM

Muscarinic(M)

M1 M2 M3

LOCATION OF RECEPTORS(PARASYMPATHETIC)

NN:- These are present in Ganglia,skeletal muscle.

NM:-These are present in Neuromuscular Junction(NMJ).

M1:-These are present in Nerve terminals, gastric glands.

M2:- These are present in smooth muscle,cholinergic nerve endings.

M3:- These are present in smooth muscle ,secretary glands.

Effects of stimulation of the parasympathetic division (rest and digest)

•Eye: miosis(contraction of circular muscles).

•Heart: decrease in heart rate and contractility. •Lung: constriction of bronchioles . •GIT: increase in tone and motility. •Salivary gland: copious and watery secretion.

•Bladder: contraction of detrusorand relaxation of trigoneand sphincter.

Effects of stimulation of the sympathetic division (fight or flight) •Eye: mydriasis(contraction of radial muscles) .

•Heart: increase in heart rate and contractility .

•Blood vessels to skin & mucous membranes: constriction.

•Blood vessels to skeletal muscles: dilatation

•Lung: dilatation of bronchioles .

•GIT: decrease in tone and motility.

•Salivary gland: thick viscous secretion.

•Bladder: relaxation of detrusorand contraction of trigoneand sphincter.

•Uterus(females): relaxation.

Differences :-Content Para-Sympathetic Sympathetic

Blood pressure Hypotension Hypertension

GIT Increase in muscle motility & tone

Decrease in muscle motility & tone

Urinary Bladder Contraction of detrusormuscles & Relaxation of sphincter

Relaxation of detrusormuscles & Contraction of sphincter

Females (Uterus) VariableRelaxation

Eye Miosis Mydriasis

Respiratory Constriction Dialation

Glands secretion Increase Decrease

Neurotransmission at cholinergic neurons(acetylcholine synthesis)

ACETYLCHOLINE

cholinestaraseCholine Acetate

Steps :

1.Synthesis of Ach

2.Storage of AChin vesicles

3.Release of ACh

4.Binding to the receptor

5.Degradation of ACh

6.Recycling of choline

DEFINATIONS : Agonist :-these have high affinity and intrinsic

activity and produce maximum biological response .

Antagonist:- These have affinity similar to agonist but no intrinsic activity thereby no biological response.

Parasympathomimetics(Cholinomimetics):-are drugs that stimulate postsynaptic muscarinic receptors. Their actions resemble acetylcholine and they are also referred to as cholinergic or parasympathetic agonists.

Parasympatholytic(cholinolytics):- are drugs that oppose the actions of the PNS at the muscarinic receptors by blocking the actions of acetylcholine. They are also referred to as anticholinergics or parasympathetic antagonists.

Parasympathomimetic:1.Cholinerigc Agonist

2.Parasympatho Agonist

3.Cholinomimetics

4.Muscarinic drugs

5.Nicotinic drugs

Parasympatholytics:

1.Cholinerigc Antagonist2.Parasympatho Antagonist3.Cholinolytics4.Anticholinerigc5. Cholinerigc blockers

PARASYMPATHETIC DRUGS CLASSIFICATION(cholinergic)

Drug type Examples

1 . Esters of choline AcetylcholineMethacholineCarbacholBethanechol

2 . Natural alkaloids PilocarpineMuscarineArecholine

3 . Synthetic alkaloids Areclidine

4 . Anticholinesterases

a . Reversible PhysostigmineNeostigminePyridostigmineEdrophonium

b . Irreversible ParathionDiazinonDyflosCarbaryl

I. ESTERS OF CHOLINE(ACETYLCHOLINE)

Acetyl choline acts on both types of receptors(N&M).

PHARMACOLOGICAL ACTION :

Heart: Decrease in heart rate and cardiac output (the vagausregulates the heart by the release of AChat the SA nod.

Blood Pressure: Decrease in blood pressure due to NO-mediated vasodilatation.

Gastrointestinal tract: Increase tone, motility and secretions. Salivary glands: Increase secretions. Lung: Bronchoconstrictionand increased bronchiolar secretions. Bladder: Increase in the tone of detrusormuscle & relaxation of

sphincter causing expulsion of urine. Eye: Enhancement of lacrimation, stimulation of the constrictor

pupillaemuscle causing miosisand constriction of the ciliarymuscle(accommodation for near vision), open canal of Schlem,(miosis).

CNS: AChmodulates sleep, wakefulness, learning, and memory.

Advers effects : It causes bradycardia, hypotension, flushing.

It causes dyspnoea by constrictine the branchioles.

It also causes diaphoresis

Therapeutic uses : Acetylcholine is not used for any therapeutic effect.

It is used only for experimental purposes.

II.NATURAL ALKALOIDS

Pilocarpine : It is an alkaloid obtained from south American shrubs,pilocarpus microphyllus and pilocarpusjaborandi.•On the eye it produces miosis.•It is mainly used for the treatment of Glaucoma.•It is available as eye drops and eye ointments.

III.ANTICHOLINESTERASE DRUGS It is also called as cholinesterase inhibitors.

REVERSIBLE : Eg:- Physostigimine

These have a structurally similar to Ach .

So they combined with both anionic and esteratic site of Acetyl cholinie esterase so this enzyme is temporarly inhibited.

PHARMACOLOGYCAL ACTIONS:

Eye: on the eye the anticholinesterase agents produce miosis .

GI: They produce increase in motility and also secretion of GI.

Skeletal muscle: These drugs produce stimulation followed by depression.

Secretions: Bronchioles, lacrimal, salivary, gastric and pancreatic secretions are increased.

Smooth muscles: Bronchioles and ureters are contracted.

THERAPEUTIC USES

The reversible anticholinesterases are used.

For reducing introcular tension in glaucoma.

For the diagnosis and treatment of myasthenia gravis.

For the treatment of curare and atropine poisoning.

For the treatment of post-operative paralytic ileus.

For the treatment of paroxysmal atrial and supraventricular tahycardia.

IRRIVERSIBLE :

ORGANOPHOSPHORUS COMPOUNDS

The irreversible anticholinesterases combined only with estric site they produce phosphorylation of the estratic site.

This produces an irreverisible inhibition of acetylcholineestarase.

These compounds are organic esters of phoshoric acid.

They are highly lipid soluble .So they can be absorbed through all routes including the skin and lungs.

The pharmacological actions of these compounds result due to inhibition of cholinesterase.

These compounds have prolonged action and high toxicity, so they have limited therapeutic use.

Poisoning with ORGANOPHOSPHORUS COMPOUNDS

Organophosphorus compound like parathion and malathion are used as insecticides. So poisoining with these compounds is quite common.

The symptoms of poisoning are:

Increase secretions like sweat, saliva and bronchial secretions.

Gastrointestinal symptoms like anorexia, nausea, vomiting, abdominal cramps and diarrhoea.

Pupillary effects like miosis and spasm of accommodation.

Respiratory symptoms like bronchospasm, cough and tightness of the chest.

Central effects like giddiness, anxiety, confusion, convulsions and coma.

TREAMENT OF POISONING

Poisoining with organophosphorus compounds can be treated by the administration of atropine and cholinesterase reactivators.

Cholinesterase reactivators (OXIMES):

Pyridine _2_aldoxime methiodide(p_2AM). Diacetylmonoxime(DAM). Obidixime chloride.

Action:

They act by dephosporylating of phosphorylatedcholineserase.

PARASYMPATHETIC DRUGS CLASSIFICATION(anticholinergic)

Drug type Example

1 . Belladonna alkaloids AtropineScopalamine(hyosine)

2 . Semisynthetic substitutes of belladonna alkaloids

HomatropineAtropine methylnitrateScopalamine methylbromideHomatropine methylbromide

3 . Synthetic substitutes of belladonna alkaloids

MethanthlinePropanthelinecyclopentolateTropicamide

GANGLIONIC STIMULATING DRUGSDrug type Example

1 . Natural alkaloids Nicotinelobeline

2 . Synthetic compound Tetramethylammonium(TMA)Dimethylphenylpiperazinium(DMPP)

GANGLIONIC BLOCKING AGENTDrug type Example

1 . Quaternary amines TetraethylammoniumPentamethoniumHexamethoniumChlorisondamine

2 . Secondary amines mecamylamine

3 . Tertiary amine TrimethaphanPempidine

NEUROMUSCULAR BLOCKING AGENTDrug type Example

A . Nondepolarizing (competitive) blockers

1 . Long acting d-tubocurarinePancuroniumPipecuroniumDoxacurium

2 . Intermediate acting Vecur oniumAtracuriumRocuronium

3 . Short acting Mivacurium

B . Depolarising blockers SuccinylcholineDecamethonium

PRESENTATION BY:

V. MAHESH