NERVOUS SYSTEM - Hadassah · Nervous System Central Nervous System ( CNS ) Peripheral Nervous...

NERVOUS SYSTEM

Nervous System

Central Nervous System( CNS )

Peripheral Nervous System( PNS )

Afferent (Sensor)Efferent (Motor)

Autonomic ( ANS )

Somatic

SympatheticParasympathetic Enteric

Autonomic nervous system

ANS: Pharmacological Viewpoint

ANS: Pharmacological Viewpoint

The synapse

The synapse

Blood pressure

Asthma

Cardiac dysfunctions

Nasal congestions

Skeletal muscle spasticity

Adrenergic Ag/Ant.; Cholinergic Ag/Ant.

Anesthesia, sedation

Relieve pain and anxiety

Suppress movement disorders and epileptic seizures

Psychotic disorders

General/local anesthetics; anxiolytics and sedative-hypnotics; opioid analgesics; antiparkinsonian agents; antiepileptics; antipsychotics; antidepressants

Enteric NS

ANS: Pharmacological Viewpoint

ADRENERGICCHOLINERGIC

Neurons, Synapses and Neurotransmitters

choline

cholineAcCoA +

ChAT

Ach

Ach

Ca 2+

Fusion

AchAch

AchAch

Ach Ach

Ach acetate + choline

Postsynaptic cholinoceptors

Ach synthesis

muscarinic nicotinic

Na+

choline

cholineAcCoA +

ChAT

Ach

Ach

Ca 2+

Fusion

AchAch

AchAch

Ach Ach

Ach acetate + choline

Postsynaptic cholinoceptors

Ach synthesis

Hemicholinium

Vesamicol

Butulinium toxin

AchE inhibitors

+ Cholinergic agonists

Cholinergic antagonists

ANS: Parasympathetic Division

Acetylcholine

(Ach)

REST AND DIGEST

ANS: Sympathetic Division

Norepinephrine / Noradrenaline

(NA)

FIGHT OR FLIGHTmidriasis

Neuro –Muscular Junction (NMJ)

Acetylcholine (Ach) receptors

Nicotonic Muscarinic

NN NM M1 M2 M3 M4 M5

NM

NN

ParasympatheticRest & Digest

Fusion

AchAch

AchAch

Ach Ach

Ach acetate + choline

Postsynaptic cholinoceptors

AchE inhibitors

+ Cholinergic agonists

Ach receptor agonists

Direct Indirect

AchE inhibitorsCholinergic agonists

reversible irreversiblemuscarinic nicotinic

ganglion NMJ

Ach receptor agonists

Direct

Cholinergic agonists

muscarinic nicotinic

Ach (choline ester)

Agonists

Choline esters Alkaloids

M N

MuscarinePilocarpine

OxotremorineBetanechol

NicotineLobeline

DMPP

N+M

MetacholineCabachol

Ach receptor agonists

Indirect

AchE inhibitors

reversible irreversible

short acting

Carbamates

PhysostigmineNeostigmine

Carbaryl

long acting (toxic, nerve gas)

Organophosphates

IsoflurophateEchothiopate

ParathionMalathion

Soman

Ach receptor agonists: clinical uses

Ach receptor agonists: clinical uses

Direct Indirect

Initiate microturtion in nonobstructiveurinary retention

Betanechole

Glaucoma treatment (miosis, outflow)Pilocarpinetopical

Glaucoma treatment (miosis, outflow)Physostigmine, Isoflurophate, Echothiopatetopical

Myasthenia Gravis Diagnosis: EdrophoniumTreatment: Ambenonium, Neostigmine, Pyridostigmine

Adverse effects:Topical : congestion, eye problems

Systemic: nausea, vomiting, abdominal cramps, diarr hea, epigastric distresssyncope, bradycardia, hypotensionbronchospasmsalivation, sweating, flushingtremor, headache

( All are competitive )Ach receptor antagonists

muscarinic nicotinic

Ganglion blocking Neuromuscular blockers

NM NMJ, somatic

NNSympathetic & Parasympathetic

M

Parasympathetic

AtropineScoploamineBenztropineDicyclomineGlycopyrrolatePropanthelineIpratropium

antagonists: (Parasympathetic)Ach receptor clinical uses

Reduce secretions before anesthesia (glands, bronch i) Atropine, Glycopyrrolate

Anti motion sickness Scoploamine

Anti Vagal block Atropine

GI spasms Propantheline

GI secretions (anti peptic ulcer) Pirenzepine

Bronchodilation and reduction of mucus (asthma, COPD ) Ipratropium

Parkinson’s and some other extrapyramidal disorders Benztropine, Trihexyphenidyl

Treatment of adverse effects after intoxication fro m Atropinecholinergic agonists or mushroom poisoning

antagonists: (Parasympathetic)Ach receptor clinical uses

Adverse effects:

Topical : Increased intraocular pressure

Systemic: Nausea, vomiting, constipationDry mouthUrinary retentionTachycardia, palpitationsMydriasis, blurred visionFeverNervousness, drowsiness, dizziness, headache

nicotinic

Ganglion blocking Neuromuscular blockersNM

NMJ, somaticNN

Sympathetic & Parasympathetic

competitive )–( all Ach receptor antagonists

Ach receptor antagonistsGanglion blocking – Nn blocking

Na+

Action Potential

Trimethaphan , Mecamylamine

Effect : mostly sympathetic – hypotension ( surgery )

Competitive antagonism (Block is reversible by AchE inhibitors)

Ach receptor antagonists

Neuromuscular blockers- NMJ, Nm

N-M blockers

Competativenondepolarizing

Noncompetativedepolarizing

Competitive nondepolarizing blocker = Competitive an tagonist

antagonist

Ach receptor antagonists

NMJ, Nm-Neuromuscular blockers

Na 2+

Action potential

Muscle Constriction

Competitive Nondepolarizing blockers

• quaternary amines

• Large bulky molecules

• Block is Reversible by AchE inhibitors

pancuronium

Ach receptor antagonists

NMJ, Nm-Neuromuscular blockers

Natural alkaloids: Tubocurarine, metocurineNot in use – side effects (histamine release - hypotension, bronchoconstriction)

Synthetic steroid derivatives: Pancuronium (blocks also M receptors), verocuronium, pipercuroniumIn use (skeletal muscle relaxation during surgery)

Competitive Nondepolarizing blockers

Ach receptor antagonistsNeuromuscular blockers- NMJ, Nm

tubocurarineSynthetic isoquinolines: Atracurium, doxacurium, mivacuriumIn use (skeletal muscle relaxation during surgery)

Ach receptor antagonistsNeuromuscular blockers- NMJ, Nm

Noncompetitive Depolarizing blockers

Noncompetitive Depolarizing blocker = Agonist more resistant to AchE

Prolonged depolarization

Contraction (phase 1)

Desensitization (block) (phase 2)Reversible by AchE inhibitors

Not reversible by AchE inhibitors

Very potent agonist

Na 2+

Action potential

Muscle Constriction (2)

Muscle Constriction (1)

• Slim aliphatic molecule

Ach receptor antagonistsNeuromuscular blockers- NMJ, Nm

Noncompetitive Depolarizing blockers

Succinylchoiline (short t 1/2) (also M agonist) , Gallamine

Ach receptor antagonistsNeuromuscular blockers- NMJ, Nm

Uses

Skeletal Muscle Relaxation for :

1. Intubation

2. skeletal muscle relaxation during surgery

3. Shock therapy trauma limitation

4. Orthopedic surgeries

No analgesic and sedative properties !!Used in combination with anesthetica!

Ach receptor antagonistsNeuromuscular blockers- NMJ, Nm

Adverse effects

Competitive nondepolarizing Noncompetitive depolariz ing

Respiratory Paralysis

Tubocurarine - histamine release -hypotension, bronchoconstriction

Pancuronium - blocks also M –tachycardia, hypertension

Painful muscle fasciculation

Increased intraocular and intragastric pressure.

Succinylcholine – also M and Nnagonist :M- bradycardia, vagal block, increased secretions.