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.