NERVOUS SYSTEM Nervous System Peripheral Nervous System Central - - PowerPoint PPT Presentation

NERVOUS SYSTEM

Nervous System

Central Nervous System ( CNS ) Peripheral Nervous System ( PNS )

Afferent (Sensor) Efferent (Motor)

Autonomic ( ANS ) Somatic Sympathetic Parasympathetic 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

ADRENERGIC CHOLINERGIC

Neurons, Synapses and Neurotransmitters

choline

choline AcCoA + ChAT Ach Ach

Ca 2+ Fusion Ach Ach Ach Ach Ach Ach Ach acetate + choline

Postsynaptic cholinoceptors

Ach synthesis

muscarinic nicotinic

Na+

choline

choline AcCoA + ChAT Ach Ach

Ca 2+ Fusion Ach Ach Ach Ach 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 FLIGHT

midriasis

Neuro –Muscular Junction (NMJ)

Acetylcholine (Ach) receptors

Nicotonic Muscarinic NN NM M1 M2 M3 M4 M5

NM NN

Parasympathetic

Rest & Digest

Fusion Ach Ach Ach Ach Ach Ach Ach acetate + choline

Postsynaptic cholinoceptors AchE inhibitors

+

Cholinergic agonists

Ach receptor agonists

Direct Indirect

AchE inhibitors Cholinergic agonists reversible irreversible muscarinic nicotinic

ganglion NMJ

Ach receptor agonists

Direct Cholinergic agonists muscarinic nicotinic

Ach (choline ester)

Agonists

Choline esters Alkaloids M N Muscarine Pilocarpine Oxotremorine Betanechol Nicotine Lobeline DMPP N+M Metacholine Cabachol

Ach receptor agonists

Indirect AchE inhibitors reversible irreversible

short acting

Carbamates Physostigmine Neostigmine Carbaryl

long acting (toxic, nerve gas)

Organophosphates Isoflurophate Echothiopate Parathion Malathion Soman

Ach receptor agonists: clinical uses

Ach receptor agonists: clinical uses

Direct Indirect

Initiate microturtion in nonobstructive urinary retention Betanechole Glaucoma treatment (miosis, outflow) Pilocarpine topical Glaucoma treatment (miosis, outflow) Physostigmine, Isoflurophate, Echothiopate topical Myasthenia Gravis Diagnosis: Edrophonium Treatment: Ambenonium, Neostigmine, Pyridostigmine

Adverse effects: Topical : congestion, eye problems Systemic: nausea, vomiting, abdominal cramps, diarrhea, epigastric distress syncope, bradycardia, hypotension bronchospasm salivation, sweating, flushing tremor, headache

( All are competitive )

Ach receptor antagonists

muscarinic nicotinic

Ganglion blocking Neuromuscular blockers

NM NMJ, somatic NN

Sympathetic & Parasympathetic

M Parasympathetic

Atropine Scoploamine Benztropine Dicyclomine Glycopyrrolate Propantheline Ipratropium

antagonists:

(Parasympathetic)

Ach receptor clinical uses

Reduce secretions before anesthesia (glands, bronchi) 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 from Atropine cholinergic agonists or mushroom poisoning

antagonists:

(Parasympathetic)

Ach receptor clinical uses Adverse effects: Topical : Increased intraocular pressure Systemic: Nausea, vomiting, constipation

Dry mouth Urinary retention Tachycardia, palpitations Mydriasis, blurred vision Fever Nervousness, drowsiness, dizziness, headache

nicotinic

Ganglion blocking Neuromuscular blockers

NM NMJ, somatic NN

Sympathetic & Parasympathetic

competitive ) – ( all

Ach receptor antagonists

Ach receptor antagonists

Ganglion 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 Competative nondepolarizing Noncompetative depolarizing

Competitive nondepolarizing blocker = Competitive antagonist

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, metocurine

Not in use – side effects (histamine release - hypotension, bronchoconstriction)

Synthetic steroid derivatives: Pancuronium (blocks also M receptors), verocuronium, pipercuronium

In use (skeletal muscle relaxation during surgery)

Competitive Nondepolarizing blockers

Ach receptor antagonists

Neuromuscular blockers- NMJ, Nm

tubocurarine

Synthetic isoquinolines: Atracurium, doxacurium, mivacurium

In use (skeletal muscle relaxation during surgery)

Ach receptor antagonists

Neuromuscular 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 antagonists

Neuromuscular blockers- NMJ, Nm Noncompetitive Depolarizing blockers Succinylchoiline (short t 1/2) (also M agonist) , Gallamine

Ach receptor antagonists

Neuromuscular 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 antagonists

Neuromuscular blockers- NMJ, Nm Adverse effects

Competitive nondepolarizing Noncompetitive depolarizing

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 Nn agonist : M- bradycardia, vagal block, increased secretions.