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

NERVOUS SYSTEM

Nervous System Peripheral Nervous System Central Nervous System ( PNS ) ( CNS ) Efferent (Motor) Afferent (Sensor) Somatic Autonomic ( ANS ) Enteric Parasympathetic Sympathetic

Autonomic nervous system

ANS: Pharmacological Viewpoint

ANS: Pharmacological Viewpoint

The synapse

The synapse

Enteric NS Blood pressure Anesthesia, sedation Asthma Relieve pain and anxiety Cardiac dysfunctions Suppress movement disorders and epileptic seizures Nasal congestions Psychotic disorders Skeletal muscle spasticity Adrenergic Ag/Ant.; Cholinergic Ag/Ant . General/local anesthetics; anxiolytics and sedative- hypnotics; opioid analgesics; antiparkinsonian agents; antiepileptics; antipsychotics; antidepressants

ANS: Pharmacological Viewpoint

Neurons, Synapses and Neurotransmitters ADRENERGIC CHOLINERGIC

Ach synthesis choline choline AcCoA + Na+ ChAT Ach Ach Ca 2 + Fusion Ach Ach Ach Ach acetate + choline Ach Ach Ach Postsynaptic cholinoceptors muscarinic nicotinic

Ach synthesis choline choline AcCoA + Hemicholinium ChAT Ach Vesamicol Ach Ca 2 + Fusion Butulinium toxin Ach AchE inhibitors Ach Ach Ach acetate + choline Ach Cholinergic agonists + Ach Ach Postsynaptic cholinoceptors Cholinergic antagonists

ANS: Parasympathetic Division REST AND DIGEST Acetylcholine (Ach)

ANS: Sympathetic Division midriasis FIGHT OR FLIGHT Norepinephrine / Noradrenaline (NA)

Acetylcholine (Ach) receptors Nicotonic Muscarinic Parasympathetic Rest & Digest N N N M M 1 M 2 M 3 M 4 M 5 N N Neuro –Muscular Junction (NMJ) N M

Ach receptor agonists Direct Indirect Cholinergic agonists AchE inhibitors reversible irreversible muscarinic nicotinic ganglion NMJ Fusion Ach AchE inhibitors Ach Ach Ach acetate + choline Ach Cholinergic agonists + Ach Ach Postsynaptic cholinoceptors

Ach receptor agonists Ach (choline ester) Direct Cholinergic agonists muscarinic nicotinic Agonists Alkaloids Choline esters N+M M N Metacholine Muscarine Nicotine Cabachol Pilocarpine Lobeline Oxotremorine DMPP Betanechol

Ach receptor agonists Indirect AchE inhibitors reversible irreversible long acting (toxic, nerve gas) short acting Carbamates Organophosphates Isoflurophate Physostigmine Echothiopate Neostigmine Parathion Carbaryl Malathion Soman

Ach receptor agonists: clinical uses

Ach receptor agonists: clinical uses Direct Indirect Glaucoma treatment (miosis, outflow) Glaucoma treatment (miosis, outflow) Physostigmine, Isoflurophate, Echothiopate Pilocarpine topical topical Myasthenia Gravis Diagnosis: Edrophonium Treatment: Ambenonium, Neostigmine, Pyridostigmine Initiate microturtion in nonobstructive urinary retention Betanechole Adverse effects: Topical : congestion, eye problems Systemic: nausea, vomiting, abdominal cramps, diarrhea, epigastric distress syncope, bradycardia, hypotension bronchospasm salivation, sweating, flushing tremor, headache

Ach receptor antagonists ( All are competitive ) muscarinic nicotinic Ganglion blocking Neuromuscular blockers M N N N M Sympathetic & Parasympathetic NMJ, somatic Parasympathetic Atropine Scoploamine Benztropine Dicyclomine Glycopyrrolate Propantheline Ipratropium

Ach receptor antagonists: (Parasympathetic) clinical uses Atropine, Reduce secretions before anesthesia (glands, bronchi) Glycopyrrolate Scoploamine Anti motion sickness Atropine Anti Vagal block Propantheline GI spasms Pirenzepine GI secretions (anti peptic ulcer) Ipratropium Bronchodilation and reduction of mucus (asthma, COPD) Benztropine, Parkinson’s and some other extrapyramidal disorders Trihexyphenidyl Atropine Treatment of adverse effects after intoxication from cholinergic agonists or mushroom poisoning

Ach receptor antagonists: (Parasympathetic) 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

Ach receptor antagonists ( all – competitive ) nicotinic Ganglion blocking Neuromuscular blockers N N N M Sympathetic & Parasympathetic NMJ, somatic

Ach receptor antagonists Ganglion blocking – Nn blocking Trimethaphan , Mecamylamine Na + Action Potential Effect : mostly sympathetic – hypotension ( surgery ) Competitive antagonism (Block is reversible by AchE inhibitors)

Ach receptor antagonists Neuromuscular blockers- NMJ, Nm N-M blockers Competative Noncompetative nondepolarizing depolarizing

Ach receptor antagonists Neuromuscular blockers - NMJ, Nm Competitive nondepolarizing blocker = Competitive antagonist antagonist Na 2+ Action potential Muscle Constriction

Ach receptor antagonists Neuromuscular blockers - NMJ, Nm Competitive Nondepolarizing blockers • quaternary amines • Large bulky molecules pancuronium • Block is Reversible by AchE inhibitors

Ach receptor antagonists Neuromuscular blockers- NMJ, Nm Competitive Nondepolarizing blockers Natural alkaloids: Tubocurarine , metocurine Not in use – side effects (histamine release - hypotension, bronchoconstriction) Synthetic isoquinolines: Atracurium , doxacurium, tubocurarine mivacurium In use (skeletal muscle relaxation during surgery) Synthetic steroid derivatives: Pancuronium (blocks also M receptors), verocuronium, pipercuronium 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 Very potent agonist Prolonged depolarization Contraction (phase 1) Na 2+ Not reversible by AchE inhibitors Action potential Desensitization (block) (phase 2) Muscle Constriction (1) Reversible by AchE inhibitors Muscle Constriction (2)

Ach receptor antagonists Neuromuscular blockers- NMJ, Nm Noncompetitive Depolarizing blockers • Slim aliphatic molecule 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 - Painful muscle fasciculation histamine release - hypotension, bronchoconstriction Increased intraocular and Pancuronium - blocks also M – intragastric pressure. tachycardia, hypertension Succinylcholine – also M and Nn agonist : M- bradycardia, vagal block, increased secretions.