Nervous System. Peripheral Nervous System ( PNS ) Central Nervous System ( CNS ) Somatic. Autonomic ( ANS ) Enteric.

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1 NERVOUS SYSTEM

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

3 Autonomic nervous system

4 ANS: Pharmacological Viewpoint

5 ANS: Pharmacological Viewpoint

6 The synapse

7 The synapse

8 Enteric NS 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 sedativehypnotics; opioid analgesics; antiparkinsonian agents; antiepileptics; antipsychotics; antidepressants

9 ANS: Pharmacological Viewpoint

10 Neurons, Synapses and Neurotransmitters CHOLINERGIC ADRENERGIC

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

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

13 ANS: Parasympathetic Division REST AND DIGEST Acetylcholine ()

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

15 Acetylcholine () receptors Nicotonic Muscarinic NN NM M1 M2 M3 M4 M5 Parasympathetic Rest & Digest NN NM Neuro Muscular Junction (NMJ)

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

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

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

19 receptor agonists: clinical uses

20 receptor agonists: clinical uses Direct Indirect Glaucoma treatment (miosis, outflow) Pilocarpine topical Initiate microturtion in nonobstructive urinary retention Betanechole 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

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

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

23 receptor (Parasympathetic) clinical uses antagonists: Adverse effects: Topical : Increased intraocular pressure Systemic: Nausea, vomiting, constipation Dry mouth Urinary retention Tachycardia, palpitations Mydriasis, blurred vision Fever Nervousness, drowsiness, dizziness, headache

24 receptor antagonists ( all nicotinic competitive ) Ganglion blocking NN Sympathetic & Parasympathetic Neuromuscular blockers NM NMJ, somatic

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

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

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

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

29 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, mivacurium In use (skeletal muscle relaxation during surgery) tubocurarine Synthetic steroid derivatives: Pancuronium (blocks also M receptors), verocuronium, pipercuronium In use (skeletal muscle relaxation during surgery)

30 receptor antagonists Neuromuscular blockers- NMJ, Nm Noncompetitive Depolarizing blockers Noncompetitive Depolarizing blocker = Agonist more resistant to E Very potent agonist Prolonged depolarization Na 2+ Action potential Muscle Constriction (1) Contraction (phase 1) Not reversible by E inhibitors Desensitization (block) (phase 2) Reversible by E inhibitors Muscle Constriction (2)

31 receptor antagonists Neuromuscular blockers- NMJ, Nm Noncompetitive Depolarizing blockers Slim aliphatic molecule Succinylchoiline (short t 1/2) (also M agonist), Gallamine

32 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!

33 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.

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