NERVOUS SYSTEM
Nervous System Peripheral Nervous System ( PNS ) Central Nervous System ( CNS ) Efferent (Motor) Afferent (Sensor) Autonomic ( ANS ) Somatic Parasympathetic Sympathetic Enteric
Autonomic nervous system
ANS: Pharmacological Viewpoint
ANS: Pharmacological Viewpoint
The synapse
The synapse
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
ANS: Pharmacological Viewpoint
Neurons, Synapses and Neurotransmitters CHOLINERGIC ADRENERGIC
synthesis choline AcCoA + choline ChAT Na+ Fusion Ca 2+ acetate + choline Postsynaptic cholinoceptors muscarinic nicotinic
synthesis choline AcCoA + choline ChAT Vesamicol Hemicholinium Fusion Ca 2+ Butulinium toxin E inhibitors acetate + choline + Cholinergic agonists Postsynaptic cholinoceptors Cholinergic antagonists
ANS: Parasympathetic Division REST AND DIGEST Acetylcholine ()
ANS: Sympathetic Division midriasis FIGHT OR FLIGHT Norepinephrine / Noradrenaline (NA)
Acetylcholine () receptors Nicotonic Muscarinic NN NM M1 M2 M3 M4 M5 Parasympathetic Rest & Digest NN NM Neuro Muscular Junction (NMJ)
receptor agonists Direct Cholinergic agonists Indirect E inhibitors muscarinic nicotinic reversible irreversible ganglion NMJ Fusion E inhibitors acetate + choline + Cholinergic agonists Postsynaptic cholinoceptors
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
receptor agonists Indirect E inhibitors reversible irreversible short acting long acting (toxic, nerve gas) Carbamates Physostigmine Neostigmine Carbaryl Organophosphates Isoflurophate Echothiopate Parathion Malathion Soman
receptor agonists: clinical uses
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
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
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
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
receptor antagonists ( all nicotinic competitive ) Ganglion blocking NN Sympathetic & Parasympathetic Neuromuscular blockers NM NMJ, somatic
receptor antagonists Ganglion blocking Nn blocking Trimethaphan, Mecamylamine Na + Action Potential Effect : mostly sympathetic hypotension ( surgery ) Competitive antagonism (Block is reversible by E inhibitors)
receptor antagonists Neuromuscular blockers- NMJ, Nm N-M blockers Competative nondepolarizing Noncompetative depolarizing
receptor antagonists Neuromuscular blockers- NMJ, Nm Competitive nondepolarizing blocker = Competitive antagonist antagonist Na 2+ Action potential Muscle Constriction
quaternary amines receptor antagonists Neuromuscular blockers- NMJ, Nm Competitive Nondepolarizing blockers Large bulky molecules pancuronium Block is Reversible by E inhibitors
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)
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)
receptor antagonists Neuromuscular blockers- NMJ, Nm Noncompetitive Depolarizing blockers Slim aliphatic molecule Succinylchoiline (short t 1/2) (also M agonist), Gallamine
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!
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.