1 / 49

Drugs affecting the parasympathetic and somatic nervous system

Drugs affecting the parasympathetic and somatic nervous system. Nervous System. CNS. PNS. Brain Spinal Cord. Autonomic NS. Somatic NS. Sympathetic. Parasympathetic. Drugs and Cholinergic Synapses. PRESYNAPTIC. POSTSYNAPTIC. Choline uptake and Ach synthesis. Metabolic Removal.

hallam
Télécharger la présentation

Drugs affecting the parasympathetic and somatic nervous system

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs affecting the parasympathetic and somatic nervous system

  2. Nervous System CNS PNS Brain Spinal Cord Autonomic NS Somatic NS Sympathetic Parasympathetic

  3. Drugs and Cholinergic Synapses

  4. PRESYNAPTIC POSTSYNAPTIC Choline uptake and Ach synthesis Metabolic Removal Choline AChE S & S ACh Action ACh M / N Receptor Binding

  5. PRESYNAPTIC POSTSYNAPTIC Choline uptake and Ach synthesis Metabolic Removal Choline AChE S & S ACh Action ACh M / N Receptor Binding

  6. PRESYNAPTIC POSTSYNAPTIC Choline uptake and Ach synthesis Metabolic Removal Choline AChE S & S ACh Action ACh M / N Receptor Binding

  7. PRESYNAPTIC POSTSYNAPTIC Choline uptake and Ach synthesis Metabolic Removal Choline AChE S & S ACh Action ACh M / N Receptor Binding

  8. PRESYNAPTIC POSTSYNAPTIC Choline uptake and Ach synthesis Metabolic Removal Choline AChE S & S ACh Action ACh M / N Receptor Binding

  9. Cholinomimetic Drugs Direct Acting Indirect Acting Receptor Agonists Cholinesterase Inhibitors ●choline esters ● carbamates ●organophosphates ● alkaloids

  10. ACh nicotinic muscarinic (N) (M) Cholinergic Receptors

  11. MUSCARINIC RECEPTOR SUBTYPES • M1: NEURONAL CNS AND ANS PRESYNAPTIC • M2: CARDIAC • M3: SMOOTH MUSCLE AND GLANDULAR • M3: VASCULAR ENDOTHELIUM • (NON-INNERVATED)

  12. CNS Muscarinic Agonists/Antagonists C ACh M N ACh T ACh 1 NE N L NE ACh 1 N SG M ACh 2 S ACh SM N

  13. Nicotinic Agonists/ Antagonists CNS C ACh M N ACh T ACh 1 NE N L NE ACh 1 N SG M ACh 2 S ACh SM N

  14. EFFECTS OF STIMULATING MUSCARINIC RECEPTORS (SLUDE) SITEEFFECT HEART BRADYCARDIA VASCULATURE VASODILATION BRONCHOSPASM AIRWAYS IRIS MIOSIS BLADDER INCREASED URINATION GI TRACT INCREASED GI MOTILITY INCREASED SALIVATION SALIVARY GLANDS INCREASED TEARS LACRIMAL GLANDS SWEAT GLANDS INCREASED SWEATNG

  15. MUSCARINIC AGONISTS ACh - no clinical use • Choline Esters bethanechol– muscarinic agonist • effects mostly on GI and urinary system when administered p.o. or s.c. • used to prevent urinary retention •adverse effects – overstimulation of muscarinic receptors • carbachol – muscarinic and nicotinic agonist • used to produce miosis during ocular surgery

  16. MUSCARINIC AGONISTS: Alkaloids pilocarpine – muscarinic agonist • •No nicotinic effects •Used topically to treat glaucoma • Orally for the treatment of xerostomia • •Somewhat selective for salivary glands • Used for Sjorgren’s Syndrome Adverse Effects: ‘over stimulation’ of muscarinic receptors

  17. Glaucoma Closed (or narrow)-angle glaucoma: The drainage angle of the eye becomes physically blocked by a narrow angle, preventing drainage of aqueous humour slowly or suddenly. Chronic open-angle glaucoma (most common): The drainage angle of the eye becomes less efficient with time causing inefficient drainage of aqueous humour and increased pressure within the eye. Gradually produces optic nerve damage.

  18. Management of Glaucoma: Lower intraocular pressure Treatment – Increase outflow of aqueous humour • mitotic agents (parasympathomimetics; e.g. pilocarpine) • Cholinesterase Inhibitors (physostigmine) • Other: prostaglandin analogs (latanoprost), alpha-2 agonists (brimonidine) Treatment – Decrease ciliary body production of aqueous humour • Carbonic anydrase inhibitors; e.g. acetazolamide) • Topical beta-blockers (timolol, levobunolol)

  19. Antimuscarinic Drugs ●atropine Natural Alkaloids ● scopolamine ● ipratropium (quaternary) Semi-synthetic Derivatives ● tiotropium (quaternary; 24h duration) ●glycopyrrolate ●oxybutynin

  20. CNS Muscarinic Antagonists ACh C X N ACh M T ACh 1 NE N L NE ACh 1 N X SG ACh M 2 S ACh SM N

  21. ANTIMUSCARINIC AGENTS • • ATROPINE BELLADONNA ALKALOIDS • • SCOPOLAMINE TX: USED WHEN A REDUCTION OF PARASYMATHETIC TONE IS DESIRABLE • • Preop to reduce salivations / bronchial secretions • • Reduce intestinal motility • • Prevent vagal stimulation during anesthesia and surgery • Treat overactive bladder • Ophthalmological examinations • Prevent motion sickness • • Treat asthma • • Treat AChE inhibitor poisoning

  22. ATROPINE: OVERVIEW OF TOXIC ACTIONS  DRY AS A BONE  HOT AS A PISTOL  REDAS A BEET  BLIND AS A BAT  MAD AS A HATTER

  23. ATROPINE: OVERVIEW OF ACTIONS • 0.5 mg: Paradoxical bradycardia; Some dryness of mouth; Inhibition of sweating • 1.0 mg: Increased xerostomia; Thirst; Mild tachycardia; Mild mydriasis • 2.0 mg: Marked tachycardia; Xerostomia; Pupilary dilation; Some blurring of vision and decrease in gastric acid secretion

  24. ATROPINE: OVERVIEW OF ACTIONS • 5.0 mg: Difficulty in speaking, swallowing and urination; Decreased intestinal motility; Restlessness; Headache; Dry hot skin • 10 mg & UP: Rapid and weak pulse; Fixed, maximally dilated pupils; Blurred vision; Ataxia; Excitement; Hallucinations and delirium; Coma.

  25. ATROPINE OVERDOSE: ANTIDOTE - Physostigmine Choline AChE ACh S & S Action ACh M Atropine

  26. ATROPINE OVERDOSE: ANTIDOTE - Physostigmine Physostigmine Choline X AChE ACh S & S ACh Action M Atropine

  27. CHOLINESTERASE (AChE) INHIBITORS AGENTS USED TO ENHANCE TRANSMISSION AT CHOLINERGIC JUNCTIONS •Short-acting (noncovalent inhibitors) •Medium-duration (‘reversible’ carbamate inhibitors) •Irreversible (organophosphates)

  28. Cholinesterase Inhibitors CNS C ACh M N ACh T ACh 1 NE N L NE ACh 1 N SG ACh M 2 S ACh SM N

  29. Cholinesterase Inhibitors - Action Ach - normally removed from synapse via AChE AChE Inhibitor X AChE ACh S & S ACh Action M / N Receptor Binding

  30. Cholinesterase Inhibitors (reversible) Carbamates; BIND TO THE ESTERATIC SITE OF AChE • PHYSOSTIGMINE - READILY PENETRATES CNS - DRUG OF CHOICE TO TREAT POISONING WITH ATROPINIC AGENTS • NEOSTIGMINE and PYRIDOSTIGMINE - DO NOT PENETRATE CNS - USED TO TREAT ALZHEIMER’S AND DEMENTIA - USED TO TREAT MYASTHENIA GRAVIS - NEOSTIGMINE USED AS ANTIDOTE FOR OVERDOSE OF “CURARE-LIKE” DRUGS - USED TO TREAT GLAUCOMA

  31. Cholinesterase Inhibitors • EDROPHONIUM - Very short acting - Diagnostic agent used to test for myasthenia gravis

  32. CHOLINESTERASE INHIBITORS: ACUTE TOXICITY SYMPTOMS DUE TO EXCESS OF ACh AT SYNAPSE • MUSCARINIC RECEPTORS - SLUDE • NICOTINIC RECEPTORS - FASCICULATION, MUSCLE CRAMPS, WEAKNESS, RESPIRATORY PARALYSIS

  33. Cholinesterase Inhibitors - Action and Reversal Ach - normally removed from synapse via AChE AChE Inhibitor X AChE ACh ACh Action M / N Receptor Binding

  34. Antidote for Overdose of Carbamate Cholinesterase Inhibitors: Atropine AChE Inhibitor X AChE ACh ACh Action M / N Atropine

  35. Cholinesterase Inhibitors • ORGANOPHOSPHATES: IRREVERSIBLY PHOSPHORYLATE • SERINE HYDROXYL AT ACTIVE SITE OF AChE INSECTICIDES • • Malathion, Parathion, Diazinon NERVE GASES • Sarin, Soman, Tabun

  36. Antidote for Overdose of Organophosphate Cholinesterase Inhibitors: 2-Pralidoxime (2-PAM)

  37. GANGLIONIC BLOCKING AGENTS • TRIMETHAPHAN • - Used to produce controlled hypotension • HEXAMETHONIUM GANGLIONIC STIMULATING AGENTS • NICOTINE

  38. NEUROMUSCULAR (NMJ) BLOCKING AGENTS

  39. CNS NMJ Blocking Agents ACh C M N ACh T ACh 1 NE N L NE ACh 1 N SG ACh M 2 S ACh SM N

  40. NMJ Blocking Agents NMJ BLOCKING AGENTS USED IN SURGERY TO PROMOTE SKELETAL MUSCLE RELAXATION • - Intubation • - Maintain controlled ventilation • - Paralysis of skeletal muscle in area • of surgery

  41. NMJ BLOCKING DRUGS NONDEPOLARIZING (competative) DEPOLARIZING (non-competative) • •SUCCINYLCHOLINE Long Duration • TUBOCURARINE Intermediate Duration • PANCURONIUM Short Duration • MIVACURIUM

  42. Nondepolarizing NMJ Blocking Agents: Mechanism of Action AChE SM ACh SM paralysis ACh N Tubocurarine

  43. Antidote for Overdose of nondepolarizing NMJ Blocking Agents: Neostigmine Neostigmine X AChE recovery from SM paralysis SM ACh ACh N Tubocurarine

  44. Depolarizing NMJ Blocking Agents: Mechanism of Action Caution: Succinylcholine may produce hyperkalemia AChE SM ACh SM paralysis ACh N Succinylcholine

  45. Antidote for overdose of Succinylcholine: ‘no pharmacological approach’; ventilation AChE recovery from SM paralysis SM ACh ACh N Succinylcholine butyrlcholinesterase

More Related