Cholinomimetics

Lecture

1. CHOLINOMIMETICS Dr Igor Khalin

2. Parasympathomimetics Sympathomimetics ( cholinomimetics ) ( adrenomimetics ) Parasyimpatholythics Sympatholythics ( cholinoblockers ) ( adrenoblockers ) Druds acting on ANS

3. Parasympathomimetics ( cholinomimetics ) Sympatholythics ( adrenoblockers ) Drugs acting on ANS

4. Sympathomimetics ( adrenomimetics ) Parasympatholythics ( cholinoblockers ) Drugs acting on ANS

5. Cholinomimetics Eye accommodation for near vision, miosis , IOP Saliva copious, liquid Bronchi constriction, secretion Heart rate, blood pressure GIT secretion, peristalsis sphincter tone Bladder detrusor sphincter tone              

6. Cholinergic neuron ATP ATP negative feedback

7. Cholinergic receptors MUSCARINIC NICOTINIC M1 M2 M3 M 4 M 5 N M N N Eye Heart Smooth muscles Exocrine glands CNS Ganglions Carotid sinus Skeletal muscles Adrenal glands CNS

8. Muscarinic receptors High affinity for muscarine M 1 – gastric parietal cells, saliva, CNS M 2 - cardiac cells, smooth muscle, CNS M 3 - bladder, exocrine glands, smooth muscle, eye, CNS M 1 &M 3 – G q M 2 - G i Amanita muscaria

9. Muscarinic receptors M 1 M 3

10. Cholinergic Agonists Direct acting Indirect acting Acetylcholine Bethanecol Carbachol Pilocarpine Edrophonium Physostigmine Neostigmine

11. Direct acting cholinergic agonists ACETYLCHOLINE - Pharmakokinetics

12. Direct acting cholinergic agonists Decrease in heart rate and cardiac output 2. Decrease in blood pressure ACETYLCHOLINE - Effects

13. Organ system effects 3. Eye Contraction of sphincter ( Miosis ) Contraction of cilliary muscle (Myopia) ACETYLCHOLINE

14. Direct acting cholinergic agonists ACETYLCHOLINE 4. Other actions diarrhea sweating nausea 4. Clinical use very rare: eye drops to obtain miosis

15. Direct acting cholinergic agonists Stimulation of atonic bladder Nonobstructive urinary retention Neurogenic atony Megacolon Ophthalmology - glaucoma -surgery

16. Direct acting cholinergic agonists PILOCARPINE - PK Tertiary nitrogen Good adsorbtion Penetrate BBB

17. Direct acting cholinergic agonists Jaborandi (Pilocarpus pennatifolius) Secretagoge (sweat, tears, saliva) Jaborandi - what causes slobbering 1. Sjögren’s syndrome Dry mouth, lack tears 2. Glaucoma PILOCARPINE - Effects PILOCARPINE – Clinical usage

18. Direct acting cholinergic agonists PILOCARPINE open-angle vs . closed angle glaucoma posterior synechiae anterior synechiae

19. Mushroom poisoning Miosis Hyper salivation Excessive sweating, lacrimation Cold, wet skin Bradycardia Polyuria Diarrhea Convulsions Atropine

20. Nicotinic receptors High affinity to nicotine N M - neuro -muscular junction N N – ganglion, adrenal gland CNS, carotid sinus

21. Indirect acting cholinergic agonists Reversible Irreversible Edrophonium Neostigmine Physostigmine Rivastigmine Galantamine Echothiophate Organophosphates

22. Mechanism of action

23. Mechanism of action

24. Mechanism of action

25. Reversible Physostigmine Calabar Bean Tertiary nitrogen Good adsorbtion Penetrate BBB

26. Reversible Physostigmine 1. Atony of intestine 2. Atony of bladder 3. Glaucoma 4. Overdose of ATROPINE, ANTIPSYCOTICS, ANTIDEPRESSANTS

27. Reversible Physostigmine Convulsions Bradycardia Paralysis of skeletal muscle

28. Reversible Neostigmine Quatenary nitrogen Poor adsorbtion Not penetrate BBB

29. Reversible Neostigmine Paralyzes Myastenia gravis Antidote of neuro-muscular blocker TUBOCURARINE

30. Reversible Neostigmine Salivation Flushing Decreased BP Abdominal pain Diarrhea Bronchospasm

31. Reversible Neostigmine Bronchial asthma Intestinal inflammation, obstruction Bladder obstruction Peritonitis

32. Reversible Edrophonium Quatenary nitrogen Poor adsorbtion Not penetrate BBB Fast elimination Duration 10-20 min

33. Reversible Edrophonium Diagnosis of myasthenia gravis Antidote of neuro-muscular blocker

34. Reversible Rivastigmine Tertiary nitrogen Good adsorbtion Penetrate BBB

35. Reversible Rivastigmine Alzheimer disease

36. Irreversible Echothiophate Glaucoma

37. Toxicology Organophosphates

38. Toxicology SLUDGEM S alivation L acrimation U rination D efecation G astrointestinal motility E mesis M iosis

39. Toxicology Reactivation of acetylcholinesterase PRALIDOXIME Not enter BBB M- cholinoblocker ATROPINE Antimuscarinic only Anticonvulsant DIAZEPAM

40. SUMMARY