Autonomic nervous system

1. Autonomic nervous system • ANS functions below the level of consciousness and control the visceral functions. • ANS supplies all organs except skeletal muscles (supplied by somatic system).

2. Autonomic nervous system

4. Autonomic nervous system TRANSMITTERS OF ANS: • Acetylcholine is the nerve transmitter of preganglionic nerves of both parasympathetic and sympathetic nervous system. • Acetylcholine is the nerve transmitter of postganlionic nerves of parasympathetic nerves system.

5. Autonomic nervous system TRANSMITTERS OF ANS: • Norepinephrine is the major nerve transmitter of postganglionic nerves of sympathetic system. • Acetylcholine is the nerve transmitter of postganlionic nerves of sympathetic nervous system supplying sweat glands.

6. Autonomic nervous system • PARASYMPATHETIC NS: The preganglionic nerves arise from 1. Midbrain – III cranial nerve. 2. Medulla – VII, IX and X cranial nerve. 3. Sacral part of spinal cord – S - 2, 3, 4 • SYMPATHETIC NS: The preganglionic fibers originate from the thoracolumbar region of the spinal cord.

18. Parasympathetic nervous system CHOLINERGIC TRANSMISSION: • Acetylcholine is synthesized by the enzyme choline acetyltransferase (ChAT). • Release of acetylcholine occurs by exocytosis with the influx of calcium ions. • Inactivation by acetyl cholinesterase is the major mechanism for termination of action of Ach.

19. Autonomic nervous system • Acetylcholine is hydrolyzed by the enzyme Cholinesterase There are two types of cholinesterase – • Acetyl cholinesterase(true)– present at all neuromuscular junction. It hydrolyses specifically Acetylcholine. • Butyryl Cholinesterase(Pseudo)– present in plasma and liver. It hydrolyzes procaine and suxamethonium.

20. Autonomic nervous system

23. Parasympathetic nervous system Acetylcholine acts on two types of receptors: • Nicotinic receptors. • Muscarinic receptors.

24. Autonomic nervous system Types of nicotinic receptors:

25. Autonomic nervous system Types of muscarinic receptors: M1, M2, M3, M4, M5

27. Autonomic nervous system ACETYLCHOLINE: • No therapeutic implications • Diffuse action • Rapid hydrolysis

28. Autonomic nervous system ACETYLCHOLINE: HEART: M2 RECEPTORS • Decrease in the heart rate • Decrease in the conduction • Decrease in the contraction BLOOD VESSELS: M3 • Vasodilation via the release of nitric oxide

29. Autonomic nervous system ACETYLCHOLINE : GIT: M1/M3 • Increase the tone and peristalsis. • Increase the secretion of the GIT glands and lacrimal gland. • Relax the sphincter. URINARY BLADDER: M3 • Contraction of detrusor. • Relaxation of trigone and sphincter.

30. Autonomic nervous system • ACETYLCHOLINE : RESPIRATORY TRACT : • Constriction of bronchus • Increases the secretions of the respiratory tree.

31. Autonomic nervous system ACETYLCHOLINE : EYE : • IRIS has parasympathetic innervation and acts on muscarinic receptors present on Circular or Sphincter muscle and Ciliary muscle (M 3 receptors ) • Radial muscle has alpha 1 receptors.

32. Autonomic nervous system

33. Autonomic nervous system

34. Autonomic nervous system

35. Autonomic nervous system ACETYLCHOLINE : • EYE : It causes the spasm of accommodation by contraction of ciliary muscle which causes the zonula to relax, thus allowing the lens to become more convex . • Thus vision is fixed for near objects.

36. Autonomic nervous system Nicotinic action of Acetylcholine : • Autonomic ganglia ( N N ) – both parasympathetic and sympathetic are stimulated . • Skeletal muscle ( N M ) : Contraction of the fibers.

37. Autonomic nervous system

38. Autonomic nervous system CHOLINERGIC AGONISTS • CHOLINE ESTERS– Acetylcholine, Methacholine, Carbachol, Bethanechol • CHOLINOMIMETIC ALKALOIDS– Pilocarpine • ANTICHOLINESTERASES

39. Autonomic nervous system

40. Autonomic nervous system DRUGS AFFECTING CHOLINERGIC TRANSMISSION : • ANTICHOLINESTERASES- Neostigmine • INHIBITING CHOLINE CARRIER -Hemicholinium • INHIBITION OF VESCICULAR STORAGE - Vesamicol • INHIBITION OF RELEASE – Botulinium toxin

41. Autonomic nervous system Choline esters– Acetylcholine, Methacholine, Bethanechol • poorly absorbed from the stomach • poor lipid solubility • poor BBB penetration

42. Autonomic nervous system

43. Autonomic nervous system • CHOLINE ESTERS: • Methacholine and Bethanechol have no nicotinic actions • Methacholine has prominent CVS action • Carbachol and Bethanechol on GIT and Urinary bladder. • Carbachol and Bethanechol are resistant to the hydrolysis by AchE

44. Autonomic nervous system CHOLINOMIMETIC ALKALOIDS– Pilocarpine • Pilocarpine – stimulates only muscarinic receptors • Used in chronic simple glaucoma, acute congestive glaucoma and as miotic.

45. Autonomic nervous system ANTICHOLINESTERASES AGENTS • These agents inhibit the AchE present in the synaptic regions . • Thus they prolong the existence of Ach released from the nerve endings. • These are of two types Reversible Anti - ChE Irreversible Anti - ChE

46. ANS • Irreversible Anti-ChE agentsare insecticides and nerve gas poisons • Insecticides– Organophosphorus compounds - Parathion, Malathion, Diazinon (TIK-20), Echothiopate • Nerve gas poisons – Soman, Sarin, Tabun

47. Nerve Agents Organophosphate insecticides Cholinesterase inhibitors Pralidoxime Enzyme active site Cholinesterase generator Chemical antagonist

48. ANS ANTICHOLINESTERASES AGENTS • Reversible : Short : Edrophonium Medium: Neostigmine, Physostigmine, Pyridostigmine, Tacrine

49. ANS ANTICHOLINESTERASES

50. ANS ANTI-CHOLINESTERASES AGENTS • Mechanism of action :Acetyl cholinesterase (AchE) is an enzyme withanionicand esteratic site. • Acetylcholine (Ach ) involves attraction of the positive charge N+ of Ach and anionic site; acetylation of serine leading to the acetylated enzyme. • The acetylated enzyme reacts with the water to produce acetic acid and free enzyme within milliseconds.