4, 9/10 Parasympathetic nervous system

exam 1, lecture 24

Where do the preganglionic neurons of the parasympathetic nervous system originate?

Craniosacral region

Where are most parasympathetic ganglia located?

Near or within the target effector

Does the parasympathetic nervous system have high or low divergence?

Low divergence

What is the approximate ratio of preganglionic to postganglionic fibers in the parasympathetic nervous system?

3:1

Why are parasympathetic effects more discrete and localized than sympathetic effects?

There is little divergence

What neurotransmitter is released by ALL autonomic preganglionic neurons?

Acetylcholine (ACh)

7. What receptor does ACh bind at the autonomic ganglia?

Nicotinic cholinergic receptors

8. What neurotransmitter is released by parasympathetic postganglionic neurons?

Acetylcholine (ACh)

9. What receptors does ACh released by parasympathetic postganglionic neurons bind on target cells?

Muscarinic receptors

10. What is the overall purpose of the parasympathetic nervous system?

Recovering/restoring energy

11. What does parasympathetic stimulation do to the pupil?

Constriction (miosis)

12. What receptor mediates parasympathetic pupil constriction?

Muscarinic receptor

13. What does parasympathetic stimulation do to GI activity?

Increases/stimulates GI activity

14. What does parasympathetic stimulation do to the bronchi?

Bronchoconstriction

15. What receptor causes parasympathetic bronchoconstriction?

Muscarinic receptor

16. What does parasympathetic stimulation do to heart rate?

Decreases heart rate → bradycardia

17. What does parasympathetic stimulation do to blood pressure?

Decreases blood pressure

18. What does parasympathetic stimulation do to insulin release?

Increases insulin release

19. What happens to blood glucose when parasympathetic activity increases insulin release?

Blood glucose decreases

20. What are the two types of cholinergic receptors?

Nicotinic and muscarinic

21. What neurotransmitter can activate both nicotinic and muscarinic receptors?

Acetylcholine

22. Where are nicotinic receptors found?

Autonomic ganglia

23. What type of receptor is a nicotinic receptor?

Ligand-gated ion channel

24. What ion permeability increases when a nicotinic receptor is activated?

Na+

25. What is the cellular sequence after nicotinic receptor activation?

↑ Na+ permeability → depolarization → excitation

26. What are the two subtypes of nicotinic receptors?

NM (muscular) and NN (neuronal)

27. Where are NM nicotinic receptors found?

Neuromuscular junction

28. What happens when NM receptors are activated?

Depolarization → skeletal muscle contraction

29. Where are NN nicotinic receptors found?

Autonomic ganglia

30. Which muscarinic receptors activate Gq?

M1

31. Which muscarinic receptors activate Gi?

M2 and M4

32. What does activation of M2 and M4 do to adenylyl cyclase?

inhibits adenylyl cyclase

33. What ion channels are activated by M2/M4 signaling?

Receptor-operated K+ channels

34. Which muscarinic receptor is found in vascular endothelium?

M3

35. Are the M3 receptors in vascular endothelium innervated or non-innervated?

Non-innervated

36. What does activation of endothelial M3 receptors release?

Nitric oxide (NO)

37. What is the result of NO release from endothelial M3 stimulation?

Activation of guanylyl cyclase → vasodilation

38. What type of chemical is acetylcholine?

Quaternary amine

39. Acetylcholine is the prototype for what type of drug?

Directly acting cholinergic agonists

40. What does acetylcholine do to blood pressure?

Rapid fall in blood pressure of brief duration

41. Why does acetylcholine decrease blood pressure?

Endothelial nitric oxide release → vasodilation

42. What does acetylcholine do to heart rate?

Decreases heart rate

43. What does acetylcholine do to cardiac conduction?

Decreases speed of conduction

44. What does ACh do to GI motility and secretions?

Increases both

45. What does ACh do to the urinary bladder?

Increases bladder contraction

46. What does ACh do to the uterus?

Increases contraction

47. What does ACh do to bronchiolar smooth muscle?

Causes constriction

48. What does ACh do to exocrine glands?

Increases secretion

49. What does ACh do to the pupil?

Miosis

50. What does ACh do to intraocular pressure?

Decreases intraocular pressure

51. Does ACh readily penetrate the CNS?

No

52. What does ACh do to the adrenal medulla?

Increases epinephrine and norepinephrine release

53. What does ACh do to skeletal muscle?

Depolarization and contraction

54. What are cholinergic agonists also called?

Parasympathomimetics

55. What do parasympathomimetics produce?

Acetylcholine-like effects on effector cells

56. What are the two main types of cholinergic agonists?

Direct-acting and indirect-acting

57. How do direct-acting cholinergic agonists work?

Directly activate cholinergic receptors on effector cells

58. How do indirect-acting cholinergic agonists work?

Cause ACh to accumulate in the synaptic junction → increased cholinergic action

59. What are indirect-acting cholinergic agonists also called?

Cholinesterase inhibitors / anticholinesterases

60. What are the two direct-acting parasympathomimetics in this lecture?

Bethanechol and pilocarpine

61. What type of drug is bethanechol?

Choline ester/direct-acting parasympathomimetic

62. What type of drug is pilocarpine?

Natural alkaloid/direct-acting parasympathomimetic

63. Where do direct-acting parasympathomimetics act?

Postsynaptic cholinergic receptors of target cells innervated by cholinergic nerves

64. What receptor does bethanechol selectively stimulate?

Muscarinic receptors

65. Is bethanechol easily hydrolyzed by acetylcholinesterase?

No

66. Is bethanechol short or long acting?

Long acting

67. What are the two main indications for bethanechol?

GI paralytic ileus and urinary retention associated with bladder muscle atony

68. What does bethanechol do to the GI tract?

Increases GI contractions/motility

69. What does bethanechol do to the urinary bladder?

Increases bladder contraction

70. Why is bethanechol useful for urinary retention caused by bladder muscle atony?

it stimulates muscarinic receptors → increases bladder contraction

71. When should bethanechol NOT be used for GI ileus?

When there is a mechanical obstruction

72. What drug could be used for GI paralytic ileus without mechanical obstruction?

Bethanechol

73. What drug could be used for urinary retention caused by bladder muscle atony?

Bethanechol

74. What receptor does pilocarpine stimulate?

Muscarinic receptors

75. What muscarinic receptor does ophthalmic pilocarpine act on?

M3

76. What does pilocarpine do to the ciliary muscle?

Causes contraction

77. What does pilocarpine do to the circular muscle of the pupil?

Causes contraction → iris sphincter constriction/miosis

78. What does pilocarpine do to aqueous humor outflow?

Increases outflow through the trabecular meshwork

79. What is pilocarpine used for in dogs?

Chronic and acute glaucoma

80. What is pilocarpine used for in keratoconjunctivitis sicca?

Increases tear production

81. What parasympathomimetic can be used to increase tear production?

Pilocarpine

82. What parasympathomimetic is used for chronic and acute glaucoma in dogs?

Pilocarpine

83. What are the major adverse effects of parasympathomimetics?

Bronchoconstriction

84. What respiratory adverse effect can parasympathomimetics cause?

Bronchoconstriction

85. What cardiac adverse effect can parasympathomimetics cause?

Bradycardia

86. What ocular adverse effect can parasympathomimetics cause?

Miosis

87. What GI adverse effects can parasympathomimetics cause?

Vomiting and diarrhea

88. What urinary adverse effect can parasympathomimetics cause?

Urinary incontinence

89. Why can parasympathomimetics be dangerous during pregnancy?

They can cause uterine contraction → abortion

90. What are examples of reversible cholinesterase inhibitors?

Physostigmine

91. What is the irreversible cholinesterase inhibitor discussed in this lecture?

Organophosphate/DFP (diisopropyl fluorophosphate)

92. What is the overall mechanism of cholinesterase inhibitors?

Inhibit AChE → ACh accumulation → increased cholinergic activity

93. How do organophosphate cholinesterase inhibitors interact with AChE?

Interact with AChE at the esteratic site

94. What happens to AChE after organophosphate binding?

A stable enzyme-inhibitor complex forms through phosphorylation of the esteratic site

95. Why are organophosphate AChE inhibitors considered irreversible?

Recovery requires de novo synthesis of new enzyme

96. How do reversible cholinesterase inhibitors work?

Reversibly combine with AChE → inhibit ACh hydrolysis → prolong ACh action

97. What happens after AChE is reactivated following a reversible inhibitor?

The reactivated enzyme hydrolyzes ACh

98. What is physostigmine used for?

Glaucoma

99. What are neostigmine and pyridostigmine used for?

Myasthenia gravis

100. What is edrophonium used for?

Reversal of neuromuscular blockade