Cholinergic System Flashcards Preview

Disease/Therapeutics 2 Exam 1 > Cholinergic System > Flashcards

Flashcards in Cholinergic System Deck (95):
1

What is the MOA of Tetrodotoxin and Saxitoxin?

Blocks Na Channels and Action Potentials

2

What is the MOA for Hemicholinium?

Blocks choline uptake (blocks ACh synthesis!)

3

What is the MOA for Black Widow Spider Venom?

Stimulates ACh release (cholinomimetic)

4

What is the MOA for Bolutinus Toxin?

Prevents ACh release (anticholinergic)

5

What is the MOA for Bethanechol?

Cholinomimetic at Muscarinic Receptors

6

What is the MOA for Nicotine?

Cholinomimetic at Nicotinic Receptors

7

What is the MOA for Atropine?

Blocks the Muscarinic effects of ACh

8

What is the MOA for Mecamylamine?

Blocks Ganglionic nicotinic receptors

9

What is the MOA for Curare?

Blocks muscular nicotinic receptors -- skeletal muscle relaxation

10

What is MOA for Physostigmine and DFP?

Inhibits AChE - (cholinomimetic)

11

What are the cardiovascular effects of Muscarinic Receptor Activation? (Parasympathomimetic)

DEC HR
DEC AV Node Conduction
DEC Contractility
Vasodilation

12

What are the GI effects of Muscarinic Receptor Activation? (parasympathomimetic)

INC Motility
Relaxes Sphincters
INC Gastric Secretions

13

What are the urinary effects of Muscarinic Receptor Activation? (parasympathomimetic)

INC Urination (micturition)

14

What are the respiratory effects of Muscarinic Receptor Activation? (parasympathomimetic)

Bronchoconstriction
INC Respiratory Secretions

15

What are the eye effects of Muscarinic Receptor Activation (parasympathomimetic)

Miosis -- contracted iris sphincter
Loss of Far Vision -- contracted ciliary muscle

16

What are the sweat gland effects of Muscarinic Receptor Activation? (sympathetic)

INC Sweating

17

Nicotinic-Neural (Nn) Receptor Effects (para or symp) (8)

1. Vasoconstriction (s)
2. Bradycardia (p)
3. Miosis + Near Vision (p)
4. GI tract (p)
5. Salivary Gland Secretion (p)
6. Sweat gland secretion (s)
7. Micturition (p)
8. Release of NE and EPI at adrenal cells (s)

18

Muscle Nicotinic (Nm) Receptor Effect

Muscle Contraction

19

Selective muscarinic receptor AGONISTS have what actions?

ACTIVATE Muscarinic Receptors
NOT nicotinic

20

Selective muscarinic receptor ANTAGONISTS have what actions?

INHIBIT Muscarinic Receptors
NOT nicotinic

21

What are the different cardiovascular effects of a LOW dose vs. HIGH dose of a muscarinic receptor AGONIST?

Low: Hypotension, Vasodilation, INC HR
High: Hypotension, Vasodilation, DEC HR, DEC AV Node Conduction, DEC Contractility

22

SLUD(E) + BBB (muscarinic receptor agonist actions)

Salivation
Lacrimation
Urination
Defecation (emesis)
Bronchoconstriction
Bradycardia (at high doses)
Blurred Vision (ciliary muscle spasm)

23

What are the 3 uses for Bethanechol?

1. Reverse GI stasis and urinary retention
2. Reverse postoperative abdominal distention
3. Reverse gastric atony following bilateral vagotomy

24

What are Carbachol and Pilocarpine used for?

Treatment of wide angle glaucoma
Also acute narrow angle glaucoma (surgery indicated for long-term treatment)

25

Adverse Effects of Muscarinic Receptor Agonists (2)

1. Stimulate excessive SLUD(E) +BBB
2. Mushrooms (Inocybe and Ciltocybe families) contain high levels of muscarine and when ingested will induce rapid onset muscarine poisoning that can be treated (reversed) by Atropine.

26

Contraindications for Muscarinic Receptor Agonists (5)

1. Asthma/COPD (bronchoconstriction)
2. Hyperthyroidism (A Fib)
3. Cardiovascular Disease (bradycardia, hypotension)
4. Coronary Insufficiency (DEC coronary blood flow)
5. PUD (INC acid secretion)

27

Cardiovascular effects of Muscarinic Receptor ANTAGONISTS

Low doses: DEC HR (CNS effect)
High doses: INC HR (direct cardiac effect)
Toxic doses: dilation of cutaneous blood vessels

28

GI Effects of Muscarinic Receptor ANTAGONISTS

DEC tone
DEC Motility
DEC Secretions

29

Urinary effects of Muscarinic Receptor ANTAGONISTS

Urinary Retention

30

Respiratory effects of Muscarinic Receptor ANTAGONISTS

Bronchodilation
DEC Secretions

31

Eye effects of Muscarinic Receptor ANTAGONISTS

Cycloplegia (relaxed ciliary muscle)
Mydriasis (relaxed sphincter muscle)

32

Skin effects of Muscarinic Receptor ANTAGONISTS

DEC Sweating (could cause hyperpyrexia)

33

CNS effects of Muscarinic Receptor ANTAGONISTS (atropine, scopolamine)

1. Atropine -- toxic doses will cause CNS stimulation, even higher doses will cause CNS depression
2. Scopolamine -- therapeutic doses = CNS depression

34

Uses of Homatropine, Cyclopentolate, and Tropicamide (3)

1. Ophthalmologic exam
2. Mydriatic effects promote exam of retina and optic disk
3. Cycloplegia effects allow measurement of refractive errors

35

Use of Glycopyrrolate

Reverses muscarinic effects of anticholinesterases that are used to reverse neuromuscular blockade

36

MOA of Glycopyrrolate

Inhibits ACh action at muscarinic receptors

37

What do we use Atropine for?

Reverse mushroom poisoning (due to excessive muscarine) and the muscarinic effects that can occur as a consequence of anti cholinesterase poisoning

38

What are Benztropine and Trihexyphenidyl used for?

Parkinsonism

39

What is Scopolamine used for?

Prophylactic treatment of motion sickness (as a transdermal patch)

40

What are Ipratropium and Tiotropium used for?

COPD and asthma

41

What conditions are contraindications for Muscarinic Receptor Antagonists? (4)

*1. Narrow Angle Glaucoma (angle closure glaucoma) (INC intraocular pressure)
2. Open Angle Glaucoma (use with caution)
3. Cardiac Disease (causes tachycardia)
4. Prostatic Hypertrophy

42

What drugs have significant antimuscarinic activity but are not in the muscarinic receptor class? (3)

1. Amitriptyline
2. H1 Receptor Antagonists
3. Phenothiazines

43

Muscarinic Receptor Antagonist toxicity manifests as (5)

Red as a Beet
Dry as a Bone
Blind as a Bat
Hot as a Firestone
Mad as a Hatter

44

Antimuscarinic poisoning can be reversed by administering what?

Physostigmine

45

What is the difference between the 2 types of nicotinic receptors?

1. Nn - in peripheral ganglia and the adrenal gland; sympathetic AND parasympathetic
2. Nm - in the NMJ; mediates skeletal muscle contraction

*Both types are activated by ACh and Nicotine

46

MOA of Non-Depolarizing/Competitive NMJ Blockers

Bind Nm receptor displacing ACh and leading to paralysis

*Non-Depolarizing = they fail to depolarize Nm

47

What are the 5 long acting Nondepolarizing/Competitive NMJ Blockers?

1. Curare
2. Tubocurarine
3. Doxacurium
4. Pancuronium
5. Gallamine

48

What are the 3 intermediate acting Nondepolarizing/Competitive NMJ Blockers?

1. Cisatracurium
2. Rocuronium
3. Vecuronium

49

What is the short acting Nondepolarizing/Competitve NMJ Blocker?

Mivacurium

50

What are non depolarizing/competitive NMJ blockers used for therapeutically?

Induce muscle paralysis as an adjunct to anesthetic during surgery

51

How are non depolarizing/competitive NMJ blockers administered?

IV

52

Do nondepolarizing/competitive NMJ blockers cause CNS effects?

No because they are quaternary ammonium drugs

53

Pharmacokinetics of Cisatracurium

Metabolized by plasma esterase
Fast onset
Short duration of action

54

Adverse Effects of Tubocurarine

Partial ganglionic block which DEC BP and causes tachycardia and stimulates histamine release from mast cells (induces bronchospasm and hypotension)

55

Pharmacokinetics of Tubocurarine

Renal elimination
Hepatic Metabolism

56

Pharmacokinetics of Mivacurium

Hydrolyzed by plasma cholinesterase (pseudocholinesterase)

57

adverse effects of Gallamine

Blocks cardiac vagus nerve --> induces tachycardia and hypertensions (due to INC CO)

58

What is the overall adverse effect of non depolarizing/competitive NMJ blockers?

Prolonged muscle paralysis/apnea

59

What is the effect of using an anticholinesterase drug (like neostigmine) along with a non depolarizing/competitive NMJ blocker?

It will reverse the effects of the blocker

60

What 3 types of drugs will enhance the activity of non depolarizing/competitive NMJ blockers?

1. Halogenated Hydrocarbon Anesthetics
2. Aminoglycoside Antibiotics (inhibits release of ACh)
3. Calcium Channel Blockers

61

What is Succinylcholine used for?

Induce rapid muscle paralysis for endotracheal intubation

62

MOA for Succinylcholine

Induces a prolonged depolarization of Nm (stable Nm agonist)

*It is resistant to acetylcholinesterase-mediated hydrolysis so it exhibits prolonged binding to Nm -- this leads to a Phase 1 Depolarizing block causing muscle paralysis.

*Succinylcholine-induced Phase 1 Depolarizing block can progress to phase 2 NON-Depolarizing block if succinylcholine is not metabolized by butrylcholinesterase, or if the dose is too high.

63

How is succinylcholine metabolized?

By a plasma cholinesterase known as Butyrylcholinesterase (terminating it's action)

64

Pharmacokinetics of Succinylcholine

IV
Will not cross BBB
Rapid onset
Short duration of action

65

What are the adverse effects of succinylcholine? (4)

1. Prolonged muscle paralysis
2. Prolonged apnea (in pts with low butrylcholinesterase activity)
2. Malignant Hyperthermia
3. Muscle Pain and Hyperkalemia (can lead to cardiac arrest)

66

What is malignant hyperthermia?

Rapid onset of muscle rigidity which increases temperature causes hypertensions and tachycardia

67

What causes malignant hyperthermia?

Genetic susceptibility (congenital myopathies) in combination with halothane anesthetics and succinylcholine

68

How do we rescue patients with malignant hyperthermia?

DANTROLENE which blocks Calcium release from SR relaxing skeletal muscle

69

What are the 2 drug interactions with Succinylcholine?

1. Anticholinesterases (like neostigmine) will prolong succinylcholine induced muscle paralysis and apnea

2. Halothane anesthetics with succinylcholine can lead to malignant hyperthermia

70

MOA of Nicotine

Low doses: stimulates Nn and Nm
High doses: first induce Nn and Nm followed by a depolarization block at Nn and Nm

71

Peripheral effects of nicotine

Induction of Nn and Nm: Excessive SLUD(E) + bronchoconstriction and blurred vision, tachycardia and hypertension and skeletal muscle fasciculation (Nm)

Depolarization block of Nn and Nm: (if dose is high) paralysis (including respiratory muscles)

72

CNS effects of Nicotine

Stimulation followed by depression of vital medullary and respiratory centers

73

Acute Nicotine Poisoning (3)

1. Well absorbed by oral mucosa, lungs, and skin
2. Excessive SLUD(E) + BB, muscle weakness followed by paralysis
3. Death may result from respiratory failure in a few minutes (central inhibition, paralysis of respiratory muscle at NMJ)

74

What is the treatment for acute nicotine poisoning?

1. vomiting of gastric lavage/wash skin
2. respiratory assistance
3. treatment of shock
4. atropine to control muscarinic effects

75

How do anticholinesterases work?

They inhibit acetylcholinesterase AND butrylcholinesterase -- this increases the levels of ACh promoting the activation of Nn, Nm, and Muscarinic Receptor

*They can potentially induce a depolarization block at Nm (due to high levels of ACh) resulting in paralysis

76

What are the 2 reversible inhibitor anticholinesterases and how do they work?

Edrophonium, Tacrine

- bind to anionic site
- competes with ACh for anionic site
- fast acting
- short duration
- reversible
- leads to INC Ach

77

What are the 2 drugs with a carbamoyl ester linkage anticholinesterases and how do they work?

Physostigmine, Neostigmine

- they carbamylate the esteratic site
- slow hydrolysis of the carbamylating drug by AChE will lead to increases in ACh

78

What are the 2 organophosphate inhibitor drugs?

1. Isoflurophate (DFP)
2. Echothiophate

79

What are the 3 Insecticide organophosphate inhibitors?

1. Malathion
2. Diazinon
3. Parathion

80

What are the 3 nerve gas organophosphate inhibitors?

1. Tabun
2. Sarin
3. Soman

81

How do the organophosphate inhibitor anticholinesterases work?

- phosphorylate the esteratic site (essentially irreversible)
- regeneration of the active enzyme requires hours
- the return of AChE activity depends on the synthesis of new enzyme
- stability of phosphorylated enzyme enhanced by "aging"
- aging occurs through the loss of one alkyl or alkoxy group which makes phosphorylated enzyme more stable -- CANNOT be reactivated

82

Pharmacokinetics of the Anticholinesterases (4)

1. Edrophonium - quaternary ammonium; NO BBB; rapid onset; short duration
2. Neostigmine - quaternary amine; NO BBB
3. Physistigmine - tertiary amine; Crosses BBB (peripheral and CNS effects)
4. Organophosphates - cross BBB

83

What are neostigmine and physostigmine used for?

Used to reverse atony of smooth muscle of intestine and bladder

84

What is Echothiophate used for?

-Chronic wide angle glaucoma
-acute angle glaucoma (surgery indicated for long-term treatment)
-Long duration of action (~1 week)
-not a first line therapy
-INC risk for cataract formation with prolonged treatment

85

What drugs are used for Alzheimer's Disease? (3)

1. Tacrine (hepatotoxicity limits use of this)
2. Donepezil
3. Rivastigmine

86

What drug is used to reverse treatment intoxication by atropine like drugs?

Physostigmine

87

What drugs will reverse the effects of nondepolarizing/competitive NMJ blockers but NOT succinylcholine? (3)

1. Neostigmine
2. Pyridostigmine
3. Edrophonium

88

What is Myasthenia Gravis?

Autoimmune disease
Abs against Nm destroys the Nm at the NMJ reducing muscle strength
*insufficient anticholinesterase

89

How do you differentiated between myasthenia graves and a cholinergic crisis?

Edrophonium Test
MG: INC muscle strength (INC anticholinesterase)
CC: DEC muscle strength (DEC anticholinesterase)

90

Treatment of Myasthenia Gravis?

Neostigmine
Pyridostigmine

91

Acute Toxic Effects of Anticholinesterases?

Significant SLUDE
bronchoconstriction
blurred vision
mitosis
Muscle fasciculation
*excessive muscarinic receptor activation/ accumulation of ACh at NMJ
*IF Nm depolarization block happens, muscle fasciculation will become muscle paralysis (could lead to resp issues)

92

Chronic effects of Anticholinesterases

-delayed neurotoxicity unrelated to cholinesterase inhibition
-certain organophosphates
-no specific therapy

93

What is special about Atropine?

It will reverse muscarinic receptor effects but has NO effect on nicotinic receptors

94

What is Pralidozime?

(2-PAM)
Cholinesterase Reactivator

95

When can you use Pralidozime?

Following organophosphate acetylcholinesterase poisoning (very high affinity for the phosphate -- pulls the organophosphate off the acetylcholinesterase)

*NOT carbamate or edrophonium poisoning

*MUST be given soon after poisoning in order to prevent the aging of the enzyme (at that point the enzyme cannot be reactivated)