Lecture 11/12 - Cholinergic Agonists Flashcards
1
Q
What are the direct acting cholinergic agonists? (six)
A
ACh Muscarine Nicotine Carbachol Bethanechol Pilocarpine
2
Q
What are the cholinesterase inhibitors? (six)
A
Edrophonium Neostigmine Pyridostigmine Physostigmine Organophosphates Pralidoxime
3
Q
What abnormality inhibits ACh release?
A
Botulism
4
Q
What can prolong the effects of ACh?
A
AChE inhibitors
5
Q
What does ACh stimulate?
A
M + N
6
Q
Where are muscarinic receptors located?
A
PNS effector organs
7
Q
What is M1+3 linked to?
A
Gq
8
Q
What is M2 linked to?
A
Gi
9
Q
Where are muscarinic receptors where the PNS is not?
A
Sweat glands
10
Q
What do nicotinic receptors respond to?
A
ACh + Nicotine
11
Q
What is a special characteristic of nicotinic recptors?
A
Rapid desensitization
12
Q
Where are nicotinic receptors found?
A
Brain
Adrenal medulla
Autonomic ganglia
NMJ
13
Q
Why can drugs select between NMJ and autonomic nicotinic receptors?
A
Both have different structures
14
Q
What is direct action?
A
Agonist binds and stimulates receptor
15
Q
What is indirect action?
A
Molecule binds to enzyme or other part of pathway that leads to a different effect of NT
16
Q
What will happen with ACh injection/
A
Slowing of HR - M2
Drop in BP - M3
17
Q
Why can’t you give ACh orally?
A
Charged, not absorbed
18
Q
What does bethanechol stimulate?
A
M receptors only
19
Q
What effects predominate with bethanechol?
A
Bladder + GI
20
Q
Does bethanechol enter the brain? Why?
A
No, charged
21
Q
What does pilocarpine stimulate?
A
M receptors only
22
Q
What are the distribution characteristics of pilocarpine?
A
Not charged, so taken orally
Gets into CNS
23
Q
What is pilocarpine used for in the eye?
A
Decrease intraocular pressure (M3)
24
Q
What is really sensitive to pilocarpine that leads to side effects? what are the effects?
A
Sweat + Salivary glands
Drooling
25
What does muscarinic stimulation do to the heart?
Vagal stimulation = Bradycardia (M2)
Atrial-muscarinic receptors
Conduction slowed through AV node
Pre-synaptic decrease NE = Decrease HR (M2)
26
What does muscarinic stimulation do to the blood vessels?
NO PNS, but M3 is present on endothelium
| ACh given IV will cause vasodilation
27
How does ACh given IV cause vasodilation?
NO
28
What happens with release of NO from endothelial cells?
cGMP production + Vasodilation
29
What is the PNS tone like in the GI tract?
High, responsible for digestion
30
What are the effects of muscarine on the GI tract?
Motility + Peristalsis increase
Tone increases
Salivary + Gastric secretions increase
Sphincters relax
31
How is carbachol used with horses?
Treatment of colic or impactions
32
What do you have to watch out for when using carbachol in horses?
If obstruction is present can lead to intestinal rupture
33
What is carbachol used for in cattle?
Rumen atony and impaction
34
What does normal PNS activity do to the bladder?
Enhances overall activity
35
What do muscarinic drugs do to the bladder?
```
Bladder tone + peristalsis increase
Void pressure increase
Bladder capacity decrease
Detrusor contracts
Trigone and sphincter relax
```
36
What is the basic end result of muscarinic stimulation of the bladder?
Increased urination
37
What drug is used for bladder effects?
Bethanechol
38
What is betahanechol used for?
Urinary atony in cats following urolithiasis
39
What do you have to watch out for when using betanechol in cats?
That the urethra is patent, so they can control urine output
40
What are the muscarinic effects in the eye?
Circular muscle contraction = Pupil smaller
Increased AH drainage = Decreased pressure
Ciliary muscle contracts = Near vision
41
How is pilocarpine used in the eye?
KCS + Glaucoma
42
What are the side effects of pilocarpine in the eye?
Blurred vision + Brow ache
43
What are the muscarinic side effects?
```
Nausea + V/D + Colic
Bladder tightness = Increased urination
Salivation
Bronchoconstriction + increased mucus
Blurred vision
Constricted pupils
```
44
What happens with muscarine toxicity?
Same as side effects just worse
| Hypotension + Shock + Bradycardia
45
What is muscarine toxicity treated with?
Atropine + Albuterol
46
What are the three main places for nicotinic receptors?
Autonomic ganglia
Skeletal muscle
Brain
47
What type of channel is nicotinic receptors?
Ligand gated Na+ channel
48
What movement of ions occurs with an activated nicotinic receptor?
```
Na/Ca = in
K = out
```
49
What, in the most general sense, does N activate?
SNS + PNS
50
What are the SNS effects with nicotinic stimulation?
Hypertension
| Tachycardia w/ vagal bradycardia
51
What are the PNS effects with nicotinic stimulation?
Nausea + Vomiting + Diarrhea + Urination
52
What happens with desensitization of the NMJ?
Initial muscle twitch/contraction + depolarization blockcade
53
What is seen with nicotine toxicity?
Vomiting
Convulsion + coma + respiratory arrest
Skeletal muscle depolarization
Hypertension + Cardiac arrythmia
54
What three things are done to treat nicotine toxicity?
Atropine + Anticonvulsants + Assist respiration
55
What are the four major drugs that affect AChE? (not toxins)
Neostigmine
Physostigmine
Pryidostigmine
Edrophonium
56
What are the five examples of Organophostphates?
DFP + Eschothiophate + Soman + Sarin + Malathion
57
What are the distribution characteristics of neostigmine?
Charged, cant be taken orally + no CNS N
| Acts mostly on skeletal muscle
58
How does pyrdiostigmine compare to neostigmine?
Longer acting
59
What are the general characteristics of Physostigmine?
Enters CNS
| U-shaped response curve
60
What is Physostigmine used for?
Atropine toxicity
61
What is the duration of action for Edrophonium?
Very short = 5 to 10 min
62
What is edrophonium used for?
Diagnosis of myasthenia-like syndrome
63
What is used to treat myasthenia-like syndrome?
Neostigmine
64
What is the problem with organophosphates?
Long-lasting effect
| Due to aging, becomes irreversible
65
What can stop oragnophosphate aging?
2-PAM, if given 3 to 4 hours post-exposure
66
How does aging occur?
Phosphorus-Oxygen bonds breaks
| Bond to AChE irreversible
67
Why does 2-PAM stop the "aging" process"?
Strong nucleophile
| Attracts organophosphate away from AChE
68
What is important to remember when using 2-PAM?
If organophosphate not present it can inhibit AChE itseld
69
What are the CNS effects of AChE inhibition?
Convulsions + respiratory arrest
70
What are the effects of AChE inhibition on the eye?
Miosis
| Near vision
71
What are the effects of AChE inhibition on GI/bladder?
V/D + Abdominal cramps + Urination
72
What are the effects of AChE inhibition on the respiratory system?
Salivation + Secretion + Bronchoconstriction
73
What are the cardiovascular effects of AChE inhibition?
PNS dominates
Prolonged ACh = M2 stimulation
Bradycardia + Decrease contraction + Decrease CO
74
What happens with low concentrations of AChE inhibitors at the NMJ?
Skeletal muscle strength increases
75
What happens with high concentrations of AChE inhibitors at the NMJ?
Twitches + Fasiculation
Blockade
Paralysis
76
What is myasthenia gravis?
Autoimmune disease
Ab's to nicotinic receptors
Not enough ACh to stimulate
Weakness and fatigue with excercise
77
What is physostigmine used for?
Eye = miosis + decrease pressure
Synechia = alternate with atropine
Rumen atony = in cattle
78
What are the side effects of AChE inhibitor toxicity?
Salivation + Lacrimation + Urination + Defecation + Gastric distress + Emesis
79
What is the withdrawal time in meat and milk for 2-PAM (pralidoxime)?
28 days for meat
| 6 days for milk
