Kruse - Cholinergic Agonists/Antagonists Flashcards
1
Q
Cholinesterase hydrolyzes at what rates?
A
ACh > methacholine > carbachol = bethanechol
2
Q
ACh mimetics act on receptors by:
A
- Direct acting mAChR and nAChR stimulants
- Indirect cholinesterase inhibitors
3
Q
Two types of direct acting cholinergic agonists
A
- Choline esters
2. Akaloids
4
Q
Choline ester names
A
ACh, carbachol, bethanechol
5
Q
Alkaloid names
A
Muscarine, nictoine, policarpine
6
Q
Choline ester:
Absoprtion -
Distribution -
A
Choline ester:
Absorption - poorly absorbed in CNS (quaternary ammonium groups)
Distribution - poorly distributed in CNS
7
Q
Choline ester metabolism location
A
Metabolism - hydrolyzed by cholinesterase in GI
8
Q
choline ester less active when given ___
A
PO
9
Q
Alkaloid
Absorption -
A
Absorption - well absorbed from most sites (i.e. noctine thru skin)
10
Q
muscarine (mushroom) ingestion is (toxic or not) and goes to what location
A
Toxic
Enters brain
11
Q
Alkaloid metabolism
A
Kidney excretion»_space; acidification of urine accelerates clearance
12
Q
Choline ester = Type of molecule = absorbed well?
Alkaloid = Type of molecule = absorbed well?
A
Choline ester = charged quaternary amine = not well absorbed
Alkaloid = uncharged tertiary amine = well absorbed
13
Q
M1 location
A
nerves
14
Q
M2 location
A
HEART, nerves, smooth muscle
15
Q
M3 location
A
glands, smooth muscle, endothelium
16
Q
M4 location
A
CNS
17
Q
M5 location
A
CNS
18
Q
Nm
A
skeletal muscle NMJ
19
Q
Nn
A
postG cell body, dendrites, CNS
20
Q
Gq M recetors
IP3, DAG
A
M1,3,5
21
Q
Gi M receptors
Inhibit cAMP
A
M2, 4
22
Q
Type of receptor and its action on skeletal muscle
A
nAChR
muscle contraction
23
Q
ParaS effect of…
A
decrease/contract everything, except:
Dilation of aa and vv.
Stimulation of bronchial glands
Detrusor contraction; trigone and sphincter relaxation
Sweat, salivary, lacrimal, naspharyngeal secretion
24
Q
ParaS eye - contraction of relaxation of iris sphincter and ciliary mm?
A
contraction to:
increase aqueous humor»_space; Schlemm»_space; ant chamber drainage
25
What are all cardiac actions mediated by?
M2 mAChR
26
PS innervation is less in ventricle or atria?
ventricles (so less physiological effect when activated)
27
Muscarinic agonists release what form endothelial cells to relax smooth muscle around blood vessels?
Endothelium Derived Relaxing Factor (EDFR)
28
EDFR is largely ___, which activates ___, and ___cGMP in smooth muscle.
Overall effect of this is: ____
NO >> activates...
GC >>
increases cGMP>>
Overall: to relax smooth muscle
29
Small doses of ACh = ____ effect on CV
| Large doses of ACh = ____ effect on CV
```
small = vasodilation = decrease BP and increased HR
large = bradycardia and decrease AV node conduction + hypOTension
```
30
GI:
M__ mACHR required for direct activation of smooth muscle relaxation
M__ mAChR reduces cAMP = reduces relaxation (increased contraction)
M2
| M3
31
NO receptor on sphincters
M3 mAChR
32
mAChR or nAChR greater # in:
1. Brain
2. SC
1. Brain = mAChR
| 2. SC = nAChR
33
inhibitory mAChR role in brain results in
tremors, hypothermia, analgesia
34
Activation of nAChRs is dependent upon what?
dose
35
Nicotine's effect (via nAChR) in CV system are primarily sympathomimetic or parasympathomimetic?
Effects?
sympathomimetic
| hypERtension, tachy-bradycardia alternation
36
nAChR effects in GI/GU tracts are primarily sympathomimetic or parasympathomimetic?
Effects?
parasympathomimetc
| nausea, vom, diarr, voiding of urine
37
Major clinical uses of direct acting cholinergic agonists:
1. Eye (glaucoma, accommodative esotropia)
| 2. GI/GU tract (post-op atony, neurogenic bladder)
38
Glaucoma -
| Muscarinic stimulants cause contraction or relaxation of the ciliary body?
Contraction
39
Glaucoma - muscarinic stimulants are replaced by what direct acting cholinergic agonist?
topical beta-blockers and prostaglandin derivatives
40
Accommodative esotropia looks like what?
cross eyed
41
Accommodative esotropia diagnosed with what direct acting cholinergic agonist?
cholinomimetic agonists
42
*Bethanechol is used most widely for:
- post-op ileus
- congenital megacolon
- urinary retention
- esophageal reflux
43
*Bethanechol is what type of direct acting cholinergic agonist?
choline ester
44
*Pilocarpine and cervimeline are used to tx what symptoms due to what disease?
dry mouth/Sjogren's
45
Nausea, vom, diarr, salivation, sweat, cutaneous vasodilation - are caused by what?
What is used to block them?
Muscarinic stimulant toxicity - Pilocarpine and choline esters
Antimuscarinics block this type of toxicity - i.e. atropine (mACHR antagonist)
46
mushroom on genus Inocybe
cause muscarinic poisoning
47
contraindiations of mAChR agonists
Asthma
Hyperthyroidism
Coronary insufficiency
Acid-peptic disease
48
Acute toxicity of nicotine
- CNS stimulation - convulsions >> coma and respiratory arrest
- skeletal muscle and End plate depol >> RESPIRATORY PARALYSIS, hypERtension, cardiac arrhythmia
49
Treatment for excess muscarinic stimulation from PS ganglia
atropine
50
Treatment for excess muscarinic stimulation - CNS stimulation
diazepam (parenteral anticonvulsant)
51
Sjogren's syndrome tx for dry mouth
dry mouth - Pilocarpine and cervimeline
52
Varenicline is used for _____.
| A ____ type of agonist.
```
smoking cessastion
partial agonist (alph4-beta2 nAChR)
```
53
Varenicline's most common side effect.
Nausea
| possible depression/suicide
54
Three types of AChE inhibitors.
Alcohols
Carbamic Acid Esters (carbamates)
Organophosphates
55
How do you reestablish termination of ACh signaling at NMJ in organosphophate poisoning?
regeneration of AChE
56
insecticide, CNS toxicity, lipid soluble, covalent and irreversible
organophosphate
57
Duration of action of each AChE inhibitor.
Alcohol - weak interaction; 2-10 minutes
Carbamic Acid Ester - 30 minutes (2 step hydrolysis)
Organophosphate - 100s of hours "aging"
58
Absorption of:
| Quaternary and charged AChE inhibitors
relatively insoluble in lipids/skin/lungs/conjunctive
59
Examples of quaternary and charged AChE inhibitors (insoluble)
neostigmine, pyridostigmine, edrophonium, echothiophate, ambenonium
60
Absorption of tertiatry and uncharged AChE inhibitors
well absorbed from all sites (including oral)
61
Examples of tertiary and uncharged AChE inhibitors
physostigmine, donepezil, tacrine, rivas tigmine, galantamine
62
Absorption of organophosphates
Oral = well
| Well absorbed from skin, lung, gut, conjunctiva
63
eye, resp tract, GI, GU innervated by:
mAChR (paraS)
64
AChR inhibitor effect on CV system (brady, CO, BP)
paraS tone dominates >> CO decreases
| Net: modest brady; decreased CO, moderately increased BP
65
MOA of AChE inhibitors
ACh accumulates in body >> activate nAChRs and mAChRs
| AChE inhibitors stop AChE from breaking down ACh to increase ACh levels = increased nAChR and mAChR effects
66
Reversal of pharacological paralysis:
| AChE inhibitors to reverse paralysis induced by anesthesia
neostigmine
| edrophonium
67
Used to treat paralytic ileus; atony of bladder; congenital megacolon
AChE inhibitors
68
AChE inhibitor role in glaucoma
reduce intraoccular pressure by stimulating mAChRs of ciliary body to contract >> outflow of aqueous humor
69
Alzheimer Disease tx and PD tx
tacrine and AChE inhibitors
70
mechanism of anticholinergic intoxication (result-cutaneous vasodilation, anhidrosis, hyperthermia, nonreactive mydriasis, delerium, hallucinations, reduction of urination,)
reduced or blocked mAChR stimulation
71
Antidote for anticholinergic intoxication (puts ACh back in)
physostigmine
72
AChE inhibitor toxicity route
1a. Ingestion Route: GI symptoms >>
| 1b. Percutanous Route: skin >> sweat and mm fasciculations
73
AChE inhibitor CNS symtoms (due to lipid soluble)
confusion, ataxia, respiratory coma, paralysis, convulsions
74
Tx for cholinergic poisoningmm
mAChR antagonist = atropine
| cholinesterase regenerator at NMJ (to regenerate AChE_
75
In what situation are cholinesterase reactivators used and name one.
pralidoxime
Used to restore response to stimulation at motor nerve (NMJ, nAChR) following a dose of organophosphorus, which blocks transmission.
76
nerve agent poisoning pretreatment (reduces injury)
pyridostigmine
77
Where antinicotinic drugs elicit their effects:
*NMJ
| nAChRs in ganglia
78
mAChR-blocker (parasympatholytic) drug example
atropine
79
atropine, tropicamide, benztropine
**mAChR-blocking drugs:
| tertiary amines for eye and CNS effects
80
ipratropium, glycopyrrolate
mAChR-blocking drugs:
| quaternary amines; charged; affects periphery
81
What mACHR-blocking drugs affects CNS more - tertiary or quaternary amines?
tertiary amines - atropine, tropicamide, benztropine
82
- Salivary, bronchial, and sweat glands (most or least sensitive to atropine?)
- Acid secretion by gastric parietal cells (most or least sensitive to atropine)
most
least
83
half life of atropine; % excreted in urine
2 hours
| 60% excreted
84
Parkinson tremor is reduced by
centrally acting muscarinic compounds
85
Ophthalmologic procedures use antimuscarinic agents to:
weaken contraction of ciliary muscles
86
scopolamine's CNS effects
drowsiness and amnesia
87
mAChR-blocker effects on resp system
bronchodilation and decerased secretion
88
mAChR-blocker effects on GI tract
Decreased salivary secretion
| Prolonged gastric emptying time and intestinal transit time
89
What can you use to treat urinary incontinence?
mAChR-blocker effects on GU tract - they relax smooth muscle and slow voiding
90
What does atropine do to sweating (symp cholinergic nerve fibers)?
sppresses thrermoregulatory sweating
91
Tx for PD
```
mAChR antagonists (ATROPINE) reduce tremors
Tertiary amines - benzotropine and trihexyphenidyl
```
92
Tx for motion sickness
scopolamine (PO, injection, or transdermal patch)
93
Atropine in anesthesia
blocks vagal reflexes
94
Atropine and anesthesia:
| atropine or glycopyrrolate paired with neostigmine to...
block paraS during reversal of sk m relaxaiton
95
All ganglion-blocking drugs are what type of amine?
Synthetic
96
MOA of ganglion-blocking drugs
competatively block ACh and similar agonists at nAChRs of both paraS and Symp autonomic ganglia >>
block all autonomic outflow
97
what tone dominates the autonomic ns?
parasympathetic tone
98
Charged or uncharged can cross BBB?
uncharged
99
Mecamylamine - what type of blocker is it?
ganglion blocker
100
Mecamylamine - what is it used to tx?
HTN
101
Mecamylamine - what type of amine is it and why is it used?
tertiary amine
| better absorption in GI tract
