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Pharm II Annie for Shelby > Cholinergics > Flashcards

Cholinergics Flashcards

1
Q

Nicotinic receptors are located where?

A

Brain

Autonomic ganglia

Skeletal muscle

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2
Q

What receptor in the brain is associated with memory?

A

M1

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3
Q

The secondary mechanism by which M2 receptors slow heart rate is what?

A

M2 receptors inhibit norepinephrine release which lowers the sympathetic stimulation

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4
Q

Stimulation of M3 receptors in the heart can cause what effect?

A

Coronary vasodilation

THIS IS NOT PARASYMPATHETIC!!!! Nitric oxide is released from endothelial cells which causes local vasodilation

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5
Q

Pre-op, scopolamine can be used for what side effects?

A

dry up secretions

sedation and amnesia

anti nausea

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6
Q

When is Echothiophate used?

A

Occasionally for narrow angle glaucoma

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7
Q

The top 4 side effects for muscarinic agonists

A

Diarrhea

Abdominal cramps

Salivation

Sweating

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8
Q

Cardiovascular effects of cholinesterase inhibitors

A

Mostly like parasympathetics

Bradycardia, lower contractile force, lower CO

Decreased sympathetic stimulation from desensitized nicotinic receptors

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9
Q

Contraindications for muscarinic agonists.

A

Peptic ulcer

Bowel obstruction

Asthma

Coronary insufficiency

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10
Q

Do carbamates cross the BBB?

A

Physostigmine is tertiary and DOES

Neostigmine and pyridostigmine are quarternary and do NOT

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11
Q

Direct-acting cholinergic agonists bind to ____ receptors while cholinesterase inhibitors indirectly stimulate _____ receptors

A

Muscarinic

Muscarinic AND nicotinic

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12
Q

Main 2 uses for Bethanechol (urecholine)

A

Stimulate GI peristalsis

Encourage urinary voiding

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13
Q

In what 2 ways does Varenicline (Chantix) work to aid smoking cessation?

A
  1. Causes just enough dopamine release to curb the craving for nicotine
  2. If the person does smoke, the Chantix blocks the nicotine receptors so the smoking is less pleasurable
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14
Q

What is myasthenia gravis?

A

Muscle weakness due to antibodies attacking nicotinic receptors on the neuromuscular endplates

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15
Q

Does ACh cross the BBB?

A

Nope

It’s quartenary

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16
Q

Cevimeline (Evoxac) stimulates what receptors? It causes less ____ than pilocarpine

A

M1 and M3

Sweating

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17
Q

What is the only systemic use for physostigmine? How does it work to help this?

A

Muscarininc antagonist poisoning

It increases ACh duration to overcome the CNS effects of the antagonist

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18
Q

Apart from SLUDGE, what are some other signs of cholinesterase inhibitors?

A

Muscarinic manifestations!

Miosis, sweating, bronchoconstriction, nausea/vomiting, diarrhea

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19
Q

Echnothiophate forms a (reversible/irreversible) bond with AChE

A

Irreversible

Long-lasting effect

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20
Q

Peripherally, nicotine effects may be similar to what?

A

BOTH parasympathetic and sympathetic neuron discharge

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21
Q

Muscarinic antagonist poisoning: what kind of toxicity and what can be used to help treat it?

A

CNS toxicity

Physostigmine (bc no good muscarinic agonists enter CNS)

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22
Q

What are the 2 nerve agents we learned?

A

Sarin

Soman

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23
Q

Would you want to use carbamates orally?

A

Only physostigmine

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24
Q

After ACh is released and it diffuses to the skeletal muscle, what happens?

A

Nicotinic receptors are stimulated

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25
Where are muscarinic receptors located?
On smooth muscle
26
What class is hexamethonium?
Ganglion blocker
27
What are the types of cholinergic receptors?
Muscarinic Nicotinic
28
Are muscarinic agonists used for open-angle glaucoma?
Nope Too many SEs
29
Pilocarpine is used when?
Emergency narrow angle glaucoma attack Last-resort
30
SEs of Chantix that are of note
Flatulence 🐈💨 Nightmares Psychosis Suicide
31
Side effects of toxic doses of scopolamine
excitement agitation hallucinations coma
32
What drug/s are used for treating dry mouth from Sjogrens or head and neck radiation?
Pilocarpine *Cevimeline (Evoxac) (DOC bc less sweating)
33
When are cholinesterase inhibitors most useful?
In diseases in which cholinergic inputs are decreased i.e. when the action of ACh needs to be extended
34
Why does Chantix give psych SEs but only a few peripheral SEs?
It’s a PARTIAL AGONIST on a nicotinic receptor in the brain
35
The degree of effect of muscarinic blockers will depend a great deal on what?
The amount of prevailing parasympathetic tone
36
Acute closed-angle or narrow angle glaucoma is commonly treated using what combo of meds until surgery can correct it?
Pilocarpine + cholinesterase inhibitor (commonly the organophosphate echothiophate)
37
Treatment for nicotine poisoning
Atropine Anticonvulsants Intubate
38
CNS effects: Low doses of nicotine cause ____ and ____. High doses of nicotine cause ____, _____, and increased _____.
Low: alertness and attention High: tremor, vomiting, increased respiration
39
🚨 Major warning signs of nicotine poisoning 🚨
Vomiting 🤮 Convulsions 🥴 HTN and arrhythmia 💔 Paralysis/respiratory arrest 😵 Coma 💀
40
Muscarinic receptors are linked to what?
G proteins
41
Side effects of Varenicline (Chantix)
Gassssssss 🐈💨 nausea/vomiting 🤮 Vivid nightmares 👹 Psychosis 🤡 Suicide 😶
42
What are the 3 carbamates?
Neostigmine Pyridostigmine Physostigmine
43
What is “aging” with organophosphates?
Over time, the bond between the AChE and the organophosphate becomes irreversible One of the phosphorus — oxygen bonds are broken off so 2-PAM cannot bind and release the substance
44
Nicotinic receptors are rapidly ______
Desensitized
45
What 2 drugs are used for long-term therapy in MG?
Neostigmine Pyridostigmine
46
Side effects of pilocarpine
Blurred vision Brow ache
47
Eye, GI, GU, and respiratory effects of cholinesterase inhibitors
Similar to muscarinic agonists because of the dominant parasympathetic tone in these tissues
48
Effects of ganglion blockers
Mydriasis Ortho hypotension Urinary retention Tachycardia
49
How do you use edrophonium to see if the dose of the long-term drug they are on for MG is at the proper dose?
Inject edrophonium. If they get stronger, the dose of the drug needs to be upped. If they get weaker, the dose of the drug was too high and should be lowered.
50
Cholinesterase inhibitor (cholinergic agonist) toxicity treatment
Atropine 2-PAM (RAPIDLY)
51
Gland secretion is MOST increased by which muscarinic agonist?
Pilocarpine
52
Organophosphate are used as _____ and _____. They are HIGHLY _____ soluble
Pesticides and nerve gasses Lipid
53
Varenicline (Chantix) is a _____ on a nicotinic receptor subtype in the _____.
Partial agonist Brain
54
Nicotinic agonists initially cause what effect at the NMJ? What happens with lasting stimulation?
Initially muscle stimulation/contraction Then de-sensitization which results in flaccid paralysis
55
Diisopropyl fluorophosphate (DFP) is what?
A pesticide/organophosphate
56
Edrophonium forms a (reversible/irreversible) bond with AChE
Reversible Remember, short duration of action
57
They majority of atropine use is ___ due to the drug's (ability/inability) to penetrate the CNS.
Peripheral Inability (*very high doses will get into the CNS as in reversal of toxicities*)
58
What is SLUDGE?
Salivation 🤤 Lacrimation 😭 Urination 🚽 Defecation 💩 Gastric Distress 🐈💨 Emesis 🤮
59
Release of ACh into the synaptic cleft is blocked by what drug?
Botox
60
When is organophosphate poisoning fatal?
If aging is not prevented
61
Tolterodine (Detrol) Fesoterodine (Toviaz) Darifenacin (Enablex) Solifenacin (Vesicare)
Overactive bladder!!!!!!!!!
62
After AChE breaks down ACh, choline is taken back up into the nerve terminals by what kind of mechanism?
High affinity transport
63
What muscarinic agonist has the MOST GU/bladder effects?
Bethanechol (Urecholine)
64
ACh stimulation causes effects similar to parasympathetic stimulation with the exceptions of what?
Vasodilation from M receptors on vessels Sweating
65
HOW do muscarinic agonists treat glaucoma?
They reduce IO pressure by causing contraction of - the iris circular muscle - AND the ciliary muscle This increases the angle between the lens and iris and aqueous humor can flow out
66
Nicotinic receptors are linked to what?
Sodium channels
67
Edrophonium is used because of it’s (long/short) duration of action
SHORT 5-10 mins
68
Pralidoxime (2-PAM) is a very strong _____
Nucleophile
69
What is glycopyrroalte (Robunil)? What drug class?
Prevents vagal bradycardia in surgery Muscarininc antagonist
70
Brain effects of cholinesterase inhibitors at low and high doses
Low dose: Improve memory via M1 and Nn High dose: desensitize nicotine receptors = convulsions and respiratory arrest
71
Oxybutynin (Ditropam) Trospium (Sanctura)
Prevent bladder spasms
72
Where are muscarinic receptor effects most pronounced?
Eye, GI, bladder, salivary and sweat glands
73
Ganglion blockers are considered ________________.
No depolarizing competitive antagonists
74
Muscarininc agonists effects on the eye: - pupil - intraocular pressure - accommodation
Pupil constriction (miosis) Intraocular pressure decreased Accommodation for near vision only (blurred vision)
75
What drug is used to help diagnose MG?
Edrophonium injection
76
Side effects of toxic doses of atropine
hallucinations delirium coma
77
MOA of 2-PAM
It’s a strong nucleophile that attracts the organophosphate and irreversibly binds to it It either prevents the organophosphate from binding to the AChE or releases it from the AChE if it’s already bound and hasn’t “aged”
78
How do you reverse a nondepolarizing blocker?
Neostigmine!! A cholinesterase inhibitor/cholinergic agonist
79
Side effect of 2-PAM
Hypertension
80
Scopolamine side effects include ____ which are do to the drug's (ability/inability) to penetrate the CNS.
Sedation and amnesia Ability (very readily!)
81
How do cholinesterase inhibitors work?
They increase the duration of action of ACh at the synaptic cleft by inhibiting its breakdown by AChE
82
Are we going to give 2-PAM with carbamate poisoning?
Maybe not It doesn’t undergo “aging” so it’s probably not useful and can make things worse by inhibiting AChE
83
The carbamates form a ____ bond with effects lasting ____
Covalent 1/2 to 6 hours
84
When will you see SLUDGE side effects?
Toxicity of cholinesterase inhibitors | Super similar to muscarine poisoning but with MSK effects too
85
NMJ effects of cholinesterase inhibitors at low and high doses
Low dose: increase strength of muscle contraction High dose: initial contraction of muscles followed by neuromuscular blockade
86
MOA of organophosphates
They phosphorylation the AChE to form a very long-lasting bond The bond then “ages” with time to make it irreversible ***MUST treat quickly!!!***
87
What 2 things will happen when you inject ACh right into the veins that would not happen with normal parasympathetic stimulation
1. Sweating | 2. Vasodilation due to direct stimulation of M3 receptors on endothelial cells that releases N.O.
88
What muscarinic agonist will have the MOST effects in the GI and urinary systems?
Bethanechol (Urecholine)
89
What are pilocarpine and cevimeline both used for, and what is the major difference between them?
Both used for dry mouth Pilocarpine will cause profound sweating Cevimeline is more selective for M1 receptors so you don’t sweat as much (Salivation is M1 and M3)
90
What kinds of signs would you see in someone with muscarinic agonist poisoning?
Diarrhea Abdominal cramps Salivation Sweating Bronchoconstriction Blurred vision Nausea/vomiting (Similar to SLUDGE but noooo MSK effects since Nicotinic receptors are not being stimulated)
91
What are the effects of nicotine at low doses and at high doses?
Low doses: alertness and attention High doses: tremor, vomiting, fast respiration
92
What kinds of peripheral effects will nicotine have?
Cardiac- will be mostly sympathetic (HTN, fast HR) Gastrointestinal- will be mostly parasympathetic (vomiting, diarrhea, urination) (Remember nicotine will act at the ganglia and cause parasympathetic and sympathetic effects)
93
When you are treating organophosphate poisoning, what will you treat it with and when will you know you’ve given enough?
1. Atropine until pupils become dilated 2. 2-PAM given RIGHT AWAY 3. Mechanical respiration
94
Organophosphates and Carbamates (neostigmine, pyridostigmine, etc) are both cholinesterase inhibitors. Which one will cause poisoning that you should give 2-PAM for?
Organophosphates
95
How do you treat atropine poisoning?
Physostigmine (gets into CNS) Valium Ice packs
96
Who should never receive Succinylcholine?
People with extensive soft tissue injury/burns May cause too much K+ to be released during prolonged depolarization and could cause cardiac arrest

Pharm II Annie for Shelby (4 decks)

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