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PHS 931 > Block 1 Lecture 7 -- Muscarinics > Flashcards

Block 1 Lecture 7 -- Muscarinics Flashcards

1
Q

HACU

A

hi-affinity choline transporter

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2
Q

ChAT

A

choline acetyltransferase

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3
Q

VAChT

A

vesicular ACh Transporter

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4
Q

Postsynaptic cholinergic receptors:

A

M1 or N

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5
Q

Presynaptic cholinergic receptors:

A

M2 or N (+ HACU)

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6
Q

Function of presynaptic M2

A

mitigate action potential-mediated release

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7
Q

Function of presynaptic N

A

potentiate action-potential-mediated ACh release

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8
Q

Where is AChE located?

A

pre and postsynaptic membranes

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9
Q

Describe the structure of the Nicotinic receptor.

A

pentamer

    • (a1)2b1dg or (a1)2b1de
    • g is fetal, e is adult
    • 2x ACh bind at a or d/e
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10
Q

What nicotinic isoform is present in the somatic nervous system?

A

a1

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11
Q

What nicotinic isoform is present in the autonomic ganglia and adrenal medulla?

A

a3

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12
Q

Describe the variability of Nicotinic isoforms? Give an ex.

A

Many CNS isoforms (alpha or beta unit variations only)

– a7 likes Ca much more than Na

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13
Q

What is the MoA of Onobotulinum Toxin A?

A

indirect mAChR and nAChR for skeletal + smooth muscle relaxation
– prevents SNARE protein complexation to prevent exocytosis membrane fusion

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14
Q

How often is Botox administered?

A

q2-3 months

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15
Q

SNARE:

A

soluble N-ethylmalemide sensitive-factor attachment receptors

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16
Q

What are SNARE proteins?

A

PM and vesicle-associated isoforms required to complex for NT-vesicle fusion to plasma membrane for exocytosis

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17
Q

What kinds of tolerances can develop to Botox?

A
    • Abs (PK)
    • upregulation of postsynaptic nAChRs (rebound hypersensitivity)

also diffusion to other areas

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18
Q

What are uses of Botox?

A

1) focal dystonias
2) abnormal muscle contractions
3) migraine and tension headache

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19
Q

What are examples of focal dystonias?

A

1) blepharospasm
2) writer’s cramp
3) carpal tunnel
4) vocal cord spasm
5) oral dysphagias/achalasia

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20
Q

What are examples of abnormal muscle contractions?

A

1) strabismus
2) MS, cerebral palsy
3) spastic bladder
4) tics (tourette’s)
5) hyperhidrosis

21
Q

What is Sjorgren’s syndrome?

A

A condition that results in the destruction of exocrine glands (mainly salivary + lacrimal) and dry mouth

22
Q

What are complications of Sjorgrens?

A

dry mouth, difficulty speaking, infection, eye damage, tooth decay

23
Q

What can cause Sjorgren’s dz?

A 
primary = autoimmune Abs-mediated
secondary = radiation, other
24
Q

What is muscarine?

A

an alkaloid from the North American Fly Agaric mushroom

25
Q

What potentially-lethal compounds are found in muscarine?

A 
ibotenic acid (excitatory AA)
muscimol (GABAa agonist)
26
Q

What is mycetism?

A

mushroom poisoning producing strong SLUDGE effects from mAChR stimulation

27
Q

How is mycetism treated?

A

Atropine (for inocybe or clitocybe-induced)

28
Q

What mushroom genera contain the most muscarine?

A

Inocybe and clitocybe

29
Q

What are uses of muscarinic agonists?

A

1) non-obstructive GI disorders with immobility
2) non-obstructive bladder disorders with immobility
3) xerostomia
4) ophth exams (miosis) and glaucoma

30
Q

What are uses for Bethanechol?

A

Spinal Cord Injury (GI tract and bladder emptying)

31
Q

What is the MoA for bethanechol?

A

M3-selective mAChR agonist that is poorly absorbed from GI and does not cross the BBB

32
Q

What are C/I’s for mAChR agonism?

A

1) PUD
2) asthma
3) MI recovery
4) BPH
5) Parkinsons

33
Q

What is the MoA of atropine?

A

non-selective, competitive mAChR antagonist

34
Q

What are other mAChR antagonists?

A

atropine
scopolamine
hyoscyamine

35
Q

What are uses of mAChR antagonists?

A

1) GI disorders (spastic colon, endoscopy, PUD)
2) OAB, neurogenic bladd, nocturnal enuresis
3) ophthalmology (midriasis)
4) asthma, COPD, emphysema (b2 adjunct)
5) surgery (intubation, PONV, amnestic)
6) mycetism and AChE-I poisoning
7) diaphoresis/hyperhidrosis
8) motion sickness/vestibular
9) PD

36
Q

How is hyperhidrosis treated?

A

local botox

37
Q

How are mAChR antagonists used for motion sickness and vestibular disturbances?

A
    • Vertigo is often associated with other ANS effects (sweating/n/v)
    • ACh is NT at vestibular sensory afferents (reduce)
38
Q

What is a cycloplegic?

A

a drug that blocks ciliary muscle activity (block accommodation for measuring refractory errors)

39
Q

How is scopolamine different from atropine?

A

more lipophilic

40
Q

What type of GPCR are M1 receptors?

A

Gq

41
Q

What type of GPCR are M2 receptors?

A

Gi

42
Q

What type of GPCR are M3 receptors?

A

Gq

43
Q

Where are M1’s located?

A

CNS (CX, HP, STR)
Enteric NS
Parietal stomach cells

44
Q

Where are M2’s located?

A

atria

presynaptic CNS

45
Q

Where are M3’s located?

A

exocrine glands
smooth muscle
endothelium

46
Q

Fx of M1 agonism

A

CNS excitation
GI motility
acid secretion

47
Q

Fx of M2 agonism

A

decreased HR

inhibit presynaptic CNS neurons

48
Q

Fx of M3 agonism

A

exocrine secretions
smooth muscle contraction; vasodilation via NO
endothelium: NO production

PHS 931 (29 decks)

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