Cholinergics Flashcards
1
Q
hemicholinium
A
blocks choline transport into the terminal, not pharmacologically useful because it blocks all cholinergic functions
2
Q
choline cotransports
A
with Na+, rate limiting step
3
Q
CAT
A
choline + acetylCoA –> Ach inhibitors are not effective
4
Q
ACh is stored
A
in presynaptic vesicles
5
Q
ACh structure
A
quarternary amine, positively changed, has an ester bond prone to rapid degredation
6
Q
uptake
A
- choline 2. ACh synthesis, 3. vesicle storage
7
Q
black widow
A
alpha latrotoxin, causes over release of ACh
8
Q
botulinum toxin
A
blocks Ach release
9
Q
release of ACh
A
basic depolarization-induced excretion-secretion coupling (calcium dependent vesicle fusion with pre synaptic membrane)
10
Q
botox is used for
A
strabismus, blapharospasm, hyperhidriosis, focal distonia, migraine, cosmetic treatment
11
Q
d-tubocurarine function
A
blocks nicotinic receptors (non-depolarizing neuromuscular blocker)
12
Q
cholinomimetic
A
cholinergic agonist ‘mimicry’
13
Q
botulinum neurotoxins
A
7 types of protease, cleave VAMP/SNAP-25/syntaxin (proteins required for fusion and exocytosis of ACh synaptic vesicles)
14
Q
botulinum neurotoxins have selective
A
activity at NMJ and cause flaccid paralysis, effects last for weeks and cause muscle atrophy
15
Q
botulinum neurotoxin precaution
A
systemic spread can block crucial functions such as respiration
16
Q
removal of ACh
A
flashlike suddeness, shorter than time to make an action potential (you’ve got one shot)
17
Q
BChE
A
pseudocholinesterase, non specific…, serum cholinesterase, prefers butyrylcholine as a substrate, generally distributed
18
Q
reversible ACE inhibitors
A
physostigmine, neostigmine
19
Q
irreversible ACE inhibitors
A
organic phosphates
20
Q
electric fish
A
contain tissue rich in nicotinic receptors (packed with ACh receptors)
21
Q
poisonous snakes
A
contain α toxins (peptides) that interact with cholinergic receptors in a way that causes irreversible antagonism
22
Q
structure of the nicotinic receptor
A
5 subunits (α, α, β, δ, γ) in a circular array, the center is a gated ion channel
23
Q
myastenia gravis is caused by
A
antibodies to ones own nicotinic receptors
24
Q
nicotinic receptors require the binding of
A
TWO ACh molecules (causes positive ion influx), all or none switch
25
goal of nicotinic receptor activation
is depolarization
26
dual response
continuous or massive nicotinic receptor stimulation causes desensitization or a failure to repolarize (initial stimulation followed by cessation)
27
N(g) blocker
6, hexamethonium (ganglionic synapses and adrenal medulla)
28
N(m) blocker
10, decamethonium (neuromuscular junctions of somatic system)
29
methonium compounds
variation in chain length, block various nicotinic receptors with specificity
30
all nicotinic receptors require
two α subunits for ACh binding
31
ganglionic nicotinic receptor subunits
2α3, 3β4
32
muscarinic receptor structure
integral membrane proteins with a single membrane spanning polypeptide (seven times)
33
M2, M4
G(i) inhibition of cAMP, increased K+ currents
34
M1, M3, M4
G(q), increase in intracellular Ca2+
35
muscarinic receptor effect
slow, graded response, synapses less structured, Ach degredation is slwoer (used to regulate organ intrinsic activity)
36
muscarinic receptor blocker
atropine
37
utility of agents depends on
specificity of receptor subtype, availability (ability to penetrate to desired sites)
38
penetration to CNS
tertiary amines, hydrophobic compounds (un charged)
39
lots of Ach
causes the activation of nicotinic receptors (and therefore, sympathetic system as well)
40
lots of ACh and atropine
increase in autonomic ganglia firing rate and an increase in BP and heart rate
41
ACh as a drug
is not much use due to rapid degredation
42
methacholine
is resistant to hydrolysis, used opthalmologically, and has muscarinic and nicotinic effects
43
bethanechol
muscarinic agonist, resistant to degradation, pronounced in GI and UT smooth muscle, NO NICOTINIC EFFECTS
44
ACE inhibitor and bethanechol
additive effects
45
Methacholine and ACE inhibitor
synergistic effects
46
bethanecol administration
orally or subcutaneously, IV/IM negates specificity (toxic)
47
bethanecol structure and purpose
quarternary amine; used to treat urinary retention, GI stasis (post-op), diagnosis of anti-cholinergic intoxication (there are better agents), locally for the eye
48
contraindications for muscarinic agonists
asthma, hypothyroidism, coronary insufficiency, peptic ulcer, physical obstruction (bronchioconstriction, hypotension, gastric secretion)
49
muscarine
muscarinic agonist, quaternary amine, found in mushrooms
50
pilocarpine
muscarinic agonist, tertiary amine, rarely used systemically, potent diaphoretic
51
pilocarpine clinical uses
topical: treatment of acute glaucoma, xerostemia, CF sweat test, sjorgen's syndrome
52
diagnostic sweat test for CF
pilocarpine
53
sjorgen's syndrome
pilocarpine (or M3 agonist), autoimmune attack of endocrine glands
54
belladonna alkaloids
night shade, atropine, muscarinic antagonist, highly specific, competitive, tertiary amines
55
atropine
competitive inhibition, tertiary amines, half life 24 hours
56
synthetic muscarinic antagonists
Tropicamide, Tolterodine, Tiotropium
57
Tropicamide
short half life, eyes
58
Tolterodine
selectivity for receptors,
59
Tiotropium
quaternary amine, lungs
60
indications for specific atropine use
cholinesterase poisoning, AHA emergency care
61
M3 selective agents treat
incontinence in the elderly
62
treatment of stable COPD
long acting β-adrenergic agonists and muscarinic antagonists
63
treatment for anti-muscarinic intoxication
AChE inhibitor (physostigmine), diazapam for psychotic effects
64
symptoms of muscarinic antagonist poisioning
cutaenous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydriasis, delirium, urinary retention
65
preanesthetic scopalamine is
better than atropine
66
cholinesterase inhibitors high doses
can cause stimulation through natural leakage of ACh
67
cholinesterase inhibitors are important for
Myasthenia Gravis, Alzheimer's, opthalmology, atony, termination of competitive cholinergic blocking drugs
68
ACE inhibitors toxic
used for insecticides and in chemical warfare
69
hexamethonium
blocks reflex effects
70
reversible competitive ACE inhibitor example
Donepezil
71
Donepezil
tertiary amine, longer acting, competitive antagonist
72
carbamoylating agents are
ACE inhibitors and are reversed by slow hydrolysis (2-6 hour half life)
73
Physostigmine
carbamoylating agent, ACE inhibitor, tertiary amine, ordeal bean
74
Neostigmine
carbamoylating agent, ACE inhibitor, quaternary amine
75
irreversible ACE inhibitor
organic phosphates, turnover is fast than enzyme removal, SARIN :(
76
sites of action for ACE inhibitors
muscarinic post-ganglionic junctions, ganglionic nicotinic junctions, nicotinic NMJs, CNS muscarinic and nicotinic junctions
77
lipid soluble ACE inhibitors
physostigmine, donepezil, organic phosphates --> reach all sites for inhibitor
78
ACE inhibitor quarternary amine
nesostigmine
79
used for parkinson's
atropine (muscarinic antagonist) - high doses lead to CNS problems
80
prevents motion sickness
scopolamine
81
rapid hydrolysis of the acetylated enzyme
restores the native enzyme
82
organic phosphates produce
phosphorylated enzymes
83
increased inhibition of ACE eventually causes
blockage of signal transduction
84
vagotomy
neostigmine is no long effective after this procedure
85
acute attacks of glaucoma are treated with
physostigmine (ACE inhibitor)
86
given for relief of abdominal distension
neostigmine
87
ACE inhibitor with good CNS penetrance
Donepezil (theoretically good for Alzhimer's)
88
ACh increase effect on skeletal muscle
facilitation followed by paralysis
89
AChE inhibitor in myastenia gravis
too little = myastenia crisis, too much = cholinergic crisis
90
why is neostigmine good for myastenia gravis?
longer acting, carbomylating, quaternary amine
91
edrophonium test
you know why
92
other treatments for myastenia gravis
immunosuppression, plasma exchange, thymectomy (ACE inhibitors treat the symptoms, not the disease)
93
lipophilic agents
easily pass into the brain
94
lipophilic agent used for Alzhimer's
Donepezil
95
effects can be local or general (ACE inhibitor poisoning)
dermal vs. pulmonary exposure
96
miosis
pupil pinpointing
97
diazapam
alleviates convulsions in ACE inhibitor poisoning
98
cholinesterase reactivator
pralidoxime, must be given before the phosphorylated enzyme ages! ONLY effective against phosphorylating enzyme
99
muscarinic antagonist
atropine
100
hexamethonium
selectively blocks ganglionic receptors
101
central effects of nicotine
sharpening of attention, development of dependence
102
nicotine stimulation of
nucleus accumbens and prefrontal cortex when activate release dopamine (reward perception)
103
why do plants make nicotine?
as a defense mechanism
104
nicotine poisoning
empty stomach via activated charcoal, DONT USE basic solution
105
varenicline
partial agonist for α4β2 nicotinic receptors
106
trimethaphan
quarternary sulfonium, inhibit nicotinic ganglionic receptors
107
sympathetically lead effects of nicotinic ganglion receptors
arterioles and veins are dominant tone, therefore blocking causes vasodilation
108
mydriasis
pupil dilation
109
nicotinic ganglionic blocker used for
hypertensive crisis, controlled hypotension, upper spinal cord injury hyperreflexia control
110
neuromuscular blocking agents
curare, methonium (2 quarternary amine dichotomy allows for activation of both receptors at one time) produce flaccid paralysis
111
competitive inhibition of NMJ
d-tubocurarine, vecuronium <-- bulky, nonflexible,
112
depolarizing agents (NMJ blocking)
methonium compounds, succinylcholine <--- long and slender molecular configuration
113
depolarizing agents block function in two phases
1. persistent depolarization 2. receptor desensitization
114
depolarizing agent vs. competitive inhibitor sequence of paralysis
limbs/neck, diaphragm last; comp. small rapid muscles first, depolarization. small rapid muscles after neck
115
densensitization
postsynaptic membrane is repolarized but the nicotinic receptors do not respond to agonists, recovery is slow
116
during phase I there can be
significant loss of K+ from muscle
117
succinylcholine
characterized by fast action, depolarizing agent, rapidly hydrolyzed by butyryl cholinesterase
118
use of neuromuscular junction blockers
muscle relaxation as a surgical anesthesia adjunct, orthopedic procedures, intubation, electroshock therapy
119
neuromuscular blocking agent drug interactions
ACE inhibitors, inhalation anesthetics, certain antibiotics, calcium channel blockers
120
neuromuscular agent disease interactions
reduced cholinesterase, malignant hyperthermia, soft tissue damage (hyperkalemia), muscular disorders
121
reduced plasma cholinesterase and succinylcholine
prolonged apnea
122
overdose of NMJ blocker
prolonged apnea, CV collapse, histamine release
