3. Neuromuscular Blockers, Reversal Agents, Muscarinic Antagonists Flashcards
(124 cards)
1
Q
nicotine receptor location
A
autonomic ganglia
2
Q
nicotine action
A
agonist
or
antagonist
3
Q
nicotine use
A
smoking cessation
4
Q
succinylcholine receptor location
A
NMJ
5
Q
succinylcholine action
A
agonist
or
antagonist
6
Q
rocuronium receptor location
A
NMJ
7
Q
rocuronium action
A
antagonist
8
Q
pancuronium receptor location
A
NMJ
9
Q
pancuronium action
A
antagonist
10
Q
vecuronium action
A
antagonist
11
Q
botulinum toxin receptor location
A
NMJ
12
Q
botulinum action
A
indirect acting antagonist
*inhibiting SNARE proteins so no NT can be released
13
Q
botulinum use
A
cosmetic
blepharospasm
cervical dystonia
focused msucle relaxant
14
Q
nicotinic receptor antagonists
A
nicotine
succinylcholine
rocuronium
pancuronium
vecuronium
botulinum toxin
15
Q
nicotinic receptor type
A
ion channel
16
Q
how many Ach molecules binding to NAchR provide max effect?
A
2 Ach bind to alpha subunits
17
Q
how is Ach broken down?
A
acetycholineesterase
18
Q
direct agonist
A
acting on the nAchR
19
Q
agonist/antagonist
A
stimulate initially
stay bound longer which would be an antagonist to target NT
20
Q
fetal receptors
A
enhanced response to D agent
relative resistance to ND agent
21
Q
margin of safety
A
- 10% need to be activated to initial muscle Action Potential
- more NT than needed for each AP
- significant reserve capacity
22
Q
Clinical evidence of block
A
75% of nicotinic receptors occupied by antagonist before clinical evidence of block
23
Q
Complete suppression
A
95% nicotinic receptors occupied by antagonist
24
Q
NMBs structure
A
NCH4+ functional group
functional duplicates of ACh
cations
25
Cations absorption
poor PO
avoid CNS penetration
- poor BBB passage
26
Depolarizing MR MOA
acts as agonist
then antagonist to Ach
binds Ach receptor
persistent depolarization of endplate
blocks Ach until it diffuses away
27
Depolarizing MR metabolism
slower than Ach
28
Non-Depolarizing MR MOA
competitive antagonist
29
Depolarizing MR Phase 1 block
depolarizing phase
persistant --> paralysis
30
Depolarizing MR phase 2 block
***only happens w/lgr than recc doses or infusions***
desensitizing phase
blocks conversion from depolarization to non-depolarizing block
MR blocks Ach
31
Depolarizing MR metabolism
slower than Ach
- not degraded by AchE
32
Non-depolarizing MR
competitive with Ach to bind w/nicotinic recepotr of end plate
bloc inhibits Ach from binding
33
how to reverse NDMR
AChE inhibitor
- neostigmine
34
surmountable
block can eventually be overcome
35
succinuylcholine onset/duration
rapid onset
- low lipid solubilty
- cation effect
- water soluble
short duration of action
- diffuses away quickly
36
Prolong Succinycholine duration
increase dose
continuous ijnfusion
decrease rate of metabolism
37
Succinylcholine metabolism
quick metabolism by pseudocholinesterase (plasma)
38
Succinylcholine DOA factors
hypothermia
- decrease hydrolysis
low enzyme (psuedocholinesterase)
- pregnancy, liver disease, renal fail
- drug interactions
- prolong 2-20 min
genetic
- heterozygotes (20-30min duration)
- homozygotes (4-8 hrs)
39
drugs that decrease psuedocholinesterase activity
neostimine
metoclopramide
esmolol
oral contraceptives
dibucaine
echothiophate
phenelzine
pancuronium
40
dibucaine number
measures enzyme function
41
dibucaine normal enzyme
80%
42
dibucaine homozygote number
20%
43
Succinylcholine drug interactions
cholinesterase inhibitors
- prolong phase 1 block
- reduce metabolism of sux
- pts w/myasthenia gravis/glaucoma
Nondepolarizing agents
- small dose may be antagonistic
- in phase 2 block, NDMR enhances
block
44
Succinylcholine dose
2 x ED95
ED95 = 0.35-0.5 mg/kg
45
Succinylcholine dose neonate
larger weight-based dose
(lgr mg/kg)
* higher Vd
46
Succ continuous infusion
2 mg/mL or 1 mg/mL
need nerve stimulation
47
Succ CV effects
- may act at ganglia and muscarinic receptors
- depends on underlying state
- leads to bradycardia w/elevated vagal tone
- peds more susceptible
- fasciculation
- hyperkalemia (incr serum0.5 mEq/L)
48
Manage Succ bradycardia
Atropine/Glycopyrrolate
49
denervation injury due to receptor upregulation
immature isoform
more spread out receptors
widespread depolarization
extensive K release
risk peaks 7-10 days post trauma
burn, trauma, neurological conds
50
Succinylcholine contraindication
underlying neuromuscular disease
risk of malignant hyperthermia
allergy to succ
homozygous atypical cholinesterase
[K] > 5.5 mEq/L
51
hyperkalemia management
insulin (prevents hypoglycemia)
calcium gluconate (for cardiac arrest)
dialysis (reduce K level)
52
succinycholine pharmacologic effects
muscle pain
pressure increases
- intragastric
- intraocular
- ICP
masseter muscle rigidity (MMR)
malignant hyperthermia
generalized contraction
prolonged paralysis
histamine release
53
NDMR onset/duration
slower onset
longer duration
compared to succinycholine
54
NMDR potency vs onset
more potent
= smaller dose
= slower onset
55
NMDR goals
facilitate atraumatic intubation
rapid intubation
require complete relaxation of:
- oral cavity
- larynx
- diaphragm
- abdomen
56
NDMR increased intubation dose
larger dose increase conc at NMJ
risk prolonged duration of action
57
NMDR priming
2 injection
10-15% of full dose 5 min before induction
58
NMDR Volume of Distribution (Vd)
central compartment
NMJ
single dose - redist to preipheral compartment
repeat dose - saturates central compartment
59
NMDR plasma cholinesterase clearance
mivacurium
60
NMDR hoffman elimination
atracurium
cisastracurium
61
NMDR hepatic clearance
vecuronium
rocuronium
62
NMDR renal clearance
pancuronium
doxacurium
63
NMDR duration of action - intermediate acting
atracurium
cisatracurium
rocuronium
vecuronium
64
NMDR duration of action - long acting
pancuronium
65
lower ED95
more potent
66
higher ED95
less potent
67
NDMR pharmacology effets
minimal CV effects
- pancuronium - vagolytic
prevents succ fasciculation
no hyperkalemia
histamine release
hypothermia prolong block
respiratory acidosis potentiate block
68
NDMR drug interactions - additive
des>sevo>iso>nitrous
pan>vec/atracurium
ca++ channel blockers
aminoglycoside abx
69
NMDR drug interactions -inhibitive
reversal agents
- suggamadex
- neostigmine
70
atracurium
onset: intermediate
DOA: intermediate
CV: stable
- some hypotension/tachycardia
- decrease SVR
bronchospasms in asthmatics
toxic metabolite: laudanosine
rare anaphylaxis
71
cisatracurium
onset: intermediate
DOA: intermediate
no HR/BP change
no histamine release
toxic metabolite: laudanosine
72
pancuronium
onset: intermediate
DOA: long
vagolytic
- hypertension
- tachycardia
renal elimination
liver metabolizes
73
vecuronium
onset: intermediate
DOA: intermediate
no BP/HR changes
74
rocuronium
onset: fast
DOA: intermedaite
no metabolism
renal/hepatic elimination
less potent = lgr dose needed
75
recovery index
offset speed to recover from 25% to 75% twitch height
76
intubation MR
succinylcholine
- rapid onset / short duration
- rapid sequence induction
77
continued paralysis
NDMR
permit reduced depth of anesthesia
78
peripheral nerve stimulator
tetany
twitch
TOF
79
fade
reduction of evoked response indicative of ND block
80
clinical recovery
correlates w/absence of fade
81
single twitch stimulation
twitch height remains normal until 75% ACh receptors blocked
82
single twitch disappears when
90-95% receptors occupied
83
TOF
train of four monitopring
progressive fade as relaxation increases
84
TOF disappearance of 4th
75% block
85
TOF disappearance of 3rd
80-85% block
86
TOF disappearance of 2nd
85-90% block
87
TOF disappearance of 1st
90-98% block
88
clinical relaxation requires ____% block
75-95% block
89
TOF ratio
ratio of response to 1 and 4 twitches
90
Recovery TOF ratio
>= 0.9
amp4/amp1
91
cholinesterase inhibitors act...
indirectly
enhance activity of Ach receptor, not directly acting on it
92
Cholinesterase inhibitors act on which esterases?
acetylcholinesterase
butyrylcholinesterase
pseudocholinesterase
93
cholinesterase inhibitors impact ______receptors
nicotinic
muscarinic
increase ACh ability to act at nAChR and mAChR
increased duration of ACh presence at cholinergic receptors
94
cholinesterase inhibitors MOA
bind to AChE
blocks ACh from binding to enzyme
ACh increases
ACh has increased duration of time present at receptors
95
acetylcholinesterase inhibitor types
1) alcohol structure - edrophonium
2) carbamic acid esters - neostigmine
96
edrophonium
reversibly binds
short-lived (2-10 min)
97
neostigmine
carbamylated enzyme more resistant to hydration
prolongs release (30min-6hrs)
98
acetylcholinesterase inhibitor clinical uses
myasthenia gravis
alzheimers
glaucoma
reversal of neuromuscular blockers
99
nicotinic effects of AChE inhibitors
ACh able to bind
increase muscle contractility
100
muscarinic effects of AChE inhibitors
ACh binds (throughout entire body)
parasympathetic response
**need antimuscarinic to block the parasympathetic effects
101
neuromuscular blocker reversal
dose based on degree of block
determined by nerve stim response
pt needs spont recovery prior to dosing
102
when to give neuromuscular blocker reversal?
sustained head lift
vital capacity
tidal volume
103
neostigmine onset/duration
onset: 5-10 min
duration: 1 hr
104
pyridostigmine onset/duration
onest: 10-15 min
duration: >2 hr
105
edrophonium onset/duration
onest: 1-2 min
duration <1 hr
106
sugammadex
selective neuromuscular reversal agent
- only for aminosteroid NDMR
- Roc/Vec
107
Sugammadex FDA indication
reversal of neuromuscular blockade in surgery or ICU
108
Sugammadex MOA
encapsulates free molecule form of roc
109
sugammadex metabolism
no metabolites
110
sugammadex elimination
renal
111
sugammadex drug interaction
can bind w/endogenous steroids
may need more when magnesium and aminoglycosides are present
112
sugammadex minimum effective dose
2 mg/kg
113
sugammadex re-dosing
must wait 24 hrs before able to redose w/roc or vec
114
sugammadex adverse effects
overall well tolerated
bitter tast
recurrence of block
irregular movement during recovery
Cost $$$
115
antimuscarinic drugs
atropine
glycopyrrolate
116
antimuscarinic absorption
Cation limits absorption/distribution
117
antimuscarinic metabolism
susceptibility to cholinesterase
118
antimuscarinic CV effects
normal hemodynamics
reverse bradycardia
block direct acting agonists
119
antimuscarinic reverses
parasympathetic effects
stimulates:
bonchodilation
increase HR
decrease GI motility
dry secretions
urinary incontinense
120
antimuscarinic side effects
tachycardia
mydriasis
urinary retention
decreased GI motility
eldery (CNS impacts)
121
antimuscarinics are combined w/cholinesterase inhibitors
to minimize muscarinis adverse effects associated w/reversal agents
122
antimuscarinic distribution
robinul does not cross BBB/placenta
more selective for heart/salivary glands
123
atropine onset/duration
onset: faster
duration: shorter
124
glycopyrrolate onset/duration
onset: slower
duration: longer
