NMB (Exam 2) Flashcards
(119 cards)
1
Q
Ganglionic Blockers originally used for
A
BP control
2
Q
Ganglionic Blockers act on
A
ganglionic nicotinic (ionophore) receptor
in BOTH symp & parasymp
3
Q
What happens when a drug blocks both symp & parasym?
A
(ie: Ganglionic Blockers)
-lose nearly all homeostatic control & fine tuning
-assumes predominant tone
-tissues lose self-regulation
-very easily shifted from one mode to the other
4
Q
Ganglia function is much more complex than the simple idea of
A
a cholinergic nerve entering & acting on a ganglionic nicotinic (ionophore) receptor.
There are several receptors in ganglia.
5
Q
Ganglionic Blockers
specificity
SEs
A
very non-specific
lots of SEs
“heavy hitters”
6
Q
“heavy hitters”
A
lots of associated SEs
7
Q
Ganglionic Blockers were effective at BP control bc…
A
predominant tone of BV is sympathetic
it blocks this
parasymp takes over
slight vessel relaxation
8
Q
Dominant tone of blood vessels
A
sympathetic
9
Q
Sympathetic stimulation
cutaneous vessels
skeletal muscle
A
cutaneous vessels: constrict (prevent blood loss; preserve BP)
skeletal muscle: dilate vessels to increase O2
10
Q
Parasympathetic effects & BVs
A
prevents constriction by symp.
cant really dilate further unless muscles fatigued or with specific medication
11
Q
Ganglionic Blockers
cardiac effects
A
dominant tone parasympathetic
blocks this completely
↑HR
bizarre heart activity; hard to predict
many systems control heart (hormones, renal fxn, ions, symp., etc)
12
Q
T/F
Ganglionic Blockers alter hormonal circulation.
A
False
partially why their SEs are hard to predict
13
Q
T/F
Multiple receptor types exist within the cholinergic ganglion.
A
True
not only nicotinic receptors
14
Q
Only _____ can trigger an output & cause an axon to fire. But ____ & ____ can modulate/attenuate/fine tune it.
A
nicotinic receptors
norepi & muscarinic inputs
15
Q
EPSP
A
excitatory post-synaptic potential
firing of a signal inside the cell
16
Q
Only _____ can generate an EPSP.
A
nicotinic receptor (N2, ganglionic nAChR)
muscarinic & norepi receptors can control it
17
Q
hexamethonium
A
standard ganglionic blocking drug
not used clinically
blocks nicotinic generated EPSP
18
Q
ACh binds to a nicotinic receptor and allows influx of ___.
A
Na
19
Q
Secondary receptors on the ganglia
A
ganglia (muscarinic, adrenergic, & others)
amplify or suppress (modulate) EPSP signal
20
Q
Only ____ ganglionic blockers can completely block the transmission through ganglia.
A
nicotinic
all others can only modulate
21
Q
Depolarizing type blockers
moA
A
initially stimulate the ganglia (like ACh)
followed by longer term block due to a persistent depolarization
(i.e. nicotine)
22
Q
hexamethonium blockade
A
non-depolarizing (no receptor stimulation)
only acts by competing for ACh binding site
“plugs” the ion channel after it opens
23
Q
Mecamylamine
moA
A
non-depolarizing blocker
non-competitive
acts at a secondary site to decrease ACh binding (negative allosterism)
(Mecamylamine = Meek (wont compete or stimulate, just binds to secondary site)
24
Q
T/F
Mecamylamine is a non-competitive, non-depolarizing blocker by acting at the ACh site.
A
false
Does not act at ACh site
Allosterically changes ACh site
25
nicotine
cardiac fx
↑ HR by **initial stimulation of the sympathetic** ganglia
or
depressing the parasympathetic cardiac ganglia,
and vice versa
-chemoreceptors & medullary centers:
send increased or decreased signals to the heart via compensatory responses
-triggers **epi release** from adrenal medulla:
↑ HR & BP
26
Nicotine
overall SE
hard to predict
depends on state of person at that moment
27
hexamethonium is an example of which type of block?
non-depolarizing
ganglionic
28
Symptoms of ganglionic block
ie: hexamethonium
↑ skin bloodflow (warm and pink)
↓ sweating, lacrimation, salivation, GI tone/motility
mydriasis & cycloplegia
↓BP
urinary retention
constipation
hypoglycemia
(Use with *any* other drug can completely change Sx)
29
What causes warm pink skin seen with ganglionic blockade?
vascular predominant tone = sympathetic
blocking this = dilation
dilation = warm, pink skin
30
Bodily fluids predominant tone
Parasympathetic
ganglionic blockade:
↓ sweating, lacrimation, salivation
urine retention
atropine (anti ACh) = dry mouth
31
Eye predominant tone
parasympathetic (constricted pupil)
ganglionic blockade:
blocks parasymp→dilates pupil (mydriasis) & cycloplegia
32
cycloplegia
inability to focus eyes close for near vision
33
.
34
T/F
Arterial status contributes most to CO.
False
primary controller of CO are the veins
no venous return = no CO
35
controls lens of the eye
ciliary muscle
36
T/F
Ganglionic blockers can give you a stiffy!
False
decreased erection
decreased blood floow
37
T/F
Ganglionic blockade is not seen with drugs currently on the market due to safety concerns.
False
Some drugs currently used cause a certain extent of ganglionic blocker
38
Only ganglionic blocker still on the market
Mecamylamine
39
Mecamylamine
uses (past & current)
current status
OG usage: severe & malignant HTN
(safer & better drugs now)
~cocaine and nicotine addictions
Orphan drug status (FDA) for:
specific nicotine-responding neurological disorders (ie: Tourette’s)
40
Orphan drug status (FDA)
not many people use (3-5k ppl/month)
drug companies do as pro-bono
no profit made back
Manufctr benefit: prohibits generic status so the company can still make some sort of profit
41
T/F
nicotinic receptors can be found in the brain
True
42
T/F
Tourette’s syndrome is a muscarinic-responding neurological disorder
False
nicotine-responding
treat with Mecamylamine
43
Mecamylamine
does it cross the CNS?
what receptors does it affect?
Crosses CNS easily
blocks nicotinic receptors in brain & ganglia
note: acts at **secondary site** to decrease ACh binding (**negative** allosterism)
44
Mecamylamine
brain fx
blockade:
↓ dopamine & norepi release
modulates neuroendocrine responses
note: mecamylamine also blocks nicotinic rcptrs in the ganglia
45
Mecamylamine
At low doses...
CNS effects are seen with few peripheral side effects
bc amount given isnt enough to block all peripheral receptors; concentrates in brain
46
neuroendocrine/neurohormonal
affects other cells at a distance
47
Mecamylamine
C/A
potential peripheral activity
Hx MI, glaucoma, cerebrovascular Dz (i.e. stroke)
Avoid sudden d/c (rebound hypersensitivity effects possible)
pregnancy (crosses placenta)
48
Mecamylamine
adverse rxns
nausea and vomiting
anorexia
constipation
**mydriasis**
syncope
weakness
fatigue
Larger dose = peripheral fx
49
peripheral effects can be seen with (small/large) doses of Mecamylamine
large
50
NMB
blocks nicotinic receptors, but they are at the NMJ (N1/NMnicotinicR)
51
Ganglia and NMJ both respond to ___.
but what makes them different?
nicotine
both ionophore
but
spacing & structure different
52
d-tubocurarine chloride
derived from…
a plant extract of Chondodendron Tomentosum
53
Curare
generic term for arrowhead poison that can kill using skeletal muscle paralysis
54
Curare is a plant ___.
alkaloid
55
Curare
first use in humans
in 1932
treat tetanus & spasticity
56
How curare became part of anesthesia
1940’s
discovered to give adequate skeletal muscle relaxation during operative anesthesia without using excessive amounts of general anesthetics
57
tubocurarine
uses
aid to mechanical respiration
prevent trauma in electroconvulsive therapy
aids diagnosis of myasthenia gravis
58
d-tubocurarine chloride
current status
taken off market; cost and better agents exist
59
Suxx structure
succinate on choline molecule
60
currently used NMB with curare-like properties
Suxx
61
Suxx breakdown
ester hydrolysis → Succinic acid + choline
(Do not confuse with ACh: acetic acid & choline)
62
example of NMB developed and utilized over the last 50 years
Pancuronium
63
competitive nondepolarizing neuromuscular blocking agents
atracurium
cisatracurium
rocuronium
vecuronium
etc
64
NM site
Adult subunits
pentameric
2 Alpha-1
Beta
Delta
Epsilon
16 variations but this most common
65
Where does ACh form a momentary fairly strong bond using its ester component?
esteratic site
Alpha subunit
bond is not as strong as covalent
66
How many ACh sites at NMJ?
2
66
Where does the qua+ernary amine portion of ACh bind to?
delta & epsilon (the negative charges here attract it)
67
binding of .... allows ACh to open NMJ receptors and allow influx of ___.
ester portion to 2 A1 subunits
quat amine to delta & epsilon subunits
Na
68
Decamethonium
structure and how it works
Depolarizing
any initial stimulation = insignificant
Quat amine sites on delta and epsilon (like ACh)
but w/ 10 C spacer:
fits perfectly across channel to block Na influx
69
Pancuronium
structure & how it works
steroid nucleus
1 quat amine (to epsilon)
2 esters (to Alpha subunits)
also stretches across & blocks Na
"ronium → 'roids → steroid"
70
Two types of depolarizing blockers
Succinylcholine
Decamethonium (stimulation very little)
71
Depolarizing blockers
moA
initial stimulation (depolarization)
followed by long-term blockade
(d/t keeping receptor depolarized, and not able to repolarize for re-stimulation).
72
Suxx
main benefit
its very short duration (1 - 2 minutes)
73
Decamethonium
(experimental only; nicotinic blocker)
10 C chain separating two tri-methyl amines (Quats).
74
Decamethonium vs Suxx
both:
Depolarizing
work at NMJ
quat amines
Suxx: dual ester provides same spacing but allows quick metabolism!
75
Ganglionic blocker vs NMB
Hexamethonium vs Decamethonium
both block nicotinic receptors!
**ganglionic**: blocked by hexamethonium
(6C spacer between 2 quat/trimethyl amines)
**NMJ**: blocked decamethonium
(10C spacer between 2 quat/trimethyl amines)
spacers show these receptors are not the same!
decamethonium too big to work on ganglionic
76
Which are competitive antagonists of ACh?
non-depolarizing
depolaring
non-depolarizing
depo = suxx = mimics ACh
non-D = roc,vec,etc = compete with ACh @ NMJ
77
Non-Depolarizing blockers
competitive antagonists of ACh @ NMJ
blocks ACh from stimulating muscle @ motor end plate
↓
muscle weakness (lower doses)
paralysis (higher doses)
78
What gives Non-D NMBs their lack of stimulating properties & competitive nature?
lipid soluble groups at both ends
repeatedly release and rebind, going to diff locations
79
Has steroidal nucleus
Panc
Roc
P.R.: personal record (gym) = steroids
80
chemical blueprint for paralytic spacers
dont memorize
81
Shortest onset & duration
Suxx
82
Succinylcholine (Anectine)
Unique in its depolarizing mechanism
shortest-acting NMB
good ETT conditions w/in 60 sec, lasts 2—3 min
83
Suxx
SEs
transient sinus brady
hypotension
arrhythmias
tachycardia
**possible cardiac arrest by increased vagal stimulation**
Primarily d/t relatively strong depolarization
Can also cause hyperkalemia.
84
🔷(I dont understand)
Suxx
pretreament
anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias.
increases ACh that can compete with suxx
85
Can we give Suxx to a severely asthmatic pt?
no
significant histamine-release
Asthmatics very sensitive to histamine
↓
B.constriction
86
Rocuronium
short-acting(?)
nondepolarizing
effective RSI alternative to Suxx (short onset & fairly short doA)
87
Mivacurium was removed and put back on the market bc...
removed d/t manfcturing & patent issues
Short DoA made it a better agent than others so we brought it back
88
considered short-acting with a longer onset time but shorter duration than Rocuronium
Mivacurium
89
Intermediate-acting agents
Atracurium
Cisatracurium (Nimbex)
Vecuronium
DoE: 30 to 60 minutes
90
long-acting agent
Pancuronium
DoE: 60-120 min
91
Atracurium
metab
**nonspecific** serum esterases
Hofmann elimination
metabolized somewhat in tissues
small amount eliminated unchanged
! Laudanosine
92
mainly metabolized by Hofmann elimination
Cisatracurium
93
Cisatracurium
metab
mainly Hofmann degradation
greater potency & lower doses
↓
**limited** laudanosine risk
94
Mivacurium
metab
primarily plasma esterases
95
Hofmann Elimination
spontaneous
chemical deamination
(moving double bond & remove amine)
naturally occurs in aqueous environments
specific temperatures and pH
increases with high T & pH
96
T/F
Atracurium should not be given in liver or renal failure.
False
Hoffman + non-specific esterase degradation
the patient’s liver and renal function is not critical
97
Increases Hoffman elimination
hot & basic
high T & pH
98
Ester Metab products
(Atracurium)
hydrolysis
split ester off
↓
Pentamethylene-1,5-diol & 2 Quat structures
99
Hoffman elimination products
(Atracurium)
removes amine
↓
2 laudanosine molecules & spacer
100
T/F
Ester hydrolysis requires adequate renal and liver fxn.
False
101
Renally eliminated agents
Pancuronium
may require dosage reduction and careful monitoring in patients with renal impairment.
Panc = Peepee
102
primarily excreted by hepatic metabolism or biliary excretion
Rocuronium & Vecuronium
precautions if hepatic Dz
("LVR" = Liver Vec Roc)
103
Myasthenia Gravis
What is it?
How does it affect NMB dosing?
slower destruction of NM ACh receptors
Have less receptors
Block more fully with lower doses
SMALL DOSES can cause complete paralysis
104
Electrolyte imbalances that potentiate NMB
low Na
high K
“KANP”
K Alta N Pequeno
105
pseudocholinesterase deficiency:
Increases HL of compound
Potential accumulation
106
Mg & Ca salts
Mag inhibits the Ca
107
Conditions/Meds that can prolong/potentiate
myasthenia gravis
renal impairment
hepatic disease
pseudocholinesterase deficiency
**potentiate nondepolarizing:**
lithium
calcium salts
magnesium salts
IAs
certain antibiotics
LAs (quinidine, procainamide, lidocaine)
108
Histamine release
Suxx: moderate
Atracurium: mild-moderate
Cisatracurium: minimal
generally dose-related
CAUTION: asthma & cardiac Dz cardiopulmonary adverse effects:
flushing
hypoTN
sinus tachycardia (reflex to ↓TN)
bronchospasm
109
Agents which lack significant histamine-releasing effects and do not block cardiac muscarinic receptors
Rocuronium & Vecuronium
110
Prolonged blockade can result in...
muscle paralysis
apnea
dyspnea
respiratory depression
111
Patients at risk for prolonged neuromuscular blockade
conditions/medications:
-impairing neuromuscular function
(e.g., myasthenia gravis)
-potentiating NMB
(e.g., electrolyte imbalance; Low Na, high K)
112
Tachycardia is most common with ____, due to...
Pancuronium
blockade of muscarinic receptors
worsened by:
age, electrolyte imbalance, and renal or hepatic failure.
113
T/F
Phlebitis and pain is a/w depolarizing neuromuscular blockers.
False
non-depolarizing
114
asthmatic patients on steroids & steroidal neuromuscular blockers while on ventilator
(e.g., Vecuronium, Pancuronium)
acute myopathy lasting days to weeks
Exact cause not known
115
Malignant Hyperthermia
IAs
Suxx
triggered by combo of certain anesthetics & NMBs
initiated by uncontrolled release of Ca++ from the sarcoplasmic reticulum in skeletal muscle
more commonly with depolarizing + anesthetic
still possible w/ suxx or IA alone
116
Sugammadex (Bridion)
first in a new class known as SRBA’s
designed for Roc reversal agent
fairly good @ vecuronium & pancuronium too
117
Sugammadex (Bridion)
FDA approval
12/15/2015
multiple rejections for allergic reactions
(Low occurrence & minor reaction)
118
Sugammadex (Bridion)
structure
complex cyclodextrin ‘cage’
high lipophilicity
binds NMB & allows removal
roids bind inside cage and rapidly removed from body
