NMB Flashcards
1
Q
what the active component of NMB
A
1930’s: active component (d-tubocurarine) isolated
2
Q
what the components of skeletal muscles
A
voluntary action.
striated muscles,
they are multinucleated,
contain contractile filaments(actin and myosin
..cells are located in the ventral horn..front
Innervated by Large myelinated alpha motor neuron.
3
Q
Whats the innervation location for Skeletal muscles per NMB
A
Neuromuscular Junctions
4
Q
The effects of innervation are felt both on the Prysynaptic and postsynaptic t/f?
A
T
these are synapses where presynaptic motor nerve endings meet postsynaptic membrane of muscle cells
5
Q
what happens to the myelin sheat of motor neuron as the y approach the target muscle fibre?
A
On approaching a target muscle fiber motor neurons lose their myelin sheath and make contact with a single muscle fiber
6
Q
through what medium does the NMJ transmit impulse
A
Via acetylcholine
7
Q
Where is ACH synthesised and stored
A
synthesized in the presynaptic neuron & stored presynaptic vesicles
8
Q
When is Ach released
A
released in response to an action potential in the presynaptic neuron & this is a Ca2+-dependent process
9
Q
What does the process of Ach release depend on
A
this is a Ca2+-dependent process
Calcium dependent calcium release…releases quanta
10
Q
The binding of ACh is this reversible?
A
diffuses across the synaptic cleft & binds reversibly to specific receptor sites on the postsynaptic membrane
11
Q
After the Ach binds to the postsynaptic membrane,what happens next?
A
Postsynaptic membrane depolarizes & triggers an action potential that leads to muscle contraction
12
Q
How is Ach eliminated
A
ACh is eliminated from the synapse by acetylcholinesterase…
.acetate and choline(choline reused to make new ach)
13
Q
What do Hoffman elimination involve
A
ph. and temp dependent.
Either partial or competitive antagonist is the mech of action
14
Q
What are the adult Nicotinic Ach receptor characteristics
A
The ADULT receptor has two ⍺ subunits in association with a single β, δ, 𝜀 subunit
these form a channel, transmembrane pore,extracellular binding pockets for ach/agonist/antagonist
each ⍺ subunit has an Ach binding site
⍺ subunits are the binding site for Ach and the binding site for NMB’s
belong to a large pentameric family of ligand-gated ion channel receptors
15
Q
Explain what happens when ACh binds to nicotinic alpha subunits
A
Binding of Ach on both ⍺ subunits initiates an action potential
channel opens:
Na+ & Ca++ move into the skeletal muscle and K+ leaves
AP’s propagate and result in muscle contraction
16
Q
In relationship to junctional location of receptors what are theirs classess
A
Prejunctional and post junctional
17
Q
Whats the mechanism of action of the Prejunctional nicotinic receptors
A
are activated by acetylcholine and function in a positive-feedback control system, which could mediate mobilization of the reserve store into the readily releasable store in case of high-frequency stimulation; this mobilization serves to maintain availability of acetylcholine when demand for it is high (e.g., during tetanic stimulation).
18
Q
What happens when prejunctional nicotinic receptors are blocked
A
Blockade of the prejunctional nicotinic receptors by nondepolarizing NMBDs prevents acetylcholine from being made available fast enough to support tetanic or train-of-four (TOF) stimulation
19
Q
Characteristics of Fetal nAch Receptors
A
Immature or fetal receptors are mostly extra junctional
ϵ-subunit is absent and is replaced by the γ-subunit
all other subunits are the same as the mature receptor
the fetal receptors proliferate in denervation
resistant to non-depolarizing NMB and SENSITIVE to Succinylcholine
prolonged open channel time leads to exaggerated K+ efflux
Once activated by acetylcholine, the mature nAChR has a shorter opening time and a higher conductance to sodium (Na+), potassium (K+), and calcium (Ca2+) than the fetal nAChR, which has a smaller, single-channel conductance and a much longer open channel time Fetal receptors(extrajunctional) proliferate in sick(denervated) states during adult life…….. Cannot give succs after 24hr of burn….potassium efflux and sodium influx)
20
Q
How does the dose of Nondepolarizing NMB vary per sensitivity between
laryngeal adductors,diaphram and adductor pollicis
A
sensitivity of the neuromuscular junctions to the effects of neuromuscular relaxants among various muscle groups varies greatly
dose of nondepolarizing NMBDs needed to block the diaphragm is 1.5 to 2 times that of the adductor pollicis
Laryngeal adductors are also resistant relative to adductor pollicis
Explanation: higher receptor density, greater release of acetylcholine, or less acetylcholinesterase activity
21
Q
how does the NMbd vary with succs in reference to diaphram/larygeal adductors and adductor pollicis
A
Succinylcholine is the exception: @ equipotent doses, Sch causes greater neuromuscular block at the vocal cords than at the adductor pollicis
22
Q
What does affects the response to succs per blood flow and density of receptors
A
Despite the relative resistance to NMBDs, the onset of neuromuscular block is significantly faster at the diaphragm and the laryngeal adductors than at the adductor pollicis
Muscle blood flow is likely the reason
1-2x NMB to relax…density of receptors …per diaphragm…blood flood is greater….will loose central receptors first before peripheral receptors
E.g…laryngeal adductors or orbicularis orculli(supracilli muscle) vs adductor policis(Thumb)
Check twithes be4 NMB
Succs work good at the laryngeal Adductors
23
Q
things to watch for while using NMBS
A
Use for skeletal muscle relaxation in anesthetized individuals
Lacks analgesic or amnestic property
Should not be admin to prevent movement
Potential of awareness during surg
Patient may still be capable of sensory perception
Monitor time course of block and depth of anesthesia
24
Q
Advantages of using NMB for intubation
A
improved the quality of intubating conditions
decreased the frequency of vocal cord lesions following intubation
decreased rate of postoperative hoarseness
reduces the rate of adverse hemodynamic effects caused by deeper levels of anesthesia
avoidance of NMBD has been associated with more difficult tracheal intubation conditions compared with NMBD use
25
whats the mode of action of depolarizing NMB(Succ)
Depolarizing NMB’s (Succinylcholine is the only one) bind to the ⍺ subunit (one or both) and result in depolarization
not hydrolyzed by acetylcholinesterase so channels remain open
results in sustained depolarization & membrane hyperpolarization(efflux of K) that prevent propagation of an action potential(absolute refractory period)
this is partial agonism
26
Mode of action of non-depo NMB
Non-depolarizing NMB’s competitively bind to one or both ⍺ subunits on the postsynaptic nAchR but do not result in depolarization
this is competitive blockade (competitive antagonists)….
27
All NMB’s are quaternary ammonium compounds structurally related to Ach…(hydrophyllic)
The ⍺ subunits that bind Ach are also the binding site for all NMB’s
True or false
T
28
For ambulatory patients what's the effects of succs per myalgias,will it be more or less
More myalgias and significant amount of rigidity
29
What happens with bedridden people per potassium with succs
More hyperkalemia with succ ..per disuse..that will give proliferation with extra junctional fetal receptors in bedridden pts
30
What happens with immobility and succs,burn pt,paralysis,paraplegia
After 24hrs in a burn/paralysis/paraplegia/quadreplegia we do not give nmb.
Fetal ach receptors up regulate in denervated conditions.they function normally but they stay open longer..
Any immobility for about 1-2weeks may give s risk with succs.
May give calcium and stabilize membrane be4 using succs…to counter balance the elevated potassium that may arise from this.
31
Structure and mechanism of action of succs
Structurally 2 molecules of Ach bound together (linked through the acetate methyl groups)
Partial agonist
Termination of action is by diffusion away from the NMJ
Depolarizes upon binding to one of the alpha subunits of the nAchR
Tetany of muscles/depolarization/fascilation
also has effect on muscarinic autonomic receptors
NOT hydrolyzed by acetylcholinesterase
Channel stays open and no further action potentials can be transmitted
32
Explain the 3 avenues that succs use to cause blockade
This mechanism results in
(1) desensitization of the nAChR,
(2) inactivation of voltage-gated Na+ channels at the neuromuscular junction, and
(3) increases in K+permeability in the surrounding membrane.
The end results are failure of action potential generation and neuromuscular blockade
33
what is the technique to reduce fasciculations
Small doses of different nondepolarizing NMBDs(Rocuronium) administered before
succinylcholine to prevent fasciculations(Does not prevent Myalgias) have an antagonistic effect on the
development of subsequent depolarizing block produced by succinylcholine
Therefore it is recommended that the dose of succinylcholine be increased after the administration
of a defasciculating dose of a nondepolarizing NMBD.
34
SUCC dose
elimination half time 47secs
Intubating dose is:
-1.0mg/kg (up to 1.5 mg/kg)
-Higher (1.5mg/kg) if defasciculating NDNMB given
Dose determines onset/inc dose …inc DOA
have to
intubate within 30-60secs
Ave time to 90% muscle recovery...9-13mins
35
Metabolism of succs
hydrolysis by butyrylcholinesterase/acetyl cholinesterase,pseudocholinesterase (plasma cholinesterase)
VD ..takes more drug to have an effect
36
Recovery from block happens by what rational
diffusion away from NMJ down a concentration gradient
37
What causes succs to have a short duration of action
The ultrashort duration of action of succinylcholine results from its rapid hydrolysis by butyrylcholinesterase to succinylmonocholine and choline. Butyrylcholinesterase has a large enzymatic capacity to hydrolyze succinylcholine, and only 10% of the intravenously administered drug reaches the neuromuscular junction
38
Characteristics of Butyrylcholinesterase
| (plasma cholinesterase) and what inhibits or potentiates it
Synthesized by liver; found in plasma
Metabolizes Succinylcholine via hydrolysis
reduced in advanced liver disease, advanced age, malnutrition, pregnancy, burns, oral contraceptives, use of MAOI’s, echothiophate (eye gtt), cytotoxic drugs, neoplastic disease, anticholinesterase drugs, metoclopramide, and bambuterol (prodrug of terbutaline), esmolol (modest increase)..neosytigmine can increase the DOA of Succs
Term pregnancy= 40% reduction in plasma cholinesterase.
does not prolong duration due to increased VD
Genetic variation can significantly prolong duration of Sch
39
Characteristics of Butyrylcholinesterase
| (plasma cholinesterase) and what inhibits or potentiates it
Synthesized by liver; found in plasma
Metabolizes Succinylcholine via hydrolysis
reduced in advanced liver disease, advanced age, malnutrition, pregnancy, burns, oral contraceptives, use of MAOI’s, echothiophate (eye gtt), cytotoxic drugs, neoplastic disease, anticholinesterase drugs, metoclopramide, and bambuterol (prodrug of terbutaline), esmolol (modest increase)..neosytigmine can increase the DOA of Succs
Term pregnancy= 40% reduction in plasma cholinesterase.
does not prolong duration due to increased VD
Genetic variation can significantly prolong duration of Sch
Neostigmine and pyridostigmine inhibit butyrylcholinesterase, as well as acetylcholinesterase
Procaine
40
How is succ terminated
the neuromuscular blockade induced by succinylcholine is terminated by its diffusion away from the neuromuscular junction into the circulation.
41
what does Butyrylcholinesterase innfluence per phamacokinetics of Succs
therefore influences the onset and duration of action of succinylcholine by controlling the rate at which the drug is hydrolyzed before it reaches, and after it leaves, the neuromuscular junction
42
Dibucaine and charateristics of interpretation
Amide local anesthetic that that can be used in the lab to test for genetic variation in plasma cholinesterase
reflects quality and not quantitiy of enzymes
1: 3500 people are homozygous for the variant; 4 to 8 hour neuromuscular block w/ Sch
Dibucaine inhibits the NORMAL enzyme to a greater extent than the ABNORMAL enzyme
Under standardized test conditions, dibucaine inhibits the normal enzyme by approximately 80% and the abnormal enzyme by approximately 20%
Have to check twitches between giving a depolarizer and nor depolarizer.
43
when should we do twitch check per NMB
Twitch check..
B4 paralytic
Onset of paralytic..
Before giving non-depolarizer
44
What are the cardiovascular effects of Succs
Actions at cardiac muscarinic cholinergic receptors can cause bradycardia
Most likely with children and/or when 2nd dose is given within ~5 minutes of first dose
ANS ganglionic stimulation can cause increased HR & BP
Autonomic stimuli can also cause ventricular dysrhythmias during laryngoscopy
Hyperkalemia: 0.5 mEq/dL increase in healthy patients
severe, life-threatening hyperkalemia in patients with burn, severe abdominal infections, severe metabolic acidosis, closed head injury, or conditions leading to upregulation of extrajunctional acetylcholine receptors
Succinylcholine is NOT routinely recommended in children due to potential for massive rhabdomyolysis, hyperkalemia, and death due to undiagnosed muscle disease
May be used in children in emergency tracheal intubation
Ventricular arrythmias,…..
Give atropine and succs together
45
What should you do if severe hyperkalemia result because of Succs
Severe hyperkalemia may follow the administration of succinylcholine to patients with severe metabolic acidosis and hypovolemia. In patients with metabolic acidosis
and hypovolemia, correction of the acidosis by hyperventilationand sodium bicarbonate administration should be attempted before succinylcholine administration. Should
severe hyperkalemia occur, it can be treated with immediate hyperventilation, infusion of 500-1,000 mg calcium chloride or calcium gluconate over 3 minutes intravenously,
and 10 units of regular insulin in 50 mL of 50% glucose for adults or, for children, 0.15 units/kg of regular insulin in 1.0 mL/kg of 50% glucose intravenously
46
NAch receptors up regulate
Gullain-Barre
Multiple sclerosis
prolonged exposure to NMb
prolonged Immobility
Burns
stroke
spinal cord injury
47
NAchr Downregulation
Myasternia gravis
Anticholinesterase poisoning
Organophosphate
48
whats the effect of upregulation of receptors
Up-regulation leads to sensitivity to Sch with life-threatening hyperkalemia and resistance to NDNMB’s
49
Side effects of succ
Myoglobinuria- usually seen only after administration to patients with malignant hyperthermia or muscular dystrophy
Increased ICP- attenuated with pretreatment with a small dose of NDNMB
Increased intragastric pressure: evidence of clinical harm unclear
Increased IOP; peaks at 2-4 min; subsides in 6 minutes..can still use
Myalgias: increased incidence in women and ambulatory patients
Masseter spasm- Sch is a trigger for malignant hyperthermia; can be an early sign heralding MH
Masseter spasm does not always herald MH
Anaphylaxis 0.06%- previous reaction may have cross-reactivity with other NMB’s- much more common in Europe/ Australia
50
For increaesed IOP with Succ ,whats the outcome
Increased IOP; peaks at 2-4 min; subsides in 6 minutes..can still use
51
How can we decrease increase IOP,and what can cause increase IOP more than Succs and is this a contraindication interms of succs?
Despite this increase in IOP, the use of succinylcholine for eye operations is not contraindicated unless the anterior chamber is open.
Although Meyers and colleagues were unable to confirm the efficacy of small (0.09 mg/kg) doses of dTc (“precurarization”) in attenuating increases in IOP following succinylcholine numerous other investigators have found that prior administration of a small dose of nondepolarizing NMBD (e.g., 3 mg of dTc or 1 mg of pancuronium) prevents a succinylcholine-induced increase in IOP
IOP: Other factors include endotracheal intubation and “bucking” on the endotracheal tube once it is positioned.
Of prime importance in minimizing the
chance of increasing IOP is ensuring that the patient is well
anesthetized and is not straining or coughing.
For instance, coughing, vomiting and maximal forced lid closure may
induce increases in intraocular pressure that are 3-4 times greater (60-90 mm Hg) than those induced by succinylcholine administration.
52
Denervation
Innnervated muscle: SCh-induced depolarization occurs only in the junctional area with limited efflux of K+ from the cell to the extracellular space.
Denervated muscle:
upregulated and extrajunctional AChRs
SCh comes into contact with all the AChRs throughout the muscle membrane
massive efflux of K + into the extracellular fluid with potentially lethal hyperkalemia
53
Compare denervationa dn innervation in relations ship to potassium in the cell and out of the cell,causing hyperkalemia with succ
Innnervated muscle: succ-induced depolarization occurs only in the junctional area with limited efflux of K+ from the cell to the extracellular space.
Denervated muscle:
upregulated and extrajunctional AChRs...
Succ comes into contact with all the AChRs throughout the muscle membrane
massive efflux of K + into the extracellular fluid with potentially lethal hyperkalemia
54
What causes malignant hypertention ,what are the symptoms,what whould be avoided
Calcium ion channel defect in the ryanodine receptor leads to failure of the Ca++ ion active transport pump following muscle contraction
Leads to sustained muscle contraction and heat production
Triggered by succinylcholine and volatile anesthetics
Triggering agents are avoided in patients with susceptibility
55
What are the symptoms of MH
Inc Etco2 and sustained for that matter…can lead to cardiac arrest,….no succs and no volatile anesthetics
56
Succ black Box Warning warning
Administration in children carries risk of cardiac arrest and sudden death
Risk due to undiagnosed skeletal muscle myopathy
X-linked, recessive Duchenne’s muscular dystrophy is the most common
Absence of dystrophin
57
Classes of non depolarizing NMB
steroidal:
Pancuronium,
Vecuronium,
Rocuronium
```
benzylisoquinolinium:
D-Tubocurarine
Atracurium
Cistracurium
Mivacurium
```
Assymetric mixed-onium Fumarates:
CW002
Gantacurium.
58
Classification of NMB per duration of action
Long Acting>50min
Pancuronium
d-Tubocurarine
Intermediate-acting(20-50min)
```
Vecuronium
Rocuronium
Atracurium
Cisatracurium
CW002
```
Short-acting(10-20)
Mivacurium
Ultrashort-acting(<10min)
Gantacurium
59
What determines the speed of onset of the NMBD
The speed of onset is inversely proportional to the potency of nondepolarizing neuromuscular blocking drugs. With the exception of atracurium, molar potency is highly predictive of a drug’s rate of onset of effect. Rocuronium has a molar potency that is approximately 13% that of vecuronium and 9% that of cisatracurium. Its onset of effect is more rapid than either of these muscle relaxants.
60
What determines the drug potency for NMBD
```
Drug potency is commonly expressed by the dose-response relationship. The dose of an NMBD required to produce
an effect (e.g., 50%, 90%, or 95% depression of baseline twitch height, commonly expressed as ED50, ED90, and ED95, respectively) defines its potency
```
61
What is the difference in onset between a potent and non potent NMDB
whats the exception to the rule
When a potent drug is administered, fewer molecules are given than in a case of a less potent drug, and the onset will be slower compared to onset of lower potency NMBD
Atracurium is an exception to this general rule
62
What amount of receptor needs to be occupied for a block to happen
A critical number of receptors at the neuromuscular junction must be occupied before appearance of neuromuscular block
90% of the receptors must be occupied before block is complete at the adductor pollicis
63
Explain the reason for slow onset in Cistracurium
Buffered diffusion causes repetitive binding and unbinding to receptors, thus keeping potent drugs in the neighborhood of the effector sites and potentially lengthening the duration of effect. This phenomenon is probably what contributes to the slower onset time for cisatracurium
64
Explain the slow onset time for MIvacurium
. However, for very short-acting drugs, the ideal ED95 might be greater (0.5-1.0 mg/kg) because rapid metabolism in the plasma destroys some of the administered muscle relaxant before it reaches the neuromuscular junction. This phenomenon can explain the relatively slow onset time for mivacurium
65
What affects the time to blockade
the intensity of maximum blockade is affected directly by the administered dose
when the dose increases in the SUBparalyzing range (maximum blockade is between 0% and 100%), time to reach maximum effect is dose-independent.
When the administered dose, however, is sufficient to effect complete disappearance of neuromuscular response, time to maximum blockade becomes dose-dependent
66
FYI
Opioids enhance muscle relaxant..
Desflurane enhances neuromuscular blockers
…..
67
Memorise slide 27
now....NMBD lecture
68
Which NMBD can be given to asthmatics
Cisatracurium
vecuronium
Rocuronium
Pancuronium
69
Know slide 29
Now
70
Know slide 30
Now
71
Characteristicsof d-Tubocurarine
no active metabolism
excreted unchanged in the urine; hepatic secondary route
not indicated in renal or hepatic failure
onset: slow
duration of action: long
HISTAMINE release
72
Atracurium charateristics
Benzylisoquinolone; intermediate acting
Racemic mixture of 10 stereoisomers
Hofmann Elimination: Spontaneous degradation at physiologic temperature and pH & ester hydrolysis
Laudanosine, a CNS stimulant, is a metabolite & can cross BBB (seizures)
70% excreted in the bile and the remainder in urine
excretion impaired in biliary obstruction
Dose 0.5mg/kg
Onset 2-2.5 minutes, max neuromuscular block 3-5 minutes
HISTAMINE RELEASE (dose dependent and greatest at doses >0.5mg/kg)
73
Explain hoffman elimination reaction
In a Hofmann elimination reaction, a quaternary ammonium group is converted into a tertiary amine through cleavage of a
carbon-nitrogen bond. This is a pH- and temperature dependent reaction in which higher pH and temperature favor elimination
74
Explain Histamine release
histamine release: flushing, hypotension, reflex tachycardia, and bronchospasm can be seen
75
Characteristics of Cisatracurium
Benzylisoquinolone; intermediate acting
1R cis–1’R cis isomer of atracurium
Hofmann Elimination (77%), renal clearance (16%)
NO ester hydrolysis
Laudanosine is also produced but at much lower amounts (1/5 of atracurium)
Dose 0.1mg/kg (about 4-5 x’s more potent than atracurium)
NO HISTAMINE RELEASE
Like atracurium, cisatracurium undergoes Hofmann elimination. It is approximately four times as potent as atracurium, and in contrast to atracurium, it does not cause histamine release,90,92 thus indicating that histamine release may be stereospecific
76
Mivacurium Characteristics
```
Benzylisoquinolone; short acting
Only short-acting NDNMB
Reintroduced in US in December 2016
Metabolized by plasma cholinesterase
HISTAMINE release
```
Mivacurium is metabolized by butyrylcholinesterase to a monoester and a dicarboxylic acid at 70% to 88% the rate at which succinylcholine is metabolized by the same enzyme.
77
Pancorunim characteristics
Steroidal non-depolarizing NMB; long-acting
Direct vagolytic and sympathomimetic activity
Renal clearance 40-60% cannot be given in renal failure.
3-OH metabolite accumulation leads to prolongation of NMB
The 3-OH metabolite is the most potent of the three metabolites, being approximately half as potent as pancuronium, and is the only one
present in detectable concentrations in the plasma. This metabolite has pharmacokinetics and duration of action similar to those of pancuronium. The 3-OH metabolite
is most likely excreted largely by the kidney. The parent compound and the 3-OH metabolite are also cleared in small amounts through a minor liver pathway. The
total clearance is delayed, and the duration of action is significantly lengthened, by severe disorders of renal or hepatic function.
78
Vecuronium characteristics
read slide 36 also
Steroidal non-depolarizing NMB; intermediate-acting
Chemical structure similar to pancuronium
Primarily hepatic metabolism; elimination: 40-50% liver & 30% renal
3-OH metabolite can accumulate as with pancuronium
Must be stored in powder form…more reliable when reconstituted….from powder form..
The principal metabolite of vecuronium, 3-desacetylvecuronium, is a potent NMBD (≈80% of the potency of vecuronium). The metabolite, however, has slower plasma clearance and longer duration of action than vecuronium
79
Characteristics of Rocuronium
read slide 37
Steroidal non-depolarizing NMB; intermediate-acting
Primarily eliminated by the liver (>70%), renal 10-25%
Shortest onset of the NDNMB’s
Can be used for RSI in high doses (1.2 mg/kg)
6-10x less potent
Terminal sterilization which causes degredation
80
memorise slide 38
now
81
What increases the potencies of nmbds
Inhalational anesthetics (desflurane increases potency the most)
Aminoglycoside antibiotics, polymyxins, lincomycin, clindamycin, tetracyclines
Hypothermia
Magnesium sulfate….
Local anesthetics (in large doses)
Some antidysrhythmics
Dantrolene
82
what decreases the potencies of nmbds
chronic anticonvulsant therapy: increase dose and frequency
| hypercalcemia
83
The order of effect of inhaled anesthetics on NMBDS per potentiation.....mostt----least
: Inhaled anesthetics also enhance the neuromuscular blocking effects of nondepolarizing NMBDs. Inhaled anesthetics decrease the required dose of NMBDs, and prolong both the duration of action of the NMBD and recovery from neuromuscular block, depending on the duration of anesthesia,
the specific inhaled anesthetic,232 and the concentration (dose) given.233 The rank order of potentiation is desflurane > sevoflurane > isoflurane > halothane > nitrous oxide/barbiturate/opioid or propofol anesthesia
84
Explain how abx and what kind of abx causes NMBDS
Most antibiotics can cause neuromuscular blockade in the absence of NMBDs. The aminoglycoside antibiotics, the polymyxins, and lincomycin and clindamycin primarily inhibit the prejunctional release of acetylcholine and also depress postjunctional nAChR sensitivity to acetylcholine.241 The tetracyclines, in contrast, exhibit postjunctional activity only. When combined with NMBDs, the aforementioned antibiotics can potentiate neuromuscular blockade.242 The cephalosporins and penicillins have not been reported to potentiate neuromuscular blockade
85
Explain RSI related to potency and onset potency
Recall: Speed of onset of action is inversely proportional to the potency of NDNMB
Low potency= rapid onset
High potency= slow onset
Rapid onset: Sch (depolarizing NMB) and Rocuronium (faster onset approaching Sch with increased dose of 1.2 mg/kg)
Rocuronium in high dose (0.9-1.2 mg/kg) or succinylcholine 1.5 mg/kg can be used interchangeably for rapid tracheal intubation because they provide adequate intubating conditions within 60 to 90 seconds
if succinylcholine is considered undesirable or contraindicated, high doses of rocuronium can be administered
86
Explain defasciculation and what to use to tackle this
10% of intubating dose of NDNMB to prevent Sch induced fasciculation
Fasciculations increase risk of hyperkalemia, myalgias, increases intra-gastric pressure and aspiration
Can temporize increase in ICP when SCh used in increased ICP
Dose of defasciculating agent:
Rocuronium = 0.06 - 0.1 mg/kg (usually 5-10 mg)
87
What causes Histamine release
When large doses of certain NMBDs are administrered rapidly.
erythema of the face, neck, and upper torso may develop
brief hypotension and a slight to moderate increase in HR
bronchospasm is very rare
effects involve chemical displacement of the contents of mast cell granules containing histamine, prostaglandin, and possibly other vasoactive substances
histamine release is most often noted following administration of the benzylisoquinolinium class of muscle relaxants
usually short duration (1-5 minutes); dose related; usually clinically insignificant
88
Explain anyphylaxis per NMBDS
Largest proportion of allergic reactions under anesthesia attributed to muscle relaxants (French study)
NMBDs (60.6%), antibiotics (18.2%), dyes (5.4%), and latex (5.2%)
Cross-reactivity occurs between NMBDs and food, cosmetics, disinfectants, and industrial materials
IGE response/ mast cell degranulation
Suspected allergic reaction: stop drug, give 100% oxygen, small doses of IV epi (10-20 mcg), give crystalloids, consider need for intubation (angioedema), +/- antihistamines & steroids
Consider cross-sensitivity in up to 70% with a previous NMBD reaction
NMB or abx account for most reactions
. Anaphylactic reactions are mediated through immune responses involving immunoglobulin E (IgE) antibodies fixed to mast cells. Anaphylactoid reactions are not immune mediated and represent exaggerated pharmacologic responses in very rare and very sensitive individuals. However, anaphylaxis to nondepolarizing NMBDs is not uncommon in patients without any previous exposure to any nondepolarizing NMBDs. Cross-reactivity occurs between NMBDs and food, cosmetics, disinfectants, and industrial materials
89
How do we maintain paralysis
main goal in dosing NMBDs should be to use the lowest possible dose that provides adequate relaxation for surgery
avoids prolonged residual paralysis & inadequate antagonism of residual blockade
Clinical management of individual patients should be guided by monitoring of the neuromuscular block, ideally with an objective neuromuscular monitoring technique
Supplemental (maintenance) doses of NMBDs should be approximately one tenth (in case of long-acting NMBDs) to one fourth (in the case of intermediate- and short-acting NMBDs) the initial dose and should not be given until quantitative evidence of beginning recovery from the previous dose is present
Relaxation can be maintained by continuous infusion of intermediate- and short-acting drugs. This approach is useful in maintaining a stable depth of neuromuscular blockade and allows adjustment of the depth of relaxation according to surgical needs
90
FYI
Combining NMBDs will either be additive or synergistic- drugs n the same class are usually additive and 2 different classes (example mivacurium with rocuronium) are synergistic
