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Anesthesia Pharm > Week 5 - Neuromuscular Junction, Relaxants & Antagonists > Flashcards

Week 5 - Neuromuscular Junction, Relaxants & Antagonists Flashcards

1
Q

How does an action potential stimulate the distal motor nerve?

A
  • Ca++ diffuses in terminal and voltage gated C++ channels open
  • Synaptic vesicles fuse to the presynaptic membrane
  • ACh is released into the cleft (10,000 molecules per vesicle)
  • Presynaptic nicotinic receptor responds to the presence of ACh by synthesizing more and mobilizing ACh vesicles (+ feedback)
  • ACh binds to the nicotinic ACh receptors on the surface of the post-junctional membrane —Contraction occurs
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2
Q

How is the Ca++ channel activated at the NMJ?

A
  • During nerve action potential
  • Na+ flows into the cell and depolarizes the voltage gated Ca++ channels
  • Ca++ influx triggers the release of ACh
  • ACh combines with postsynaptic nicotinic receptors
  • BOTH alpha subunits must be occupied to open the ion channel (Na & Ca diffuse IN; K diffuses OUT)
  • Ca++ influx continues until depolarization and the channels inactivate
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3
Q

How is ACh hydrolyzed?

A

by ACh esterase (AChE) to Choline and Acetic Acid

-Choline is taken up by presynaptic terminal for resynthesis of ACh

ACh depolarizes the NMJ and is rapidly metabolized by AChE

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4
Q

What is the release of neurotransmitters dependent upon?

A

The entry of Ca++

Hypocalcemia decreases release
Hypercalcemia increases release

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5
Q

How does hypo- and hypermagnesemia affect neurotransmitter release?

A

Hypomagnesemia increases release

Hypermagnesemia decreases release

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6
Q

What is the structure of the nicotinic ACh receptor?

A

a five subunit complex with 2 alpha, 1 beta, 1 delta, and 1 gamma

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7
Q

What occurs in up-regulated ACh receptors?

A
  • ACh receptor agonists see increased sensitivity
  • ACH receptor antagonists see decreased sensitivity (ie NDMRs)
  • These patients require increased dosages or shorter redosing intervals of the NMDRs

*Occurs in denervation injuries – burns

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8
Q

What occurs in down-regulated ACh receptors?

A

Occurs in Myasthenia Gravis

  • ACh receptor agonists see decreased sensitivity and require higher doses (Sux)
  • ACh receptor antagonists see increased sensitivity and require lower dosages of NDMR and longer intervals between redosing
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9
Q

What is the mechanism of action of depolarizing muscle relaxants

A

depolarize the nicotinic ACh receptor — NOT competitive

-action similar to ACh

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10
Q

Where does SUX attach to the nicotinic receptor?

A

SUX attaches to the 2 alpha subunits and causes depolarization

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11
Q

How is SUX metabolized?

A

By Butyryl-cholinesterase (BCH-esterase)
-NOT present in the NMJ but found in the plasma

  • After depolarization, SUX remains in the synaptic cleft until plasma level lowers and creates a concentration gradient out of the cleft
  • When it moves out of the cleft, circulating BCH-esterase metabolizes the remaining SUX
  • About 80-90% of a SUX dose is metabolized in the blood on the way to the NMJ
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12
Q

What is the mechanism of action of Non-Depolarizing muscle relaxants?

A

Competitive block – compete for ACh binding sites on the nicotinic receptor

  • When NDMRs bind to the nAChr it prevents the ion channel from opening preventing depolarization of the membrane
  • NDMRs completely BLOCK ACh from binding to the receptor and the post-synaptic membrane remains polarized (non-depolarized block)
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13
Q

What are characteristics of a non-depolarized block?

A
  • it is from competitive inhibition of nAChr
  • Shows FADE on TOF monitor (4 twitches can be different strengths)
  • Can see post-tetanic facilitation (increase in TOF after tetanic stimulation)
  • Can be antagonized (reversed) by AChE
  • Do NOT see fasciculations (no depolarization)
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14
Q

What are the benefits of muscle relaxation?

A

Improve surgical conditions

Facilitate endotracheal intubation

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15
Q

What are the risks associated with muscle relaxation?

A

No analgesic or anesthetic properties whatsoever by themselves

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16
Q

What’s the difference between neuronal nAChr and fetal nAChr?

A

Neuronal (mature): presynaptic nerve ending – has a shorter burst duration and higher conductance of Na, K, and Ca than fetal

Fetal - post-synaptic; during development and denervation, and in immobilization and burn injury

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17
Q

When is the nicotinic ACh receptor closed and open?

A

Closed during resting states

Opens when ACh binds to the 2-alpha subunits and a conformational change occurs

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18
Q

What does the ED50 of a muscle relaxant mean?

A

the dose at which a muscle relaxant produces a 50% depression of twitch tension in the nicotinic ACh receptor

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19
Q

What does a depolarizing neuromuscular blocker do?

A

1) Desensitizes the nACh receptor
2) Inactivates the voltage gated sodium channel and the NMJ
3) Increases potassium permeability in the surrounding membrane

*Due to these no action potential can be generated and ACh blockade occurs

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20
Q

What is the sensitivity of fetal nACHr to NDMRs and Succinylcholine?

A

Resistant to NDMRs

More sensitive to Succinylcholine

*Fetal nACHr are low-conductance channels, thus ACh release causes brief activation and reduced probability of channel opeing

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21
Q

Neuromuscular blockade develops faster, is less profound (deep), and wears off (recovers) sooner in ______ located muscles?

A

centrally located muscles – i.e. larynx and diaphragm

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22
Q

What percent of nAChr need to be blocked for twitch to be completely eliminated?

A

90%

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23
Q

What are clinical tests that can be used to monitor cessation of neuromuscular block and return of muscle function?

A

1) 5-second, unaided, maintained head lift - equivalent to a NIF of -55 cmH2O - can be done with TOF ratio as low as 50%
2) Lift legs off the OR table - NIF of -50 cmH2O
3) Strong handgrip from which you cannot remove your two fingers
4) Tidal volume - requires only return of diaphragmatic muscle tone (can still pull 5 mL/kg with 80% of nAChr still occupied by NDMR)
5) Head lift and hand grip may be only 38% and 43% of control strength when inspiratory/expiratory flow rates are 90% of baseline
6) Inspiratory force may be only 70% of baseline when vital capacity and expiratory flow rates are 90% of control values

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24
Q

What type of compounds are all neuromuscular blockers?

A

Quaternary Ammonium Compounds

  • positive charges at these sites mimic the quaternary nitrogen atom of ACh and allow the blockers to attach to the nicotinic ACh receptor at the NMJ
  • also affect other nACh receptor sites (autonomic ganglia, sympathetic/parasympathetic ANS, and prejunctional nicotinic/muscarinic receptors in the NMJ)
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25
Q

What is the mechanism of action of Succinylcholine?

A

Depolarizing muscle relaxant — agonist at the NMJ (may have action at both muscarinic and nicotinic receptors)

-Mimics the action of ACh by binding the alpha subunits of the cholinergic nicotinic receptor at the NMJ and also at nicotinic ganglionic muscarinic autonomic receptors in the autonomic ganglia

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26
Q

What is the duration of action, onset time, recovery time, and ED95 of SUX?

A

Duration of Action = Ultrashort (rapid onset/rapid offset)

Onset = 0.5 - 1.5 min (45-60 seconds at 1 mg/kg)

Duration to 90% recovery = 8-15 minutes (9-13 min) at 1 mg/kg dose

ED95 = 0.25 - 0.3 mg/kg

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27
Q

What is the dosing for SUX? How is it supplied?

A

Typical Dose = 0.3 - 1 mg/kg

Classic Dose = 1 mg/kg — (results in complete suppression of neuromuscular response in 60 seconds)

Newer Dose = 0.5-0.6 mg/kg

*provided in a concentration of 20 mg/mL in a 10mL vial (200mg/vial)

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28
Q

What diseases or drugs prolong the duration of action of SUX?

A

Liver Disease — Advanced Age — Malnutrition — Pregnancy — Burns — Oral Contraceptives — MAOIs — Ecothiophate — Cytotoxic Drugs — Neoplasms — Anticholinesterases — Tetrahydroaminacrine — Hexafluorenium — Metoclopramide

(All decrease BCH-esterase activity, thus less SUX metabolism and prolonged duration of action)
*longest duration related to these issues has been reported as 23 minutes

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29
Q

What is the Dibucaine number?

A

It communicates how inhibited the action of BCH-esterase is by Dibucaine (tests for atypical BCE genetic variant)

  • Normal = 70-80 — will have a normal duration of action of succinylcholine
  • Homozygous atypical BCE person = 20-30 — will have prolonged action of SUX up to 4-8 hours and possible 24 hrs
  • Heterozygous atypical BCE person = 50-60 — will have 50-100% longer duration of action of SCX (~30 minutes)

*High # = normal action Low # = poor action

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30
Q

What are the CV side effects of SUX?

A
  • At low doses: BOTH negative inotropic and chronotropic effects may occur (decreased contractility/HR)
  • At higher doses: tachycardia may occur
  • Cardiac dysrhythmias, sinus brady, junctional and ventricular dysrhythmias
  • sinus brady especially in children (they have lots of vagal tone and SUX simulates cardiac muscarinic receptors in the SA node)
  • ventricular dysrhythmias may occur due to the increase in catecholamines and potassium increase (33%) after SUX dose
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31
Q

Why does hyperkalemia occur with SUX administration?

A

Via depolarization of the NMJ, Na+ moves into cells and K+ moves out of cells
-causes temporary 0.5 mEq/L increase in K+ levels

  • Usually tolerated well in healthy patients
  • Significant increase in pt’s with hypovolemia and metabolic acidosis
  • Increased risk in conditions that lead to an increase in extrajunctional receptors
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32
Q

How do you treat severe rapid onset of Hyperkalemia?

A
  • Hyperventilation
  • 1-2 mg Calcium Chloride IV
  • 50 mL D50 IV + 10 units IV insulin (Adults) or 1 mL/kg D50 + 0.15 U/kg insulin (Peds)
  • 1 mEq/kg Sodium Bicarb
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33
Q

What effect does SUX have on Intra-Ocular Pressure?

A

Results in increased Intraocular Pressure within 1 minute, peaks 2-4 min, and subsides in 6 min

-SUX is contraindicated in eye injuries that result in an open anterior chamber

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34
Q

What effect does SUX have on Intra-gastric pressure?

A

it increases intra-gastric pressure

  • Normal pressure = 20 cmH2O
  • Greater than 28 cmH2O to vomit
  • SUX raises pressure to 30 cmH2O

*may be an issue in pt’s with gastroesophageal junction issues – May increase risk of aspiration

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35
Q

What effect does SUX have on ICP?

A

It does increase ICP but clinical significance has not been determined

36
Q

What are side effects of SUX?

A
  • Modest stimulation of autonomic ganglia
  • Histamine release
  • Tachycardia is common but bradycardia also, esp in children
  • Decreased BP
  • Hyperkalemia
  • Increase intraocular pressure
  • Increased intra-gastric pressure
  • Increased ICP
  • Myalgias (muscle pain)
  • Masseter Spasm (exaggerated contraction of NMJ in the jaw)
  • Malignant hyperthermia
37
Q

What is malignant hyperthermia?

A

hereditary familial disease in which inhalation agents or succinylcholine “trigger” muscle rigidity producing a hypermetabolic state resulting in tachycardia, respiratory and metabolic acidosis, hyperkalemia, hypercarbia, and dramatic increases in temperature (up to 107)

  • myoglobinemia and dramatic increase in CPK occur
  • renal failure is a potential complication as well as cardiac failure and death

*muscle contracture during MH is NOT reversible by non-depolarizing muscle relaxants

38
Q

What are early signs of malignant hyperthermia?

A 
Abrupt increase in EtCO2
Tachycardia
Tachypnea
High EtCO2 despite adequate tidal volume
Purple baralyme
Dysrhythmias
Mottling of skin

*Elevation of core temp is a late sign

39
Q

What is Dantrolene and its mechanism of action?

A

Specific treatment for malignant hyperthermia

It inhibits calcium release from the sarcoplasmic reticulum

40
Q

What is the dosing of Dantrolene?

A

Initial dose 2 mg/kg
Repeat 2 mg/kg up to 10 mg/kg

  • it is supplied in 20 mg of dantrolene bottles with sodium hydroxide and mannitol – needs to be reconstituted with sterile water
  • Decreasing temperature, decreasing EtCO2 will indicate enough dantrolene has been given
  • may need to redose later to prevent recurrence (in ICU or PACU after initial crisis has been managed)
41
Q

When might malignant hyperthermia occur?

A
  • After multiple unremarkable anesthetics
  • During the maintenance phase of anesthesia or in the postop period
  • In patients with no prior family history
42
Q

How does the dose of SUX affect onset and recovery?

A

Lower doses have a slower onset but a faster recovery

43
Q

What can occur with excessively large doses, repeat doses of SUX or SUX infusions?

A

Can result in a Phase II Block which acts more like a non-depolarizing blockade of the NMJ

*if TOF has a fade pattern SUX has probably gone into a phase II blockade

44
Q

How does anticholinesterases affect SUX?

A

AChE also inhibit Butrylcholinesterase (BCE) which is responsible for the termination of action of SUX

*if given at the end of a case and then SUX is given for some reason its action will be prolonged by 30-60 minutes from baseline

45
Q

Where do non-depolarizing muscle relaxants (NDMRs) bind?

A

Competitively bind with ONE of the two alpha subunits on the post-junctional nicotinic cholinergic receptor

*prevents the action of ACh at the NMJ receptor

46
Q

What are the two main groups of NDMRs?

A

Benzylisoquinolinium or Curariform: d-Tubocurarine, Metocurine, Atracurium, Cis-Atracurium, Doxacurium

Aminosteroid Compounds: Pancuronium, Vecuronium, Rocuronium, Pipercuronium

47
Q

Typical dosing of NDMRs is _____ times the ED95.

A
  1. 5 to 2 times the ED95
    * intubating dose is 2x the ED95
    * Ensures that patients who may be resistant to the effects of the particular relaxant develop at least a 90% blockade
48
Q

How does the potency of Benzylisoquinoliniums affect onset of action and side effects?

A

As potency increases, the speed of onset of action (muscle relaxation) decreases

  • Less Potent = Fast Onset
  • More Potent = Slow Onset

As potency increases, side effects decrease
-More Potent = less total molecules of drug given to achieve desired effect = less side effects (CV side effects in particular decrease)

49
Q

How do Benzylisoquinoliniums affect heart rate?

A

They lack vagolytic properties so no increase in heart rate is seen with a standard intubating dose

50
Q

Do Benzylisoquinoliniums cause histamine release?

A

BZQs do have increased histamine release compared to other available NDMRs

  • Histamine may cause bronchospasm in an asthmatic or significant hypotension related to capillary vasodilation
  • Histamine release is dependent upon the total dose given and speed of injection
51
Q

How are Benzylisoquinoliniums excreted?

A

By the kidneys

52
Q

What NDMRs undergo Hofmann elimination?

A

Atracurium and Cis-Atracurium

  • undergo Hofmann elimination at normal temp and pH
  • Do NOT need a functional liver or kidney for metabolism
53
Q

What is d-Tubocurarine and its ED95, dose, duration, elimination?

A 
BZQ compound (NDMR): monoquaternary ammonium compound with significant histamine release and ganglionic blockade
-Longer acting NDMR (not clinically available)
  • ED95 = 0.5 mg/kg
  • Dose of 0.3 mg/kg = lower SBP
  • Dose > 0.6 mg/kg = sig. histamine release (severe HoTN)
  • Duration 75-85 min
  • Eliminated unmetabolized by the kidneys, minor by liver
  • renal/liver failure = T1/2 increased to 100 min
54
Q

What is Atracurium and its ED95, onset, and duration?

A

BZQ Compound (NDMR)

  • ED95 = 0.25 mg/kg
  • Onset = 3-5 min
  • Duration = 30-45 min
  • 2x ED95 (0.5mg/kg) speeds onset to 2-3 min and increases duration to 60 min
  • Can easily be antagonized by neostigmine, pyridostigmine, or edrophonium
  • if given rapidly or higher doses - may cause HoTN and tachycardia
55
Q

How is Atracurium metabolized?

A

via ester hydrolysis and Hofmann elimination

*higher pH and temperature favoring elimination

56
Q

How is Cis-Atracurium related to Atracurium?

A

It is the 1Rcis-1’Rcis isomer of Atracurium

4x as potent as Atracurium

57
Q

What are the characteristics of Cis-Atracurium and its ED95, onset, and duration and its intubating dose?

A
  • Does NOT cause histamine release at typical anesthetic doses (thus no CV side effects)
  • Undergoes Hofmann elimination
  • Great NDMR to use in pt’s with poor or unknown renal or liver function status
ED95 = 0.05 mg/kg
Onset = 3-5 min
Duration = 20-35 min

Typical intubating dose 0.1 - 0.2 mg/kg (Duration 60-70 min)

58
Q

What is Pancuronium?

A

a bisquaternary aminosteroid NDMR that has two acetyl ester groups on the A and D rings of the steroid molecule

Highly potent drug that does NOT cause hypotension (does cause tachycardia due to vagolysis)

59
Q

What is the ED95, onset, duration, intubating dose, and elimination of Pancuronium?

A 
ED95 = 0.07 mg/kg
Onset = 3-5 min
Duration = 60-90 min
Intubating dose = 0.08-0.1 mg/kg (has such a long DOA)
Eliminated 80% by the kidneys
60
Q

What is the vagolysis and relative tachycardia a result of when Pancuronium is administered?

A

Result of action at the muscarinic receptor in the autonomic nervous system and inhibition of catecholamine reuptake at the sympathetic nerve terminals

*tachy occurs because of selective blockade of cardiac muscarinic receptors (primarily in the SA node)

61
Q

What are the characteristics of Pipecuronium?

A

Steroidal Neuromuscular Blocker:
Derived from Pancuronium – lesser (10 fold) vagolytic effect

20-30% more potent than Pancuronium – use good for very long surgeries where extubation is not likely
*concerns about residual neuromuscular blockade and the development of respiratory depression, pneumonias, etc make ultra-long acting NDMRs inappropriate for many cases

Excreted unmetabolized by the kidneys and minorly by the liver

Does NOT block autonomic ganglia, produce vagolysis, or cause histamine release (CV stable)

62
Q

What is Vecuronium?

A

A monoquaternary steroidal NDMR that is synthetically made and was designed to eliminate all CV side effects

It is unstable in solution so it comes as a lypholized powder that is reconstituted

More potent than Pancuronium but duration of action is only 1/2 to 1/3 that of Panc

63
Q

What is the ED95, onset, duration, intubating dose, infusion dose, and elimination of Vecuronium?

A

ED95 = 0.03-0.05 mg/kg
Onset = 3-4 min
Duration = 25-40 min (w/ 0.1-0.2 mg/kg dose)
Intubating Dose = 0.1-0.2 mg/kg (can go as high as 4x ED95 with no CV side effects) – higher doses result in longer durations but without side effects
Infusion Dose = 2-8 mcg/kg/min
Eliminated unchanged in the bile (30-40%) and renal excretion (25%)

  • supplied 10mg vial, dilute to 1mg/mL
  • only available for peds ICU infusions
64
Q

What is Rocuronium?

A

A monoquaternary aminosteroid NDMR with rapid onset and intermediate duration of action

7-8x less potent than Vec but has more rapid onset due to greater number of drug molecules

Mild vagolytic properties with rare increases in HR (not typically seen at intubating dose range)
*does not cause ganglionic blockade or histamine release

65
Q

What is the ED95, onset, duration, intubating dose, and elimination of Rocuronium?

A

ED95 = 0.3 mg/kg
Onset = 3-5 min
Duration = 18-30 min
Intubating Dose = 0.4-0.6 mg/kg (duration 25-45 min)
*can achieve 60 sec intubating conditions with 1.2 mg/kg but this increases duration to 60-120 min

Eliminated unmetabolized by both the liver (unchanged in the bile) and the kidneys (30%)
*renal/liver failure results in increased duration of action

66
Q

What can residual NDMR lead to?

A

Respiratory complications such as pneumonia
Aspiration
Inability to sit up without assistance
General muscle weakness
Visual disturbances
Inability to swallow or speak
Decreases the response to hypoxic ventilator drive due to inhibition of carotid bodies neural response to hypoxia

67
Q

What factors affect how quickly reversal of NDMR activity occurs?

A
  • Intensity of the blockade (the more intense the block at the time of reversal, the longer it will take for enough NDMR to move away from the NMJ) – should wait until there are 4 twitches on TOF to give AChE
  • The onset of action of the AChE chosen
  • Dose given (larger doses will antagonize faster than smaller doses) – very large doses may cause muscle relaxant effects themselves
  • Dose of inhalation anesthetic (have synergistic effects with NDMR) – lower inhalation agent prior to admin AChE
  • Rate of clearance of NDMR (faster NDMR is cleared the sooner the blockade can be reversed)
68
Q

What is the order of fastest to slowest onset in a medium amount of residual muscle paralysis of AChE drugs?

A

Edrophonium > Neostigmine > Pyridostigmine

69
Q

What two sites can AChE drugs bind to to prevent action of AChE?

A

An Anionic site (quaternary amines attracted to this site and are reversible competitors of AChE)

An Esteratic site (binding creates a carbamylated enzyme that has a T1/2 of 30 min allowing ACh to build up)

70
Q

What is Edrophonium and its benefits?

A

Shorter acting Anticholinesterase – binds to anionic site

Reversal agent for NDMRs

Benefits: Fast onset and weaker muscarinic effect

*weak muscarinic effect so less slowing of the HR (lower doses of Atropine needed)

71
Q

What is the onset and typical dose of Edrophonium? What drug is administered with it?

A 
Onset = 45-120 seconds
Dose = 0.5-1.0 mg/kg
  1. 007-0.014 mg Atropine per 1 mg Edrophonium
    * Edrophonium and Atropine have similar onset of action times
72
Q

How is Edrophonium excreted?

A

Renal excretion 75%

T1/2 increased from 110 min to 206 min in renal failure

73
Q

What is Neostigmine and its benefits?

A

Anticholinesterase – binds to the anionic AND esteratic site on AChE

Benefits: longer duration than edrophonium, better for deep blockade reversal

74
Q

What is the onset, duration, and typical dose of Neostigmine? What drug is administered with it?

A 
Onset = 5 min  peak 10 min
Duration = 60+ min
Dose = 0.04-0.08 mg/kg

0.2 mg Glycopyrrolate per 1 mg Neostigmine

  • Glycopyrrolate and Neostigmine onset is similar (less tachycardia seen than with atropine)
  • Atropine can be used at 0.02-0.03 mg/kg
  • Excessive doses (>0.08mg/kg or 5mg total dose) can create muscular weakness
  • shouldn’t be given in situations of “deep” block because residual NDMR may outlast duration of action (re-paralyze pt later)
75
Q

What are the CV effects of Neostigmine?

A

Profound bradycardia due to vagal ACh stimulation

Dysrhythmias and arrest have been reported

  • Glycopyrrolate blocks muscarinic effects of ACh
  • Stimulation of autonomic ganglia and release of epinephrine from adrenal medulla results in increased HR/BP
76
Q

What are the respiratory effects of Neostigmine?

A

Bronchoconstriction

Increased oral secretions

77
Q

How is Neostigmine excreted? What is its T1/2?

A

Renal clearance (50%)

T1/2 = 80 minutes (180 min in renal failure)

*T1/2 shorter in infants — children require less reversal agent but it may last a shorter time

78
Q

What is Pyridostigmine and its benefits?

A

Anticholinesterase (analog of Neostigmine) – binds to the anionic AND esteratic site on AChE

Benefits: slightly longer duration and less muscarinic side effects

*CV effects are the same as Neostigmine (bradycardia, dysrhythmias)

79
Q

What is the onset, duration, and typical dose of Pyridostigmine? What drug is administered with it?

A 
Onset = 10-15 min
Duration = >2 hrs (good for reversal of deep blockade by long acting NDMR)
Dose = 0.1-0.25 mg/kg

0.05 mg Glycopyrrolate per 1 mg Pyridostigmine

80
Q

How is Pyridostigmine excreted? What is its T1/2?

A

Renal elimination (75%)

T1/2 = 90-110 min (350+ min in renal failure)

81
Q

What is Suggamadex and its mechanism of action?

A
  • A selective relaxant binding agent (aminosteroid NDMR reversal agent – only works with the “-onium” agents)
  • It is a modified gamma-cyclodextrin with a lipophilic core and hydrophilic exterior
  • 8 carboxyl thio ether groups attached to the 6 carbon positions which are negatively charged
  • These extensions electrostatically bind to the positively charged quaternary nitrogen of the NDMR
  • Once bound, the NDMR is basically inactive at the NMJ

*NO inhibition of AChE thus no buildup of ACh across the body (no need to admin antimuscarinic)

82
Q

What is the dosing and onset of action of Suggamadex?

A

“DEEP” block (absolutely no twitches on TOF): dose = 4 mg/kg — should see a return of TOF to 90% in about 2.1-4.3 minutes

“MODERATE” block (at least 2 twitches on TOF): dose = 2 mg/kg – should see return of TOF to 90% in 1.2-1.7 minutes

83
Q

What is the duration of action of Suggamadex?

A

Since it really binds the NDMR molecule irreversibly and is excreted via the kidneys as a Suggamadex-NMDR complex, it doesn’t really have a defined “duration of action”

*effects of Suggamadex don’t ware off so NO risk of re-paralyzing (possible when dose of Suggamadex is not sufficient to achieve proper reversal)

84
Q

What are the benefits of Suggamadex?

A
  • No “upper limit” dose that if exceeded may itself cause relaxation
  • No need to give anti-muscarinic
  • No dose adjustment needed in geriatric pts
  • No dose adjustment needed related to pulmonary issues
  • No dose adjustment needed for cardiac co-morbidities
  • No dose adjustment needed in mild to moderate renal impairment
85
Q

What are the concerns/issues of Suggamadex?

A
  • Binds other molecules including hormonal contraceptives (need alternative contraceptive for 7 days after admin)
  • if another drug is present that Suggamadex binds to instead, the NDMR will remain active and pt may not be reversed (still monitor the TOF)
  • Excessive dosing of it is associated with increased PT/PTT/INR
  • Not recommended for pts with severe renal impairment or failure

Anesthesia Pharm (18 decks)

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