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APEX Pharmacology > PHARMACOLOGY-neuromuscular blockers AND reversal agents > Flashcards

PHARMACOLOGY-neuromuscular blockers AND reversal agents Flashcards

1
Q

What components make up the neuromuscular junction

A 
Axon terminal (presynapse)
Synaptic cleft (space between)
Motor end plate (postsynapse)
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2
Q

What are the 2 types of nicotinic ACh receptors at the neuromuscular junction

A
  1. Prejunctional Nn, on the presynaptic nerve

2. Postsynaptic Nm on motor endplate

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3
Q

Describe the structure of a postsynaptic nicotinic receptor

A

Pentameric
Ligand-gated ion channel
5 subunits around ion-conducting pore
Subunits = 2 alpha, 1 beta, 1 delta, 1 epsilon

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4
Q

How does a nicotinic ACh receptor become active

A

1 ACh molecule binds to each alpha subunit
The pore channel opens when both subunits are occupied
Na+ and Ca++ enter the cell and K+ exits

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5
Q

Which ions are conducted through the nicotinic ACh channel

A

Na+ and Ca++ in

K+ out

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6
Q

Once the nicotinic receptor is activated by ACh, what happens to the charge of the neuron

A

When ions pass through the pore, the inside of the neuron becomes positive and activates an action potential

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7
Q

How do nicotinic receptors initiate action potentials

A

Once the pore opens and conducts Na+ and Ca++ inside, the positive charge activates voltage-gated Na+ channels causing depolarization and an action potential

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8
Q

After depolarization of the myocyte occurs, what happens next

A

Depol instructs the sarcoplasmic reticulum to release Ca++ into the cytoplasm
Ca++ engages with myofilaments and initiate muscle contraction

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9
Q

How are nicotinic receptors turned off

A

Acetylcholinesterase is positioned around the receptors and hydrolyzes ACh into choline and acetate. This occurs almost immediately after ACh binds the nicotinic receptor

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10
Q

Describe 2 pathologic variants of nicotinic receptors

A
  1. has a gamma subunit instead of an epsilon

2. Has 7 alpha subunits

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11
Q

What factors increase the presence of extra-junctional nicotinic receptors

A

Denervation

Prolonged immobility

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12
Q

Where are extrajunctional nicotinic receptors located

A

NOT at the NMJ site

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13
Q

What are patients with extrajunctional receptors at risk for with succinylcholine administration

A

Hyperkalemia

Serum K+ can increase by 0.5 - 1.0 mEq/L

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14
Q

In what conditions is succinylcholine contraindicated (9)

A
  1. Upper or lower motor neuron injury
  2. Spinal cord injury
  3. Burns
  4. Skeletal muscle trauma
  5. CVA
  6. Tetanus
  7. Severe sepsis
  8. Muscular dystrophy
  9. Prolonged chemical denervation (Mg, long term NMB)
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15
Q

How do extrajunctional nicotinic receptors respond differently to succinylcholine

A

They remain open for a longer time, allowing more Na+ to enter the cell

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16
Q

Why can extrajunctional nicotinic receptors increase K+

A

The receptors are open for longer time allowing more K+ to leak out

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17
Q

What can depolarize the a7 type of nicotinic receptor

A

Succinylcholine AND choline (succ metabolite)

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18
Q

How is succinylcholine-induced hyperkalemia treated (4)

A
  1. IV calcium chloride
  2. Hyperventilation
  3. Sodium bicarb
  4. glucose + insulin
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19
Q

How do patients with upregulated extrajunctional receptors respond to nondepolarizers

A

The receptors are resistant to ND-NMB
The nondepolarizers have decreased potency
More receptors = more drug needed

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20
Q

What causes fade during train-of-four stimulation

A

Antagonism of the presynaptic nerve nicotinic receptor (nondepolarizer)
This blocks the mobilization of ACh for potential release with stimulation

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21
Q

What action occurs when ACh binds to receptors of the presynaptic nerve

A

It mobilizes more ACh in the nerve terminal

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22
Q

Why doesn’t succinylcholine produce fade

A

Because it agonizes the presynaptic nicotinic receptor, mobilizing ACh vesicles for immediate release

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23
Q

What triggers ACh vesicles to release ACh into the synaptic cleft

A

An action potential opens VG gated Ca++ channels allowing Ca++ into the nerve terminal
Increased Ca++ destabilizes the proteins holding ACh vesicles
The vesicles exit the nerve terminal via exocytosis

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24
Q

What action does ACh take in the synaptic cleft

A
  1. Binds to postynaptic Nm receptors, opening ion channels

2. Binds to presynaptic Nn receptors, mobilizing more ACh vesicles for immediate release

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25
Q

How do nondepolarizing NMB act on presynaptic Nn receptors

A

The competitively antagonize the receptor, inhibiting the ability of more mobilization of ACh vesicles for release

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26
Q

Does succinylcholine block cause fade?

A

NO because it is an agonist that mimics the action of ACh

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27
Q

What distinguishes the difference between phase 1 and phase 2 block

A

The presence or absence of fade

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28
Q

Describe a phase 1 block

A

It is produced by succinylcholine which agonizes the presynaptic Nn receptors and allows for normal ACh mobilization in the nerve terminal. The result is plenty of ACh for release with TOF stimulation

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29
Q

Describe a phase 2 block

A

It is produced with nondepolarizers or excessive succinylcholine dose

The ACh mobilization mechanism is impaired due to antagonism at the presynaptic Nn receptors. Since the Nn receptors don’t function to mobilize ACh, there is less ACh available and the supply is exhausted quickly producing fade

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30
Q

How can succinylcholine produce a phase 2 block

A
  1. High dose >7 - 10 mg/kg

2. continuous exposure >30 - 60 minutes

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31
Q

How is a phase 1 block distinguished from a phase 2 block with a nerve stimulator

A

There is no fade with a phase 1 block. All responses have the same intensity

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32
Q

What characteristic responses are seen with a phase 2 block

A
  1. Fade with tetany

2. Prolonged duration

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33
Q

Describe how post-tetanic potentiation is affected by phase 1 block

A

Post-tetanic potentiation is absent

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34
Q

Describe how double burst stimulation is affected by phase 1 block

A

Constant but diminished response to double burst stimulation

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35
Q

Describe how post-tetanic potentiation is affected by phase 2 block

A

It is present unlike with a phase 1 block where it is absent

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36
Q 
Describe the corresponding percentage of receptors still blocked with each bedside test of NMB recovery
Vt 6 mL/kg
VC >20 mL/kg
4/4 twitches w/o fade
Inspiratory force -40 cmH2O
A

Vt 6 mL/kg = 80%
VC >20 mL/kg = 70%
4/4 twitches w/o fade = 70-75%
Inspiratory force -40 cmH2O = 50%

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37
Q

What is the sequence of muscles types blocked by neuromuscular blockers

A

central muscles are more resistant to NMB effects and recover sooner than peripheral muscles

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38
Q

Which muscle causes eyebrow twitch

A

corrugator supercilii

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39
Q

Which muscle closes the eyelid

A

Orbicularis oculi

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40
Q

Which nerve is stimulated when assessing the corrugator supercilli and orbicularis occuli

A

the facial nerve (CN 7)

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41
Q

Which location is best to measure onset of block with nerve stimulation (muscle and nerve)

A 
Orbicularis oculi or corrugator supercilii
Facial nerve (CN 7)
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42
Q

Which location is best to measure recovery of blockade with nerve stimulation (muscle and nerve)

A 
M = Adductor pollicis or flexor hallucis
N = Ulnar nerve or posterior tibial
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43
Q

Which muscle adducts the thumb

A

Adductor pollicis

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44
Q

Which muscle causes big toe flexion

A

Flexor hallucis

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45
Q

When the adductor pollicis is stimulated with TOF, what can be assumed for recovery from NMB

A

The return of upper airway muscle function

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46
Q

At what ratio is residual NMB defined

A

TOF < 0.9

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47
Q

Patients who have inadequately recovered from NMB are at risk for 2 problems

A
  1. Airway obstruction

2. Aspiration (d/t pharyngeal dysfunction)

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48
Q

What are 4 of the most sensitive bedside recovery tests for NMB recovery

What is the max percentage of occupied receptors

A
  1. Inspiratory force -40 cmH2O
  2. Head lift >5 s
  3. Hand grip same as preinduction
  4. Holding tongue blade against force

50% receptors occupied

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49
Q

What clinical assessment is normal with a max percentage of occupied receptors at…
80%
70%
60%

A 
80% = normal Vt
70% = No TOF fade VC normal
60% = No fade with sustained tetanus or DBS
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50
Q

How can succinylcholine illicit bradycardia

A

Stimulating the M2 receptor in the SA node

A second dose increases the risk for bradycardia or asystole

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51
Q

How can bradycardia with succinylcholine be prevented or treated

A

Don’t repeat the dose

Give an antimuscarinic/anticholinergic like atropine

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52
Q

How can succinylcholine cause tachycardia

A

It mimics ACh action at the sympathetic ganglia causing tachycardia and HTN

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53
Q

How can succinylcholine increase serum K+

A

Upregulation of extrajunctional nicotinic receptors increases K+ release

Hyperkalemia increases resting membrane potential and raises the risk of dysrhythmias

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54
Q

How does succinylcholine affect intraocular pressure

A

Transiently increases IOP 5 - 15 mmHg for 10 minutes

This can be significant in patients with an open globe injury

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55
Q

How does succinylcholine affect intracranial pressure

A

Temporarily increased

Can be minimized with defasciculating dose

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56
Q

How does succinylcholine affect intragastric pressure

A

Causes contraction of abdominal muscles increasing intragastric pressure
It raises lower esophageal sphincter tone
These cancel each other out

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57
Q

How can succinylcholine-induced malignant hyperthermia be assessed

A

Increased masseter muscle tone and spasm can be an initial sign of MH

If this occurs in the absence of other MH d/dx, then there is no risk for Mh

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58
Q

What are 5 terms for the mechanism of succinylcholine metabolism.
Primary location =

A
  1. Butyrylcholinesterase
  2. Pseudocholinesterase
  3. Type 2 cholinesterase
  4. False cholinesterase
  5. Plasma cholinesterase

Primary location = plasma

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59
Q

What are 5 terms for the mechanism of acetylcholine metabolism
Primary location =

A
  1. Acetylcholinesterase
  2. Genuine cholinesterase
  3. True cholinesterase
  4. Type 1 cholinesterase
  5. Specific cholinesterase

Location = NMJ

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60
Q

Where is pseudocholinesterase produced

A

In the liver

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61
Q

How does reduced pseudocholinesterase activity affect succinylcholine

A

Prolongs the duration

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62
Q

Name 5 drugs that can prolong succinylcholine duration and why

A
  1. Metoclopramide
  2. Esmolol
  3. Neostigmine
  4. Oral contraceptives/estrogen
  5. MAO inhibitors

Why = they reduce pseudocholinesterase activity

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63
Q

Name 5 conditions that can prolong succinylcholine duration and why

A
  1. Atypical PChE
  2. Severe liver disease
  3. Burns
  4. Neoplasm
  5. Late-stage pregnancy

These conditions reduce PChE activity

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64
Q

What variant of pseudocholinesterase cannot hydrolyze succinylcholine?
What is the result?

A

Atypical PChE

Result = prolong succs duration

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65
Q

What is the dibucaine test

A

Dibucaine is an amide LA that inhibits normal plasma cholinesterase. It has no effect on atypical PChE

The number reflects the percentage of NORMAL enzyme that is inhibited by dibucaine

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66
Q

What is a normal dibucaine number and test

A

Normal = 80

Dibucaine inhibits 80% of PChE

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67
Q

What is an abnormal dibucaine number and test

A

Atypical pseudocholinesterase is not inhibited

Any number <70

68
Q

What is succinylcholine duration with a dibucaine number of 50 - 60

A

Duration = 20 - 30 minutes

69
Q

What is succinylcholine duration with a dibucaine number of 20 - 30

A

Duration = 4 - 8 hours

70
Q

What does heterozygous PChE variant mean

A

The dibucaine number is 50 - 60 and succinylcholine duration can last 20 - 30 minutes

71
Q

What does atypical homozygous PChE variant mean

A

the dibucaine number is 20 - 30 and succinylcholine duration is 4 - 8 hours

72
Q

Why is Ca++ used in the treatment of hyperkalemia

A

Because it increases the threshold potential making action potential propagation harder to attain with the higher resting membrane potential

73
Q

What is the most likely cause of cardiac arrest following succinylcholine administration in children <8.

A

Undiagnosed Duchenne Muscular Dystrophy

74
Q

What is the treatment for hyperkalemic cardiac arrest in children who received succinylcholine

A
  1. Stabilize myocardium
    - Calcium chloride 20 mg/kg
    - Calcium gluconate 60 mg/kg
  2. Shift K+ into cells
    - Hyperventilation
    - Glucose + insulin
    - Sodium bicarb
    - Albuterol
  3. Enhance K+ elimination
    - Furosemide
    - Volume resuscitation
    - Hemodialysis
    - Hemofiltration
75
Q

What is the origin of myalgia following succinylcholine use

A

The uncoordinated muscle contraction (from depolarizing) before flaccid paralysis

76
Q

Who is at risk for myalgias following succinylcholine

A
  1. Young adults
  2. Women > men
  3. Those that don’t routinely perform strenuous activity
77
Q

What populations are at lowest risk for succinylcholine induced myalgia

A

Children
Elderly
Pregnant

78
Q

What are some methods to minimize succinylcholine induced myalgias

A
  1. Pretreat w/ nondepolarizer
  2. NSAIDS
  3. Lidocaine 1.5 mg/kg
  4. Higher dose of succs
79
Q

What medications do not decrease the incidence of succinylcholine induced myalgias

A

opioids

80
Q

What dose of nondepolarizer can be given to minimize myalgias from succinylcholine

A

One-tenth of the ED95 for ND-NMBD
Rocuronium = 2 mg
Atracurium = 1.5 mg
Vecuronium = 0.3 mg

81
Q

How is dosing for succinylcholine affected when a defasciculating dose of a nondepolarizer given
Why

A

Succs dose should be increased 1.5 - 2.0 mg/kg

B/c the nondepolarizer competitively antagonizes the nicotinic receptor more succs is needed to outcompete the ND

82
Q

When should a defasciculating dose be avoided

A

Pre-existing skeletal muscle weakness

Myasthenia gravis

83
Q

Name 5 conditions that can increase the risk of succinylcholine-induced hyperkalemia

A
  1. Guillain-Barre
  2. Hyperkalemic periodic paralysis
  3. Malignant hyperthermia
  4. Multiple sclerosis
  5. up-regulation of ACh receptors
84
Q

Name 4 conditions that increase sensitivity to nondepolarizing NMB

A
  1. Guillain-Barre
  2. Huntington chorea
  3. Multiple sclerosis
  4. Myasthenia gravis
85
Q

What are the 2 classes of nondepolarizing NMB

A

Benzylisoquinolinium

Aminosteroid

86
Q

Which nodepolarizers belong to the benzylisoquinolinium class

A
  1. Atracurium
  2. Cisatracurium
  3. Micavurium
87
Q

Which nodepolarizers belong to the aminosteroid class

A
  1. Rocuronium
  2. Vecuronium
  3. Pancuronium
88
Q

How are benzylisoquinolinium compounds metabolized

A

Spontaneous degradation in the plasma via Hofmann elimination or non-specific plasma esterases

89
Q

What is the metabolite of atracurium and cisatracurium. Describe possible side effects of metabolite

A

Laudanosine

CNS stimulation which can produce seizures

90
Q

Why does renal insufficiency prolong the duration of nondepolarizers

A

Because they are ionized and undergo renal elimination as an unchanged drug

91
Q

Which nondepolarizers are a good choice in patients with renal or hepatic insufficiency and why

A

Benzylisoquinolinium class

They are degraded in the plasma and not dependent on hepatic or renal function

92
Q

How is atracurium metabolized

A

33% Hofmann elimination

66% non-specific plasma esterase (NOT pseudocholinesterase)

93
Q

How is cisatracurium metabolized

A

Hofmann elimination

94
Q

How is mivacurium metabolized

A

Pseudocholinesterase (similar to succs)

95
Q

What altered physiology affects Hofmann elimination

A

Alkalosis/hyperthermia = FASTER reaction

Acidosis/hypothermia = SLOWER reaction

96
Q

What is Hofmann elimination dependent on

A

Blood pH

Temperature

97
Q

What is the primary method of rocuronium metabolism and elimination

A 
Metabolism = NONE
Elimination = Biliary excretion
98
Q

What is the primary method of vecuronium metabolism and elimination

A 
Metabolism = Liver
Elimination = 50/50 Liver and renal
99
Q

What is the primary method of pancuronium metabolism and elimination

A 
Metabolism = Liver (20%)
Elimination =  Renal > liver
100
Q

What are the metabolites of
Rocuronium
Vecuronium
Pancuronium

A 
Rocuronium = NONE
Vecuronium = 3-OH vecuronium
Pancuronium = 3-OH pancuronium
101
Q

Which 2 nondepolarizing NMB don’t produce a metabolite

A

Rocuronium

Mivacurium

102
Q

Which 2 nondepolarizers produce laudanosine metabolite

A

Atracurium

Cisatracurium

103
Q

Name 4 NMB that undergo organ-independent elimination

A

Atracurium
Cisatracurium
Mivacurium
Succinylcholine

104
Q

Which drugs can potentiate nondepolarizing NMB

A 
Volatile anesthetics
Abx
Antidysrhythmics
Local anesthetics
Diuretics
Dantrolene
Cyclosporin
Tamoxifen
Lithium
105
Q

List, from greatest to least, the potentiation effect of volatile anesthetics on nondepolarizers

A

Des > sevo > Iso > N2O

106
Q

Which antibiotics can prolong nondepolarizing NMB duration (5)

A 
Aminoglycosides
Polymyxins
Clindamycin
Lincomycin
Tetracycline
107
Q

Which antidysrhythmics can prolong nondepolarizing NMB duration (4)

A

Verapamil
Amlodipine
Lidocaine
Quinidine

108
Q

How does lithium affect the duration of action for nondepolarizers

A

Activation of the potassium channels alters resting membrane potential

109
Q

Which electrolytes can prolong nondepolarizer NMB duration and why

A

Increase Magnesium = decreases ACh release
Decreased Calcium = decreases ACh release
Decreased potassium = Decreases RMP

110
Q

How can temperature affect the duration of nondepolarizing NMB

A

Hypothermia decreases metabolism and clearance

111
Q

How does succinylcholine produce tachycardia

A

By stimulating the autonomic ganglia

112
Q

Which NMB drugs release histamine

What are the effects

A

Succinylcholine
Atracurium
Mivacurium

Effects = tachycardia and vasodilation

113
Q

In which patients should histamine releasing NMB drugs be avoided

A

Patients who are sensitive to higher HR or reduced afterload

114
Q

What are 3 unique CV effects of pancuronium

A

Vagolytic effects

  1. Inhibition of M2 receptors at the SA node
  2. Stimulates catecholamine release
  3. Inhibits catecholamine reuptake in adrenergic nerves
115
Q

In what condition should pancuronium be avoided and why

A

Hypertrophic cardiomyopathy

The anterior leaflet of the mitral valve can occlude the LVOT with forceful ventricular contraction causing systolic anterior motion (SAM). This prohibits CO through aortic valve

116
Q

Which NMB can alter HR independent of histamine release due to autonomic effects

A
  1. Succinylcholine
  2. Pancuronium
  3. Rocuronium (minimally)
117
Q

Which NMB drug can cause tachycardia by stimulating the autonomic ganglia

A

Succinylcholine

118
Q

How does the chemical structure of NMB drugs preclude this class to allergic reactions

A

They contain one or more antigenic quaternary ammonium group (charged), which interact with IgE causing mast cell and basophil degranulation

119
Q

Which 2 NMB drugs have the highest incidence of anaphylaxis

A

Succinylcholine

Rocuronium

120
Q

How do AChE inhibitors increase available ACh

A

Indirectly allowing increased ACh concentration at the NMJ to outcompete the concentration of the NMB

121
Q

What happens to the duration of succinylcholine if given after neostigmine

A

It is prolonged because neostigmine inhibits pesudocholinesterase in the plasma

122
Q

What are the 2 mechanism AChE inhibitors increase the concentration of ACh at the NMJ

A
  1. Enzyme inhibition

2. Presynaptic effects

123
Q

How doe AChE inhibitors (reversal agents), bind to acetylcholinesterase sites

A
  1. Electrostatic attachment
  2. Formation of carbamyl ester
  3. Phosphorylation
124
Q

What interaction does neostigmine have at acetylcholinesterase site

A

It forms a carbamyl ester complex with the positive esteratic site (cleavage site)

125
Q

What interaction does edrophonium have with acetylcholinesterase

A
  1. Binds an electrostatic bond with the anionic site (holds ACh)
  2. Forms a hydrogen bond with the esteratic site (cleaves ACh)
126
Q

What are 3 examples of AChE inhibitors that form carbamyl ester inhibition

A

Neostigmine
Pyridostigmine
Physostigmine

127
Q

What is an example of AChE inhibitor that forms an electrostatic attachment with acetylcholinesterase

A

Edrophonium

128
Q

What are 2 possible presynaptic mechanisms of AChE inhibitor effects

A
  1. Stimulation of presynaptic receptor, causing release of ACh
  2. Inhibiting AChE near presynaptic receptor sites, increasing ACh concentration
129
Q 
Edrophonium
Dose = 
Onset = 
Duration = 
Metabolism = 
Elimination =
Anticholinergic =
A 
Dose = 0.5 - 1.0 mg/kg
Onset = 1 - 2 min
Duration = 30 - 60 min
Metabolism = RENAL 75%
Elimination = LIVER 25%
Anticholinergic = Atropine
130
Q 
Neostigmine
Dose = 
Onset =
Duration = 
Metabolism = 
Elimination =
Anticholinergic =
A 
Dose = 0.02 - 0.07 mg/kg
Onset = 5 - 15 min
Duration = 45 - 90 min
Metabolism = Renal 50%
Elimination = Liver 50%
Anticholinergic = Glycopyrrolate
131
Q 
Pyridostigmine
Dose = 
Onset =
Duration = 
Metabolism = 
Elimination =
Anticholinergic =
A 
Dose = 0.1 - 0.3 mg/kg
Onset = 10 - 20 min
Duration = 60 - 120 min
Metabolism = Renal 75%
Elimination = Liver 35%
Anticholinergic = glycopyrrolate
132
Q

How are cholinergic side effects reduced when giving AChE inhibitors

A

Administer anticholinergic drug before AChE inhibitor

133
Q

How does renal failure affect duration of AChE inhibiors

A

It prolongs the duration of the reversal agent AND NMB

134
Q

What effect do AChE inhibitors have when the dose administered exceeds the dose required for reversal

A

There is a ceiling effect and dose not produce a better recovery from paralytic

135
Q

How does the degree of neuromuscular blockade affect the onset of AChE inhibitors

A

The deeper the block the longer the onset time for the reversal agent

136
Q

What type of effect occurs when AChE inhibitors are mixed

A

ADDITIVE effect (not synergistic)

137
Q

Which AChE inhibitors pass through the BBB and why

A

Physostigmine passes through the BBB because it is a tertiary amine

138
Q

Which AChE inhibitors do NOT pass through the BBB and why

A

Edrophonium, neostigmine, pyridostigmine

They are quaternary amines (+ charge)

139
Q

At what TOF ratio is risk of airway obstruction, hypoxemic events, and postop pulmonary complications increased

A

TOF < 0.9

140
Q

What use and effect does intrathecal neostigmine ellicit

A

Produces analgesia

Side Effects = N/V, pruritus, prolonged sensory and motor block

141
Q

In addition to physostigmine’s reversal effects, what postoperative benefits does it have

A

When dosed at 40 mcg/kg, it reduces the incidence of postop shivering

142
Q

List 4 drugs that reduce the incidence of shivering in the PACU

A
  1. Meperidine
  2. Clonidine
  3. Dexmedetomidine
  4. Physostigmine
143
Q

Which 2 AChE inhibitors are best paired with glycopyrrolate

A

Neostigmine

Pyridostigmine

144
Q

Which AChE inhibitor has a tertiary amine structure

A

Physostigmine

145
Q

What type of effects are elicited from increased ACh concentration

A

Parasympathetic side effects

146
Q

List 9 parasympathetic side effects of AChE inhibitors

A

DUMBBELLS

  1. Diarrhea
  2. Urination
  3. Miosis
  4. Bradycardia
  5. Bronchoconstriction
  6. Emesis
  7. Lacrimation
  8. Laxation
  9. Salivation
147
Q

What class of drugs are reversal agents (3)

A
  1. Acetylcholinesterase inhibitors
  2. Cholinergics
  3. Muscarinics
148
Q

What class of drugs antagonize the effects of reversal agents (2)

A
  1. Anticholinergics

2. Muscarinic antagonists

149
Q

Which muscarinic antagonist increases HR the most

A

Atropine > glycopyrrolate > scopolamine

150
Q

Describe the sedating effects of the following anticholinergics
Atropine
Scopolamine
Glycopyrrolate

A 
Atropine = minimal
Scopolamine = Greatest sedative
Glycopyrrolate = non-sedating
151
Q

From greatest to least, compare the antisialagogue effect of atropine, glycopyrrolate and scopolamine

A

Scopolamine > Glyco > atropine

152
Q

From greatest to least, compare the antiemetic effects of atropine, glycopyrrolate, and scopolamine

A

Scop > Atropine

glyco has no antiemetic effects

153
Q

Describe the effects of muscarinic agents on pupil diameter

A

Antimuscarinics cause dilated pupils (mydriasis)

Scop produces mydriasis greater than atropine

Glyco has no dilating effects

154
Q

How does the structure of atropine and scopolamine compare to glycopyrrolate

A

Atropine/Scop = tertiary amine

Glyco = quaternary ammonium (ionized)

155
Q

How does the differing structure between atropine/scopolamine vs glycopyrrolate have on each drugs effect

A

Atropine/Scop:
Lipophilic, non-ionized
Cross lipid membrane i.e. placenta, GI tract, and BBB causing CNS side effects

Glyco:
Ionized, limited ability to cross membranes
No CNS or placental effect

156
Q

What effect do antimuscarinics have on patients with a heart transplant

A

The heart is denervated so there is no effect on the patients HR

they do still have other cholinergic effects from AChE inhibitors and should receive antimuscarinics

157
Q

Describe the structure of sugammadex

A

Gamma-cyclodextrin made up of eight sugars assembled in a ring

158
Q

Which NMB does sugammadex have NO effect on

A

Succinylcholine

Benzylisoquinolines (atracurium, cisatracurium, mivacurium)

159
Q

What is the mechanism of action for sugammadex

A

The ring structure encapsulates the NMB making it inactive and unable to engage at the nicotinic receptor

160
Q

How does sugammadex augment NMB transfer from the NMJ to the plasma

A

by encapsulating NMB the free concentration is reduced. The concentration gradient between the NMJ and plasma is increased increasing NMB transfer away from the NMJ

161
Q

From greatest to least, compare the affinity of sugammadex to vecuronium, pancuronium, and rocuronium

A

Rocuronium > vecuronium > pancuronium

162
Q

How is the sugammadex-NMB complex excreted

A

Unchanged via the kidneys

163
Q

What is the dosing for sugammadex

A

TOF 2+/4 = 2 mg/kg
TOF 0+/4 = 4 mg/kg
Immediately after Roc 1.2 mg/kg dosing = 16 mg/kg

164
Q

What are the options for re-paralysis if sugammadex <4 mg/kg has been given in the last 24 hours

A
  1. If it’s between 5 min and 4 hrs of dosing, re-administer rocuronium at 1.2 mg/kg
  2. If it has been >4 hrs, rocuronium 0.6 mg/kg or vecuronium at 0.1 mg/kg
165
Q

If >16 mg/kg of sugammadex has been used within 24 hours and a patient requires re-paralysis, which drug is the best choice.

A

Benzylisoquinolinium (non-aminosteroid)

  • Cisatracurium
  • Atracurium
  • Mivacurium

Succinylcholine

166
Q

What are 3 risks associated with sugammadex

A
  1. Anaphylaxis (0.3% of pts)
  2. Bradycardia and arrest
  3. Reduced oral contraceptive effectiveness for <7 days

APEX Pharmacology (8 decks)

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