Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology #1 > Module D-1 Neuromuscular Blockers > Flashcards

Module D-1 Neuromuscular Blockers Flashcards

1
Q

Mediator in Ach release from Presynaptic

A

Voltage gated Ca channels

Doubling extra cellular calcium causes 16-fold increase in Ach release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How much Ach is released into Synaptic cleft and why?

A

At least 200 quanta, 1 quanta= 5000 Ach

Rapid transmission and increased margin of safety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Function of Schwann cell in NMJ

A

Synapse maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe events in synaptic cleft

A

Approximately 50% of ACh is degraded rapidly by acetylcholinesterase or diffuses out of cleft.

Degraded to acetate and choline- this terminates activity

Choline is recycled by Presynaptic terminal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe postsynaptic membrane

A

Highly corrugated with deep invaginations- surface area

“Shoulders” have high concentration of AChReceptors

Voltage gated Na channels are in the folds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe postjunctional nicotinic ACh receptor

A

Pentameric, ligand gated ion channel with 5 subunits

2-alpha, 1-beta, 1-delta, 1-epsilon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Location of the ACh receptor binding site, subunits

A

At interface of α-δ and α-ε subunits

The end terminus of each subunit creates binding site

Alpha-delta may be most important

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe ion flow when ACh receptor is agonized

A

Influx of Na and Ca, efflux of K

This will depolarize the membrane when threshold is reached

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Threshold current vs supramaximal current

A

Lowest current required to depolarize the most sensitive fibers to elicit a detectable response

10-20% higher intensity than is required to depolarize

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe TOF

A

Four stimuli every 0.5 sec (2Hz)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

TOF ratio
TOFR

A

Amplitude of the fourth response is divided by the amplitude of the first response

Control should be 1.0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Explain fade

A

Competition of NMBA and ACh for pre-synaptic NicotinicAChR results in progressively less and less reputake of choline from the synaptic cleft so less acetylcholine is available to be released with each neuron firing

Block of positive feedback loop involving presynaptic receptors and choline

Progressively less twitch

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Role of Ca in Presynaptic NMJ terminal

A

Voltage gated Ca channels open in response to neuronal firing which brings Ca into the Presynaptic terminal and promotes movement of vesicles toward release into NMJ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Double burst stimulation

A

Two short bursts of 50Hz titanic stimulation separated by 750 ms

Easier to detect fade i.e. recovery from blockade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Tetanus

A

Rapid electrical stimulus, 50/100Hz

Produces sustained muscle contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Succinylcholine’s MOA

A

Mimics ACh and depolarizes post-synaptic membrane

But it is not hydrolysis by acetylcholinesterase so it has prolonged binding which prevents any further depolarization- resulting in relaxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What hydrolyzes succinylcholine?

A

PLASMA cholinesterase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Sux dosing and relationship to potency

A

ED95 of 0.3-0.6 mg/kg
Intubating dose=1-1.5 mg/kg to achieve intubating conditions within a minute

Speed of onset is inversely related to potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Sux Duration and clearance

A

Plasma half-life of 2-4 minutes

Recovery in 13 minutes

Hydrolyzed by plasma cholinesterase (also called pseudo cholinesterase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Explain why dibucaine number is important

A

There are over 75 mutations of pseudocholinesterase which result in prolonged blockade

The dibucaine number is used to identify individuals who have an atypical genotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Explain dibucaine percentages

A

Dibucaine number is the % of PChE that was inhibited

Dibucaine inhibits normal PChE to a greater degree than atypical PChE

80 (normal)= 80% of PChE activity inhibited
20 (homozygous atypical)= 20% was inhibited
50 (heterozygous atypical)= 50% was inhibited but will likely not display a prolonged block with Sux

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe differences between ACh Receptors

A

Nicotinic (NMJ pre and post synapse) NAchR
-ligand gated ion channel (ionotropic)
-Signal skeletal muscle contraction

Muscarinic (mAchR)
-G-protein coupled
-parasympathetic nervous system with diverse functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Myasthenia Gravis

A

Disorder of postsynaptic neuromuscular transmission

Caused by antibody-mediated reduction in number of functioning postsynaptic AChRs

Leads to loss of postsynaptic folds and voltage gated Na channels

Characterized by fluctuating fatigable weakness in skeletal muscle

Congenital recessive syndrome

24
Q

Where are large stores of Ca in the muscle?

A

Sarcoplasmic reticulum

25
Ryanodine
Receptor that allows Ca to move out of Sarcoplasmic reticulum and cause muscle contraction MH is the abnormal release of Ca and muscle contraction….
26
Sux contraindications
Hyperkalemia-ESRD okay if serum K is up to date and acceptable Burn patients (variable criteria)- may be safe in first 24hrs Severe muscle trauma (crush) Upper motor neuron/ lower motor neuron disease Severe sepsis Muscle wasting (disuse atrophy/denervation) Malignant hyperthermia Skeletal myopathy (duchenne) Atypical PChE H/o anaphylaxis/allergy
27
Sux Adverse effects
Tachycardia Bradycardia- severe in repeat dosing (muscarinic ACh receptors) Increased potassium Increased ICP/IOP Masseter muscle spasm
28
Why do we not give Sux to kids
Emergencies only due to likelihood of undiagnosed duchenne muscular dystrophy Which can lead to hyperkalemic rhabdomyolysis
29
Pathological conditions with potential for hyperkalemia with succinylcholine
Upper/lower motor neuron defect Spinal cord trauma Prolonged chemical denervation- muscle relaxants, magnesium, clostridia’s toxins Direct muscle trauma, tumor or inflammation Select muscular dystrophies Thermal trauma Disuse atrophy Stroke Tetanus Severe infection
30
List the benzlisoquilnolinium compounds
Atracurium Cisatracurium Mivacurium
31
Atracurium
Competitive antagonism or AChR pre and post synapse Onset up to 3 minutes, duration 30-60 minutes Hoffman elimination HISTAMINE RELEASE-tachycardia and hypotension- stimulation of histamine receptors-NO DIRECT action on cardiac muscle
32
Do muscle relaxants cross the BBB?
NO mother fucker Water soluble at physiologic pH
33
Hoffman elimination
Spontaneous, base-catalyzed non-enzymatic chemical reaction that cleaves NMBDs into two molecules Slowed by hypothermia and acidosis
34
Cisatracurium
Competitive antagonist Does not provoke histamine release IV bolus (2x ED95) 0.1 mg/kg =relaxation within 3 minutes Intermediate acting and dose dependent- 2xED95= 45 min 4xED95= 68 min Hoffman elimination, some renal elimination but recovery is not impacted by liver or renal failure Active metabolite- laudanosine
35
Mivacurium
Ultra short acting Not available in US due to severe bronchospasm(histamine release) -pseudocholinesterase? Short duration of action but long onset time makes intubating conditions transient
36
List steroidal NMBDs
Pancuronium Vecuroium Rocuronium
37
Pancuronium
Not recommended due to long duration of action of 60-90 minutes Onset~4minutes Renal excretion and should not be used in renal dysfunction Also hepatic elimination in the bile-should be avoided in cirrhosis
38
Vecuronium
Intermediate acting- 36 min after 0.1 mg/kg ED95 0.05 mg/kg At 2xED95 (0.1) onset is 3 min Elimination halftime is 51-90 min-hepatic clearance Avoid continuous admin due to metabolite with 50% potency Decrease dosing in elderly
39
Rocuronium
Faster onset than Vec and also intermediate duration Onset 45-90 seconds 0.6-1.2 mg/kg (2-4xED95) Drug of choice for RSI if sux is contraindicated Elimination half-life of 60-120 min Hepatobiliary excretion with 33% renal If re-dosing is required consider changing to Cisatracurium as to not depend on renal clearance
40
Hypothermia and NMBDs
Prolonged block Decreased efficacy with reversals Critical to maintain euthermia during perioperative period
41
Most commonly implicated drugs in an anaphylaxis situation when giving a “routine” anesthetic (9-13) drugs
Rocuronium and succinylcholine
42
Why do we not stimulate the muscle for TOF?
We want to stimulate the Presynaptic terminal to depolarize to evaluate the NMJ, directly stimulating muscle is postsynaptic and misleading
43
Describe potency and onset
With low potency agents we need to used more of it, its a numbers game at the NMJ-if we flood it with more drug the onset time will decrease
44
Why do we use NMBD?
Improve intubating conditions Mitigate vocal cord injuries/ voice hoarseness Improve operating conditions Mechanical ventilation
45
Effective Dose NMBD
Dose required to produce effect ED50: 50% reduction in twitch height ED95: 95% reduction in twitch height
46
What slows Hoffman elimination?
Hypothermia and acidosis
47
Metabolite of Atracurium and Cisatracurium
Laudanosine: crosses BBB, causes seizures Only concern if long term infusion
48
Best place to measure onset of blockade (intubating conditions)
Muscle= orbicularis oculi (closes eyelid) or corrugator supercilii (eyebrow twitch) Nerve= facial nerve
49
Best place to measure recovery of blockade (return of upper airway function)
Muscle= adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion) Nerve= ulnar nerve or posterior tibial nerve
50
Mechanism of bradycardia w/ succinylcholine
Stimulation of M2 receptor in SA node
51
Treating hyperkalemia- K shift and elimination
Calcium-stabilize myocardium Glucose + insulin Sodium bicarbonate Hyperventilation Albuterol Lasix Volume resuscitation HD Hemofiltration
52
Ion flow through Post synaptic AchR
Calcium and sodium influx Potassium efflux
53
Why does Sux cause increase in ICP?
Transient effect Venous congestion due to fasciculation of neck muscles and increased cbf Offset with ND NMDA or. IV induction agents
54
Why is sux prolonged in liver failure?
Pseudocholinesterase is produced in the Liver- typically not a significant consideration
55
Impairment in what organ can prolong sux duration
Liver It produces pche
56
Opiates that act differently?!?
Tramadol-norepinephrine and serotonin reuptake blocker Methadone- NMDA receptor antagonism
57
What do you do with nmbd dosing if your patient is on anticonvulsants?
Give more!!

Pharmacology #1 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions