Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

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
Q

Ryanodine

A

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
Q

Sux contraindications

A

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
Q

Sux Adverse effects

A

Tachycardia

Bradycardia- severe in repeat dosing (muscarinic ACh receptors)

Increased potassium

Increased ICP/IOP

Masseter muscle spasm

28
Q

Why do we not give Sux to kids

A

Emergencies only due to likelihood of undiagnosed duchenne muscular dystrophy

Which can lead to hyperkalemic rhabdomyolysis

29
Q

Pathological conditions with potential for hyperkalemia with succinylcholine

A

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
Q

List the benzlisoquilnolinium compounds

A

Atracurium
Cisatracurium
Mivacurium

31
Q

Atracurium

A

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
Q

Do muscle relaxants cross the BBB?

A

NO mother fucker
Water soluble at physiologic pH

33
Q

Hoffman elimination

A

Spontaneous, base-catalyzed non-enzymatic chemical reaction that cleaves NMBDs into two molecules

Slowed by hypothermia and acidosis

34
Q

Cisatracurium

A

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
Q

Mivacurium

A

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
Q

List steroidal NMBDs

A

Pancuronium
Vecuroium
Rocuronium

37
Q

Pancuronium

A

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
Q

Vecuronium

A

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
Q

Rocuronium

A

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
Q

Hypothermia and NMBDs

A

Prolonged block
Decreased efficacy with reversals
Critical to maintain euthermia during perioperative period

41
Q

Most commonly implicated drugs in an anaphylaxis situation when giving a “routine” anesthetic (9-13) drugs

A

Rocuronium and succinylcholine

42
Q

Why do we not stimulate the muscle for TOF?

A

We want to stimulate the Presynaptic terminal to depolarize to evaluate the NMJ, directly stimulating muscle is postsynaptic and misleading

43
Q

Describe potency and onset

A

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
Q

Why do we use NMBD?

A

Improve intubating conditions
Mitigate vocal cord injuries/ voice hoarseness
Improve operating conditions
Mechanical ventilation

45
Q

Effective Dose NMBD

A

Dose required to produce effect
ED50: 50% reduction in twitch height
ED95: 95% reduction in twitch height

46
Q

What slows Hoffman elimination?

A

Hypothermia and acidosis

47
Q

Metabolite of Atracurium and Cisatracurium

A

Laudanosine: crosses BBB, causes seizures

Only concern if long term infusion

48
Q

Best place to measure onset of blockade (intubating conditions)

A

Muscle= orbicularis oculi (closes eyelid) or corrugator supercilii (eyebrow twitch)

Nerve= facial nerve

49
Q

Best place to measure recovery of blockade (return of upper airway function)

A

Muscle= adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion)

Nerve= ulnar nerve or posterior tibial nerve

50
Q

Mechanism of bradycardia w/ succinylcholine

A

Stimulation of M2 receptor in SA node

51
Q

Treating hyperkalemia- K shift and elimination

A

Calcium-stabilize myocardium

Glucose + insulin
Sodium bicarbonate
Hyperventilation
Albuterol

Lasix
Volume resuscitation
HD
Hemofiltration

52
Q

Ion flow through Post synaptic AchR

A

Calcium and sodium influx
Potassium efflux

53
Q

Why does Sux cause increase in ICP?

A

Transient effect

Venous congestion due to fasciculation of neck muscles and increased cbf

Offset with ND NMDA or. IV induction agents

54
Q

Why is sux prolonged in liver failure?

A

Pseudocholinesterase is produced in the Liver- typically not a significant consideration

55
Q

Impairment in what organ can prolong sux duration

A

Liver

It produces pche

56
Q

Opiates that act differently?!?

A

Tramadol-norepinephrine and serotonin reuptake blocker

Methadone- NMDA receptor antagonism

57
Q

What do you do with nmbd dosing if your patient is on anticonvulsants?

A

Give more!!

Pharmacology #1 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions