Neuromuscular Blockers Flashcards
What are the two groups of non-depolarizing agents?
• what drugs fall into each of these groups?
Non-depolarizing Agents
Isoquinoline Derivatives
• Atracurium
• Cisatracurium
• D-Tubocurarine
Steroid Derivatives
• Rancuronium
• Rocuronium
• Vecuronium
What is the only depolarizing agent used as a paralytic?
Succinylcholine
What agents are used to reverse the action of paralytic drugs?
Edrophonium
Pyridostigmine
Neostigmine
Sugrammedex
Which Ach receptor is acted on by all of the paralytic agents?
Nicotinic m receptor - this is multimeric ligand-gate ion channel that allows exchange of monovalent cations (Na+ influx, K+ efflux) when 2 molecules of Ach bind.
Contrast the MOA of Non-depolarizing agents like rocuronium and the Depolarizing age Succinylcholine.
Non-depolarizing drugs:
• Completely prevent the channel from working and the channel is locked in the OFF state (no ion flux)
Depolarizing drugs:
• Succinylcholine binds on the receptor but also binds to phyically block the opened channel and prevents repolarization => This causes initial muscle contraction followed by flaccid paralysis
What is displayed by this graph?
This just shows how muscle tension is increased initially when you administer Succinylcholine but as the drug wears off (unbinds from the receptor) you get increased muscle tone again (blue line).
What is the point of the Train of 4?
• what do we see in a normal patient and what is our target when giving them paralytics?
• What’s the point of doing this?
TOF: using a peripheral nerve stimulator to make the thumb jump with 4 impulses. In a normal non-drugged person you’ll get 4 equal flexions (see left). If you add a nondepolarizing agent you’ll get decreased flexion with each impulse. In Phase II of depolarizing agents is the same as nondepolarizing while phase I shows 4 impulses with reduced flexion.
Target:
• typically we want to see between 2 and 4 twiches in a patient after administering drug
What’s the point?
• Reduce time patients spend in paralytic state and the time that they have to be ventillated
Characterize Phase I of Succinylcholine action with respect to:
• End Plate Potential
• Onset
• Dose-dependence
• Recovery
• Train of 4 and tetanic stimulation
• AchE inhibition
• Muscle Response
Characterize Phase II of Succinylcholine action with respect to:
• End Plate Potential
• Onset
• Dose-dependence
• Recovery
• Train of 4 and tetanic stimulation
• AchE inhibition
• Muscle Response
Explain the effect of Acetylcholine Esterase Inhibitor in phase I of succinylcholine action vs. phase II.
Increased Acetylcholine will ENHANCE the effect of Succinylcholine in Phase I because it will lead to more open channels that get stuck open.
In contrast, AchE inhibitors will reverse succinylcholine in phase II
Compare and contrast mechanisms of elimination for Depolarizing and non-depolarizing drugs and the determinants of duration of action.
Duration of action correlates closely with Half-Life
• this is an indicator that these drugs bind transiently and they their effects are only in locations to which they are localized
Steroidal Agents:
• Hepatic and Renal elimination with renal being rate limiting
Isoquinolones:
• Hepatic and Non-enzymatic elimination
If given the option to give your patient either Atracurium or Cisatracurium. Which would you choose and why?
Atracurium is metabolized to laudanosine, a metabolite known to cause SIEZURES, additionally it is highly dependent on Hepatic elmination, and is known to trigger HISTAMINE release.
Cisatracurium has all the benefits of atracurium without these side effects so its typically used.
Succinylcholine
• Duration of Action?
• Reasons for Variability?
Duration of Action:
5-10 minutes
• Short duration of action can be attributed to PSEUDOCHOINESTASE in the plasma
NOTE: presence in plasma means only a SMALL percentage of IV dose actually makes it to the neuromuscular junction
GENETICS determine Duration of Action in Succinylcholine:
• Some people have more enzyme or more active enzyme and some have less
How do we account for the variability that we’re likely to see after administering succinylcholine?
• what happens when this drug diffuses away from the cleft?
- Dibucaine (drug that inhibits normal enzyme much more significantly than the abnormal enzyme) acts as an indicator of how long the drug will act via a colormetric test.
- Drug that diffuses away from synaptic cleft is destroyed
Why is succinylcholine still frequently used clinically?
Its SHORT DURATION OF ACTION IS BENEFICIAL
With which of the Non-Depolarizing agents would you consider using in someone with wire loop patterns in their glomeruli?
• Which would be least desirable to use in this patient?
Good:
Atracurium and Cisatracuriumare the only two drugs eliminated spontaneously
BAD:
• Pancuronium and Tubocurarine (note that these two drugs are the longest acting in their respective classes and are both renall eliminated)
Would you ever give a patient with renal dysfunction succinylcholine?
YES, this drug is broken down mostly in the plasma by pseudocholinesterase with a small amount getting broken down by butyrylchoninesterase in the liver
What are the most potent NMBs?
• how are they eliminated?
Pancuronium and Vecuronium
What is the least potent of the NMBs?
Succinylcholine
What NMB drugs may have side effects of disturbing the autonomic nervous system?
• How can they do this?
• What could be some of the side effects?
Tubocurarine and Succinylcholine both bind Nn receptors in the ganglia so they can cause autonomic disturbances
Tubocurarine:
• Is a blocker so you’d likely see side effects like urinary retention, dry eyes, mouth, decreased GI motility, pupillary dilation
Succinylcholine:
• Is a stimulator so you’d see increased mucous secretion, pupillary constriction, and other parasypathetic adaptations
What NMBs may cause increased heart rate, which could cause decreased heart rate?
Increased Heart Rate:
• Pancuronium - blocks the M2 receptor in the heart that when stimulated decreased ionotropy and chronotropy
Decreased Heart Rate:
• Succinylcholine - stimulates the M2 receptor reducing heart rate and the force of contraction
What NMBs could induce symptoms of anaphylatic shock (hypotension, tachycardia, etc.)?
Atracurium, Tubocurarine, and Succinylcholine
What is the mechanism for Malignant Hyperthemia for succinylcholine?
Some drugs causes uncontrolled Ca2+ release from the SR
These leads to constant cycling and use of ATP to:
1. Bind to ATP binding site on myosin to aid in muscle contraction
2. Bind to ATPase that is used to pump Ca2+ back into SR to trigger the next contraction
The constant need for oxidative phosphorylation leads to Hyperthermia
The outcome of this is RIGOR, HEAT, CO2, and LACTATE
What are two methods of terminating a NMB?
- Given enough Ach to outcompete the NMB
- Act directly on NMB to prevent its action
What effects might you see if you gave an AchE inhibitor without an antimuscarinic?
What antimuscarinic(s) is/are most likely to increase your HR?
What antimuscarinic(s) is/are most likely to give you dry mouth?
What antimuscarinic is most likely to cause sedation?
Do any of the AchE inhibitors cross the BBB?
NO
How does Sugammadex work?
Its a Pore that wraps around the Steroidal NMB from accessing the receptors
What are the therapeutic uses of NMBs?
