Non-Depolarizing Muscle Relaxants (3) Flashcards
How do we decide which NDMB to use?
influenced by differences in
* Onset
* Duration of action
* Rate of recovery
* Metabolism
usually base choice on DOA and comorbidities of the pt
What is the MOA of NDMB?
- Act at pre-junctional sites to block Ach release
- Competitive inhibitors for alpha subunits on nACHRs
- Bind and do not cause conformation change
What are characteristics of NDMB associated with nerve stimulation and reversals?
- Decreased twitch response to a single stimulus
- Unsustained response (fade) to continuous stimulus
- TOF ratio < 0.7
- Post-tetanic potentiation
- Potentiation of other non-depolarizing drugs
- Antagonism by anticholinesterase drugs
- No fasciculations during onset
What does the “fade” with NDMB suggest?
Some fibers are contracting while some are blocked
- some are more susceptible to NMBD
What are adverse side effects to NDMB?
- Cardiovascular effects
- Critical illness myopathy
- Altered responses
What causes cardiovascular effects associated with NDMBs?
- release of histamine
- effects at cardiac muscarinic receptors
- effects on nAchRs at autonomic ganglia
What are the cardiovascular effects associated with NDMBs?
- Varies between patient d/t underlying disease and preop meds
- rarely clinically significant
What is a autonomic margin of safety?
Difference between dose that produces blockade (ED95) and dose that creates circulatory effects
What is the autonomic margin of safety for pancuronium?
Same as the normal dose
What is critical illness myopathy?
Skeletal muscle weakness
When can critical illness myopathy occur?
- Weeks to months after NMBD discontinued
- patient with multiorgan fx vent >6 days
- usually from aminosteroid blocker
What potentially enhances risk of critical illness myopathy?
Large dose glucocorticoids prior to NMBD
What is the MOA of critical illness myopathy?
unknown
Why do you want to stick with the same NDMB once you pick one?
If you switch to another one to redose then they compound on each other and it will be hard to get pt reversed
How do volatiles affect NMBs?
Dose dependent enhancement of muscle relaxation with onset as early as 30 minutes
Des>Sevo>Iso
What are some drugs that enhance or antagonize blockade and what is the MOA?
Diuretics, Corticosteroids, Metoclopromide, LA
- increase Ach release
- depression of cholinesterase activity
- depression of nerve conduction
Magnesium ________ blockade of NMBs
enhances
What is MOA of magnesium increasing non depolarizing NMBs?
- decreases prejunctional release of Ach
- decreases sensitivity to postjunctional membranes
What does giving ephedrine prior to non-depolarizing NMBs cause?
Decrease onset time from increase in CO and skeletal muscle flow
How does esmolol prior to induction affect non-depolarizing NMBs?
delays onset of the paralytic
Why is it important to prevent hypothermia in patients?
Even mild hypothermia double duration of vec and pancuronium through slowing of hepatic enzyme activity
Which NDMB are somewhat temperature dependent on metabolism?
Atracurium and Cisatracurium
- hoffman elimination and ester hydrolysis (need to have pretty close to normal body temp or the drugs action will be prolonged)
What changes in potassium are associated with NMBDs?
Acute hypokalemia
- hyperpolarize the cell
- resistance to depolarizing NMBDs
- increased sensitivity to non depolarizing NMBD
Acute hyperkalemia
- decreases Vrm (partial depolarizes cell)
- increases effects of depolarizing NMB
- resistance to non-depolarizing NMBs
When do burn patients have increased resistance to non-depolarizing NMBs?
10 -60 days post injury → need more of drug to have the same effect
Double the dose of __________ will have onset similar to succinylcholine
Rocuronium (1.2mg/kg)
double length of paralytic though
What are NMBD considerations for a patient that has paresis/hemiplegia?
- paralyzed arm: nAChRs are resistant to muscle relaxant compared to unaffected side
- unaffected arm: still somewhat resistant to the muscle relaxant compared to normal patient
What is the MOA of resistant to NMBD on affect side of a stroke compared to unaffected side?
Proliferation of extrajunctional nAchRs
Which NMB is most likely to cause an allergic reaction?
Succs (although still uncommon)
likely more of a histamine reaction
Which NMB is the least likely to cause an allergic reaction?
Cisatracurium
What can cause cross reactivity with NMB?
Quaternary ammonium group→ seen with soaps and cosmetics that can cause allergic reactions with NMBDs
Why are women more sensitive to NMBDs than males?
Women have less muscle mass and more fat (NMB lasts longer)
- need 22% less Vec
- need 30% less Roc
What is the TI for pancuronium?
1: toxic dose is the same a effective dose
What is the intubating dose, onset, and duration of Pancuronim?
0.1 mg/kg
Onset: 3-5 min
Duration: 60-90 min
What is the main reason pancuronium isnt used?
Vagolytic properties (tachycardia)
What is the metabolism of Pancuronium?
80% elimination unchanged in urine
How does elimination of pancuronium change in renal failure, liver disease, and aging?
In renal failure
- 30-50% decreased plasma clearance
- 10-40% deasacetylpancuronium metabolite ½ as active (by liver)
In liver disease
- Increased VD
- Larger initial dose is needed
Prolonged elimination ½ time
In aging
- Decreased plasma clearance d/t renal function
What are CV effects of Pavulon?
↑ HR, MAP, CO
- d/t vagal blockade
- Mostly at SA node
- BP increase d/t HR
d/t SNS activation
- Release of NE presynaptically
- Blockade of NE reuptake
No changes in SVR or inotropy
No histamine release
How do you decide which intermediate acting NMBD if they all have the same onset and duration?
Look at differences in metabolism (co-morbidities of the patient)
Onset, duration, CV effects of intermediate NMBs compared to Long acting NMBs:
- Similar onset of maximum blockade
(except high dose roc) - Approximately 1/3 duration of action
- Minimal/absent cardiovascular effects
- Antagonized by anticholinesterase drugs approx 20 min.
What is the dose, onset, duration, and trade name for Vecuronium?
- Norcuron
- 0.1mg/kg
- O: 3-5 min
- D: 20-35 minutes to be reversible
How is Vecuronium metabolized/excreted?
- Hepatic metabolism: Primary organ of elimination (70%)
- Metabolite: 3-desacetylvecuronium 50-80% as potent but rapidly converted to metabolite 1/10 as potent
- Renal excretion: 30% unchanged, prolonged 1/2 time with renal dysfxn
What are considerations when giving Vec to elderly pts?
- Decreased Vd (less muscle mass)
- Decreased plasma clearance (less hepatic flow)
What are considerations with Vec and pregnant women?
- insignificant effects to fetus
- increased clearance in 3rd trimester (progesterone)
- prolonged duration early postpartum (give IBW)
How does acid-base imbalances affect blockade with Vecuronium?
Depends on when the acid-base status changed
- Prior to NMBD→ no prolonged block
- Resp Acidosis after NMBD given→ prolonged block
How does acidosis affect MOA of Vec?
- Acidosis decreases bound amount→ paralyzed longer than if pH was normal
- change in ionization at receptor increases attachment time
What would be a concern in post op if patient had vec during procedure?
Hypoventilation→ acidosis
What are CV effects of Vec?
none and no histamine release 🤠
What is the dose, onset, duration, and trade name for Rocuronium?
- Zemuron
- 0.6 mg/kg or 1.2 mg/kg (high dose parallels to succs onset but pancuronium offset)
- O: 3-5 min, 1-2 min (high dose)
- D: 20-35 min, 60-90 min (high dose)
How is Rocuronium metabolized?
- Excreted unchanged in bile (longer DOA in liver fx and elderly d/t decrease clearance and increase Vd)
- 10-30% renal excretion (marginal affect in renal fx)
What NMBDs would we want to avoid in liver pts?
Vecuronium
Rocuronium
What are CV effects of Rocuronium?
none, no histamine release
What is the dose, onset, duration, and trade name for Cisatracurium?
- Nimbex
- 0.1mg/kg
- O: 3-5 min
- D: 20-35 min
How is Nimbex metabolized?
Degradation
- Hoffman elimination (temp dependent)
- Doesnt use non-specific plasma cholinesterases as much as Atracurium
Cisatracurium is the ____ isomer
Cis (no histamine)
Recovery from infusion not affected by time
What pt pops affect pharamcokinetics of Nimbex?
- Elderly: delay in onset (1 min) d/t CO
- Obese: DOA prolonged if dosed on actual body weight d/t Vd
What are CV effects of Nimbex?
None, no histamine release
Are there any short acting non-depolarizing NMBDs on the market currently?
Nope
What is the dose, onset, duration, and trade name of mivacurium?
- Mivacron
- 0.15mg/kg
- O: 2-3 minutes
- D: 12-20 minutes (short)
Why is Mivacron no longer on the market?
Did not provide a great paralysis “MOVE-acron🥴”
What was Mivacron good for when it was in clinical use?
Super fast procedures:
- drilling pin in finger
- mediastinoscopy for node biopsy in trachea
How it mivacurium metabolized?
3 stereoisomers
- Cis-cis
- Cis-trans (NM blocking ability)
- Trans-trans (NM blocking ability)
Cleared by plasma cholinesterases
What CV effects are associated with Mivacron?
Minimal
Histamine release
- >3X ED95 (transient MAP drop)
- more common with rapid, large doses
- MAP drop more in HTN pts
