SS25 NMBDs: Non-depolarizing (Exam 3) Flashcards
What are the 4 main differences between all of the non-depolarizing muscle blockers?
- Onset;
- Duration of action;
- Rate of recovery;
- Metabolism
What is the MoA of non-depolarizing blockers?
- Pre-junctional sites → block ACh release;
- Post junctional → Compete with ACh at nACh-R for alpha subunits → no conformational change
Which type of neuromuscular blocking drug will cause a conformational change of the nicotinic ACh receptor?
Succinylcholine
What are the characteristics of a non-depolarizing block?
- ↓ 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
Why would you not give an intubating dose of rocuronium and then give vecuronium as the rocuronium starts to offset?
Non-depolarizing neuromuscular blockers will potentiate each others effects.
When would you use a priming dose of a non-depolarizing paralytic?
ONLY with succinylcholine to avoid its side effects (fasciculations, eye weakness, etc.)
What is fade?
Fade suggestssomefibers are contracting while some are blocked (muscle contraction is all or nothing)
What causes the adverse CV effects of non-depolarizing blockers?
- Release of histamine;
- Effects at cardiac muscarinic receptors;
- Effects on nACh-R at autonomic ganglia
Why do the adverse CV effects of non-depolarizing blockers vary between patients?
- Underlying diseases
- Pre-op meds
What is the “Autonomic Margin of Safety”?
Essentially Therapeutic Index
Difference between dose thatproducesblockade (ED95) and dose thatcreatescirculatory effects.
Which non-depolarizing blocker has a required dose that both causes blockade and adverse CV effects?
Pancuronium
Essentially no therapeutic index
What adverse event have non-depolarizing blockers been shown to have in critically ill patients?
When does this occur?
- Critical Illness Myopathy
- Weeks to months after NMBD discontinuation
Who is most often affected by critical illness myopathy?
- Had MODS for > 6 days;
- Usually had an aminosteroid NMBD;
- Administered Glucocorticoids prior to NMBD
Why is critical illness myopathy thought to occur?
Possible ↓ clearance or active metabolites
Which volatile gasses exhibit a dose-dependent enhancement of NMBDs?
Why is this?
- Desflurane > Sevoflurane > Isoflurane
- Thought to occur due to solubility allowing rapid movement into muscular partition/compartment.
What drug classes and/or drugs will enhance or prolong neuromuscular blockade?
- Diuretics
- Corticosteroids
- Metoclopramide
- Local Anesthestics
How does Magnesium affect non-depolarizing blockers and SCh?
Why is this thought to occur?
Enhances blockade
- ↓Release of ACh and
- ↓sensitivity to ACh
How will sympathomimetics such as ephedrine or epinephrine affect NMBDs?
↓ onset time (Drug works faster)
How will sympatholytics such as esmolol affect NMBDs?
↑ onset time (Drug works slower)
How does Hypothermia affect non-depolarizing blockers?
Does this occur for CYP450 metabolism or hoffman elimination?
Hypothermia will increase NMBD duration
This occurs whether the process is CYP450 dependent or hoffman elimination dependent
How doesacute hypokalemiaaffect non-depolarizing blockers?
↓ Vᵣₘ
- Resistance to depolarizing NMBDs
- Sensitivity to non-depolarizing NMBD’s
How does acute hyperkalemia affect non-depolarizing blockers?
↑ Vᵣₘ
- Sensitivity to depolarizing NMBDs;
- Resistance to non-depolarizing NMBDs
With ↑K⁺ we are sensitive to succ & resistant to roc
How do burns affect non-depolarizing blockers?
Burns patients within the 10 - 60 day time from burn will have a resistance to NMBDs.
What percentage of the body needs to be affected by burns to cause altered response to non-depolarizing blockers?
- 30% BSA or >
