NMBDs: Non-depolarizing (Exam III) Flashcards
(71 cards)
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
- Phase II drug
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?
* What non-depolarizing NMBD would you give and how much?
ONLY with succinylcholine to avoid its side effects (fasciculations, eye weakness, etc.)
* 5mg of Rocuronium as a defasiculating dose for SUX
What is fade?
- Fade suggestssomefibers are contracting while some are blocked (Some of the fibers are more susceptible to NMBDs)
- Skeletal muscle contraction is either all or nothing.
What are the 3 major adverse side effects of non-depolarizing NMBD?.
- Cardiovascular effects
- Criticall illness mypopathy
- Altered responses
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
True/False
The cardiovascular adverse effects of non-depolarizing NMBDs are rarely clinically significant?
True
What is the “Autonomic Margin of Safety”?
- Essentially Therapeutic Index
Difference between dose thatproducesblockade (ED95) and dose thatcreatescirculatory effects.
* The autonomic margin of safety is the same for pancuronium (has essentially no therapeutic index) but very different doses for vec, roc, and cis.
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 (skeletal muscle weakness)
- 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?
When is the onset?
Why is this?
- Desflurane > Sevoflurane > Isoflurane
- Onset as early as 30 minutes.
- Thought to occur due to solubility allowing rapid movement into muscular partition/compartment. Possible dose dependent inhibition of the nACh-R
What drug classes and/or drugs will enhance or prolong neuromuscular blockade?
How does this work?
- Diuretics
- Corticosteroids
- Metoclopramide
- Local Anesthestics
- They increase ACh release
- Depress cholinesterase activity
- Depress nerve conduction.
How does Magnesium effect non-depolarizing blockers and SCh?
Why is this thought to occur?
Enhances blockade
- ↓prejunctional release of ACh (for non-depol)
- ↓sensitivity to postjunctional membranes (for non-depol)
- MOA for SUX is unlcear but thought to be due to a more rapid shift to a phase II block (oversedation with SUX).
How will sympathomimetics such as ephedrine or epinephrine affect NMBDs?
↓ onset time (Drug works faster) due to an increase in CO and skeletal muscle flow.
How will sympatholytics such as esmolol affect NMBDs?
↑ onset time (Drug works slower)/ delays onset of drug
How does Hypothermia affect non-depolarizing blockers?
Does this occur for CYP450 metabolism or hoffman elimination?
- Hypothermia will increase NMBD duration. Even mild hypothermia will double the duration of Panc and Vec.
- MOA = temperature slowing of hepatic enzyme activity.
This occurs whether the process is CYP450 dependent (ester hydrolysis) or hoffman elimination dependent
How does acute hypokalemiaaffect non-depolarizing blockers?.
- Hyperolarizes the cell membrane creating an even more negative VrM.
- Resistance to depolarizing NMBDs
- increased Sensitivity to non-depolarizing NMBD’s
How does acute hyperkalemia affect non-depolarizing blockers?
- partially depolarizes or hypolarizes the cell membrane casuing an increase in VrM.
- Sensitivity to depolarizing NMBDs;
- Resistance to non-depolarizing NMBDs
With ↑K⁺ we are sensitive to succ & resistant to roc
