Non Depolarizing Muscle Relaxers No Reversal Flashcards
1
Q
What are the 4 main differences between all of the non-depolarizing muscle blockers?
A
- Onset;
- Duration of action;
- Rate of recovery;
- Metabolism
2
Q
What is the MoA of non-depolarizing blockers?
A
- Pre-junctional sites → block ACh release;
- Post junctional → Compete with ACh at nACh-R for alpha subunits → no conformational change
3
Q
What are the characteristics of a non-depolarizing block?
A
- ↓ 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
4
Q
What is fade?
A
- Fade suggestssomefibers are contracting while some are blocked (muscle contraction is all or nothing)
5
Q
What causes the adverse CV effects of non-depolarizing blockers?
A
- Release of histamine;
- Effects at cardiac muscarinic receptors;
- Effects on nACh-R at autonomic ganglia
6
Q
Why do the adverse CV effects of non-depolarizing blockers vary between patients?
A
- d/t underlying diseases, preop meds;
- Adverse effects are rarely clinically significant
7
Q
What is the “Autonomic Margin of Safety”?
A
- Difference between dose thatproducesblockade (ED95) and dose thatcreatescirculatory effects
8
Q
Which long term non-depolarizing blocker has the same dose that both causes blockade and adverse CV effects?
A
- Pancuronium;
- Vec, Roc, Cis all have very different ED95 doses and doses that produce CV effects
9
Q
What adverse event have non-depolarizing blockers been shown to have in critically ill patients? What is another name for this condition?
A
- Skeletal muscle weakness for weeks to months after the blocker is D/C;
- Critical illness myopathy
10
Q
For patient affected by critical illness myopathy, what three things did they have in common?
A
- Had MSOF and vented for > 6 days;
- Usually had an aminosteroid NMBD;
- Administering Glucocorticoids prior to NMBD may ↑ risk
11
Q
What is the MoA of critial illness myopathy?
A
- Unknown;
- Maybe ↓ clearance or Active metabolites?
12
Q
What are some altered responses of non-depolarizing blockers when using volatile anesthetics? MoA of this?
A
- Dose-dependent enhancement;
- Desflurane>Sevoflurane>Isoflurane;
- Onset as early as 30 minutes..;
- MoA is unkown → maybe dose dependent inhibition of nACh-R
13
Q
How do diuretics, corticosteroids, metoclopramide and LAs affect non-depolarizing blockers?
A
- Enhances or prolong blockade;
- ↑ acetylcholine release;
- ↓ cholinesterase activity;
- ↓ nerve conduction
14
Q
How does Magnesium affect non-depolarizing blockers and SCh? MoA for this?
A
- Enhances blockade;
- MoA non-depol: ↓prejunctional release of Ach and ↓sensitivity to postjunctional membranes;
- MoA SCh: unkown → maybe more rapid shift to PH2 block
15
Q
How do SNS drugs affect non-depolarizing blockers? MoA for this?
A
- Give Ephedrine p/t non-depolarizers = ↓ onset time d/t ↑ CO and skeletal muscle blood flow;
- Give Esmolol p/t non-depolarizers = delayed onset of muscle block
16
Q
How does Hypothermia affect non-depolarizing blockers? MoA for this?
A
- Mild hypothermia = 2x the DoA for Vecuronium, Pancuronium;
- MoA = Temp slowing of hepatic enzyme activity;
- Mild hypothermia = ??? for Atracurium, Cisatracurium;
- MoA = Temp dependent eliminatio process (ester hydrolysis and Hoffman elimination)
17
Q
How doesacute hypokalemiaaffect non-depolarizing blockers?
A
- Hyperpolarizes cell membrane;
- Causes resistance todepolarizingNMBDs;
- ↑ sensitivity tonon-depolarizingNMBD’s
18
Q
How doesacute hyperkalemiaaffect non-depolarizing blockers?
A
- ↓ resting membrane potential (partially depolarizes cell membrane);
- ↑ effects ofdepolarizingNMBDs;
- Resistance tonon-depolarizingNMBDs
19
Q
How do burns affect non-depolarizing blockers? MoA?
A
- Causes resistance to non-depolarizers;
- Begins approx. 10 days post injury;
- ↓ after 60 days;
- MoA: Altered affinity of nACh-Rs (its not r/t altered # of receptors)
20
Q
What percentage of the body needs to be affected by burns to cause altered response to non-depolarizing blockers?
A
- 30% BSA or >
21
Q
For a patient with burns, how can we offset the resistance to non-depolarizing blockers the burn causes?
A
- using 1.2 mg/kg dose of Rocuronium
22
Q
How does Paresis or Hemiplegiaaffect non-depolarizing blockers? MoA?
A
- Paretic arm → will be resistant compared to unaffected side;
- Unaffected arm → will be resistant compared to normal patients;
- MoA:Proliferation of extrajunctional nACh-Rs
23
Q
Which depolarzing/non-depolarizing blocker is the most likely to cause allergic reactions? Which is least likely to cause reaction?
A
- SCh > Pancuronium, Vecuronium, Rocuronium;
- Cisatracurium least likely
24
Q
What makes a cross sensitivity reaction possible for depolarizing/non-depolarizing blockers?
A
- Quaternary ammonium group
25
How can a patient get an allergic reaction from a depolarzing/non-depolarizing blocker on their 1st exposure?
* Represents prior sensitization → Soaps/cosmetics (women > men)
26
How does Gender affect non-depolarizing blockers? MoA?
* Women more sensitive (need 22% less Vec or 30% less Roc);
* Duration of blocker greater in women;
* MoA: unknown
27
What is the most common long acting NMBD?
* Pancuronium (Pavulon)
28
What is the chemical classification of Pancuronium? What properties does this drug have?
* Bisquaternary aminosteroid;
* Vagolytic properties
29
What is the intubating dose, onset and duration of Pancuronium?
* Dose: 0.1mg/kg;
* Onset: 3-5 minutes;
* Duration: 60-90 minutes
30
How is the majority of Pancuronium metabolized?
* 80% eliminated unchanged in urine
31
What changes in metabolism of Pancuronium do we see with a renal failure patient?
* 30-50% decreased plasma clearance;
* 10-40% deasacetylpancuronium metabolite ½ as active (by liver)
32
What changes in metabolism of Pancuronium do we see with a liver disease patient?
* Increased VD;
* Larger initial dose is needed;
* Prolonged elimination ½ time
33
What changes in metabolism of Pancuronium do we see with an elderly patient?
* Decreased plasma clearance d/t renal function
34
What CV effects do we see with Pancuronium?
* ↑ HR;
* ↑ MAP;
* ↑ CO;
* No changes in SVR or inotropy
35
Does pancuronium cause histamine release?
* no
36
What are the two main causes for the CV effects of Pancuronium?
* Vagal blockade → mostly at SA node and ↑ BP is d/t HR ↑;
* SNS activation → presynaptic release of NE and block NE reuptake
37
What are the 4 intermediate acting non-depolarizing blockers?
* Vecuronium;
* Rocuronium;
* Cisatracurium;
* Atracurium
38
Compared to LA, NMBDS have...?
* 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.
39
What chemical classification is Vecuronium?
* Aminosteroid
40
What is the intubating dose, onset and duration of Vecuronium?
* Intubating Dose: 0.1 mg/kg;
* Onset: 3-5 minutes;
* Duration: 20-35 minutes
41
What is the main way Vecuronium is metabolized?
* Hepatic is principle method of elimination;
* 3-desacetylvecuronium 50-80% as potent (but rapidly converted to metabolite with 1/10 the effects)
42
With renal excretion, what percentage of Vecuronium appears unchanged in urine? How does renal dysfuction affect it?
* Approx 30% appears unchanged (*70% metabolized in liver);
* E 1/2 time ↑
43
How does metabolism of Vecuronium change with the elderly?
* ↓ volume of distribution (less muscle mass);
* ↓ plasma clearance (less hepatic flow / delayed recovery with infusions)
44
How does metabolism of Vecuronium change with an obstetric patient?
* Insignificant effects to fetus;
* ↑ clearance in 3rd trimester (progesterone);
* ↑ duration early postpartum (give IBW)
45
How do Acid-Base changes prior to NMBD affect Vecuronium?
* No prolonged blockade
46
How do Acid-Base changes after NMBD affect Vecuronium?
* Respiratory acidosis followin NMBD administration will prolong blockade
47
How does respiratory acidosis that occurs after Vecuronium administration prolong the blockade?
* Activity inversely proportional to bound drug...acidosis decreases bound amount;
* Change in ionization at receptor increases attachment time;
* Watch out for postop hypoventilation
48
What CV effects does Vecuronium have? Does it release histamine?
* No CV effects to worry about;
* No histamine release
49
What chemical class is Rocuronium?
* Aminosteroid
50
What is the intubating dose, onset and duration of Rocuronium?
* Dose: 0.6 mg/kg or 1.2 mg/kg;
* Onset: 3-5 minutes; 1-2 minutes;
* Duration: 20-35 minutes
51
How does a large dose of Rocuronium compare to SCh and Pancuronium?
* Larger doses of Roc parallel onset of SCh but offset of pancuronium (quicker onset, longer duration)
52
How is Rocuronium excreted?
* Unchanged in bile
53
Why will Rocuronium have a longer DoA in the elderly or with liver failure patients?
* d/t ↓ clearance and ↑ Vd
54
What percentage of Rocuronium is excreted renally?
* 10-30% → only marginally affected by liver failure
55
What are the CV effects of Rocuronium? Does it release histamine?
* No CV effects (maybe slight vagolytic effect);
* No histamine release
56
What chemical class is Cisatracurium?
* Benzylisoquinolone
57
What is the intubating dose, onset and duration of Cisatracurium?
* Intubating Dose: 0.1 mg/kg;
* Onset: 3-5 minutes;
* Duration of action: 20-35 minutes
58
What is unique about the metabolism of Cisatracurium?
* Cis- isomer of atracurium;
* Recovery from infusion NOT affected by time;
* Degraded by Hoffman elimination;
* Degradation DOES NOT use non-specific plasma cholinesterase as much as Atracurium
59
What changes occur in Cisatracurium when used in an elderly patient? What changes occur in an obese patient?
* Elderly: Slight delay in onset d/t CO;
* Obese: Duration of action prolonged IF dosed at actual body weight d/t ↑ Vd
60
What CV effects does Cisatracurium have? Does it release histamine?
* CV stabile;
* No histamine release
61
What is the only clinically useful short acting non-depolarizing blocker?
* Mivacurium
62
What chemical class is Mivacurium?
* Benzvlisoquinolone
63
What is the intubating dose, onset and duration of Micacurium?
* Intubating Dose: 0.15 mg/kg;
* Onset: 2-3 minutes (Conditions less desireable);
* Duration: 12-20 minutes
64
What 3 isomers occur in the metabolism of Mivacurium? Which isomers have NM blocking ability?
* Cis-cis;
* Cis-trans → NM blocking;
* Trans-trans → NM blocking
65
How is mivacurium cleared from plasma?
* by plasma cholinesterase
66
What are the CV effects of Mivacurium?
* Minimal
67
What negative side effects does Mivacurium have?
* Release histamine;
* Giving > 3 xED95 = transient MAP drop (More common with rapid, large doses);
* MAP drops more in HTN pts than non-HTN pts
