Neuromuscular Blocking Drugs & Reversal

Question 1

How many molecules of a nondepolarizing NMB must bind to an alpha subunit to produce a neuromuscular block?

Answer 1

One molecule to one alpha subunit

Question 2

How does succ produce membrane hyperpolarization?

Answer 2

Produces prolonged depolarization of endplate region resulting in desensitization of nicotinic ACh receptors

Inactivation of voltage gated Na channels at NMJ

Increase in K permeability

Question 3

What catalyze the hydrolysis of succinylcholine?

Answer 3

Plasma cholinesterase

Question 4

Majority of NMBD are synthetic alkaloids except?

Answer 4

Tubocurarine

Question 5

Long acting NMBD

Answer 5

D-Tubocurarine

Pancuronium

Question 6

Intermediate-acting NMBD

Answer 6

Rocuronium
Vecuronium
Atracurium
Cisatracurium

Question 7

Short-acting NMBD

Answer 7

Mivacurium

Question 8

Most important curare alkaloid (Benzylisoquinolinium)

Answer 8

Tubocurarine

Question 9

Where do steroidal compounds interact with nicotinic ACh receptors?

Answer 9

Postsynaptic muscle membrane

Question 10

Tubocurarine

Answer 10

Monoquarternary, long acting Benzylisoquinolinium

O: slow
D: long
Recovery: slow

E: unchanged in urine; liver secondary (not suitable for renal or liver failure)

Int: 0.5-0.6 mg/kg
Maint: 0.1-0.2 mg/kg

Question 11

Atracurium elimination

Answer 11

Depend on liver (70% excreted in bile; impaired in pts w/ biliary obstruction)

Designed to undergo spontaneous degradation at physiologic temp and pH by Hofmann elimination to Laudanosine & monoquarternary acrylate metabolite

Laudanosine easily crosses BBB & stimulates CNS

Question 12

Cisatracurium undergoes how much Hoffman elimination?

Answer 12

77% of clearance

Question 13

Mivacurium

Answer 13

Only currently available short-acting NMBD
D/c in US

May produce Histamine release if given rapidly

Question 14

Pancuronium

Answer 14

Potent long acting

Vagolytic & butyrylcholinesterase inhibiting

E: around 50% kidneys; 11% bile; 15-20% deacetylation in liver

Remains stable for 6 months at room temp

Question 15

Accumulation of what metabolite is responsible for prolongation of the duration of Pancuronium?

Answer 15

3-OH

Question 16

Vecuronium

Answer 16

Monoquarternary with intermediate duration of action

Slight decrease in potency compared to panc
Loss of vagolytic properties
Molecular instability in solution explaining shorter duration
Increased lipid solubility=greater biliary excretion (30-40%)

Question 17

____ has 80% the neuromuscular blocking potency of Vec & w/ prolonged administration may contribute to prolonged neuromuscular blockade

Answer 17

3-OH

Question 18

Rocuronium

Answer 18

Intermediate acting monoquaternary with fast onset

6 times less potent than Vec

E: liver & bile, 30% unchanged in urine

Remains stable for 60 days at room temp

Question 19

What order do inhalation anesthetics potentiate neuromuscular blocking effect?

Answer 19

Des> Sevo> Iso > Halothane > Nitrous oxide, barbiturates, propofol

Question 20

Mechanisms for potentiation:

Answer 20

Central effect on alpha motoneurons & interneuronal synapses

Inhibition of postsynaptic nicotinic ACh receptors

Augmentation of antagonist’s affinity at receptor site

Question 21

Which antibiotics potentiate neuromuscular blockade and how?

Answer 21

Aminoglycoside
Polymyxins
Lincomycin
Clindamycin

Inhibiting the prejunctional release of ACh & depressing postjunctional nicotinic ACh receptor sensitivity

Question 22

What antibiotic potentiate neuromuscular blockade by exhibiting post junctional activity only?

Answer 22

Tetracycline

Question 23

How can high magnesium concentrations potentiate NMBD?

Answer 23

It inhibits Ca channels at presynaptic nerve terminals that trigger release of ACh

Question 24

Onset of action is inversely proportional to?

Answer 24

Potency of NMBD

Question 25

Low potency=?

Answer 25

Rapid onset

Question 26

High potency=?

Answer 26

Slow onset

Question 27

Molar potency is highly predictive of a drugs time to onset of effect except for which drug?

Answer 27

Atracurium

Question 28

Buffered diffusion

Answer 28

The process in which diffusion of a drug is impeded b/c it binds to extremely high-density receptors within a restricted space Can be seen w/ high potency drugs

Question 29

Tubocurarine is associated with marked ganglion blockade resulting in:

Answer 29

Histamine manifestations (hypotension, reflex tachycardia, bronchospasm) in asthmatics

Question 30

What class of NMB cause histamine release? Except?

Answer 30

Benzylisoquinoliniums; except cisatricurium

Question 31

Which NMB are benzylisoquinoliniums?

Answer 31

Tubocurarine Atracurium Cisatracurium Mivacurium

Question 32

Which NMB are steroidal compounds?

Answer 32

Pancuronium (long acting) Vecuroniumn (intermediate acting) Rocuronium (intermediate acting)

Question 33

What antibodies are involved in anaphylactic reactions?

Answer 33

Immunoglobulin E antibodies fixed to mast cells

Question 34

Treatment of anaphylaxis

Answer 34

100% O2 IV Epi 10-20 mcg/kg Consider early tracheal intubation if angioedema develops Fluids (crystalloids &/or colloids) NorEpi or Phenylephrine may be needed until fluid status restored Treat dysrhythmias Antihistamines & steroids controversial

Question 35

Half-life of succ

Answer 35

47 sec

Question 36

Which order kinetics does succ follow

Answer 36

First order (fractionated)

Question 37

How does succ cause bradycardia, junctional rhythm, and sinus arrest?

Answer 37

Mimics physiologic effects of ACh at cardiac muscarinic cholinergic receptors Usually when 2 doses give < 5 min apart

Question 38

Not widely accepted in open eye cases. Why?

Answer 38

Succinylcholine; can increase IOP

Question 39

Succ Phase I

Answer 39

Skeletal muscle paralysis occurs b/c depolarized post junctional membrane & inactivated Na channels cannot respond to release of ACh Absence of fade and tetanic to TOF

Question 40

Succ Phase II

Answer 40

Present when post junctional membrane has become repolarized but still does NOT respond normally to ACh Has more characteristics of NDMB & fade is seen in response to TOF

Question 41

What causes leaking of K from interior of cells with Succ?

Answer 41

Sustained opening of Na channels

Question 42

Succinylcholine should not be given to pts 24-72 hrs after:

Answer 42

Major burns Trauma Extensive denervation of skeletal muscles

Question 43

what decreased likelihood of cardiac responses to succ?

Answer 43

Atropine 13 min before

Question 44

Twitches with drug

Answer 44

``` 4= 75% or less receptors blocked 3= 85% or less receptors blocked 2= 95% or less receptors blocked 1= 99% or less receptors blocked 0= 100% receptors blocked ```

Question 45

Onset matches for AChe inhibitors and anticholinergics:

Answer 45

Atropine 7-10 mcg/kg & Endrophonium 0.5-1.0 mg/kg (both rapid) Glycopyrrolate 7-15 mcg/kg & Neostigmine 40-70 mcg/kg (both slower)

Question 46

Why do we give glycopyrrolate with Neostigmine?

Answer 46

Anticholinergic to minimize muscarinic CV side effects of AChe inhibitors

Question 47

Neostigmine supply

Answer 47

5mg/5ml

Question 48

Anticholinergic effects

Answer 48

Flushing, dry secretions, mydriasis (blurred vision), confusion, hyperthermia

Question 49

Cholinergic effects (SLUDGEM)

Answer 49

``` Saliva Lacrimation (tearing) Urination Defecation/Diarrhea GI effects/ cramping Messi Miosis (pinpoint pupils)/ Muscle cramping ```

Question 50

Robinul supply

Answer 50

0.2mg/ml

Question 51

Neostigmine

Answer 51

Usually 1mg/ml

Question 52

How much glyco & Neostigmine for full reversal stick?

Answer 52

0.8 mg (4ml) of glyco + 5mg (5ml) Neostigmine

Question 53

Suggamadex most effective to least order

Answer 53

Roc> Vec > Pancuronium

Question 54

Sugammadex should be avoided in?

Answer 54

Pts with creatinine clearance < 30ml/min

Question 55

Sugammadex supply

Answer 55

100mg/ml - 200mg/2ml vial or 500mg/5ml vial