Mm Chapter 9. Neuromuscular Blocking Agents

Front 1

Depolarizing
vs
nondepolarizing muscle relaxants function

Back 1

Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists, whereas nondepolarizing muscle relaxants function as competitive antagonists.

Front 2

depolarizing muscle relaxants are not metabolized by

Back 2

acetylcholinesterase

Front 3

depolarizing muscle relaxants metabolized

Back 3

depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by another enzyme, pseudocholinesterase (nonspecific cholinesterase, plasma cholinesterase, or butyrylcholinesterase).

Front 4

Muscle relaxants owe their paralytic properties to mimicry of

Back 4

ACh.

For example, succinylcholine consists of two joined ACh molecules.

Front 5

Succinylcholine is considered contraindicated in the routine management of children and adolescents because of the risk of 3x

Back 5

hyperkalemia,
rhabdomyolysis,
and cardiac arrest in children with undiagnosed myopathies

Front 6

Normal muscle releases enough potassium during succinylcholine-induced depolarization to raise serum potassium by

Back 6

by 0.5 mEq/L.

Front 7

2 NDMB partially excreted by the kidneys, and their action is prolonged in patients with renal failure.

Back 7

pancuronium, vecuronium

Front 8

Atracurium and cisatracurium undergo degradation

where

Back 8

in plasma at physiological pH and temperature by organ-independent Hofmann elimination.

Front 9

___________ like succinylcholine, is metabolized by pseudocholinesterase

Back 9

Mivacurium

Front 10

Hypertension and tachycardia may occur in patients given pancuronium. These cardiovascular effects are caused by 2x

Back 10

combination of vagal blockade and catecholamine release from adrenergic nerve endings

Front 11

Skeletal muscle relaxation can be produced by 3x

Back 11

deep inhalational anesthesia, regional nerve block, or neuromuscular blocking agents

Front 12

The region of approximation between a motor neuron and a muscle cell is the

Back 12

neuromuscular junction

Front 13

The cell membranes of the neuron and muscle fiber are separated by a narrow (20-nm) gap, the _________________.

Back 13

synaptic cleft

Front 14

Neuromuscular Transmission

How it works
steps

Back 14

a nerve's action potential depolarizes its terminal,
an influx of calcium ions through voltage-gated calcium channels into the nerve cytoplasm allows storage vesicles to fuse with the terminal membrane and release their contents of acetylcholine (ACh).
The ACh molecules diffuse across the synaptic cleft to bind with nicotinic cholinergic receptors on a specialized portion of the muscle membrane, the motor end-plate.

Front 15

Each neuromuscular junction contains approximately _______ of these receptors

Back 15

5 million

Front 16

Each ACh receptor in the neuromuscular junction normally consists of

Back 16

five protein subunits, two subunits and single , , and subunits

Front 17

Cations flow through the open ACh receptor channel
how

Back 17

(sodium and calcium in; potassium out),

Front 18

Eaton–Lambert myasthenic syndrome =

Back 18

decreased release of ACh

Front 19

myasthenia gravis =

Back 19

decreased number of receptors

Front 20

ACh is rapidly hydrolyzed into

Back 20

acetate and choline

Front 21

ACh is rapidly hydrolyzed into acetate and choline by

Back 21

acetylcholinesterase

Front 22

When generation of action potential ceases, the sodium channels in the muscle membrane also close. Calcium is resequestered in the

Back 22

sarcoplasmic reticulum

Front 23

Depolarizing muscle relaxants very closely resemble ACh and therefore readily bind to ACh receptors, generating a muscle action potential. Unlike ACh, however, these drugs are not metabolized by _____________

Back 23

cetylcholinesterase

Front 24

phase I block

Back 24

end-plate cannot repolarize as long as the depolarizing muscle relaxant continues to bind to ACh receptors;

Front 25

phase II block

Back 25

After a period of time, prolonged end-plate depolarization can cause ionic and conformational changes in the ACh receptor that result in a phase II block, which clinically resembles that of nondepolarizing muscle relaxants.

Front 26

Nondepolarizing muscle relaxants bind ACh receptors but are incapable of inducing

Back 26

are incapable of inducing the conformational change necessary for ion channel opening. Because ACh is prevented from binding to its receptors, no end-plate potential develops. Neuromuscular blockade occurs even if only one subunit is blocked.

Front 27

depolarizing muscle relaxants act as _____________.

Back 27

ACh receptor agonists

Front 28

nondepolarizing muscle relaxants function ___________________.

Back 28

competitive antagonists.

Front 29

up-regulation causes an ____________________ to depolarizing muscle relaxants (with more receptors being depolarized), but a resistance to nondepolarizing relaxants (more receptors that must be blocked).

Back 29

exaggerated response

Front 30

Because depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by another enzyme,____________.

Back 30

pseudocholinesterase

Front 31

def
Tetany:

Back 31

A sustained stimulus of 50–100 Hz, usually lasting 5 s.

Front 32

def
Twitch:

Back 32

A single pulse 0.2 ms in duration.

Front 33

def
Train-of-four:

Back 33

A series of four twitches in 2 s (2-Hz frequency), each 0.2 ms long.

Front 34

def
Double-burst stimulation (DBS):

Back 34

Three short (0.2 ms) high-frequency stimulations separated by a 20-ms interval (50 Hz) and followed 750 ms later by two (DBS3,2) or three (DBS3,3) additional impulses (see Figure 6–32).

Front 35

what is fade

Back 35

gradual diminution of evoked response during prolonged or repeated nerve stimulation, is indicative of a nondepolarizing block

Adequate clinical recovery correlates well with the absence of fade

Front 36

Fade may be due to

Back 36

prejunctional effect of nondepolarizing relaxants that reduces the amount of ACh in the nerve terminal available for release during stimulation

Front 37

posttetanic potentiation causes

Back 37

in ACh mobilization following tetanic stimulation.

Front 38

succinylcholine enters the circulation, most of it is rapidly metabolized by ______________into ______________.

Back 38

pseudocholinesterase into succinylmonocholine.

Front 39

One in _____ patients has one normal and one abnormal (atypical) pseudocholinesterase gene, resulting in a slightly prolonged block (20–30 min).

Back 39

50

Front 40

(1 in _____) patients have two abnormal genes (homozygous atypical) that produce an enzyme with little or no affinity for succinylcholine

Back 40

3000

Front 41

dibucaine number

Back 41

The percentage of inhibition of pseudocholinesterase activity

Front 42

Prolonged paralysis from succinylcholine caused by abnormal pseudocholinesterase (atypical cholinesterase) should be treated how?

Back 42

continued mechanical ventilation until muscle function returns to normal

Front 43

cholinesterase inhibitors and depolarizing phase I block

Back 43

By inhibiting acetylcholinesterase, they lead to a higher ACh concentration at the nerve terminal, which intensifies depolarization. They also reduce the hydrolysis of succinylcholine by inhibiting pseudocholinesterase.

Organophosphate pesticides, for example, cause an irreversible inhibition of acetylcholinesterase and can prolong the action of succinylcholine by 20–30 min

Front 44

Succinylcholine stimulates

Back 44

all ACh receptors

Front 45

Succinylcholine's cardiovascular actions

Back 45

Stimulation of nicotinic receptors in parasympathetic and sympathetic ganglia and muscarinic receptors in the sinoatrial node of the heart can increase or decrease blood pressure and heart rate. Low doses of succinylcholine can produce negative chronotropic and inotropic effects, but higher doses usually increase heart rate and contractility and elevate circulating catecholamine levels.

Front 46

Following denervation injuries,The risk of hyperkalemia usually appears to peak

Back 46

7–10 days following the injury, but the exact time of onset and the duration of the risk period vary.

Front 47

Administration of rocuronium __________ mg/kg prior to succinylcholine

Back 47

0.06–0.1

rocuronium 0.06–0.1 mg/kg prior to succinylcholine has been reported to be effective in preventing fasciculations and reducing postoperative myalgias.

Front 48

depolarizing muscle relaxants
Chemically they are either 2x

Back 48

benzylisoquinolines or steroidal compounds

Front 49

Volatile agents decrease nondepolarizer dosage requirements by at least ____%.

Back 49

15

Front 50

pancuronium (and gallamine) block ______ receptors in the _________, resulting in tachycardia.

Back 50

vagal muscarinic

sinoatrial node

Front 51

Only__________ and ___________ are metabolized to any significant degree by the liver.

Back 51

pancuronium and vecuronium

Front 52

atracurium, cisatracurium, mivacurium, and rocuronium is independent of _________ function.

Back 52

kidney

Front 53

Acid–base Balance
and
nondepolarizing relaxants

Back 53

Respiratory acidosis potentiates the blockade of most nondepolarizing relaxants and antagonizes its reversal. This could prevent complete neuromuscular recovery in a hypoventilating postoperative patient

Front 54

Hypermagnesemia, as may be seen in preeclamptic patients being managed with magnesium sulfate, potentiates a nondepolarizing blockade by

Back 54

by competing with calcium at the motor end-plate.

Front 55

nondepolarizing block.
Electrolyte Abnormalities
augment x2

Back 55

Hypokalemia and hypocalcemia augment a nondepolarizing block.

Front 56

Metabolism & Excretion

Atracurium

Back 56

Ester Hydrolysis
Hofmann Elimination

Front 57

Metabolism & Excretion


cisatracurium

Back 57

degradation in plasma at physiological pH and temperature by organ-independent Hofmann elimination

Nonspecific esterases do not appear to be involved in the metabolism of cisatracurium.

Front 58

Pancuronium



Physical Structure

Back 58

Pancuronium consists of a steroid ring on which two modified ACh molecules are positioned

Front 59

Pancuronium

Metabolism & Excretion

Back 59

Pancuronium is metabolized (deacetylated) by the liver to a limited degree. Its metabolic products have some neuromuscular blocking activity. Excretion is primarily renal (40%),

Front 60

Pancuronium

cardiovascular effects

Back 60

These cardiovascular effects are caused by the combination of vagal blockade and sympathetic stimulation. The latter is due to a combination of ganglionic stimulation, catecholamine release from adrenergic nerve endings, and decreased catecholamine reuptake. Pancuronium should be given with caution to patients in whom an increased heart rate would be particularly detrimental (eg, coronary artery disease, idiopathic hypertrophic subaortic stenosis).

Front 61

Vecuronium



Physical Structure

Back 61

Vecuronium is pancuronium minus a quaternary methyl group (a monoquaternary relaxant). This minor structural change beneficially alters side effects without affecting potency.

Front 62

Vecuronium

Metabolism & Excretion

Back 62

Vecuronium is metabolized to a small extent by the liver. It depends primarily on biliary excretion and secondarily (25%) on renal excretion

Front 63

1. With regards to neuromuscular transmission, what ion is responsible for the release of ACh into the synaptic cleft?
a. Na++ in
b. Na++ out
c. Ca++ in
d. Ca++ out

Back 63

c

Front 64

2. When ACh attaches to a nicotinic cholinergic receptor, what needs to occur to generate the action potential?
a. ACh needs to attach to one α subunit to induce a conformational change.
b. ACh needs to attach to two α subunits to induce a conformational change.
c. ACh needs to bind to five protein subunits to induce a conformational change.
d. ACh needs to attach to any subunit to induce a conformational change.

Back 64

b

Front 65

3. Which ion is responsible for the actual muscle contraction?
a. Na
b. K
c. Mag
d. Ca

Back 65

d

Front 66

4. What happens in persons with Eaton-Lambert myasthenic syndrome that affects neuromuscular transmission?
a. Decreased release of ACh
b. Increased release of ACh
c. Decreased number of receptors
d. Increased number of receptors

Back 66

a

Front 67

5. What happens in persons with myasthenia gravis that affects neuromuscular transmission?
a. Decreased release of ACh
b. Increased release of ACh
c. Decreased number of receptors
d. Increased number of receptors

Back 67

c

Front 68

6. What is phase I block
a. The relaxation that occurs when a nondepolarizing muscle relaxant is given and antagonizes ACh receptors
b. The relaxation that occurs when a depolarizing muscle relaxant is given and after initial depolarization and contraction, the action potential disappears and the membrane returns to the resting state which results in muscle relaxation
c. The relaxation that occurs when a large dose of a depolarizing muscle relaxant is given and the quality of relaxation resembles that of a nondepolarizing block
d. None of the above

Back 68

b

Front 69

7. What occurs with muscle denervation injuries with regards to different muscle relaxants?
a. Exaggerated response to both depolarizing and nondepolarizing muscle relaxants
b. Exaggerated response to non-depolarizing MR but resistant to depolarizing MR
c. Resistant to both depolarizing and non-depolarizing MR
d. Exaggerated response to depolarizing MR but resistant to non-depolarizing MR

Back 69

d

Front 70

8. What occurs with myasthenia gravis with regards to different muscle relaxants?
a. Resistance to depolarizing MR but increased sensitivity to nondepolarizing MR
b. Resistance to both depolarizing MR and nondepolarizing MR
c. Increased sensitivity to both depolarizing and nondepolarizing MR
d. Resistance to nondepolarizing MR and increased sensitivity to depolarizing MR

Back 70

a

Front 71

9. Succinylchoine is:
a. Ionized because of its steroid structure
b. Ionized because of its benzyl isoquinoline structure
c. Ionized because of its quaternary ammonium structure
d. Ionized because of its tertiary ammonia structure

Back 71

c

Front 72

10. Why is such a large dose of Succinylcholine (mg/kg) needed to evoke muscle relaxation
a. Sux is not a potent drug
b. Most of the drug is metabolized by specific cholinesterase before reaching the NMJ
c. There are a lot of NM receptors that the drug needs to occupy
d. Most of the drug is metabolized by pseudocholinesterase before reaching the NMJ

Back 72

d

Front 73

11. You had given a normal dose of sux to a patient for an ENT procedure. It took him 7 hours to recover from that dose. You would expect:
a. His dibucaine number to be 20% indicating that he was homozygous for atypical cholinesterase
b. His dibucaine number to be 20% indicating that he had very low levels of plasma cholinesterase
c. His dibucaine number to be 20% indicating that he was heterozygous for atypical cholinesterase
d. His dibucaine number to be 80% indicating that he only had 80% of plasma cholinesterase

Back 73

a

Front 74

12. Which of the following drugs does NOT decrease pseudocholinesterase?
a. Neostigmine
b. Glycopyrolate
c. Echotiophate
d. Trimethaphan

Back 74

b

Front 75

13. Magnesium sulfate:
a. Increases a depolarizing block while decreasing a nondepolarizing block
b. Increased a nondepolarizing block while decreasing a depolarizing block
c. Decreases both nondepolarizing and depolarizing blocks
d. Increases both nondepolarizing and depolarizing blocks

Back 75

d

Front 76

14. Why is atropine given before sux in children?
a. Sux excites sympathetic receptors in the SA node inducing bradycardia
b. Sux blocks sympathetic receptors in the SA node inducing bradycardia
c. Sux excites cholinergic receptors in the SA node inducing bradycardia
d. Sux blocks cholinergic receptors in the SA node inducing bradycardia

Back 76

c

Front 77

15. You are giving a defasiculating dose to a 70 Kg patient. How much sux are you going to give?
a. .7 mg IV
b. 70mgIV
c. 105mg IV
d. 1.5mg IV

Back 77

c

Front 78

16. Which of the following side effects of Succinylcholine is not prevented by giving a defasiculating dose?
a. Myalgia
b. Increased Intraocular pressure
c. Increased intragastric pressure
d. Hyperkalemia

Back 78

d

Front 79

17. How does pancuronium cause tachycardia?
a. It blocks cholinergic receptors in the SA node
b. It causes a release of NE and epi from the adrenal medulla
c. It excites beta cells in the myocardium
d. It excites cholinergic receptors in the SA node

Back 79

a

Front 80

18. Which volatile agent causes the most potentiation of nondepolarizing muscle relaxants?
a. Iso
b. Sevo
c. Des
d. Halothane

Back 80

c

Front 81

You are going to dose your septic patient with a nondepolarizing MR, how would you want to dose them and why?
a. You would want to increase your dose because they are in a hyperdynamic state and will metabolize the drug more quickly
b. You would want to decrease your dose because acidosis potientiates the blockade
c. You would dose them the same as anyone else

Back 81

b

Front 82

For a patient with cirrhotic liver disease and chronic renal failure, how would you want to dose your nondepolarizing muscle relaxants?
a. Larger initial dose and larger maintenance dose
b. Smaller initial dose and smaller maintenance dose
c. Larger initial dose and smaller maintenance dose
d. Smaller initial dose and larger maintenance dose

Back 82

c

Front 83

How is atracurium metabolized?
a. By pseudocholinesterase and Hoffman elimination
b. By nonspecific esterases and Hoffman elimination
c. By the liver
d. By acetylcholinesterase and Hoffman elimination

Back 83

b

Front 84

With regards to Nimbex, what factors may effect it’s metabolism?
a. The Dibucaine number
b. Temperature
c. pH
d. Both B and C

Back 84

d

Front 85

Which Anticholinesterase would be the best to reverse a blockade caused by Mivacurium?
a. Neostigmine
b. Physostigmine
c. Edrophonium
d. None of the above- mivacurium cannot be reversed

Back 85

c

Front 86

24. Which of the following affects initial dose requirements for vecuronium?
a. Gender
b. Age
c. Race

Back 86

a