Chapter 12 Review Questions-Neuromuscular Blocking Drugs

Front 1

1. What nondepolarizing agents are short acting? Long acting? And intermediate acting?

Back 1

Long: pancuronium;
intermediate: vec, roc, atracurium, cisatracurium;
short acting: mivacurium

Front 2

2. In a nerve transmission, acetylcholine binds to what post-synaptic receptors? Mu, Kappa, Nicotinic, or Muscarinic?

Back 2

Anwer: nicotinic; ach binds to these receptors causing a change in membrane permeability to ions, mainly K and Na. This altered permeability causes a decrease in the transmembrane potential from –90 mv to -45 mV, causing propagation of the action potential to the muscle fibers , causing them to contract.

Front 3

3. How do extrajunctional receptors cause hyperkalemia?

Back 3

Answer: When activated they stay open longer and permit more ions to flow. This response is also the reason for resistance or tolerance to nondepol agents

Front 4

4. How does the action on the alpha receptor vary between the administration of succs vs nondepol?

Back 4

Answer: when nondepol agents occupy one or both subunits it causes the ion channel to remain closed so the ion flow to produce depolarization cannot occur. When succs attaches to the alpha sites, it causes the ion channel to remain open resulting in prolonged depol.

Front 5

5. Why is the duration of action of pancuronium the longest of all nondepol agents?

Back 5

Answer: it is a bisquaternary aminosteroid and structurally resembles Ach of all ndbd’s

Front 6

6. For pre-treatment with a nondepolarizing NMBD during intubation with succs, what dose of the nondepol should be used?....what dose of succinylcholine should be used?

Back 6

Answer: 1. 5-10% of the intubating dose 2-4 minutes p/t succs administration 2. Increased dose by 70%

Front 7

7. An atypical dibucain number will affect what two NMBDs?...will a patient with liver disease have an altered dibucain number?

Back 7

Answer: 1. Sch and mivacurium 2. No…dibucain number reflects quality of plasma cholinesterase not quantity, and with liver disease, the quantity decreases but quality remains intact.

Front 8

8. Pretreatment with nondepolarizers for intubation with Succs can be used to alleviate all of the following except: a. sinus bradycardia b. fasciculations c. hyperkalemia d. myalgia

Back 8

Answer: hyperkalemia; the excess potassium leak from the stimulation of extrajunctional receptors upregulation cannot by attenuated by nondepol administration

Front 9

9. How much can plasma K levels increase with succs administration in the absence of extrajunctional receptor proliferation?

Back 9

Answer: ~0.5 mEq/L; this K increase can be far greater with the proliferation of extrajunctional receptors

Front 10

10. What are some factors that may increase nondepol doa and decrease nondepol doa?

Back 10

Answer: increase: volatile agents, aminoglycosides, antibiotics, local anesthetics, cardiac antidysrthythmics, dantroline, mag, lithium, tamoxifen, hypothermia. Decrease: calcium, steroids, phenytoin, burn injuries, CVA’s

Front 11

11. Why does pancuronium cause an increase in HR?

Back 11

Answer: C; panc selectively blocks cardiac muscarinic receptors having an atropine-like effect

Front 12

12. What are the clinically acceptable tests of NM transmission?

Back 12

Answer: tidal volume>5 ml/kg=80% blockade; TOF with no fade: 70% blockade; vital capacity (20 ml/kg)=70% ; sustained tetanus=60%; duble burse with no fade=60%; 5 sec head lift=50%; 5 sec hand grasp=50%

Front 13

neuromuscular blocking drugs (NMBDs) interrupt :ransmission of nerve impulses at the___________.

Back 13

neuromuscular Junction (NMJ)

Front 14

Among the nondepolarizing NMBDs, _______________ most closely resembles the onset characteristics of SCh.

Back 14

rocuronium

Front 15

The two principal clinical uses of NMBDs

Back 15

produce skeletal muscle relaxation for facilitation of tracheal intubation and to provide optimal surgical working conditions.

Front 16

The NM] consists of a ?.

Back 16

The NMJ consists of a prejunctional motor nerve ending separated from the highly folded postjunctional membrane of the skeletal muscle by a synaptic cleft.

Front 17

Neuromuscular transmission is initiated by arrival of an

Back 17

impulse at the motor nerve terminal with an associated influx of calcium ions and resultant release of the ligand ACh. ACh binds to nicotinic cholinergic receptors (the ligand-gated channel) on pos~unctional membranes and thereby causes a change in membrane permeability to ions, principally potassium and sodium.

Front 18

ACh binds to ___________ receptors

Back 18

nicotinic cholinergic

Front 19

I,Ch binds to nicotinic cholinergic receptors (the ligand-gated channel) on postjunctional membranes and thereby causes a change in membrane permeability to what 2 ions

Back 19

principally potassium and sodium.

Front 20

This change in permeability and movement of ions causes a decrease in the transmembrane potential from about ____________ .

Back 20

-90 m V to -45 m V.

Front 21

ACh is rapidly hydrolyzed by

Back 21

(within 15 msec) by the enzyme acetylcholinesterase (true cholinesterase), thus restoring membrane permeability (repolarization) and preventing sustained depolarization.

Front 22

Acetylcholinesterase is primarily located in...

Back 22

Acetylcholinesterase is primarily located in the folds of the end-plate region, which places it in close proximity to the site of action of ACh.

Front 23

ACh is synthesized in ....

Back 23

motor nerve terminal.

Front 24

_____________ facilitate replenishment of the motor nerve terminal, which can be stimulated by SCh and neostigmine and depressed by small doses of nondepolarizing NMBDs.

Back 24

Presynaptic receptors, aided by calcium.

Front 25

Postjunctional receptors

Back 25

are glycoproteins consisting of I five subunits. he subunits of the receptor are arranged such that a channel is formed that allows the flow of ions along a concentration gradient across cell membranes.

Front 26

Extrajunctional receptors retain the two _________ but may have an altered ___________ by the substitution of an c-unit.

Back 26

a-subunits

y- or g-subunit

Front 27

the binding sites for ACh and the sites occupied by NMBDs.

Back 27

The two a-subunits

Front 28

3X associated with a proliferation of extrajunctional receptors.

Back 28

Prolonged inactivity, sepsis, and denervarion or trauma (burn injury) to skeletal muscles may be associated with a proliferation of extrajunctional receptors.

Front 29

SCh is (structure wise)

Back 29

SCh is two molecules of ACh linked by methyl groups

Front 30

he post junctional nicotinic cholinergic receptor consists of five subunits ___________ arranged to form an ion channel.

Back 30

a,a,b,d,g

Front 31

NMBD most closely related to ACh structurally.

Back 31

Pancuronium bisquatemary aminosteroid NMBD

Front 32

Vecuroniurn and rocuroniurn are monoquaternary analogs of ________ .

Back 32

pancuronium.

Front 33

If a subparalyzing dose of a nondepolarizing NMBD (pretreatment with 5% to 10% of its 95% effective dose [ED9SD is administered 2 to 4 minutes before injection of SCh to blunt fasciculations, the dose of SCh should be increased by about _____%

Back 33

70%

Front 34

SCh mimics the action of ACh and produces a sustained depolarization of the ______________.

Back 34

postjunctional membrane

Front 35

Skeletal nuscle paralysis occurs because ?

Back 35

a depolarized postjunctional membrane and inactivated sodium channels cannot respond to subsequent release of ACh (hence, the designation depolarizing neuromuscular blockade).

Front 36

phase I blockade is

Back 36

Depolarizing neuromuscular blockade is also referred to as phase I blockade

Front 37

Phase IT blockade is

Back 37

present when the postjunctional membrane has become repolarized but still does not respond normally to ACh (desensitization neuromuscular blockade).

Front 38

urthermore, the sustained opening of sodium channels produced h-y SCh is associated with leakage of potassium from the interior of cells sufficient to increase plasma concentrations of potassium by about________ .

Back 38

0.5 mEqlL.

Front 39

Hydrolysis of SCh to inactive metabolites is

Back 39

by plasma cholinesterase (pseudocholinesterase)

Front 40

plasma cholinesterase (pseudocholinesterase) is produced in

Back 40

the liver

Front 41

The neuromuscular blockade produced by SCh is terminated by

Back 41

its diffusion away from the NMJ into extracellular fluid.

Front 42

)otent anticholinesterases, as used in the treatment of myasthenia gravis, and certain chemotherapeutic drugs (nitrogen mustard, cyclophosphamide) may so decrease plasma cholinesterase activity that ......

Back 42

prolonged skeletal muscle paralysis follows the administration of SCh.

Front 43

Atypical plasma cholinesterase lacks the ability to hydrolyze ester bonds in drugs such as SCh and mivacurium. The presence of this atypical enzyme is often recognized only after an otherwise healthy patient experiences prolonged skeletal muscle paralysis (> 1 hour) after the administration of a conventional dose of SCh or mivacurium. Subsequent

Back 43

ability to hydrolyze ester bonds in drugs such as SCh and mivacurium. The presence of this atypical enzyme is often recognized only after an otherwise healthy patient experiences prolonged skeletal muscle paralysis (> 1 hour) after the administration of a conventional dose of SCh or mivacurium.

Front 44

Subsequent determination of the dibucaine number permits diagnosis of the presence of atypical plasma cholinesterase. Dibucame IS an anude local anesthetic that inhibits normal plasma activity by about 80%, whereas the activity of atypical enzyme is inhibited by about 20%

Back 44

the presence of atypical plasma cholinesterase. Dibucame IS an anude local anesthetic that inhibits normal plasma activity by about 80%, whereas the activity of atypical enzyme is inhibited by about 20%

Front 45

Dibucaine is an amide local anesthetic that inhibits...

Back 45

normal plasma activity by about 80%.

Front 46

the dibucaine number reflects the...

Back 46

quality of plasma cholinesterase (ability to ' metabolize SCh and mivacurium) and not the quantity of enzyme that is circulating in plasma.

or example, decreases in plasma cholinesterase activity because of liver disease or anticholinesterases are often associated WIth a normal dibucaine number.

Front 47

SCh usually should not be given to patients ...
Why?

Back 47

24 to 72 hours after major burns, trauma, and extensive denervation of skeletal muscles because it may result in acute hyperkalemia and cardiac arrest.

Front 48

Administration of SCh to apparently healthy boys with unrecognized muscular dystrophy has resulted in ....

Back 48

acute hyperkalemia and cardiac arrest.6 For this reason, the Food and Drug Administration has issued a warning against the use of SCh in children, except for emergency control of the airway.

Front 49

the Food and Drug Administration has issued a warning against the use of SCh in children, except for

Back 49

emergency control of the airway.

Front 50

CARDIAC DYSRHYTHMIAS

That may follow the administration of SCh.

Back 50

Sinus bradycardia, junctional rhythm, and even sinus arrest

Front 51

CARDIAC DYSRHYTHMIAS Sinus bradycardia, junctional rhythm, and even sinus arrest may follow the administration of SCh. These responses reflect ..

Back 51

the action of SCh at cardiac postganglionic muscanruc receptors, where this drug mimics the normal effects of ACh

Front 52

Cardiac dysrhythmias are most likely to occur when (R/T SCh)...

Back 52

a second intravenous dose of SCh is administered about 5 minutes after the first dose.

Front 53

used before SCh to decrease the likelihood of these cardiac responses ..

Back 53

Intravenous administration of atropine or subparalyzing . doses of nondepolarizing NMBDs (pretreatment) 1 to 3 minutes before SCh decreases the likelihood of these cardiac responses.

Front 54

Hyperkalemia sufficient to cause cardiac arrest may follow the administration of SCh to patients with unhealed skeletal muscle injury, as produced by third-degree burns or trauma, or with denervation injury, as caused by spinal cord transection, and lead to skeletal muscle atrophy. The risk for hyperkalemia in these patients increases with time and usually peaks___________ after the injury.

Back 54

7 to 10 days

Front 55

Pretreatment with nondepolarizing NMBDs ___________ influences the magnitude of potassium release evoked by SCh and cannot be relied on as a safeguard.

Back 55

minimally

Front 56

Patients with renal failure and SCh.

Back 56

are not susceptible to exaggerated release of potassium, and SCh can be safely administered to these patients, assuming that they do not have uremic neuropathy.

Front 57

Prevention of fasciculations by

Back 57

prior administration of subparalyzing doses of a nondepolarizing NMBD a (pretreatment) or lidocaine will decrease the incidence but not totally prevent myalgia.

Front 58

SCh causes a maximum increase in intraocular pressure "when?"

Back 58

2 to 4 minutes after its administration

Front 59

SCh causes unpredictable increases in ________ pressure.

Back 59

intragastric

Front 60

Renal disease markedly alters the pharmacokinetics of only the ...

Back 60

long-acting nondepolarizing NMBDs, such as pancuronium.

Front 61

The intermediate-acting NMBDs are eliminated by the liver ________, by metabolism bv plasma cholinesterase ___________, by Hofmann elimination ___________, or by a combination of these mechanisms.

Back 61

(rocuronium)

(mivacurium)

(atracurium or cisatracurium)

Front 62

Cardiovascular Effects

Nondepolarizing NMBDs may exert minor cardiovascular effects through

Back 62

drug-induced release of histamine

Front 63

_____are the triggering drugs for more than 50% of the anaphylactic and anaphylactoid reactions occurring during anesthesia; such reactions occur at a rate between 1 in 1000 and 1 in 25,000 anesthetics.

Back 63

NMBDs

SCh is the most common offender.

Front 64

Pancuronium onset

duration

elemination

Back 64

of action of 3 to 5 minutes and a duration of action of 60 to 90 minute

80% of a single dose of pancuronium is eliminated unchanged in urine.

Front 65

Pancuronium with renal failure

Back 65

:n the presence of renal failure, plasma clearance of pancuronium is decreased 30% to 50%, thus resulting in a prolonged duration of action. An estimated 10% to 40% of pancuronium undergoes hepatic . deacetylation to inactive metabolites, with the exception of 3 -desacetylpancuronium, which is approximately 50% as potent as pancuronium at the NMJ.

Front 66

Pancuronium CARDIOVASCULAR EFFECTS

Back 66

Pancuronium typically produces a modest 10% to 15%. output. The increase in heart rate reflects pancuroniumoutput. The increase in heart rate reflects pancuroniuminduced selective blockade of cardiac muscarinic 2 receptors (atropine-like effect), principally in the sinoatrial node.

Front 67

Histamine and pancuronium.

Back 67

Histamine release and autonomic ganglion blockade are not produced by pancuronium.

Front 68

Vecuronium onset

duration

elemination

Back 68

an onset of action on to 5 minutes and a duration of action of 20 to 3S minutes
this drug undergoes both hepatic and renal excretion. [he effect of renal failure on the duration of action of vecuronium is small, but repeated or large doses may result in prolonged neuromuscular blockade.

Front 69

Atracurium Clearance

Back 69

his drug is by a chemical mechanism (spontaneous . nonenzymatic degradation at normal body temperature and pH known as Hofmann elimination) and l biologic mechanism (ester hydrolysis by nonspecific plasma esterases).
The two routes of metabolism occur simultaneously and are independent of hepatic and renal function, as well as plasma cholinesterase activity.

Front 70

Cisatracurium
onset

duration

elemination

Back 70

action of 3 to 5 minutes and a duration of action of 20 to 35 minutes.

This drug principally undergoes degradation by Hofmann elimination to laudanosine.

Front 71

Cisatracurium and histamine

Back 71

istamine- releasing contrast to atracurium, is devoid of histamine-releasing effects, so cardiovascular changes do not accompany the rapid intravenous administration of even large doses of Cisatracurium

Front 72

he most reliable method to monitor the pharmacologic effects of NMBDs.

Back 72

Evaluation of the mechanically evoked responses produced by electrical stimulation delivered from a peripheral nerve stimulator

Front 73

innervated solely by the ulnar nerve,

Back 73

adductor pollicis muscle

Front 74

Facial nerve stimulation muscle

Back 74

orbicularis oculi muscle

Front 75

the response of the orbicularis oculi muscle to facial nerve stimulation more closely reflects the onset of neuromuscular blockade at the ___________ than does the response of the adductor pollicis to ulnar nerve stimulation

Back 75

larynx

Front 76

acceptable skeletal muscle relaxation for performance of intra-abdominal surgery in the presence of an adequate concentration of volatile anesthetic.

Back 76

Depression of the twitch response greater than 90% or elimination of two to three twitches of the TOF

Front 77

TOF (four electrical stimulations at 2 Hz delivered every 0.5 second) is based on the concept that

Back 77

ACh is depleted by successive stimulations.

Front 78

DOUBLE BURST SUPPRESSION

why?

Back 78

Accurate estimation of the TOF ratio is not reliable clinically by either visual or manual assessment. Difficulty in estimating the TOF ratio may be due to the fact that the two middle twitch responses interfere with comparison of the first and last twitch response. In this regard, double burst suppression (two bursts of three electrical stimulations separated by 750 msec) is perceived by the observer . as two separate twitches (see Fig. 12-13).23 The observer's ability to detect a TOF ratio less than 0.3 is improved with double burst suppression, but the ability to conclude that the TOF ratio is greater than 0.7 is still not ensured.

Front 79

TETANUS is

Back 79

retanus (continuous or tetanic electrical stimulation for 5 seconds at about 50 Hz) is an intense stimulus for the release of ACh at the NMJ. In the presence of effects produced at the NMJ by nondepolarizing NMBDs, the response to tetanus is not sustained (fades), whereas in the presence of SCh-induced effects at the NM},

\t the cessation of tetanus, there is an increase in the immediately available stores of ACh such that the subsequent twitch responses are transiently enhanced (post-tetanic facilitation)

Front 80

Anticholinesterase drugs work by

Back 80

accelerate the already established pattern of spontaneous recovery at the NMJ by inhibiting the activity of acetyl- n cholinesterase and thereby leading to the accumulation 1 of ACh at nicotinic (NMJ) and muscarinic sites.

Front 81

indicates a TOF ratio greater than 0.7.

Back 81

a sustained response to tetanus or the ability to maintain head lift for 5 to 10 seconds usually indicates a TOF ratio greater than 0.7. Grip strength is also a useful indicator of recovery from the effects of NMBDs.