Nsp: Neuromuscular Blocking Agents (Garrett)

Front 1

What are the Therapeutic Uses of Neurmuscular Blocking agents? (4)

Back 1

1. Muscle relaxation during surgery
2. Intubation of the trachea
3. Control of Ventilation (improve thoracic compliance and decrease amount of energy expended)
4. Treatment of Convulsions

Front 2

What is the site of action of neuromuscular blocking agents?

Back 2

neuromuscular nicotinic cholinergic receptor

*have little effect on autonomic nicotinic receptor*

Front 3

Can neuromuscular blocking agents pass across membranes?

What about the blood-brain barrier?

Back 3

not easily across membranes (water soluble

NONE can cross the BBB

Front 4

Which neuromuscular blocking agents are orally active?

Back 4

none

administered IV

Front 5

Are the neuromuscular blocking agents, since they look like acetylcholine, metabolized by acetylcholine esterase?

Back 5

no

succinylcholine and mivacurium are metabolized by "pseudocholine esterase" (butyrylcholine esterase)

Front 6

What muscles are affected first?

What muscles recover first?

Back 6

small muscles of eyes, jaw, and larynx >>larger muscles of the trunk and limbs >>>> diaphragm

recovers in reverse order, diaphragm recovering first

Front 7

What are the nondepolarizing neuromuscular blockers?

Back 7

Benzylisoquinolone derivatives (atracurium, cisatracurium, mivacurium, D-tubocurarine)

Aminosteroid derivatives (pancuronium, rocuronium, vercuronium)

Front 8

What is the mechanism of action of nondepolarizing neuromuscular blockers?

Back 8

muscle nicotinic receptor ANTAGONISTS

**produce flaccid paralysis**

Front 9

What are the side effects of isoquinoline class of drugs (atracurium, cisatracurium, mivacurium, D-tubocurarine)

Back 9

release histamine causing bronchospasm, skin flushing, and hypotension due to vasodilation

Front 10

Which nonpolarizing NMB has moderatel rapid onset (2-3 min), intermediate duration, and causes histamine release?

Back 10

atracurium

Front 11

What isoquinolone does not release histamine?

Back 11

cisatracurium

Front 12

How is cisatracurium degraded?

Back 12

spontaneously in plasma at physiological pH and temperature by Hofmann elimination, therefore normal liver and kidney fxn is not required for metabolism and elimination

Front 13

Mivracurium has _______ onset of action and ________duration

Back 13

Mivacurium has MODERATELY RAPID ONSET of action (2-4 min) and SHORT duration (12-18 min)

Front 14

What NMB agent is metabolized by butyrylchoine esterase?

Back 14

Mivacurium

Front 15

What NMB drug is the prototype of non-depolarizing blocking agents and was the first NMB drug?

Back 15

D-tubocurarine

*isolated from the Strychnos species in Amazon*

Front 16

What isoquinoline blocks autonomic ganglia and is seldom used due to other LONG and MEDIUm acting drugs?

Back 16

D-tubocurarine

Front 17

What are the aminosteroid derivatives?

Back 17

1. pancuronium
2. rocuronium
3. vercuronium

Front 18

What nonpolarizing NMB is especially suitable for long surgical procedures due to it's mod. rapid onset of action (2-3 min) and long duration (60-120 min)

Back 18

pancuronium

Front 19

What does pancuronium increase the risk for arrhythmias?

Back 19

pancuronium blocks cardiac muscarinic receptrs (vagolytic) and stimulates the sympathetic nervous system causing tachycardia and hypertension increasing the risk for arrhythmias

Front 20

What is the only non-polarizing NMB w/ rapid onset?

Back 20

rocuronium

*intermediate to long duration of action*

Front 21

Which aminosteroid derivative has Mod rapid onset of action, intermediate duration and LITTLE cardiovascular effects?

Back 21

vercuronium

Front 22

What is the depolarizing NMB named and how does it work?

Back 22

Succinylcholine

prolonged depolarization causes voltage gated Na channels to stay in the inactive conformation

Front 23

Describe the phases of NMB by depolarizing agents?

Back 23

Phase 1: initial fasciuclations followed by flaccid paralysis (this can cause muscle pain afterwards)

Phase 2: flaccid paralysis; the membrane potential returns to resting levels, but the receptors cannot be activate to produce action potentials in the muscle due to desensitization of the receptors

Front 24

What is onset and duration of succinylcholine?

Back 24

Rapid onset (<60sec) and SHORT duration (5-10min)

Used when rapid intubation is required

Front 25

What are the side effects of succinylcholine?

Back 25

Hyperkalemia
Stimulation of autonomic ganglia (low doses: bradycarida; high doses: tachycardia)
intraocular pressure
malignant hyperthermia
Histamine release
Muscle pain

Front 26

What do you administer to reverse NMB?

Back 26

Acetylcholinesterase inhibitor such as neostigmine or edrophonium

Front 27

What is an analog of GABA (GABA agonist) that crosses the BBB?

Back 27

Baclofen

Front 28

What are the sites of action of Baclofen?

Back 28

GABAb receptors at the nerve terminals of the corticospinal neurons innervating the alpha motor neurons and primary afferent fibers.

GABAb receptors are also located on cell bodies and dendrites of the alpha motor neurons

Front 29

What is the mechanism of action of Baclofen?

Back 29

activation of presynaptic GABAb receptors inhibits glutamate release by inhibiting calcium entry into nerve terminals

activation of GABAb receptors on cell bodies causes hyperpolarization by activating K+ channels

Front 30

Is Baclofen orally active?

Back 30

yes but can also be given intrathecally

Front 31

What are the side effects of Baclofen?

Back 31

sedation, drowsiness, and fatigue

*tolerates w/ chronic administration
*Can cause withdrawal syndrome so discontinue slowly

Front 32

What drug is a alpha-2 adrenergic receptor Agonist similar to clonidine, but has fewer CV effects due to low doses needed to reduce spasticity?

Back 32

Tizanidine

Front 33

What is the MOA of Diazepam?

Back 33

facilitates action of GABA at GABAa receptors

causes sedation

Front 34

What is the MOA of Dantrolene

Back 34

reduces spasticity due to the blockade of Ca++ release from SR (blocks RyR1)

(RyR2 are in cardiac and smooth muscle)

Front 35

What are the major side effects of Dantrolene?

Back 35

muscle weakness
sedation
occaisonal hepatitis

Front 36

What antispasmodic can treat malignant hyperthermia caused by general anesthesia during surgery?

Back 36

Dantrolene

Front 37

What inhibits the release of acetylcholine from the alpha motor unit by digesting SNARE proteins?

Back 37

Botulinum Toxin (BOTOX)
esp. Type A toxin