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3rd Quarter > Pharm Quiz #3 > Flashcards

Pharm Quiz #3 Flashcards

1
Q

What is the pharmacologic effect of neuromuscular blocking agents?

A

interrupt nerve impulse transmission at neuromuscular junction

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2
Q

What are the two classifications of NMB agents?

A
  1. depolarizing

2. non-depolarizing

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3
Q

How does depolarizing agent provide NMB?

A

by mimicking acetylcholine (acetylcholine makes the muscle contract)

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4
Q

How does non-depolarizing agents provide NMB?

A

by blocking the actions of acetylcholine

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5
Q

The non-depolarizers in use today are primarily _____ acting and the two categories of them are….?

A

intermediate;

  1. benzylisoquinolinium
  2. aminosteroid compounds
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6
Q

What are some examples of benzylisoquinolinium NMB agents?

A
  1. nimbex

2. atricurium(nibex’s daddy)

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7
Q

What are some examples of amino steroid compounds?

A
  1. pancuronium
  2. rocuronium
  3. vecuronium
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8
Q

What are the 3 types of blocks?

A
  1. phase I
  2. phase II
  3. non-depolarizing block
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9
Q

How are NMB agents potency measured?

A

by ED 95; equal potency between NMB agents measured by dose required to suppress 95% of single twitch responses.

  • ED95 measured under nitrous-barb-opioid anesthesia
  • ED95 greatly reduced under volatile anesthesia
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10
Q

So the onset and duration of NMB is monitored by?

A

PNS

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11
Q

What are the principle sites of PNS and what are the characteristics of each?

A
  1. adductor pollicis(slow twitch)

2. obicularis oculi(fast twitch)

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12
Q

NMB affects _____ first and the _____ last.

A
  • small, rapidly moving skeletal muscles first(eye lids)

- diaphragm last

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13
Q

What is the first muscle to return after NMB?

A

diaphragm

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14
Q

Non-depolarizing NMB onset is more rapid yet less intense at _____ muscle than the _____.

A

laryngeal; diaphragm

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15
Q

Laryngeal muscles(fast twitch) equilibrate more _____ with plasma NMB {} than slow twitch muscles(adductor pollicis).

A

rapidly

  • acetylcholine receptor density greater with fast twitch muscles
  • laryngeal muscle relaxation is brief(is declining by time of maximal diaphragmatic relaxation occurs)
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16
Q

Dose required to produce a degree of NMB at diaphragm is 2 X that required for an equal block at adductor pollicis or obicularis oculi. The _____ muscle the _____ it takes.

A

bigger, more

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17
Q

What muscle does PNS at the adductor pollicis best monitor?

A

diaphragm; poor indicator of laryngeal relaxation

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18
Q

What muscle does PNS at the obicularis oculi best monitor?

A

laryngeal

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19
Q

Single twitch response give?

A

POST-junctional data

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20
Q

Tetanus and TOF give?

A

data on POST-juctional membranes

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21
Q

Do you have fade with TOF using depolarizing NMB agents?

A

nope

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22
Q

What is the PNS indicator that differentiates between depolarizing NMB agents and non-depolarizing NMB agents?

A

TOF-NOT SINGLE TWITCH

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23
Q

What is Wedensky inhibition?

A
  • a positive TOF fade seen when using non-depolarizing NMB agents.
  • continous refractory state preventing repolarization; occurs when nerve is stimulated with high electrical frequencies and ends when application of current stops
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24
Q

NMB agents have quaternary ammonium groups which makes them(4)?

A
  1. unable to cross the BBB
  2. highly ionized
  3. water soluble at physiologic pH
  4. poorly lipid soluble
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25
Q

Poor lipid solubility gives NMB _____ volume of distribution.

A

small

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26
Q

What 4 lipid membranes are NOT crossed by NMB?

A
  1. BBB
  2. renal tubular epithelium
  3. GI
  4. placenta
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27
Q

So what is the summary of pharmacokinetics of NMB?

A
  • no CNS effects(dosent cross BBB)
  • oral absorption very poor
  • not crossing renal tubular epithelium causes poor tubular reabsorption
  • no placental crossing-no effects to the newborn
  • plasme clearance, Vd, elimination 1/2 times influenced by: age, volatile agent, hepatic/renal disease
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28
Q

Are the pharmacokinetics altered by long acting NMB agents in patients with ESRD?

A

yes

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29
Q

Are NMB bound to plasma proteins?

A

NOT highly bound to plasma proteins

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30
Q

Describe the rate of disappearance of long acting NMB.

A

rapid initial decline by REDISTRIBUTION followed by a slower decline via CLEARANCE

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31
Q

What type of effects does inhaled anesthetics have on NMB?

A

minimal effects

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32
Q

With hypovolemia, equal drug doses produce _____ effects to due to greater plasma {}.

A

exaggerated

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33
Q

What are the 4 clinical uses of NMB agents?

A
  1. provide optimal conditions for laryngeal intubation
  2. improve surgical conditions during GA
  3. management of patients undergoing mechanical ventilation
  4. treatment of laryngospasm
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34
Q

What percent single twitch response is required for optimal surgical conditions with NMB?

A

90% suppression of single twitch response

-if patient has no twitches they are over paralyzed

35
Q

How much ED95 dose of non-depolarizing NMB is required to aid laryngeal intubation?

A

2 X ED95(typically dose we give)

36
Q

For laryngospasm, doses as small as _____ mg/kg of succinylcholine are effective.

A

0.1 mg/kg

37
Q

TOF > then _____ provides adequate return of skeletal muscle strength for spontaneous ventilation.

Quiz Question

A
  1. 7

- if you wait until you have 4 twitches before reversing you will never take the “walk of shame”

38
Q

4 additional indicators of muscle strength.

A
  1. grip strength
  2. sustained head lift
  3. VC
    4 NIF
39
Q

What is the only non-depolarizer NMB with onset similar to succinylcholine, by at an intermediate duration?

A

Rocuronium

reasons to use: securing airway, break laryngospasm, lead chest(maybe)

40
Q

What factors determine depolarizer vs non-depolarizer?

A

speed of onset
duration of action
drug effects at other than NMJ

rapid onset-brief duration may indicate succinylcholine

41
Q

What are 2 situations where a non-depolarizer might be used instead of a depolarizer.

A
  1. sustained NMB is needed

2. for GA when rapid intubation is not required

42
Q

Neuromuscular blockers affect _____ moving muscles before muscles of the _____ & _____.

A

small rapidly moving muscles(eyes & digits) before muscles of the trunk and abdomen.

*the last muscles paralyzed are the intercostals and the diaphragm(skeletal muscle recovery occurs in reverse order with the diaphragm first)

43
Q

Pre-treatment of NMB agents can produce:

A
  • difficulty focusing
  • mandibular weakness
  • ptosis
  • diplopia
  • dysphagia
  • decreased hearing due to middle ear muscle relaxation
44
Q

Which NMB most resembles acetylcholine and how?

A

succinylcholine-2 molecules of acetylcholine linked by acetate methyl groups

45
Q

What do quaternary ammonium compounds bind to?

A

Quaternary ammonium compounds with at least 1+ charged nitrogen atom binds to alpha subunit of post-synaptic cholinergic receptors.

46
Q

Describe the structure of succinylcholine.

A

long, flexible, slender structure binds to and activated cholinergic receptors

47
Q

Describe the structure of Non-depolarizing NMB.

A

bulky and rigid molecules that contain acetylcholine structures but can’t bind to & activate cholinergic receptors

48
Q

Quaternary ammonium groups are found in _____ NMB.

A

all

49
Q

Describe the structure of acetylcholine.

A

acetylcholine has a + charged quaternary ammonium group(4 carbons attached to a nitrogen) that attaches to negative charged cholinergic receptors.

50
Q

Most NMB have bisquaternary ammonium structures. What does that mean?

A

Bisquaternary ammonium structures give electrical attractions between the 2+ charged areas of the NMB molecule and anionic groups at:

  1. NMJ cholinergic receptors
  2. Cholinergic receptors not @ NMJ(cardiac muscarinic & autonomic ganglia nicotinic receptors)
51
Q

Is the pre-junctional nerve ending myelinated or non-myelinated?

A

non-myelinated

52
Q

What do the non-myelinated pre-junctional nerve endings contain?

A
  • mitochondria
  • endoplasmic reticulum
  • synaptic vesicles which make acetylcholine
53
Q

What is the resting membrane potential across nerve/skeletal muscle membranes?

What maintains this resting membrane potential?

A

-90 mv;maintained by unequal distribution of K+ and Na+ ions across the membrane

54
Q

Describe the 3 types of cholinergic nicotinic receptors found at the NMJ.

A

Two are at the post-synaptic on skeletal muscle surfaces

  1. post-synaptic junctional
  2. post-synaptic extra junctional
  3. pre-synaptic on the nerve ending
55
Q

Where are post-synaptic receptors located?

A

in the junctional folds; opposite nerve ending sites where acetylcholine is released

56
Q

What are some characteristics of extra-junctional receptors?

A
  • not normally involved in nerve impulse transmission

- may proliferate in nerve or muscle damage

57
Q

What is the characteristic of TOF twitches in phase 1 NMB in a depolarizing block?

A

constant by diminished twitches

58
Q

What is the characteristic of TOF twitches in phase 2 NMB in a depolarizing block?

A

twitches with fade

59
Q

What is a depolarizing phase II block related to?

A

usually due to a large dose or repeated dose of succinylcholine

60
Q

What is the characteristic of TOF twitches NMB using a non-depolarizing block?

A

fade

61
Q

What is the characteristic of tetanus twitches in phase 1 of NMB in a depolarizing block?

A

constant but diminished

62
Q

What is the characteristic of tetanus twitches in phase 2 of NMB in a depolarizing block?

A

fade

63
Q

What is the characteristic of tetanus twitches NMB using a non-depolarizing block?

A

fade

64
Q

What is the characteristic of post-tetanic potentiation twitches of a phase I depolarizing block?

A

NO TWITCHES(absent)

65
Q

What is the characteristic of post-tetanic potentiation twitches of a phase 2 depolarizing block?

A

present

66
Q

What is the characteristic of post-tetanic potentiation twitches of a non-depolarizer block?

A

present

67
Q

Should a phase 2 block be reversed?

A

typically don’t try to reverse a phase 2…its important to check twitches before giving a ND agent to make sure its not a phase 2 block

68
Q

The neuromuscular junction neurotransmitter is?

A

acetylcholine

69
Q

What is the classification of acetylcholine?

A

Quaternary ammonium ester

70
Q

Acetylcholine in the motor nerve endings is made by what and controlled by what?

quiz question

A

made by acetylation of choline;controlled by the enzyme choline acetylase

71
Q

Where is acetylcholine stored?

A

in the synaptic vesicles in motor nerve endings

72
Q

How is acetylcholine released?

always on quiz

A

Released in synaptic cleft as packets or quanta-1000 molecules

73
Q

How does acetylcholine cause a muscle contraction?

A
  • nerve impulse arrives causing release of 100’s of quanta to bind to nicotinic cholinergic receptors on post-synaptic membranes causing membrane permeability change in ions.
  • permeability change decreases transmembrane potential from -90 to -45 mV(threshold potential)
  • at threshold potential, action potential spreads causing contraction
74
Q

What is the receptor acetylcholine binds to on the post-synaptic membrane

A

nicotinic receptors

75
Q

Where are nicotinic receptors located and what are they made up of?

A
  • present in large numbers on post-junctional membranes
  • proliferate in skeletal muscle with deficient nerve stimulation
  • are 250K Dalton weight glycoproteins
76
Q

Post-junctional nicotinic cholinergic receptors consist of how many subunits concentrically arranged?

A

5

77
Q

What are the names of the 5 post-junctional nicotinic cholinergic receptors?

A
  • alpha(x2)
  • beta
  • gamma
  • delta
78
Q

Where specifically at the post-synaptic junction are nicotinic cholinergic receptors located?

A

-located mainly on the shoulders of post-junctional membrane folds, exactly opposite pre-junctional acetylcholine release

79
Q

Each neuromuscular junction has _____ of post-junctional receptors and a burst of acetylcholine opens at least how many receptors?

A

millions; at least 400K receptors

-currents flows through open receptors, depolarizes endplates, starting action potentials

80
Q

What is the basis for neuromuscular transmission?

A

the flow of ions

81
Q

In addition to binding acetylcholine, the 2 alpha units(alpha, beta, gamma, delta) are the sites of what?

A

sites of action for NMB drugs

Non-depolarsing NMB show preference for 1 of 2 alpha subunits

82
Q

What is the result of occupation of the 1 of 2 alpha subunits by non-depolarizing NMB?

A

causes ion channel formed by receptors to remain closed
when we pretreat with a non-depolarizer(preventing fascinations)

-ion flow ends and depolarization can not occur

83
Q

If 2 alpha subunits are occupied simultaneously, what happens?

A

ion channels opens and fasciculations occur

3rd Quarter (22 decks)

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