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Pharmacology 1, 680 > Neuromuscular Blockade: Pathophysiologic Implications > Flashcards

Neuromuscular Blockade: Pathophysiologic Implications Flashcards

1
Q

Factors associated with Resistance to Nondepolarizing NMB (decreases block)

A

Due to decrease activity of AChE, or induced cytochrome P-450 in the liver causes increased metabolism (?), or increased number of ACh receptor sites (increased amt. of NMB required)

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2
Q

Drugs and their resistance to non depolarizing NMB

A

Phenytoin – causes shorter duration
Rocuronium 20% of control
Vecuronium 37% of control
Pancuronium 40% of control

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3
Q

Chronic use of _____ cause increased resistance to steroidal relaxants like vecuronium

A
  • corticosteriods
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4
Q

Corticosteriods often used as tx in what condition?

A

Myasthenia gravis

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5
Q

how do Aminophylline and Theophylline create resistance to NMBs?

A

inhibit phosphodiesterase - increase the cyclicAMP needed to synthesize and release ACh (greater dose of NMB to compete with more Ach)

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6
Q

how does furosemide increase resistance to NMBs

A

in large doses, 1-4 mg/kg, inhibits phosphodiesterase, increasing cAMP (same as azathioprine, Imuran

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7
Q

Resistance begins 10 days after ____ injuries

A

Burn
*peaks at 40 days, and declines after 60 days (463 days); requires 30% or more burned BSA;

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8
Q

Cannot give Sux 24-48 hrs after for burn victims due to risk of

A

hyperkalemia- extrajunctional receptors

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9
Q

Burn injures cause resistance to NMB due to

A

decreased sensitivity of the postjunctional receptors to either ACh or nondepolarizing NMB.

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10
Q

increased ______ receptors create resistance due to _____

A

*extrajunctional cholinergic receptors
*denervation

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11
Q

Example of patients that have increased extrajunctional receptors

A

hemiplegics or patients with paralyzed limbs

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12
Q

condition that causes resistance due to prolonged response due to co existing skeletal muscle weakness or having increased extrajunctional cholinergic receptors

A

multiple sclerosis

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13
Q

conditions that can lead to increased extrajunctional cholinergic receptors

A

*massive trauma
*immobilization
*chronic hyperkalemia

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14
Q

how does chronic hyperkalemia cause increased resistance

A

decreasing the resting potential of the membrane (moves it closer to depolarization), even partially depolarizes it (increases sensitivity to SCh)

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15
Q

How do volatile anesthetics increase Sensitivity to Nondepolarizing NMB?

A

decreases the skeletal muscle tone and decreases the sensitivity of muscle membranes to depolarization to lower the ED95; greatest impact on long-acting NMB

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16
Q

How do local anesthetics increase Sensitivity to Nondepolarizing NMB?

A

– interfere with the release of ACh from the prejunctional receptors (decrease competitor), block ion channels, and directly depress skeletal muscle tone. – makes pt more sensitive
ester LA compete with SCh for plasma cholinesterases which may result in prolonged SCh effect

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17
Q

How do antibiotics increase Sensitivity to Nondepolarizing NMB?

A

magnesium-type effect to decrease release of ACh to make reversal unreliable (can give calcium).

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18
Q

Antibiotics that have NO NEUROMUSCULAR EFFECT are

A

penicillins, cephalosporins (Ancef), and macrolides (erythromycin).

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19
Q

How does lidocaine increase Sensitivity to Nondepolarizing NMB?

A

when given to a patient who is recovering from a nondepolarizing NMB, the block is potentiated by the blockage of the prejunctional release of Ach
Blunts airway reflexes

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20
Q

How does Quinidine increase Sensitivity to Nondepolarizing NMB?

A

potentiates nondepolarizing NMB and SCh.

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21
Q

How does Lithium (cation) increase Sensitivity to Nondepolarizing NMB?

A

synergist(1+1=3 effect on nondepolarizing and additive effect(1+1=2) (prolonged onset and duration) on depolarizing
Lithium accumulates in nerve endings and decreases ACh synthesis- makes patient more sensitive to NMB
Similarity to sodium ion – the lithium influx intracellularly into the muscle - hypopolarizes the membrane and therefore potentiates depolarizing neuromuscular blockers (succ)

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22
Q

How does Lasix increase Sensitivity to Nondepolarizing NMB?

A

<1mg/kg – decreased cyclicAMP production

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23
Q

How does Cyclosporine increase Sensitivity to Nondepolarizing NMB?

A

Leg cramps, contractions
*Based on retrospective study of renal transplant patients who required postoperative ventilation – either atracurium or vecuronium

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24
Q

How does Succinylcholine increase Sensitivity to Nondepolarizing NMB?

A

– reduces dose required possibly due to membrane desensitization causing enhanced (not prolonged) blockade by the nondepolarizing NMB, succ makes pt more sensitive to NonDepolarizer

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25
Q

How does other non depolarizing NMBs increase Sensitivity to Nondepolarizing NMB?

A

synergistic effect with two drugs with different sites of action (pancuronium and metocurine) allowed smaller doses of each to minimize side effects – typically drugs from different classes.

26
Q

How do calcium channel blockers increase Sensitivity to Nondepolarizing NMB?

A
  • usual site of action is on the slow channels, not fast channels like the postjunctional receptors. Unpredictable effects have been reported.
27
Q

How does hydrocortisone increase Sensitivity to Nondepolarizing NMB?

A

acute administration may potentiate nondepolarizing NMB, becomes sensitive to steroid class of drugs (ronium)
Development of critical illness myopathy

28
Q

How do antihypertensives increase Sensitivity to Nondepolarizing NMB?

A

– ganglionic blockers – trimethaphan, hexamethonium – can decrease sensitivity of the muscle membrane to cause relaxation of its own and potentiate nondepolarizing NMB; they also inhibit plasma cholinesterase activity to cause prolongation of depolarizing block

29
Q

How does hypothermia increase Sensitivity to Nondepolarizing NMB?

A

prolongs duration by slowing clearance via hepatic enzymes and renal pathways and via Hofmann elimination and ester hydrolysis

30
Q

How does hypokalemia increase Sensitivity to Nondepolarizing NMB?

A

increases membrane potential (hyperpolarization, further from depolarization) and increases sensitivity to nondepolarizing NMB (resistant to SCh)

31
Q

How does hypermagnesium increase Sensitivity to Nondepolarizing NMB?

A

decreased release of ACh from prejunctional receptors (enhanced block); pregnant women with toxemia being treated with magnesium should receive a reduced dose of relaxant- very sensitive to non depolarizer

32
Q

How does hypernatremia increase Sensitivity to Nondepolarizing NMB?

A

dehydration causes decreased volume of distribution of NMB, thus more drug reaches the receptors (increased concentration of drug)

33
Q

how does gender increase Sensitivity to Nondepolarizing NMB?

A

differences in muscle mass from men cause greater block in women with similar mg/kg dose.

34
Q

Myasthenia gravis =

A

chronic autoimmune disorder caused by a decrease in functioning acetylcholine receptors at the NMJ (destroyed by IgG antibodies)

35
Q

muscles that are first to show symptoms of fatigue, weakness (undiagnosed) with myasthenia gravis

A

Ocular, pharyngeal, laryngeal muscles

36
Q

Myasthenia gravis treatment

A

anticholinesterases and immunosuppressive drugs which may cause resistance to non depolarizers

37
Q

Myasthenia gravis shows a ____
sensitivity to nondepolarizing NMB due to ____ receptors for which to compete.

A

*increased
*fewer
- prolonged effect so NMB may need to be avoided with these patients

38
Q

what is important/needed in order to determine the dose of myasthenia gravis patient?

A

baseline TOF-Titrate initial dose to response to peripheral nerve stimulator (reduce ½ to 1/3).

-No correlation between base TOF and clinical severity
Some correlation between base TOF and dose required

39
Q

Myasthenic syndrome – Eaton Lambert=

A

Seen with oat cell carcinoma of the lung; autoimmune disease where presynaptic calcium channels are destroyed by antibodies. (vs. post synaptic channels in myasthenia gravis
*Think about possibility in known cancer patients and those having diagnostic or biopsy procedures for lung cancer.

40
Q

what drugs are ineffective with Myasthenic syndrome – Eaton Lambert, which are sensitive?

A

Anticholinesterase drugs are ineffective.
Sensitive to both SCh and nondepolarizing NMB

41
Q
A
42
Q

diagnostic or biopsy procedure where Eaton Lamberts condition is discovered

A

Thoracoscopy

43
Q

drug that HAs a black box warning to the pediatric population

A

SCh
-hyperkalemia and asystole potential similar response as with MH as with muscular dystrophy

44
Q

What drug is contraindicated for muscular dystrophy

A

SCh

45
Q

Sch may cause ____ ____ of NMB when muscle weakness and atrophy exists

A

prolonged duration

46
Q

SCh causes ___ ____ in myotonia dystrophica

A

prolonged contraction
-give short acting that does not need to be reversed because ACH (ACH increased when giving anticholinesterase) will cause depolarization of the muscle membrane and contraction

47
Q

Amyotrophic lateral Sclerosis (ALS) also known as

A

Lou Gehrig’s disease

48
Q

ALS is a degenerative disease that affects the ___ ____ and spinal _____ tracts

A
  • motor ganglia
  • pyramidal tracts
49
Q

ALS causes prolonged responses to

A
  • non depolarizing NMB and Hyper K with SCh
  • skeletal muscle atrophy
50
Q

Giving a water soluble drug to a baby causes the drug to be

A

more diluted out since greater water amt in their bodies

51
Q

Drug that causes a quicker onset in infants and children and why

A

Vecuronium due to faster circulation times

52
Q

Vecuronium has prolonged recovery in ___ and ___ while children recover faster

A
  • infants and neonates
53
Q

Due to Atracuriums histamine release neonates required a 25% lower

A
  • dose by weight due to increased sensitivity
54
Q

Elderly have decreased ____ and ____ so doses will be more

A

body fluid and lean muscle mass
- concentrated

55
Q

these 2 drugs shows a prolonged duration in the elderly

A

Vecuronium and Rocuronium

56
Q

ELderly have decreased plasma ___,

A

proteins=so more unbound drug that can have an effect
- also have decreased cardiac output, kidney function, and hepatic blood flow

57
Q

in the elderly, the priming technique resulted in decreased ____ ____ and ____

A
  • pulmonary parameters,
  • desaturation
58
Q

drug that is age and organ independent so indicated for the elderly

A

Atracurium- however histamine release is greater

59
Q

for Obese patients, SCh is dosed based on ___ body weight because?

A

total body weight, obese patients have more plasma cholinesterase so a bigger dose of drug is needed to prevent SCh from being “eaten up” and not enough of drug able to make it to the receptor sites

60
Q

Blood flow matters!! increased cardiac output =

A

faster onset and vice versa

61
Q

ephedrine- partial direct and indirect acting- affects alpha 1 receptors to cause ______ but also effects/stimulates beta 1 receptors to increase______

A

vasoconstriction
- HR and stroke volume
-given prior to administration of rocuronium, decreased onset time by 22%

62
Q

Esmolol blocks beta 1 receptors which _____ onset time by 26%

A

increases
-application- someone on chronic beta blockers may have increased onset times during induction

Pharmacology 1, 680 (3 decks)

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