Neuromuscular Relaxants Flashcards Preview

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Flashcards in Neuromuscular Relaxants Deck (25):
1

Describe the mechanisms by which skeletal muscle nicotinic receptor activation stimulates skeletal muscle contraction, including the agonists, receptors, and postsynaptic mechanisms that initiate contraction.

1. pre-synaptic neuron releases ACh into the synaptic cleft
2. muscle nicotinic receptors (Nm) act as binding sites for the ACh
3. activation of Nm receptors opens up Na+ channels for depolarization
4. sufficient Na+ influx causes depolarization to travel down the T-Tubules (requires enough Na channels in the resting state)
5. calcium influx leads to muscle contraction

2

Compare the 2 distinct mechanisms by which depolarizing and non-depolarizing neuromuscular blockers mediate their effects on the motor end plate.

NON-DEPOLARIZING = competitive antagonists
- block the nicotinic ACh receptors (curare crayons)
- overcome by excess ACh via tetanic stimulation or cholinesterase inhibitors (neostigmine store owner yells at curare kid)
- at higher concentrations, nicotinic channel pore is blocked => not as sensitive to excess ACh

DEPOLARIZING = agonists

3

Compare the pharmacokinetics of the 2 classes of neuromuscular blockers.

NON-DEPOLARIZING
- competitive binding of nicotinic receptors prevents membrane depolarization and end-plate potential
- rapid distribution
- t1/2 depends on route of elimination (kidney > liver > plasma cholinesterase (metabolic))
=> avoid drugs metabolized by the liver if the patient has liver failure
=> avoid drugs metabolized by the kidney if the patient has renal failure
- biological half-life is longer than therapeutic effect due to receptor reserve

DEPOLARIZING
- more rapid onset that ND
- rapidly metabolized by plasma cholinesterases
- action terminated by diffusion out of the synapse
- genetic variations in cholinesterase can prolong drug effect
- clinical manifestation: arm => neck => leg => diaphragm

4

Describe how cholinesterase inhibition affects the paralysis produced by each type of neuromuscular blocker.

NON-DEPOLARIZING
- overcome paralysis when given ChE inhibitors

DEPOLARIZING
- Phase I - exacerbation
- Phase II - overcome paralysis

5

List the mechanisms by which the action of both classes of neuromuscular blockers are terminated.

ND
- AChE inhibitors

D
- Phase I - diffusion
- Phase II - AChE inhibitors

6

Describe the prominent side effects of each class of skeletal muscle relaxants.

NON-DEPOLARIZING
- non-analgesic
- apnea
- drug interactions with inhalant anesthetics (enhanced effect)

DEPOLARIZING
- non-analgesic
- apnea
- muscle pain
- stimulation of nicotinic autonomic and muscarinic cardiac receptors (arrhythmia, HTN, bradycardia)
- hyperkalemia due to K+ release from motor end plate
- malignant hyperthermia
- drug interactions with local anesthetics (enhanced effect)
- drug interactions with cholinesterase inhibitors (enhances Phase I)

7

List the antidote for either class of neuromuscular blockers.

NON-DEPOLARIZING
- cholinesterase inhibitors (neostigmine store owner yells at curare kid)
- muscarinic blockers to minimize cholinesterase inhibitor action on the muscarinic receptors (glycopyrrolate)

DEPOLARIZING
- Phase I = none; rapidly hydrolyzed by plasma cholinesterase
=> atropine for bradycardia due to muscarinic effects
- Phase II = cholinesterase inhibitors

8

Describe the characteristics of phase I and phase II block with depolarizing neuromuscular blockers and describe why phase II should be avoided.

- Phase I - succinylcholine binds to the nicotinic ACh receptor and causes motor end plate depolarization => transient contraction => succinylcholine is NOT degraded by acetylcholinesterase (requires plasma cholinesterase) => continuous depolarization of the AChR => not enough time for Na+ channels to return to resting => inactivated Na+ channels => no further AP => flaccid paralysis
=> tx with ChE inhibitors will augment blockade

- Phase II - succinylcholine enters the pore => membrane becomes repolarized, but receptor is desensitized;
=> acts like non-depolarizing muscle block
=> overcome by treatment with cholinesterase inhibitors or tetanic stimulation
=> but must confirm that Phase I is over b/c ChE inhibitors will augment muscle block when in Phase I
=> monitor patient for muscle action
=> avoid this phase by co-treatment with ChE inhibitors

9

Describe the characteristics of pancuronium, rocuronium, and vecuronium. Why is one agent preferable over another in long term ventilation, intubation of a healthy patient, or patient with renal failure for a short procedure or a moderate lengthy orthopedic surgery.

1. long-term ventilation - roc
2. intubation of a health patient - roc
3. patient with renal failure for a short procedure - roc, mivac
4. longer orthopedic surgery = pan

- avoid drugs metabolized by the liver if the patient has liver failure
- avoid drugs metabolized by the kidney if the patient has renal failure

10

Describe the mechanisms by which baclofen and benzodiazepines alter somatic motor neuron excitation.

- reduce activity of Ia fibers that excite the primary motor neuron
- enhance activity of the internuncial inhibitory neuron

11

List the major side effects of baclofen and benzodiazepines and discuss how the route of delivery can reduce side effects.

major SE = drowsiness

12

List the following for Tizanidine.
- MOA
- SE
- use

TIZANIDINE
- MOA: alpha-2 agonist (promotes inhibition of sympathetic activity in spinal cord)
- SE: drowsiness, hypotension
- use: MS and spinal spasticity

13

Define muscle twitch, clonus, and tetany.

twitch - action potential-dependent increase in intracellular calcium followed by reduction (sequestered in SR)

clonus - increased frequency of stimulation leads to incomplete relaxation;

tetany - no reduction in calcium between stimuli => muscle contraction

14

Describe how receptor reserve relates to the pharmacodynamics of curare compounds (non-depolarizing competitive antagonists).

- high receptor occupancy is required before an effect is observed
- % receptors occupied to inhibit contraction is proportional to (~) receptor reserve
- ex: 75% receptor occupancy is required before seeing any detriment in function, while 100% is required for full muscle relaxation
- biological half-life of curare compounds is longer than their therapeutic effect

15

Describe how receptor reserve creates a characteristic onset of drug effect for curare compounds (non-depolarizing competitive antagonists).

- different muscle beds have different receptor reserve and thus require different plasma concentration of curare to inhibit contraction
=> respiratory muscles > larger limb and trunk > fine muscles

EFFECTS
extraocular => hands and feet => head and neck => abdomen and extremities => diaphragm and respiratory muscles

This is because the lower the receptor reserve, the quicker therapeutic effects are reached (muscle weakness and paralysis)

16

What are the clinical uses for non-depolarizing and depolarizing neuromuscular relaxants?

ND
- muscle relaxation for surgeries
- intubation (rocuronium, mivacurium)
- ventilation

D
- endotracheal intubation
- controlling convulsions during EST

17

What are the contraindications for depolarizing muscle blockers?

- hx of familial malignant hyperthermia

18

List the following for baclofen:
- MOA
- clinical use
- side effects

- MOA: GABAb agonist => GABA binds to GABAb receptor on pre-synaptic nerve terminal => reduces calcium influx => inhibits excitatory transmitter release

- clinical use: spinal spasticity

- side effects: drowsiness

19

List the following for benzodiazepams (diazepam, clonazepam).
- MOA
- clinical use
- side effects

- MOA: enhances GABA effect by binding to GABAa on the post-synaptic neuron => Chlorine influx => hyperpolarizes the neuron => less likely to cause AP
- clinical use: spinal spasticity and MS
- side effects: sedation and drowsiness

20

List the following for dantrolene:
- MOA
- SE
- use

- MOA: blocks intracellular calcium release from CA (block ryanodine receptor)
- SE: sedation, muscle weakness
- use: spasticity and malignant hyperthermia (characterized by prolonged calcium release)

21

List the following for pancuronium:
- duration
- MOA
- elimination route
- use

- duration: 30-60 min
- MOA: non-depolarizing competitive antagonist of nicotinic ACh receptors
- RoE: renal
- use: surgical anesthesia, abdominal wall relaxation, and orthopedic procedures

22

List the following for D-tubocurarine:
- duration
- MOA
- elimination route
- use

- duration: >60 min.
- MOA: non-depolarizing competitive antagonist of nicotinic ACh receptors
- RoE: liver clearance and renal elimination
- use: prototype; lethal injection

23

List the following for rocuronium:
- duration
- MOA
- elimination route
- use

- duration: 25 min.
- MOA: non-depolarizing competitive antagonist of nicotinic ACh receptors
- RoE: liver
- use: intubation, muscle relaxation during surgery, ventilation

24

List the following for mivacuronium:
- duration
- MOA
- elimination route
- use

- duration: 15-20 min.
- MOA: non-depolarizing competitive antagonist of nicotinic ACh receptors
- RoE: metabolic plasma cholinesterases
- use: intubation, muscle relaxation during surgery, ventilation with renal failure patients

25

List the following for vecuronium:
- duration
- MOA
- elimination route
- use

- duration: 30-45 min.
- MOA: non-depolarizing competitive antagonist nicotinic ACh receptors
- RoE: liver clearance and renal elimination
- use: surgical anesthesia, abdominal muscle relaxation, orthopedic surgeries