Muscle Relaxants Flashcards
Neuromuscular junction and Ach receptor
- binding of 2 Ach molecules to the paired alpha (not beta) subunits results in Na and Ca to flow down their [ ] gradients into the cell and K to flow down its [ ] gradient out of the cell
- movement of cations leads to end-plate potential and depolarizes perijunctional membrane, leading to opening of voltage-gated Na channels–>action potential
- action potential activates Na channel receptors on T-tubule system and Ca is released by sarcoplasmic reticulum–>contraction
Myasthenia Gravis and effect on neuromuscular blockade
- autoimmune or congenital, antibodies to AchR
- decreased sensitivity to sux: increased dosage of a depolarizing agent is required to achieve Phase 1 blockage because you must active enough Ach receptors
- increased sensitivity to non-depolarizers: reduced dose of nondepolarizer needed because there are fewer Ach receptors (fewer receptors to occupy for a given effect)
Eaton-Lambert Syndrome (ELS)
aka myasthenic syndrome
- reduced amount of presynaptic Ach–>up-regulation of AchR at NMJ
- increased sensitivity to both NDNMB and sux
- sux: more receptors=easier to depolarize=smaller dose needed
- non-depolarizers (competitive inhibition w/Ach): less Ach=less competition=smaller dose needed
Meaning of fade on TOF
- non-depolarizing muscle relaxants
or - phase II block w/sux
Phase II block
-prolonged depolarization of the perijunctional muscle endplate results in conformational changes to the Ach-R, such that it resembles the block of a nondepolarizer
TOF=% blockade
1/4=90%
2/4=80%
3/4=75%
Succinylcholine and fasciculations
- increased ICP and abdominal pressure (strongest correlation)
- diffuse myalgia (strong association, but not 100%)
- increased abdominal pressure offset by increase in LES tone (no change in aspiration risk)
- intraocular pressure increases w/sux independent of fasciculations
Most common side effect of muscle relaxants
- Benzylisoquinolones (-curium)
- Steroidals (-curonium)
- Benzylisoquinolones (-curium): histamine release–>flushing, vasodilation, and bronchospasm
- mivacurium and atracurium most likely
-Steroids (-curonium): vagolytic–>tachycardia and HTN
Effect of giving neostigmine before succinylcholine
Prolonged duration of action of sux
-neostigmine inhibits pseudocholinesterase
Causes of muscle blockage prolongation
- Volatiles
- Magnesium
- Hypocalcemia
- Hypokalemia
- Acidosis
- Hypothermia
- Neonates (more sensitive than adults)
Anti cholinesterase drugs and effect on succinylcholine
- neostigmine
- physostigmine
- edrophonium
- neostigmine: inhibits pseudocholinesterase–>prolongs sux duration
- physostigmine: inhibits pseudocholinesterase (less than neostigmine)–>slightly prolongs sux duration
- edophonium: no effect on pseudocholinesterase–>no change in sux duration
Cerebral Palsy effect on muscle relaxants
- normal response to sux: no increased risk of hyperkalemia, even in setting of contractures, as there is no proliferation of exntrajunctional nicotinic AchR
- resistant to nondepolarizers
Extensive burns and effect on muscle relaxants
- resistance to nondepolarizers (increased receptors)
- hyperkalemia w/sux (extrajunctional proliferation)
SLE and effect on muscle relaxants
Sensitivity to nondepolarizers AND depolarizers
*autoimmune disorders in general have hypersensitivity to all muscle relaxants (likely only true for those disorders with rheumatologically derived weakness)
Cisatracurium Metabolism
- Hoffman elimination- organ-independent, occurs in plasma, slowed by hypothermia
- Laudanosine- byproduct metabolized in liver and excreted by kidneys, CNS excitation at high levels (no intrinsic neuromuscular blockade)
- Atracurium also produces laudanoside: atra is less potent than cis, so greater dose required and thus increased levels of laudanosine w/atra compared to cis
*cisatricurium not associated w/histamine release (atracurium is)
