skeletal muscle relaxers Flashcards
two groups of skeletal muscle relaxers
depolarizing and non-depolarizing
5 steps of normal neuromuscular function
- Axn potential arrives at nerve terminal
- influx of Ca++ and release of Ach
- Ach diffuses across synaptic cleft
- Nicotine receptors activated on nerve endplate
- Muscle contracts
what are the non-depolarizing (antagonist) agents ?
” - curiums” and “-roniums”
what is the depolarizing (agonist) agent ?
succinylcholine
MOA of neuromuscular blocking agents
Agents block cholinergic transmission between motor nerve ending and nicotinic receptors on skeletal muscle
uses for neuromuscular block?
Facilitate tracheal intubation
Provide complete muscle relaxation
adjunct to anesthesia (decreased anesthesia dose and faster recovery)
what are the two groups of non-depolarizing (antagonist) neuromusc. blocking agents?
short acting ( 30-60min) long acting( 60-120min)
what are the short-acting non-depolarizing NM blocking agents?
Atracurium
Cisatracurium
Rocuronium (VERY rapid onset, short DOA)
Vecuronium
what is the long-acting non-depolarizing NM blocking agent?
Pancuronium
MOA of non-depol. NM blockers
competitive antagonists - block Ach from binding to receptor and activating it
clinical effect of non-depol NM blockers
progression- muscle weakness then complete muscle paralysis
large or small muscles more resistant to NM blockade ? what does this mean?
large muscles, paralyzed last but recover first
all NM blocking agents (depol and nondepol) are polar or nonpolar, why is this significant?
polar: can’t get into CNS when given orally so NEED to be IV.
you can get an increase NM blockade when giving nondepol agents with _______
antibiotics (usually aminoglycosides- GNATS)
- the abx DECREASE the release of Ach which enhances the blockade but INCR. RESPIRATORY DEPRESSION
how can you reverse the effect of nondepol NM blockers?
they are competative antagonists, so you can FLOOD with an agonist (Ach)
- give acetylcholinesterase inhibitors (e.g. neostigmine) so you have more Ach
what is the MOA of succinylcholine?
this is our “agonist” depolarizing agent.
- mimics Ach to depolarize NM, stays attached and constantly is depolarizing… unable to depol again while this drug is present.
when are you using succinylcholine?
adjunct to general anesthesia
- help tracheal intubation, skeletal muscle relaxation during surgery or mechanical ventilation in adequately sedated patients
what is the metabolism of of succinylcholine (depol NM block) ?
Metabolized by plasma pseudocholinesterase
DOA: 4-30 minutes
-drug disappears rapidly after discontinuation
what is the “genetic variant” for succinylcholine?
some people (w/ this variant) have PROLONGED effects from the drug
4 ADRs of depolarizing NM blocker (succinycholine)?
- apnea
- hyperkalemia
- muscle pain
- malignant hyperthermia
how can succinycholine cause apnea?
Deficiency/atypical form of plasma cholinesterase leads to prolonged apnea from diaphragm paralysis
how can succinycholine cause hyperkalemia? why is this significant?
Succinylcholine increases K+ release from intracellular stores.
- Damaged tissue ( burns, nerve damage, trauma, etc) has rapid loss of K+
- can lead to cardiac arrest
what 4 things can cause malignant hyperthermia ?
inhaled anesthetics + succinylcholine OR
-Genetic excitation-contraction coupling defect, burn victims, muscular dystrophy
what is malignant hyperthermia? what can it ultimately lead to?
Uncontrolled increased in skeletal muscle metabolism with SUDDEN, PROLONGED RELEASE OF Ca++
(overwhelm’s body’s capacity to supply O2, remove CO2 and regulate temp)
-fast rise in BODY TEMP, SEVERE MUSCLE CONTRACTIONS
- circulatory collapse and death !!
what would you use to txt succinylcholine+inhaled anesthetic - induced malignant hyperkalemia?
dantrolene
“when you hear allergy to Ach-drug think of ….”
malignant hyperthermia!
- if pt has allergy to a cholinergic, could potentially get malignant hyperthermia from inhaled anesthesia + succinycholine
- txt with dantrolene!
MOA of Dantrolene
a direct acting skeletal muscle RELAXANT
-prevents release of Ca+ in skel. muscle
two clinical uses of Dantrolene
- Txt of spasticity associated with upper motor neuron disorders (eg, spinal cord injury, stroke, cerebral palsy, or multiple sclerosis)
- Malignant hyperthermia - IV
All Spasmolytics are _____ _______ except for dantrolene. why is this significant?
centrally acting
-Provide significant relief from painful muscle spasm but don’t really help improve meaningful function
E.g., mobility or returning to work
what is Diazepam (Valium) used for?
Spasmolytic:
relief of skeletal muscle spasm due to inflammation, trauma or upper motor neuron disorders (cerebral palsy, MS)
ADR of Diazepam (valium) ?
Significant CNS sedation at doses needed for spasm relief
MOA of Baclofen?
A spasmolytic: Agonist of GABAb receptor
= decrease release of excitatory NT and decrease Ca++ influx
MOA of Tizanidine (Zanaflex)
Alpha-2 agonist
Decrease spasticity be increasing presynaptic inhibition to reduce muscle spasms
Overall: decrease facilitation of spinal motor neurons
what are the “non-spasmolytic” “other” drugs use to treat muscle spasm?
Cyclobenzaprine (Flexeril), the protoype Orphenadrine (Norflex) Carisoprodol (Soma) Metaxalone (Skelaxin) Methocarbamol (Robaxin)
what do we use “other” drugs for muscle spasm for in particular? what do we NOT use them for?
- Relief of acute muscle spasm caused by tissue trauma or strain (**nonspecific back pain) NOT for spasm from spinal cord or brain
- Don’t use in spinal cord or brain injuries
what is the major ADR of the “other” drugs for muscle spasm?
Strongly antichlolinergic (anti sludgemm),
what 4 drugs are used for true severe muscle spasm due to neurologic injury?
Diazepam, Baclofen, Tizanidine, Dantrolene
what population should spasmolytics and the “other” spasm drugs be used in caution with?
elderly:
little clear benefit and the ADRs are more pronounced in the elderly ( we do use these but really should not)
4 types of anesthesia
Local: +/- sedation
Conscious sedation
Regional
General
what is used for conscious sedation?
IV pain med and mild sedative are used (not local)
S-H (midazolam), fentanyl, morphine
*pt is sleepy but can maintain airway
what is regional anesthesia?
block sensation to particular part of body
4 goals of general anesthesia
Smooth, rapid induction with rapid recovery
Drug to maintain anesthesia
Wide therapeutic margin
Few side effects
what is most commonly used as pre-medication (step 1) for anesthesia?
midazolam (S-H) that sedates, decreases anxiety and often causes amnesia
what is often used for anesthesia induction? (step 2)
pre-oxygentate then…
IV use ultra short acting barbiturates (methohexital/brevital) or Propofol
principle of maintenance (step 3)
Use inhaled anesthetics and/or intravenous combined with IV agents in regimens of balanced anesthesia
what are the 3 spasmolytic drugs that we care about?
diazepam (valium)
baclofen (Lioresal)
Tizanidine (Zanaflex)
which spasmolytic is AS effective as Valium but with less CNS sedation?
Baclofen
what is zanaflex used for?
spasticity from cerebral or spinal injury
when is baclofen used?
- severe spastic disorders
- used for alcohol abstinence to decrease cravings
