L20- Skeletal Muscle Relaxants Flashcards
name the two types of skeletal muscle relaxants and their uses (include subtypes)
Neuromuscular Blockers: surgical procedures and in ICUs –> paralysis
- agonists - depolarizing blocker
- antagonists - non-depolarizing blocker
Spasmolytics: reduce spasticity in variety of neurological conditions
- acute spasm
- chronic spasm
list the non-depolarizing blockers
(antagonists) Benzylisoquinolines: -mivacurium -atracurium, cisatracurium -tubocurarine (prototype)
Ammonio-steroids:
- rocuronium, vocuronium
- pancuronium
______ is the only depolarizing blocker, include structure
succinylcholine: 2 ACh molecules linked end-to-end
Non-depolarizing blockers work as (1) agents at NMJ. (2) is the prototype. Their effects can be overcome by (3), as seen with the use of (4) drugs, often used for recovery post-anesthesia.
1- competitive antagonists at AChR
2- tubocurarine
3- inc [ACh] in synapse
4- neostigmine, edrophonium (AChE inhibitors)
describe the effect of non-depolarizing blockers on muscles during anesthesia
- first cause motor weakness
- skeletal muscles become totally flaccid
- inexcitable to stimulation
Succinylcholine is an agonist of (1) receptors, initially causing (2) in muscles. Since succinycholine is not readily (3) in the synapse, (4) continues and (5) is the end result.
1- nAChR 2- fasciculations 3- metabolized by AChE 4- membrane remains depolarized --> unresponsive to additional impulses 5- flaccid paralysis
discuss the onset and duration of action of succinylcholine, explain
Onset- rapid, <1 min
Duration: rapid, 5-10 mins — rapid hydrolysis via plasma pseudocholinesterases (BChE)
Neuromuscular blockers:
- (1) is an important group that gives the agents strong (polar/non-polar) qualities
- due to this quality, (3) and (4) are the main drawbacks
- (5) is the main benefit of this quality (hint- related to (4))
1- quaternary ammonium
2- highly polar – poorly soluble in lipids
3- inactive if given by mouth — give IV, IM
4- penetrates cell membranes poorly
5- doesn’t cross BBB
list the non-depolarizing blockers by duration of action
Short: mevacurium
Intermediate:
- atracurium, cisatracurium
- rocuronium, vecuronium
Long:
- tubocurarine
- pancuronium
describe the mechanism of elimination of each benzylisoquinoline and relationship to duration of action
Mivacurium- plasma pseudocholinesterases, 15min
Atracurium- enzymatic, non-ezymatic ester hydrolysis, 45min
Cisatracurium- spontaneous (80%), renal, 45min
Tubocurarine- renal, hepatic, 80min
______ is a non-depolarizing blocker that can degrade spontaneously
cisatracurium
describe the mechanism of elimination of each ammonio-steroid and relationship to duration of action
Recuronium, Vecuronium: hepatic (80%), renal; 30min, 45min respectively
Pancuronium: renal (80%), hepatic, 90min
Atracurium may produce (1) as one of its metabolites that can cause (2). (3), a stereoisomer of atracurium forms much less (1) in addition to a decrease in (4) release. Therefore (3) has mostly replaced atracurium.
1- laudanosine
2- hypotension, seizures
3- cisatracurium
4- histamine release
(1) is the only short-acting non-depolarizing blocker due to its hydrolysis via (2).
1- mivacurium
2- plasma BChE // plasma pseudocholinesterases — short b/c metabolism is not dependent on liver, kidney
(1) has the most rapid onset among the non-depolarizing blockers, and can be used as an alternative for (2) in (3) situations
1- rocuronium
2- succinylcholine
3- rapid sequence intubation
what is the key factor to investigate in patients before giving a short-acting neuromuscular blocker (name them) and how would it be treated
succinylcholine and mivacurium:
- BChE polymorphisms / variants => prolonged action of these neuromuscular blockers
- must check FHx
-treat with mechanical ventilation until muscle function returns
(1) is the main AE seen with benzylisoquinolines due to (2) and (3) activity
(4) is the main AE seen with ammonio-steroids due to (5) actions; (4) may possibly develop into (6)
1- hypotension
2- histamine release
3- ganglionic blockade
4- tachycardia
5- M2 blockade
6- arrhythmias
(1) is often given before the administration of benzylisoquinolines in order to avoid (2). (3) list strength of the effect based on each agent.
1- antihistamine
2- hypotension via histamine release
3- tubocurarine»_space; mevacurium, atracurium
(1) neuromuscular blocker may block nAChRs in (2) areas in order to cause hypotension and (3)
(ganglion blockade)
1- tubocurarine
2- autonomic ganglia, adrenal medulla
3- reflex tachycardia
(1) is a neuromuscular blocker that can cause moderate tahycardia due to (2) mechanism, although (3) is usually not an issue with (1) in general
1- pancuronium
2- M2 blockade
3- CVS effects usually not an issue
Succinylcholine:
- (1) mechanism of AEs
- (2) importantly absent group of AEs
1- activates nAChR in SNS/PSNS ganglia and mAChR in heart (+ histamine release)
2- CNS effects, doesn’t cross BBB
list the many AEs of succinylcholine based on MOA
nAChR: muscle pain (irregular contraction –> K+ release), hyperkalemia, inc intraocular P (EOM contractions), inc intragastric P, malignant hyperthermia
mAChR: bradycardia
Histamine release
list the drugs that enhance neuromuscular blockade
- inhaled anesthetics
- aminoglycosides
- tetracyclines
Name the disease or process that has the following effects on non-depolarizing neuromuscular blockers:
- (1) inc neuromuscular blockade
- (2) prolongs blockade due to dec drug clearance
- (3) and (4) patients are resistant to non-depolarizing muscle relaxants due to proliferation of (5)
1- myasthenia gravis
2- ageing
3- severe burns
4- UMN injury
5- extrajunctional receptors
list the contraindications to non-depolarizing neuromuscular blockers
- h/o malignant hyperthermia
- h/o skeletal muscle myopathies
- major burns
- multiple traumas
- denervation of skeletal muscle
- UMN injury
list the main uses of neuromuscular blockers
1) ALL- adjuvants in surgical anesthesia –> skeletal muscle relaxation
2) Succinylcholine- facilitate endotracheal intubation during anesthesia induction + used in ECT
______ is often given after completion of surgical procedure to reverse muscular blockade
(AChE inhibitors)
neostigmine
edrophonium
______ are often given during anesthesia with neuromuscular blockers in order to prevent bradycardia
(ammonio-steroids blockade – need antimuscarinics to prevent M2 blockade)
- atropine
- glycopyrrolate
list the Spasmolytic drugs: act on CNS for chronic spasms
- diazepam
- baclofen
- tizanidine
list the Spasmolytic drugs: act on skeletal muscle for chronic spasms
- dantrolene
- botulinum toxin
Chronic Spasms, CNS:
______ facilitates action of GABA via GABA(a) receptor modulation
diazepam
Chronic Spasms, CNS:
______ is a GABA agonist at GABA(b) receptors
baclofen
Chronic Spasms, CNS:
______ is an agonist at α2-adrenoreceptors
tizanidine- inhibits neurotransmitter release
Dantrolene:
- (1) uses
- (2) MOA
1- chronic muscle spasms; malignant hyperthermia
2- binds ryanodine receptor in SR of skeletal muscle –> prevents Ca release from SR
(1) has been used increasingly more for generalized spastic disorders like cerebral palsy by working on skeletal muscles with (2) actions
1- botulinum toxin
2- prevents ACh release
Acute muscle spasms:
- (1) is the main cause
- (2) is the location drugs primarily act, (3) is the prototype – structurally related to (4)
- (3) has strong (5) AEs
1- local trauma, strain 2- brainstem 3- cyclobenzaprine 4- TCAs 5- antimuscarinic AEs
