Relaxants Flashcards
the only depolarizing NMJ-blocking drug
Succinylcholine
Muscle relaxants
block the neuromuscular junction (NMJ) by binding to acetylcholine (ACh) receptors located on it
All NMJ-blocking drugs cause respiratory arrest (apnea) by paralyzing the diaphragm and intercostal muscles, requiring patients to be artificially ventilated.
Skeletal muscle relaxants are used as adjuncts to anesthetic agents:
-Laryngeal intubation and rapid sequence induction of anesthesia : drugs with fast onset of action (e.g., succinylcholine, rocuronium)
-Artificial ventilation (during anesthesia or in intubated ICU patients)
-Abdominal muscle relaxation during laparotomy
-Prevents the patient from moving during surgery
-Facilitates physical manipulation (e.g., surgical incisions, moving the patient)
Antagonists to nondepolarizing drugs
neostigmine, pyridostigmine, sugammadex
Succinylcholine does not have a specific antagonist.
Inhibition of acetylcholinesterase → increase in acetylcholine concentration in the synaptic cleft → competitive displacement of the muscle relaxant from the ACh receptor
Neostigmine, pyridostigmine, and edrophonium are usually coadministered with anticholinergics, such as atropine or glycopyrrolate, to counter muscarinic effects like bradycardia, nausea, and bronchospasm.
Sugammadex : a selective relaxant binding agent and rapid-acting antidote for rocuronium and vecuronium
Cyclodextrin - for aminosteroid NDMR (ve-, ro-)
Succinylcholine - mechanism
(!!!suxamethonium!!!)
Depolarization -> skeletal muscle fasciculations
0,6-1,5 mg/kg FAST administration
Acetylcholinesterase cannot break down succinylcholine → persistent depolarization of the motor end plate → unresponsiveness of the motor end plate to subsequent nerve impulses (depolarized block) →* flaccid paralysis* of the skeletal muscles
K+ leakage
Onset ~ 60 sec
Within 5–10 minutes, plasma cholinesterases metabolize succinylcholine (a short-acting muscle relaxant) = duration time
Patients with atypical plasma cholinesterase: prolonged paralysis
SCh -Neuromuscular monitoring - phases
Phase I - Persistent depolarization,, Phase I blockade is potentiated by the effects of cholinesterase inhibitors.
Train-of-four stimulation shows an equal decrease in the amplitude of all 4 muscle twitches
Phase II - frequent doses, the postsynaptic membrane repolarizes and becomes desensitized, (i.e., resistant to depolarization by acetylcholine) leading to prolonged muscle relaxation.
Cholinesterase inhibitors may reverse the effects of phase II blockade.
Train-of-four stimulation shows a fade-off in the amplitude of the muscle twitch.
NDMR
Compete with ACh to bind with the (nicotinic) ACh receptors - nondepolarization block
Highly ionised - don’t cross BBB, placenta, no CNS effect, min tubular reabs
Histamine release - decrease BP (tubo>meto>atra>miva)
No fasciculation
+ tetanic fade, posttetanic potentation
+antagonised by anticholinoesterases (increase of ACh, competition)
AE:
Cardiac dysrhythmias, brady<3, hyper K+ (cardiac arrest), myalgia, triasmus
Increased ICP, OCP, intragastric pressure
Short acting NDMR
Mivacurium (15-20 min)
- Histamine release → rash, bronchospasm, hypotension
- Facilitation of tracheal intubation
- 90%: enzymatic hydrolysis - renal clearance
Mivacurium dose
Intub: 0,07-0,25 mg/kg
Mainten. 0,1 mg/kg
Infusion 0,4-0,6 mg/kg/h
Intermediate-acting NDMR
At VeRo
Rocuronium
Vecuronium 60-90 min
Atracurium 14-60 min
Cisatracurium
Long acting NDMR
PanTalony
Pancuronium 90-120 min
D-Tubocurarine 60-120 min
Metocurine, gellamine, pipecuronium, doxacurium
Start in 3-5 mins,
Renal excretion 40-95%
Rocuronium
60-90 min
70% hepatic metab
0,6-1 mg/kg intubation, 0,1 maintenance
** Rapid-sequence induction** of anesthesia when succinylcholine is contraindicated - starts after 1 min
No histamine release - cardiostable
Specifically antagonized by sugammadex
AE: HT
Vecuronium
60-90min
100mcg/kg intub, 20-30mcg/kg mainten
Alternative to rocuronium and succinylcholine for rapid sequence induction
Recommended for patients with cardioVascular disease (No sympathomimetic properties)
AE: ongoing paralysis
No histamine release
Specifically antagonized by sugammadex
Atracurium
70%: enzymatic hydrolysis
30%: Hofmann elimination (a process in which a compound spontaneously degrades in the plasma and tissue)
Degradation dependent on body temp and pH
Intubation 0,3-0,6 mg/kg
Maintenance 0,1
Ideal for patients with renal and hepatic insufficiency
Histamine release → rash, bronchospasm, hypotension
Bradycardia, hypotension
Laudanosine - metabolite - CNS stimulant -> prolonged use may precipitate seizures
Pancuronium
90-120min
0,07 mg/kg
Used if skeletal muscle paralysis > 1 hour is required
Respiratory depression or apnea
Sympathomimetic properties - selective cardiac vagal blockade - increase BP, HR
Dose adjustments required in renal/hepatic insufficiency
Adverse effects - DMR
- hyperkalemia - depolarization cause efflux of potassium ions
[Succinylcholine is contraindicated in case of hyperkalemia or in conditions associated with a high-risk of hyperkalemia, including:
*Burn injuries
*Rhabdomyolysis
*Demyelinating disorders (e.g., Guillain-Barré syndrome, multiple sclerosis, ALS)
*Stroke
*Spinal cord injury]
-Hypercalcemia
-Postoperative muscle pain due to muscle fasciculations
-Prolonged muscle paralysis, respiratory depression and/or apnea in patients with a congenital deficiency of plasma cholinesterase
-Malignant hyperthermia
-Cardiac arrhythmias
-Raised intragastric pressure → emesis
NDMR Adverse Eff
Adverse effects due to histamine release (atracurium, mivacurium): rash, bronchospasm, hypotension
Tachycardia (pancuronium)
Respiratory depression or apnea
Critical illness myopathy
Neuromuscular monitoring
objectively determines degree of muscle paralysis with the help of a peripheral nerve stimulator
Method: train-of-four response
->Four electric stimuli are administered along the ulnar nerve every 2 seconds
Interpretation
0 twitches indicates profound NMJ block
1–2 twitches indicate a partial block.
1 twitch per electric stimulus indicates no NMJ block. - reversal agent can be safely administered
Atropine
Muscarinic antagonists: inhibit the effect of acetylcholine on muscarinic receptors (the majority of anticholinergic drugs)
[mydriasus, delirium, flushing, dryness, urinary retetion, tachycardia]
First drug of choice in unstable (symptomatic) sinus bradycardia (IV)
Premedication: prior to intubation to decrease salivary, respiratory, and gastric secretions
Ophthalmology: uveitis
Urinary urgency, urge incontinence, urinary frequency and/or nocturia (symptoms resulting from, e.g., overactive bladder syndrome)
Antidote for anticholinesterase poisoning: atropine reverses the muscarinic effects of cholinergic poisoning (e.g., bronchoconstriction) but does not reverse the nicotinic effects (e.g., muscle weakness, paralysis).
Scorpion stings
