Paralytics Flashcards
In the neuromuscular junction, how is acetylcholine synthesized?
It is synthesized from choline and acetate in the presence of acetylcholine transferase
How is acetylcholine released?
It’s released from nerve endings in response to an impulse traveling down a motor nerve. Calcium enters the nerve terminal, combines with calmodulin, and facilitates discharge of acetylcholine
What happens after acetylcholine is discharged in the neuromuscular junction?
it stimulates nicotinic cholinergic receptors on post-junctional skeletal muscle membranes to initiate excitation-contraction coupling. It’s then hydrolyzed by acetylcholinesterase
What are the two types of paralytics?
depolarizing and non-depolarizing
List the popular depolarizing paralytics
succinylcholine and decamethonium
What are the two sub groups of non-depolarizing paralytics?
benzylisoquinoliniums and aminosteroids
List two examples of a benzylisoquinolinium
atracurium, cisatracurium
List three examples of an aminosteroid
pancuronium, rocuronium, vecuronium
What is the order of muscle relaxation sequence with a paralytic?
OUTER TO INNER!
oculomotor –> palpebral and facial –> tongue and pharynx –> jaw and tail –> limbs –> pelvic –> caudal abdominal –> cranial abdominal –> intercostal –> larynx –> diaphragm
What is the molecular structure of succinylcholine?
two acetylcholine molecules joined back to back
What is the mechanism of action of succinylcholine?
succinylcholine attaches to one or both of the alpha subunits of the nicotinic acetylcholinergic receptors and mimics action of acetylcholine
The hydrolysis of succinylcholine is slower than that of acetylcholine causing sustained depolarization of receptor ion channels
Why does neuromuscular blockade develop with succinylcholine?
because the depolarized postjunctional membrane is unable to respond to a subsequent release of acetylcholine. There is a depolarizing, or Phase 1, neuromuscular blockade
What is a phase II block?
with repeated doses, CRIs, or a large dose of succinylcholine, postjunctional membranes may not respond normally to acetylcholine even after repolarization. The mechanism is not known, however
How is succinylcholine metabolized and excreted?
duration of action id depending on hydrolysis of succinylcholine by plasma cholinesterase (pseudocholinesterase) enzyme. The initial metabolite is succinylmonocholine which is hydrolyzed to succinic acid and choline
What are the CNS effects of succinylcholine?
none
What are the CV effects of succinylcholine?
sinus bradycardia, junctional rhythm, and sinus arrest (IN PEOPLE) d/t the cardiac muscarinic effects.
Heart rate can also increase d/t ganglionic stimulation at autonomic nervous system ganglia
What are the respiratory effects of succinylcholine?
Respiratory arrest occurs d/t the paralysis of skeletal muscle
What are the musculoskeletal effects of succinylcholine?
- initial muscle contraction
- flaccid skeletal muscle paralysis
What are the gastrointestinal effects of succinylcholine?
inconsistent increases in gastric pressure
What are the urinary effects of succinylcholine?
myoglobinuria may occur d/t skeletal muscle damage associated with the muscle fasciculations
Anything weird about eyes and succinylcholine?
Yes, an increase in IOP has occurred after administration of succinylcholine, likely due to contraction of extraocular muscles
When is succinylcholine contraindicated?
patients predisposed to malignant hyperthermia
What is the molecular structure of a non-depolarizing paralytic?
variable based on classification but, all are quaternary ammonium compounds with at least one positively charged nitrogen atom that binds to alpha subunit of postsynaptic cholinergic receptors
What is the specificity of the drugs for the NMJ versus the autonomic ganglia nicotinic receptors dependent on? (non-depolarizing)
the length of the carbon chains separating the 2 positively charged ammonia groups. Neuromuscular blockade occurs when 10 carbon atoms are present. Maximal autonomic ganglion blockade occurs when 6 carbon atoms are present
What is the mechanism of action for a non-depolarizing paralytic?
combine with nicotinic acetylcholine receptors without activating them. THey can act competitively with acetylcholine at the alpha subunits of the post-junctional acetylcholine receptors without changing their configuration. They can also act by blocking the ion receptor channels. They can also act at prejunctinoal acetylcholine receptors
How is atracurium metabolized and excreted?
hydroysis in plasma and Hoffman elimination
What is Hoffman elimination?
spontaneous degradation in plasma and tissue at normal body pH and temperature
How is cisatracurium metabolized and excreted?
Hoffman elimination
How is pancuronium excreted?
renal, 80% unchanged
How is rocuronium excreted?
biliary excretion (50-70% unchanged) and renal excretion (10-25% unchanged)
How is vecuronium excreted?
biliary excretion 40-75% unchanged and renal excretion (15-25%) unchanged
How is vecuronium excreted?
biliary excretion 40-75% unchanged and renal excretion (15-25%) unchanged
What is something that all nondepolarizing NMBs are dependent on for degradation?
temperature!!
atracurium and cisatracurium are also dependent on pH
What is the elimination of pancuronium, rocuronium, and vecuronium dependent on?
Renal function
rocuronium and vecuronium are also dependent on liver function
What CNS effects to nondepolarizing paralytics have?
none
What CV effects do nondepolarizing paralytics have?
- pancuronium increases HR, MAP, and CO d/t selective vagal blockade and increases in cardiac dysrhythmias when also receiving digitalis
- atracurium can result in decreased BP and increased HR d/t histamine release
what are the respiratory effects of nondepolarizing paralytics?
none directly. respiratory arrest occurs d/t paralysis of skeletal muscle
What musculoskeletal effects do nondepolarizing paralytics have?
flaccid skeletal muscle paralysis
What GI effects do nondepolarizing paralytics have?
none
What are the urinary effects of a nondepolarizing paralytic?
none
What are the drug interactions of nondepolarizing paralytics to be aware of?
volatile anesthetics - dose dependent enhancement of magnitude and duration of NMB
Antibiotics - aminoglycosides enhance NMB, reversal of paralytics can be unpredictable
Diuretics - furosemide enhances NMB, mannitol does NOT have an effect
Local anesthetics - small doses can enhance NMB
Magnesium - enhances NMB
What is a particular side effect of atracurium to be aware of?
histamine release!!
