Flashcards in Neuromuscular Blocking Drugs Deck (62)
What are the non-depolarizing isoquinoline derivatives?
-D-tubocurarine (off the market)
What are the non-depolarizing steroid derivatives?
What is the only depolarizing agent?
What are the reversal agents for NMBs?
What are reversal agents used for?
They are given post‐procedurally to reverse the residual effects of the paralytic agent and restore normal neuromuscular activity and tone.
What are the types of cholinergic receptors?
and muscarinic receptors.
Where do paralytic agents act?
nicotinic M receptors found on post-synaptic skeletal muscle (the other type is the nicotinic N receptors- can be found on pre-synaptic terminal)
Describe the nicotinic acetylcholine receptor.
It is a multimeric ligand-gated ion channel for sodium influx into the cell, leading to depolarization
What must occur for the nicotinic acetylcholine receptor to activate?
2 molecules of Ach must bind
How are depolarizing paralytics different from non-depolarizing paralytics?
Non-depolarizers bind the receptor and prevent the opening of the receptor channel (thus preventing initial activation of muscle contraction) while depolarizing agents actually open the gate and causes persistent depolarization which prevents gate closure and repolarization
What is the result of depolarizing paralytics (i.e. succinylcholine)?
The initial, intense muscle contraction is replaced by flaccid paralysis from preventing repolarization to occur
How does a peripheral nerve stimulator (PNS) work?
It delivers 4 sequential stimuli at 2 Hz. Each stimuli causes release of Ach from synaptic vesicles. In the absence of neuromuscular blockade, the 4th twitch of the adductor polices muscle is as strong as the first. This is called 'fade'
Only the first twitch is registered in a PNS when what percentage of receptors is bound?
Which twitches can be seen when 70-8% of receptors are bound?
How are the non-depolarizing drugs metabolized?
rapid initial distribution into tissue with slower elimination and duration of action correlated closely with half life.
How are the non-depolarizing drugs eliminated?
more rapidly eliminated via liver than kidney
What is a potential downside of Atracurium?
it is intermediate acting with hepatic metabolism and Hofmann elimination which produced laudanosine, a metabolite linked to seizure
What are the advantages of Cisatracurium over atracurium?
it is less dependent on hepatic inactivation, thus producing less laudanosine and it also releases less histamine
How is succinylcholine eliminated?
broken down in situ by pseudocholinesterase enzyme (not present in synaptic cleft) (plasma) or by hydrolysis by butyrylcholinesterase (liver)
decreased pseudocholinesterase may be seen in older patients
How long does succinylcholine act?
only 5-10 minutes. However, Note the predisposition of some patients, with variant pseudocholinesterase activity, to experience prolonged drug action
When else has increased duration of action been seen in succinylcholine?
with ester-type anesthetic agents
What test can be performed to identify the extent of pseudocholinesterase activity?
Dibucaine test (inhibits normal enzyme by 80% and abnormal by only 20%)
Alternatively a simplified colorimetric screening test can be performed using the Acholest Test Paper, a substrate-impregnated test paper, a similar colorimetric reaction occurs
How are atracurium and cisatracurium eliminated? Tubocurarine?
spontaneously at site of action (tubocurarine is really mostly)
Which isoquinolone lasts longest? shortest?
longest- tubocurarine (50+ min)
shortest- atracurium (20-35 min)
How are the steroidal eliminated?
mostly renal in pancuronium with rocuronium and vecuronium being mostly hepatic elimination
Which isoquinolones can cause Ach binding to other receptors?
atracurium and tubocurarine (more so) can cause histamine release and tubocurarine can weakly block autonomic ganglia
Which steroidals can cause Ach binding to other receptors?
pancuronium can cause slight block of cardiac M receptors to cause tachycardia
What do cardiac M receptors do?
The activation of the M2 receptor in the heart is important for closing calcium channels in order to reduce the force and rate of contraction, so inactivation can lead to diminished CV capability.
What can succinylcholine cause Ach binding to other receptors?
stimulation of autonomic ganglia, cardiac M receptors and slight histamine release
AEs of succinylcholine?
-hemodynamic changes (brady, tachycardia, HTN)
-prolonged neuromuscular blockade
What conditions can hyperkalemia be seen in with succinylcholine?
-large burn injuries, trauma
-upper or lower motor neuron injuries, muscular dystrophy, or prolonged immobilization
Why would hyperkalemia only been seen in these states?
Normally, the acetylcholine receptors (AChRs) are located only in the junctional area. In certain pathologic states, such as those listed here, there is up-regulation (increase) of AChRs spreading throughout the muscle membrane, with the additional expression of two new isoforms of AChRs. The depolarization of these AChRs that are spread throughout the muscle membrane by succinylcholine and its metabolites leads to potassium efflux from the muscle, leading to hyperkalemia
Other AEs of succinylcholine?
-malignant hyperthermia (MT)
-anaphylaxis (histamine release)
What causes malignant hyperthermia?
drugs that cause an uncontrolled release of calcium from the SR
What drugs can cause MT?
-all volatile (liquid at room temp) anesthetic agents including desflurane and iso/sevoflurane
How is MT treated?
-hyperventilate with O2
-correct hyperkalemia and acidosis from lactate production, cool core temp
How can aminoglycosides affect neuromuscular function?
Enhancement of blockade (pre-junctional P-type Ca2+ channels) and Depressed Ach release similar to that caused by magnesium
How can local anesthetics affect neuromuscular function?
Can depress via a pre-junctional neural effect and can block neuromuscular transmission in large doses
The depolarizing effect of succinylcholine can be antagonized by administering a small dose of what?
a non-depolarizing blocker
What is a main way to reverse neuromuscular blockade?
increase levels of Ach by preventing metabolism of this endogenous ligand by AchE.
What are the AchE inhibitors used to reverse neuromuscular blockade?
What is the recommended anticholinergic to give with Neostigmine?
What is the recommended anticholinergic to give with Edrophonium?
What is the recommended anticholinergic to give with Pyridostigmine?
What is the quickest onset AchE inhibitor?
Neostigmine and Edrophonium act within 5-10 min (period- 10-20 min)
DOA of AchE inhibitors?
Neo- 45-90 min
Edro- 30-60 min
Pyrido- 60-120 min
Can any AchE inhibitor cross the BBB?
Which anticholinergic given with a AchE inhibitor is most likely to prevent bradycardia?
Atropine (others can work if needed, Glycopyrrolate over Scopolamine)
Which anticholinergic given with a AchE inhibitor is most likely to prevent bronchoconstriction?
Atropine or Glycopyrrolate (scopolamine can work if needed)
Which anticholinergic given with a AchE inhibitor is most likely to promote sedation?
scopolamine (glycopyrrolate will not help at all and atropine can work if needed)
Which anticholinergic given with a AchE inhibitor is most likely to promote antisialogogue (decrease saliva secretions)?
scopolamine or glycopyrrolate (atropine can work if needed)
AEs of AchE inhibitors?
-bronchospasm, increased secretions
-diffuse cerebral excitation
-increased peristalsis and bladder tone
What is the effect of Sugammadex?
Rapidly encapsulates steroids like rocuronium and vecuronium to cause reversal of any depth of neuromuscular blockade, including profound blockade
T or F. Sugammadex is inactive against non-steroidal neuromuscular blocking agents, like succinylcholine and cisatracurium
What are some of the uses of NMBs?
As adjuvant in surgical anesthesia
(Permits lower doses of anesthetics; reduced adverse events. Does not substitute for anesthetic. No relief of pain, no amnesia)
For short orthopedic procedures
Dislocations; alignment of fractures
Laryngoscopy, bronchoscopy, esophagoscopy
What parts of the body are affected first by NMBs?
Small, rapidly moving muscles such as those of the eyes, jaw, and larynx relax before those of the limbs and trunk.
Ultimately, the intercostal muscles and finally the diaphragm are paralyzed, and respiration then ceases
Recovery of muscles usually occurs in the reverse order to that of their paralysis, and thus the diaphragm ordinarily is the first muscle to regain function.
How are NMBs given?
What is the function of nicotinic N receptors?
help mobilize pre-synaptic vesicles to the pre-synaptic surface to be ready to be released with the next impulse (these are also blocked with NMBs and is the basis of 'fade')
NMBs act upon which type of receptors?
What is the difference between nicotinic and muscarinic receptors?
nicotinic receptors are ion channels and muscarinic receptors are g-coupled receptors
What is a classic sign of MT?
coca-cola urine and muscle rigidity