neuromuscular blocking agents Flashcards
neuromuscular blockers
The original neuromuscular blockers were darts poisons derived from biological sources and used by
various tribes in the Amazon. They were called ‘wooari’ (later corrupted to curare) or ‘flying death’!
Neuromuscular blockers are only used
Neuromuscular blockers are only used in anesthesia to relax the skeletal muscles. They cause paralysis of all the skeletal muscles so the animal cannot move but is fully conscious. Full paralysis also means that the respiratory muscles are paralyzed (intercostal muscles and diaphragm) and so ventilation is required (intermittent positive-pressure ventilation (IPPV)). These drugs should NOT be used unless appropriate equipment and monitoring are available and the user is knowledgeable.
The neuromuscular blockers are all
The neuromuscular blockers are all quaternary compounds so they are always charged (have poor oral absorption and do not readily cross tissue barriers). They are typically used parenterally (IV preferred) and do not cross the blood-brain barrier. (Incidentally this is why they can be fatal when administered via a dart but then the meat can be eaten without causing problems for the one ingesting it). There are two functional subclassification of NMB; depolarizing and competitive.
Depolarizing neuromuscular blockers (non-competitive)
Succinylcholine,
Succinylcholine Mechanism of action
- Depolarizing NMB exhibit a biphasic mechanism of action.
o Phase I block: Activation of nicotinic acetylcholine receptors similar to what ACh would
do. The depolarizing NMB prolongs depolarization of the motor end-plate and prevents complete repolarization and thus stimulation by acetylcholine.
During this phase muscle fasciculation (transient) followed by flaccid paralysis.
o Phase II block: In phase II the nicotinic receptors stay in an inactivated state and cannot
respond to acetylcholine.
If phase II block is reached the paralysis duration will be longer
How are NMB usually given?
As with other NMB these are usually given IV (rarely IM)
How does Succinylcholine act in
Act in one circulation time (30-60 seconds) and last several minutes. They are hydrolyzed by
plasma and liver pseudocholinesterase (PChE), much slower than breakdown of acetylcholine.
o Different species have differing levels of PChE – ruminants have less and so the duration
of action is longer in that species.
o Canines have a long duration of action, up to 20 minutes
What are some of the syptoms of Succinylcholine?
Asynchronous muscle twitching is seen initially which can be painful and last ~30 seconds. This is followed by flaccid paralysis starting in the face/tail and then limbs, swallowing, abdominal muscles, and respiratory muscles (intercostal muscles and diaphragm).
o Nicotinic receptors at autonomic ganglia can be affected but are less sensitive than those at the NMJ. Ganglionic stimulation can cause hypertension in awake animals.
o Transient bradycardia may be seen, may be increased cardiac susceptibility to digitalis, increased intraocular pressure (IOP), hyperkalemia (K+ release from skeletal muscles).
Clinical uses for depolarizing NMB
Clinical uses for depolarizing NMB might include facilitation of endotracheal intubation
o “Crash induction”, prevention of laryngeal spasm, or difficult to intubate species
o Rarely used for relaxation during surgery
o It should not be used to facilitate euthanasia (inhumane)
Cautions of Succinylcholine
o Apnea – artificial respiration is required
o Muscle fiber damage – increases in creatinine kinase and postoperative muscle pain
o Hyperkalemia, bradycardia
o Increased cardiac sensitivity to catecholamine-induced arrhythmias
o Malignant hyperthermia possible in susceptible animals
o There is no specific reversal agent – supportive care until the drug is metabolized.
o Things that alter metabolism prolong the effect of these drugs, irreversible cholinesterase
inhibitors (e.g. organophosphates) can slow hydrolysis of these drugs for up to 30 days!
o Spontaneous hydrolysis of the drug can occur in vitro – keep chilled
o Avoid with cholinesterase inhibitors, glaucoma or cardiac disease
Drug-drug interactions (all of these will prolong or increase the effects of depolarizing NMB):
Drug-drug interactions (all of these will prolong or increase the effects of depolarizing NMB):
o Magnesium and aminoglycoside antibiotics (as they inhibit acetylcholine release)
o Local anesthetics and cholinesterase inhibitors (slow metabolism of NMB)
o Centrally acting muscle relaxants (additive effects)
o Digitalis (increased toxicity)
Competitive neuromuscular blockers (non-depolarizing):
Pancuronium,Atracurium, Vecuronium, Rocuronium
What is the mechanism of action for competitive NMB?
The competitive neuromuscular blockers are all similar in mechanism of action. They are competitive antagonists with acetylcholine for the nicotinic receptors at the motor end-plate that will result in generalized flaccid muscle paralysis.
What are the compeitive NMB used for?
These are used more commonly than the depolarizing NMBs and are sometimes used for thoracic surgeries/procedures (to allow control over thoracic wall and lung movement).
There are obsolete drugs that should not be used
There are obsolete drugs that should not be used include tubocurarine, gallamine, alcuronium, fazadinium and pipecuronium.
