MSKS Pharmacology Lecture 1_Neuromuscular Blocking Agents Flashcards
What are the three main usese of Neuromuscular Blockers
1) Induce paralysis during surgical procedures (In adjunct to general anesthesia)
2) Facilitation of tracheal intubation
3) Control of muscle contraction in status epilepticus
What is the mechanisium of action of Neuromuscular junction blockers (NMBs). What are the two classes of NMBs?
Signals from the motor neuron to skeletal muscle cells are blocked at the nicotinic receptor in the muscle. There are two classes of NMBs depolarizing agents and non-depolarizing agents.
What kind of NMB agent is succinylcholine
It is a depolarizing agent (an agonist of the nicotinic receptor). This is because it’s structure is very similar to ACh.
What kind of NBM agent are d-tubocurarine and pancuronium
Both d-tubocurarine and pancuronium are non depolarizing agents (antagonists of the nicotinic receptor)
How does a depolarizing NMB agent (agonist of the nicotinic receptor) cause paralysis? What are the two phases of paralysis?
Phase 1: One molecule of the drug will bind and open the nicotinc channel. A second molecule of the same drug will bind in the opening and keep the channel open. This prevents the muscle from being able to enter the refractory period thus it never repolarizes and cannot refire.
Phase 2: Nicotinic receptors become desensitized and there is loss of response to agonist
How quickly does succinylcholine act and how long is its duration
Phase 1 paralysis takes effect in 1 to 2 minutes and lasts for 5 to 10 min.
How is succinylcholine metabolised in the body
It is metabolized by plasma cholinesterase (also called pseudocholinesterase or butyrylcholinesterase)
What can happen in patients of european decent when administering succinylcholine?
1 in 25 will have defficent pseudocholinesterase. This can lead to overdosing. There is no antidote to succinylcholine so an overdose is fatal.
What are the Adverse Drug Responses
and Contraindications of succinylcholine?
• Muscle weakness and pain (myalgia)
• Jaw rigidity
• Rhabdomyolysis (caused by extreme muscle destruction) with acute renal failure, especially in
patients with myopathies ( This makes it Contraindicated in Duchenne’s muscular dystrophy
• Bradycardia, arrhythmia, and cardiac arrest can occur
due to off-target agonism of NN and M receptors
• Increased intraocular pressure (should not be used in patients with eye injury)
How does succinylcholine cause hyperkalemia and what does this contraindicate?
Because succinylcholine holds nicotinic receptors open (anion channels) K+ is able to leave the cell and enter the serum causing hyperkalemia. This makes succinylcholine contraindicated in patients at risk of hyperkalemia like Patients with burn, crush, closed-head, denervation or other traumatic injuries and those in with end stage renal disiease.
What is Rare Malignant Hyperthermia, What causes it, who is most at risk
It is an increase in skeletal muscle metabolism that results in increased temperature. It is caused by an autosomal dominant mutation that leads to defective RyR1 receptors (ryanodine receptors in skeletal muscle) that can lead to massive release of Ca from the SR when succinylcholine is administered. In addition to a family history of the mutation, patients on SSRI’s and other neuroleptics are more at risk.
How can Rare Malignant Hyperthermia (RMH) be treated?
By administering dantrolene which blocks RyR1 and prevents the release of Ca. Dantrolene does have a black box warning of 10% toxicity. untreated, RMH has an 80% fatality rate.
How do Acetylcholinesterase inhibitors interact with succinylcholine?
Acetylcholinesterase inhibitors may prolong the effects of succinylcholine. This makes sense because Acetylcholinesterase inhibitors increase the amount of endogenouse ACh present in the body.
How do antibiotics effect the action of succinylcholine?
They may enhance the neuromuscular-blocking effects
What are the 2 tubocurarine prototype Non-depolarizing Neuromuscular Blockers?
Atracurium and Cisatracurium
