Neuromuscular Blocking Drugs Flashcards
What neuromuscular blocking drugs that we talk about target the CNS
Baclofen
Tizanidine
Diazepam
What neuromuscular blocking drugs target the actual muscle
Dantrolene
Why is it clinically necessary to block tranmission at the neuromuscular end plate of Ach
Needed for surgical relaxation, tracheal intubation, and control of ventilation
What is the process of Ach getting across the synapse
- AP sent down nerve, inside becomes more positive and causes Ca2+ channels to open
- Ca2+ comes in it becomes more positive, which activated the vesicles contains Ach and cause Ach to be released
- once ACh goes across synapse, it binds to the Na+ channels to open them (Nm is Na channel)
- Na+ influx into the muscle fiber
- small amount of K flux out of fiber
- this causes contraction
Ach receptor
2 alpha subunits that Ach has to bind
What are the two types of neuromuscular blocking drugs
- Non-depolarizing
2. Depolarizing
No depolarizing neuromuscular blocking drugs
Tubocurarine Atracurium Pancuronium Vecuronium Rocuronium Cisatracurium
MOA of nondepolarixing neuromuscular blocking drugs
Nicotinic antagonist-competitive antagonists, compete with Ach for receptor
- prevent action of Ach at NMJ.
- competitive blockers, can be overcome by increasing Ach
- bind to and block the Nm receptor, no Na can get in, cause relaxation
What is a nondepolarizing neuromuscular blocking drug reversed with
Achase inhibitor
What are the effects of nondepolarizing neuromuscular blocking drugs on the cardiac and smooth muscle
None because it only works on No receptors
CNS effects of nondepolarizing neuromuscular blocking drugs
None
Analgesia and sedation with nondepolarizing neuromuscular blocking drugs
They dont have these affects. Have to give these first before the nondepolarizing drug so the patient doesn’t feel pain
Clinical use for nondepolarixing neuromuscular blocking drugs
Used mainly in anesthesia protocols or in the ICU to afford muscle relaxation and or immobility
Atracurium
- nondepolarizing neuromuscular blocking drugs
- forms laudanosine, which can cause seizures
Cisatracurium
- Nondepolarizing neuromuscular blocking drug
- forms less laudanosine than atracurium
- one of the most commonly used muscle relaxants in clinical practice
What is the most commonly used muscle relaxant in clinical practice
Cisatracurium
What’s the difference between atracurium and cisatracurium
Cisatracurium does not produce as much laudanosine, which means less risk of seizures
Duration of action of nondepolarizing neuromuscular blocking drugs
- long acting ones are more potent and require low concentrations. Tubocurarine, pancuronium
- intermediate actions of vecuronium, rocuronium, atracurium, cisatracurium
- most are pretty short acting
Reversal of non-depolarizing agents
- neostigmine: Achase inhibitor, allows more Ache to be in the cleft to compete with drug
- sugammadex: encapsulates and binds with molecules of rocuronium or vecuronium, thereby rapidly reversing their neuromuscular blocking effect
Depolarizing (non-competitive) neuromuscular blocking drugs
Succinylcholine
What is succinylcholine
Depolarizing (non-competitive) neuromuscular blocking drug
-2 Ach stuck together
MOA of succinylcholine
Classic depolarizing agent
- stimulates all cholinergic receptors
- binds directly to the postsynaptic Ach receptors of the NMJ causing continuous stimulation of these receptors.
- leads to transient fasciculations followed by muscular paralysis
- composed of 2 Ach molecules
- STRONG ACH RECEPTOR AGONIST
- sustained depolarization and prevents muscle contraction
- acts like a nicotinic agonist and depolarizes the NMJ
What is succinylcholine broken down by
Pseudocholinesterase
What is a problem with succinylcholine?
Since it stays bound to the Nm receptor, the receptor stays open, allowing Na to go in and K to come out, too much K going out can cause hyperkalemia
-people need tested to make sure K levels are not increased
Clinical use of succinylcholine (depolarizing neuromuscular blocking drugs)
Used extensively in the emergency setting, due to its rapidity of onset and offset, and the consistent intubating conditions it provides
Side effects of succinylcholine (depolarizing neuromuscular blocking drug)
-hyperkalemia
When is succinylcholine contraindicated
Inherited myopathies Malignant hyperthermia family HS Stroke over 72 hours Rhabdomyolysis Hyperkalemia Burns, after 72 hours Crush injuries, after 72 hours
The last two things cause a lot of K to be released into the body due to cell damage and lysis
Dosing of succinylcholine
It is far better to overestimate the dose than underestimate
-larger doses result in the same level of paralysis and do not increase the risk to the patient; inadequate doses can leave the patient inadequately paralyzed and difficult to intubate
Succinylcholine is absolutely contraindicated in people with a family history of __________
Malignant hyperthermia and in patients deemed to be at high risk of developing severe hyperkalemia
-Ca2+ channels staying open generates heat, muscle damage also increases K levels
What can be used as a rescue medication is bradycardia occurs when taking succinylcholine
Atropine
A myopathic metabolic disorder that is characterized by sympathetic hyperactivity, muscular rigidity, acidosis, and hyperthermia
Malignant hyperthermia
Reversal of blockade (depolarizing neuromuscular blocking drug)
Phase I
Phase II
Phase I of reversal of blockade (depolarizing neuromuscular blocking drug)
Depolarization, fasciculation, prolonged depolarization, flaccid paralysis
Phase II of reversal of blockade (depolarizing neuromuscular blocking drug
Desensitization
What phase of depolarizing neuromuscular blocking drugs does achase inhibitors increase
Phase I
- succinylcholine is bound, so achase inhibitors are not going to work.
- there could be Ach and succinylcholine bound to the same receptor. Ach can just keep binding, but if the succinylcholine is there, it wont matter
What phase of depolarizing neuromuscular blocking drugs do achase inhibitors possibly reverse
Phase II
-receptor kinda numb, Ach may or may not bind. Will eventually wear off
GABA a
Ion gated
GABA B
G coupled proteins
Examples of centrally acting skeletal muscle relaxants
Benzodiazepines
Baclofen
What do benzodiazepines target
GABA a
What does baclofen target
GABA b
Spasmolytic drugs
Do not resemble Ach in structure or effect
Act in CNS
Block NT release, no AP release, will never reach muscle.
Slide effects of spasmolytics
drowsiness, confusion, fatigue
Dantrolene
RyR1 receptor blocked, no Ca2+ flowing. Good for malignant hyperthermia
What drug is good to use with malignant hyperthermia
Dantrolene
What drug is not good to use with malignant hyperthermia
Succinylcholine
Treatment for malignant hyperthermia
Dantrolene
Botox
- inhibits release of Ach out of vesicles
- can reduce pain caused by severe spasm
What are the drugs used for chronic spasm
Baclofen
Diazepam
Dantrolene
Botox
