Skeletal Muscle Relaxants Flashcards
What is the clinical use of blocking drugs?
muscle relation for surgery and for electroshock therapy
What is the clinical use of anticholinesterases?
diagnosis and therapy of myasthenia gravis
Is the whole length of the muscle DIRECTLY affected by synapse activities?
nooooo
Random reminders about skeletal muscle APs
Ach is NT (released from vesicles), Na+ channel, all-or-none.
What about the Ach receptors?
nicotinic, ligand-gated, pentameric
How does Botox work?
inhibits release of Ach from vesicle
What does Acetylcholinesterase?
in post-synaptic receptors, stops depolarizaion by hydrolizing Ach
What are the 3 major conformations or states of the skeletal muscle nicotinic acetylcholine receptor?
resting, open, desensititized
Which states of the Ach receptor do the nicotinic agonists stabilize?
the open and desensitized
Which states of the Ach receptor do the competitive antagonists stabilize?
the resting state
During the desensitized state, is the Na channel open or closed? What is the purpose of this state?
There is still high affinity for the agonist, but the channel is closed. Purpose is protective from overstimulation
non-depolarizing muscle relaxants AKA…?
nicotinic receptor antagonists
What is the prototype non-depolarizing drug?
Vecuronium
What is an adverse effect of Vecuronium? Why?
hypotension. it is not selective for skeletal muscle nicotinic receptors and therefore also has affinity for autonomic nicotinic receptors.
What is Neostigmine?
Anticholinesterase
What does Neostigmine (anticholinesterase) do?
Reversal of Vecuronium block (there is competition between the anticholinesterase and the non-depolarizing drug)
What causes the adverse effect of hypotension with Vecuronium?
basophil histamine release, blockade of autonomic neurotransmission
How is Vecuronium eliminated?
largely by biliary secretion
What is Atracurium?
another non-depolarizing drug thats spontaneously breaks down at physiological pH
depolarizing muscle relaxants AKA…?
Nicotinic Agonists
What is the prototype nicotinic agonist/depolarizing blocker?
Succinylcholine
What is succinylcholine?
essentially a stable form of Ach
What are the two stages of SuCH block?
depolarizing, non-depolarizing
What do anticholinesterases do to stage 1 SuCH block?
they fail to reverse stage 1 block
What are fasciculations?
muscle twitches with use of depolarizing drug (succinulcholine). produce post-operative soreness
Which stages of SuCH block are important when SuCH is used for tracheal intubation?
Only the first, depolarizing stage. Stage 2 block is not observed because of its slow onset
Which stage block for tracheal intubation?
stage 1 (depolarizing)
Which stage block for desensitization?
stage 2 (non-depolarizing)
What are the ion channel states during stage one block (depolarizing, tracheal intubation)?
nicotinic receptor open, sodium channel closed (refractory)
What are the ion channel states during stage 2 block (non-depolarizing, desensitization)?
nicotinic receptor closed (desensitized), sodium channel read to open
What are some disadvantages of depolarizing blockers (4)?
1) muscle soreness of SuCH-induced muscle relaxation
2) inability to reverse stage 1 block with anti-ChEs
3) K+ release may be life-threatening in burn patients displaying skeletal muscle denervation hypersensitivity
4) SuCH biotransformation is abnormally slow in certain people
Which drug can be used for treatment of malignant hyperthermia and spasticity disorders?
Dantrolene
How does Dantrolene work?
relaxes muscle in a unique way, but inhibiting Ca ion release from skeletal muscle sarcoplasmic reticulum
What is Myasthenia Gravis?
autoimmune loss of muscle nicotinic ACh receptors
Which drugs are used to treat myasthenia gravis?
Neostigmine and Pyridostigmine
How are Neostigmine and Pyridostigmine administered and what are their durations of action?
administered orally, intermediate durations of action
Which drug is used for diagnosis of myasthenia gravis?
Edrophonium
What else is Edrophonium used for and how?
adjustment of antiChE dose. If Edro produces improvement in contractility, then patient is under-medicated. if worsens contractility, over-medicated.
What happens when the patient is under-medicated with a long-duration cholinesterase inhibitor?
myasthenic weakness
What happens when the patient is over-medicated?
cholinergic crisis
