L13 - Muscle Relaxants Flashcards
What are the points involved in the nervous system in muscle contraction?
- signal from brain
- to spinal cord
- motor neuron
- NMJ
- muscle
What are the 2 types of muscle relaxants?
- neuromuscular blockers
- spasmolytics
What is the difference between the 2 types of muscle relaxant?
neuromusclar blockers - paralytic agents - paralyse normal functioning muscles spasmolytics - anti-spasmotics - relax overactive muscles rather than cause paralysis
When are the 2 types of muscle relaxant used?
neuromuscular blockers (NMB) used in anaesthesia spasmolytics used in variety of neurologic conditions - act in CNS of muscle
What are the process occurring at the NMJ?
- motor neuron AP to NMJ
- release of neurotransmitter (ACh)
- ACh across synaptic cleft to nicotinic receptors on muscle fibre
- ACh receptor activation causes Na+ influx and K+ outflux causing muscle membrane depolarisation
- Ca2+ release causes muscle contraction
- ACh in synaptic cleft removed by aceylcholinesterase (AChE)
What are the 2 types of neuromuscular blocker?
- non-depolarising: nicotinic receptor antagonists
- depolarising: cause persistent activation of ACh receptors = excessive depolarisation
What is an example of a non-depolarising neuromuscular blocker?
tubocurarine
How do non-depolarising NMBs work?
- they are competitive antagonists of ACh at the motor end plate
- must block 70-80% of post-synaptic receptors to block transmission
- has to overcome ‘safety factor of transmission’ ACh is released in excess of what is needed
Is the effect of NMB reversible? If yes, how?
NMB effect is reversible
- can be reversed by the addition of aceylcholinesterase inhibitor e.g. neostigmine to increase ACh concentration
In what order does paralysis due to non-depolarising NMBs occur?
first: small muscles
- eyes
- facial muscles
larger muscles
- limbs
- pharynx
last: respiratory muscles
What are the side effects of non-depolarising NMBs?
- consciousness and pain awareness not affected (must give anaesthesia before paralytic drugs during surgery)
- hypotension because some also block ganglionic nAChRs (newer NMBs are more selective for NMJ)
- tachycardia because some (e.g. pencuronium) can block muscarinic receptors
What is the difference in the effect of paralysis that is achieved with non-depolarising and depolarising NMBs?
non-depolarising = flaccid paralysis depolarising = muscle spasms before paralysis
What is an example of a depolarising NMB?
suxamethonium - the only depolarising NMB used clinically
What is the structure of suxamethonium?
- 2 ACh molecules linkde together
- acts just like ACh at the receptor
causes prolonged depolarisation at the motor endplate = loss of excitability
Is the effect of depolarising NMBs reversible? If yes, how?
not reversible by AChE
In what order does paralysis occur when using a depolarising NMB?
first: larger muscles
- arm, neck, leg muscles
small muscles
- facial and pharyngeal muscles
last: respiratory muscles
What are spasmolytics intended to be used for?
- reduce pain due to muscle spasm - not cause paralysis
- reduce spasticity
- retain function
What are 4 spasmolytic drugs that work in the CNS?
- diazepam
- baclofen
- tizanidine
- gabapentin
What are the two main classes of neurotransmitter in the brain?
glutamate
- excitatory
GABA
- inhibitory
What are the subtypes of GABA receptors?
GABAA receptors:
- ionotropic = ion channel
- target for drugs that are sedatives + reduce overactive neurons in the brain (anti-epileptic)
GABAB receptors:
- metabotropic GCPR
- important for nerve transmission in spinal cord
- target to reduce painful muscle spasm
What effect does diazepam have? What mechanism?
- sleeping pill
- acts on GABAA receptors
What effect does baclofen have? What mechanism?
- used as drug for painful muscle spasms
- acts on GABAB receptors
What effect does tizanidine have? What mechanism?
- causes suppression of brain activity
- acts on alpha2 adrenoreceptor on motor neurons
What effect does gabapentin have? What mechanism?
- reduction in nerve activity
- acts on voltage dependent calcium channels
What are examples of spasmolytic drugs that acts in the periphery (PNS)?
dantrolene
botox - botulinum toxin
What are the indications for dantrolene? i.e. when is it used?
- muscle spasticity
- malignant hyperthermia: triggered in some people when under GA = muscle contractions generating heat + lactic acid accumulation
What is the mechanism of action for dantrolene?
dantrolene interferes with the release of calcium during skeletal muscle contraction
- affects skeletal muscle more than cardiac and smooth because different calcium channels
= reduces skeletal muscle strength
What are the uses for botox?
- cosmetic
- for painful muscle spasm (cervical dystonia - head and neck muscles)
What effect does botox have? What adverse effects?
- completely relaxes the local area of muscle for months
- adverse effects = local muscle paralysis
What is the mechanism of action for botox?
- SNARE proteins are required for transport of neuromusclar vesicles to the membrane and ACh release into the cleft
- botox cuts the SNARE proteins which prevents ACh release
= why effect persists for so long as cell must produce new SNARE proteins
