Skeletal muscle relaxants Flashcards
A healthy 25-year-old man is undergoing a brief surgical procedurerequiring general anesthesia. He underwent an unremarkable
intubation and induction of anesthesia using IV succinylcholine and inhaled halothane. During the surgery the patient develops muscle rigidity and tachycardia, and his temperature rapidly rises.
What drug should immediately be given to the patient, and what is its mechanism of action?
the patient is experiencing Malignant Hypothermia –> we administer a muscle relaxant –> Dantrolene (Spasmolytic drug)
MoA: Blocks CA+2 channels from the sarcopmalsmic reticulum–> interacts with the RyR1
Skeletal muscle contraction is evoked by a
———————— transmission process.
Nicotinic Cholenergic transmission
MoA of Skeletal muscle relaxants drugs
1) Neuromuscular blocking drugs–> Act at the skeletal neuromuscular junction (motor end plate) –> may cause paralysis–> used for surgery and assistant ventilation
2) Palsomlytic drugs –> act on CNS –> reduce abnormally elevated tone –> used for neurologic or muscle end plate disease
What are the 2 Categories Neuromascualr blocking drugs?
- Non- depolarizing neuromuscular blocking drugs. (non-depolarizing NMBD)
- Depolarizing neuromuscular blocking drugs (NMBD)
Neuromuscular blocking drugs (Exmaples)
1) Rocuronium, Vecuronium, Atracurium, Tubocuarine (Non-depolarizing NMBD)
2) Succinylcholine (NMBD)
MoA of neuromascular blocking drugs
Act at the skeletal neuromuscular junction either:
- pre-synaptically to inhibit ACh synthesis or release
- post-synaptically –> muscle paralysis
MoA of non-depolarizing NMBD
(Rocuronium, vecuronium, Atracurium, Tubocurarine)
–> prevent the action of ACh at the skeletal muscle end plate
–> Act at the SNMJ:
- Pre-synaptically to inhibit synthesis or release of ACh.
MoA of depolarizing NMBD
Continuous depolarization at the neuromuscular end plate.
- Nicotinic agonist –> depolarizes the Neuromuscular end plate.
Administration route of Neuromuscular blocking drugs
IV Administration
Indication of Rocuronium, Vecuronium, Atracurium, Tubocuarine
- surgery.
–> No effect on cardiac,smooth muscles, or
CNS
Indication of Succinylcholine
- surgery.
- Assisted ventilation
PK of Rocuronium, Vecuronium, Atracurium, Tubocuarine
- Highly polar drugs –> does not cross BBB.
- metabolized in liver or bile.
- short durations of action.
- Tubocurarine –> eliminated by the kidney –> b/c longer action duration.
- Competitive antagonists –> Reversible and AChE inhibitors.
PK of succinylcholine (aka Suxamethonium)
- Continuous depolarization –> causes muscle relaxation and paralysis.
- metabolized by cholinesterase in liver and plasma.
- Short duration of action
Adverse effects of Neuromuscular blocking drugs
- Respiratory paralysis –> Mechanical ventilation required.
- Tubocurarine (non-depolarizing NMBD)–> Histamine release
- Succinylcholine –> Muscle pain and damage;
- Hyperkalemia.
- Peripheral nerve dysfunction.
- intragastric & intraocular pressure.
MoA of spasmolytic Drugs
Act on the CNS –> reduction of excessive skeletal muscle tone without reduction of strength –> reduction of pain and improved mobility
Spasmolytic Drugs
1) Baclofen
2) Tizanidine
3) Dantrolene
4) Diazepam
5) Botulinum toixn
MoA of Baclofen
Facilitates spinal inhibition of motor neurons.
- GABAb receptor agonist + ↓ release of glutamate.
PK of Baclofen + Administration route
- Act in the spinal cord.
Administration route –> orally/ intrathecal for sever spasticity
MoA of Tizanidine
α2 agonist
PK of Tizanidine + Administration route
- Act in the spinal cord.
- Administered orally for acute and chronic spasms.
Indication of Baclofen
sever spasticity
Indication of Tizanidine
acute and chronic spasms
MoA of Dantrolene
Blocks Ca2+ channels from sarcoplasmic reticulum –> interacts with RyR1
Pk of Dantrolene
- Act in the skeletal muscles –> sensory nerve.
- Weakens muscle contraction by reducing
myosin-actin interaction
MoA of Diazepam
- BZP
Facilitated GABA-ergic transmission in CNS –>
GABA activation
Pk of Diazepam
Act in the spinal cord.
MoA of Botulinum toxin
- Acts onn the skeletal muscles motor nerve
- Injected into selected muscles –> reduce pain and severe spasm.
administration of Botulinum toxin
IM injection
Indication of Botulinum toxin
- reduce pain and severe spasm.
- Ophthalmic purposes.
Adverse effects of Spasmolytic drugs
- Sedation;
Diazepam > baclofen > dantrolene. - Tolerance occurs with chronic use
AE of Tizanidine
- asthenia.
- drowsiness.
- dry mouth.
- hypotension.
–> Contraindicated in cardiac patients.
AE of Dantrolene
significant muscle weakness.