~Teachingcenter的醫學筆記~

骨骼肌肉鬆弛劑

Skeletal Muscle Relaxants

可以一併參考
http://teachingcenter1.pixnet.net/blog/post/353552897

Depolarizing Neuromuscular Blocking Agent

Succinylcholine

1. Mechanism of action
   • Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions.
   • Depolarizes.
   • May stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors.
2. Effects
   • Initial depolarization causes transient contractions, followed by prolonged flaccid paralysis.
   • Depolarization is then followed by repolarization that is also accompanied by paralysis.
3. Clinical applications
   • Placement of endotracheal tube at start of anesthetic procedure.
   • Rarely, control of muscle contractions in status epilepticus.
4. Pharmacokinetics, toxicities, interactions
   • Rapid metabolism by plasma cholinesterase (butyrylcholinesterase).
   • Normal duration: 5 min.
   • Toxicities: arrhythmias, hyperkalemia, transient increased intra-abdominal pressure, increased intra-ocular pressure.
   • Post-operative muscle pain.

Non-Depolarizing Neuromuscular Blocking Agents

d-Tubocurarine

1. Mechanism of action
   • Competitive antagonist at nicotinic ACh receptors, especially at neuromuscular junctions.
2. Effects
   • Prevents depolarization by ACh, causes flaccid paralysis.
   • May induce histamine release with hypotension.
   • Weak block of cardiac muscarinic ACh receptors.
3. Clinical applications
   • Prolonged relaxation for surgical procedures.
   • Superseded by newer non-depolarizing agents.
4. Pharmacokinetics, toxicities, interactions
   • Renal excretion.
   • Duration 40~60 min.
   • Toxicities: histamine release, hypotension, prolonged apnea.

Cisatracurium

1. Mechanism of action
   • Similar to tubocurarine.
2. Effects
   • Like tubocurarine but no histamine release and no antimuscarinic effects
3. Clinical applications
   • Prolonged relaxation for surgical procedures.
   • Relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit.
4. Pharmacokinetics, toxicities, interactions
   • Not dependent on renal or hepatic function.
   • Duration: 25~40 min.
   • Toxicities: prolonged apnea but less toxic than atracurium.

Rocuronium

1. Mechanism of action
   • Similar to cisatracurium.
2. Effects
   • Like cisatracurium but slight antimuscarinic effect.
3. Clinical applications
   • Like cisatracurium.
   • Useful in patients with renal impairment.
4. Pharmacokinetics, toxicities, interactions
   • Hepatic metabolism.
   • Duration: 20~35 min.
   • Toxicities: like cisatracurium.

Mivacurium: rapid onset, short duration (10~20 min), metabolized by plasma cholinesterase.

Vecuronium: intermediate duration, metabolized by liver.

Centrally Acting Spasmolytic Drugs

Baclofen

1. Mechanism of action
   • GABA(B) agonist.
   • Facilitates spinal inhibition of motor neurons.
2. Effects
   • Pre- and Post-synaptic inhibition of motor output.
3. Clinical applications
   • Severe spasticity due to cerebral palsy, multiple sclerosis, stroke, etc.
4. Pharmacokinetics, toxicities, interactions
   • Oral or intra-thecal use.
   • Toxicities: sedation, weakness.

Cyclobenzaprine

1. Mechanism of action
   • Poorly understood inhibition of muscle stretch reflex in spinal cord.
2. Effects
   • Reduction in hyperactive muscle reflexes.
   • Antimuscarinic effects.
3. Clinical applications
   • Acute spasm due to muscle injury.
   • Inflammation.
4. Pharmacokinetics, toxicities, interactions
   • Hepatic metabolism.
   • Duration: 4~6 hours.
   • Toxicities: strong antimuscarinic effects.

Chlorphenesin, methocarbamol, orphenadrine, others: like cyclobenzaprine with varying degrees of antimuscarinic effect.

Diazepam

1. Mechanism of action
   • Facilitates BABAergic transmission in central nervous system.
2. Effects
   • Increases interneuron inhibition of primary motor afferents in spinal cord.
   • Central sedation.
3. Clinical applications
   • Chronic spasm due to cerebral palsy, stroke, spinal cord injury, etc.
   • Acute spasm due to muscle injury.
4. Pharmacokinetics, toxicities, interactions
   • Hepatic metabolism.
   • Duration: 12~24 hours.
   • Toxicities: weak, respiratory depression.

Tizanidine

1. Mechanism of action
   • Alpha2-adrenoceptor agonist in the spinal cord.
2. Effects
   • Pre- and post-synaptic inhibition of reflex motor output.
3. Clinical applications
   • Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis, etc.
4. Pharmacokinetics, toxicities, interactions
   • Renal and hepatic elimination.
   • Duration: 3~6 hours.
   • Toxicities: weakness, sedation, hypotension.

Direct-Acting Muscle Relaxant

Dantrolene

1. Mechanism of action
   • Blocks ryanodine receptor type 1 (RyR1) calcium-release channels in the sarcoplasmic reticulum of skeletal muscle.
2. Effects
   • Reduces actin-myosin interaction.
   • Weakness skeletal muscle contraction.
3. Clinical applications
   • Intravenous: malignant hyperthermia.
   • Oral: spasm due to cerebral palsy, spinal cord injury, multiple sclerosis, etc.
4. Pharmacokinetics, toxicities, interactions
   • Intravenous and oral use.
   • Duration: 4~6 hours.
   • Toxicities: muscle weakness.