Muscle Relaxants Flashcards
Anti-spasmodics (spasmolytics)
Work Centrally Chlorzoxazone Cyclobenzaprine Orphenadrine Methocarbamol Diazepam Equally effective as NSAIDs
Anti-spastics
Central or Muscle-acting Baclofen Tizanidine Gabapentin Botulinum toxin Diazepam Dantrolene Sodium
Chloroxazone
Anti-spasmodic (spasmolytic)
Onset: 60 minutes (long)
Duration: 1.2 hours (short)
Mechanism: unclear (depress polysynaptic reflexes)
Cyclobenzaprine
Anti-spasmodic (spasmolytic)
Onset: 60 minuets (long)
Duration: 12-24 hours (LONG)
Mechanism: reduces tonic somatic motor activity (alpha and gamma motor neurons) (depress polysynaptic reflexes)
Structure: related to TCA
Serotonergic, noradrenergic
SHORT TERM treatment of skeletal muscle spasms
Side effects: drowsiness, loss of coordination, anticholinergic, dizziness
ADDICTION, PHYSICAL DEPENDENCE
Orphenadrine
Anti-spasmodic (spasmolytic) Onset: 60 minutes (long) Duration: 2-4 hours (medium) Mechanism: ANTICHOLINERGIC (atropine-like) (depress polysynaptic reflexes) Use: lumbargo, sciatica
Methocarbamol
Anti-spasmodic (spasmolytic)
Onset: 30 minutes (SHORT)
Duration: 1-2 hours (short)
Mechanism: unclear (depress polysynaptic reflexes)
Structure: related to TCA
General CNS depression?
SHORT TERM treatment of skeletal muscle spasms
Side effects: drowsiness, loss of coordination, anticholinergic, dizziness, BLUE-GREEN URINE
ADDICTION, PHYSICAL DEPENDENCE
High doses: CNS and respiratory depression
Diazepam
Anti-spasmodic
Baclofen
Anti-spastic
GABA-B receptor agonist
–GPCR
–Presynaptic: decrease NT release (inhibit Type Ia presynaptic terminals by decrease Ca2+ influx)
–Postsynaptic: bing GABA-B receptor –> activate K+ ch –> activate 2nd messenger pathway (arachidonic acid)
–Reduces substance P
Oral: decrease spasticity of MS and SC injury (not effective for stroke); hiccups, neuropathic pain (trigeminal neuralgia)
Intrathecal: lower dose (ug v mg), fewer SE, cerebral palsy, anoxic brain injury, MS, stroke, SC injury, AV malformation, SC infection
Tizanidine
Anti-spastic Alpha-2 adrenergic receptor agonist Inhibits excitatory AA release in spinal interneurons t1/2: 2.5h Use: MS, SC injury
Gabapentin
Anti-spastic
N-type Ca2+ channels –> reduce neuropathic pain
Reduce anxiety
Modulates glutamate decarboxylase (GAD) and branched chain aminotransferase (BCAT) (GABA biosynthesis increased)
Botulinum toxin-A
Anti-spastic
Decrease spasticity by cerebral palsy, stroke, TBI, advanced MS, dystonia, hyperhidrosis
MOA: inhibits ACh release from pre-synaptic nerve terminals (chemodenervation)
Focal muscle paralysis 24-72h post-injection
Lasts 12-16 weeks
Antibodies can develop (lowered efficacy)
C/i: excess weakness, may not be exact (not entirely contained)
Dantrolene sodium
Anti-spastic
Muscle acting.
Decrease spasticity with UMN lesions, strokes, and SC injury
Treat malignant hyperthermia (inhalant anesthetic-induced)
Treat neuroleptic malignant syndrome
Acts on fast muscle fibers (block contraction), reduces depolarization-induced release of Ca2+
[peak] 3-6 hours after oral admin
liver metabolism; t1/2 15h
Contraindications: causes muscle weakness (ALS)
Spasm
Long-lasting contraction of muscle
Over-stretching, repetitive strain, wrenching of a joint, tearing of tendon/ligament
DAMAGE TO MUSCLE
Overuse –> activate nociceptor –> alpha/gamma motor neurons –> increased contraction –> compress bv –> ischemia –> pain
Spasticity
Increase in tonic stretch reflexes
Hyperactivity of stretch reflexes, tendon jerks
Loss of supra spinal inhibition on alpha-motor neurons
Velocity-dependent contractions (faster = greater resistance)
Causes: trauma, ischemia, MS, cerebral palsy, metabolic (ADRENOLEUKODYSTROPHY, ALS, PKU)
CNS DAMAGE
Benzodiazepines (diazepam)
Adjunct to Baclophen (calm patients)
Binds GABA-A receptors (Cl- channel) (increases Cl- conductance –> pre-synaptic inhibition)
2 active metabolites (nordazepam, oxazepam)
