Skeletal muscle relaxants

NMJ blocking drugs

 Non-depolarizing
– Tubocurarine, pancuronium, atracurium, vecuronium, rocuronium
 Depolarizing
– Succinyl choline
Spasmolytic drugs (antispastic drugs)
• Drugs for chronic spasm
– Diazepam, baclofen, botulinum toxin, tizanidine, dantrolene, mephenesin
• Drugs for acute muscle spasm
– Chlorzoxazone, carisoprodol, metaxalone, methocarbamol,
cyclobenzaprine, chlorphenesin, orphenadrine
Non-depolarizing NM blocking drugs
MOA
• Prevents action of Ach. at skeletal muscle end plate
• Effects reversed by cholinesterase inhibitors- neostigmine
Depolarizing NM blocking drugs
Succinylcholine
• Depolarizes NM end plate
• Has short duration of action
A/E
• Resp. paralysis, hyperkalemia, peripheral nerve dysfunction
• Stimulates autonomic ganglia
Interactions: Inhaled anesthetics, aminoglycosides
 Spasmolytic drugs
• Used to Rx skeletal muscle spasms that occur due to injury or a neurologic disease
to compliment physical therapy; or in severe conditions as M Sclerosis. & C Palsy to
control rigidity and pain
• They ↓ abnormally elevated muscle tone(spasm) without causing paralysis e.g.
baclofen, dantrolene
• Action: CNS, skeletal muscle cells
Drugs for Rx of Chronic pain
• Diazepam-GABA mediated inhibition at the spinal cord
• Baclofen - GABAB agonist, acts through G protein–coupled receptors which when
activated, ↓ motor neuron excitability
• Tizanidine- centrally acting α2- agonist; reinforces both pre- and post synaptic
inhibition in the spinal cord resulting in decreased spasticity without a reduction in
muscle strength (contraction)
Dantrolene
- ↓ release of activator Ca2+ from sarcoplasmic reticulum, decouples the
excitation-contraction at the muscle endplate & directly relaxes skeletal
muscle
Indications - Rx of
- Malignant hyperthermia mainly due to G/anaesthetics e.g. halothane
- Neuroleptic malignant syndrome -high-potency antipsychotics
- Spasticity from such disorders as after strokes, paraplegia, cerebral palsy, or in
patients with MS
Mephenesin - centrally acting muscle relaxant used as an antidote for strychnine
poisoning
Botulinum toxin A(Botox®) - paralyzes muscles by blocking the release of Ach. -
Rx upper- limb spasticity in stroke patients, blepharospasm (spasms of the
eyelids), dystonia & other symptoms of PD, for strabismus (“cross-eyed”),
Others: Progabide, glycine
 Drugs for Rx of acute muscle spasm
 Chlorzoxazone, carisoprodol, metaxalone, methocarbamol, cyclobenzaprine,
chlorphenesin, orphenadrine
- Thought to act in the spinal cord & brain stem by interfering with polysynaptic reflexes
that maintain skeletal muscle tone
- Most are sedatives
- Used for relief acute muscle spasms due to local trauma or strain
 Chlorzoxazone - Centrally acting muscle relaxant used to Rx muscle spasm, acute pain
& tension headache.
• Acts on the spinal cord by depressing reflexes.
• Usually combined with paracetamol
 Carisoprodol – A GABAergic drug used for short-term Rx of muscle spasms caused by
musculoskeletal conditions
 Metaxalone - a moderately strong muscle relaxant with relatively low A/E used to
relieve pain caused by strains, sprains, & other musculoskeletal conditions.
A/E- N/vomiting, drowsiness, dizziness, headache, & irritability
 Methocarbamol: Centrally acting muscle relaxant used for short-term
musculoskeletal pain but ineffective for cerebral palsy and related d/orders. A/E
dizziness, anaphylaxis, confusion, seizures & hepatotoxicity. Not recommended in
pregnancy and breastfeeding mothers
 Cyclobenzaprine - indicated for short-term Rx of muscle spasms caused by acute
painful, musculoskeletal conditions
- Ineffective in muscle spasms due to spinal cord injury e.g. MS, ALS or cerebral palsy
but have strong antimuscarinic and sedative effects
- A/E confusion and hallucination in some patients
 Chlorphenesin – A centrally acting relaxant that has been withdrawn due to A/E and
availability of better drugs e.g. benzodiazepines
 Orphenadrine - An old (1940s) anticholinergic drug closely related to
diphenhydramine that was used to Rx muscle pain and for motor control in
Parkinson's disease, but now superseded by better drugs