Chapter 17

Muscle Relaxants
Onur Melen, M.D. R2 Lee Seung Il

Classification
Neuromuscular blocking agents - an adjunct to general anesthesia to facilitate endotracheal intubation and muscle relaxation Anti-spasticity drugs - for treatment of spasticity and associated painful flexor and extensor spasm due to disorders of CNS Drugs for short term relief of pain and muscle spasm due to acute musculoskeletal conditions

Antipasticity drugs
Spasticity

Anti-spasticity Drugs

- involuntary increase in muscle tone during muscle stretch - motor disorder - caused by long term reduction in inhibition rather than increase in excitation of alpha motor neurons Pre-synaptic inhibition is mediated by GABA - major inhibitory neurotransmitter in the CNS - reduces the amount of neurotransmitter release by Ia fiber terminals - inhibits sensory signals from muscle spindles

Anti-spasticity Drugs
Drug that reduce spasticity act (1) centrally - enhance inhibitory neurotransmission - benzodiazepines, anticonvulsants, baclofen, tizanidine (2) peripherally - on contractile elements of the skeletal muscle - dantrolene, botulinum toxin

Centrally Acting Muscle Relaxants

Benzodiazepine : Diazepam & Clonazepam
MECHANISM OF ACTION - CNS - spinal cord level GABA presynaptic inhibition - interneurone GABA release GABA binding to GABA-A receptor decrease transmitter release from Ia affernets to motor neurons and reduce motor neuron output indirect GABA-ergic agents Diazepam - effective in patients with spinal cord disease and injury - less in cerebral palsy, spastic hemiplegia due to stroke

Centrally Acting Muscle Relaxants

Benzodiazepine : Diazepam & Clonazepam
PHARMACOKINETICS, DOSE, AND TOXICITY - , - placenta , - side effect : dizziness, somnolence, lassitude, confusion increased reaction time, memory loss, ataxia digestive disturbance, anxiety, irritability, euphoria hypomania, depression, paranoia, suicidal ideation - baclofen, barbiturates, narcotics side effect - withdrawal symptom: delirium, seizures Clonazepam - myoclonus, akinetic, petit mal seizures, panic disorders - spasticity

Centrally Acting Muscle Relaxants

Anticonvulsants : Baclofen
MECHANISM OF ACTION - GABA-B agonist - spinal cord origin spasticity : cord injury, multiple sclerosis - spinal cord level GABA-B receptor suppresses the release of excitatory neurotransmitters inhibits excitator afferent terminals - less sedation than diazepam PHARMACOKINETICS, DOSE, AND TOXICITY - side effects : somnolence, dizziness - confusion, ataxia, hallucinations - low lipid solubility BBB - intrathecal administration effective : systemic side effect

Centrally Acting Muscle Relaxants

Anticonvulsants : Tiazanidine (Zanaflex)
MECHANISM OF ACTION - centrally acting alpha-2 agonist - antinociceptive properties - treatment of both spasticity and rheumatologic condition (painful spasm) PHARMACOKINETICS, DOSE, AND TOXICITY - side effects : asthenia, headache, digestive disturbance somnolence, dry mouth, hallucination - 80% - BP, pulse rate , antihypertensive drug

Peripherally Acting Muscle Relaxants

Dantrolene (Dantrium)
MECHANISM OF ACTION - direct muscle relaxant - act on contractile elements of muscle - calcium release from sarcoplasmic reticulum activate myosin ATPase & excitation-contraction coupling muscle contraction - dantrolene block the release of calcium hypotonia, muscle weakness - useful in spinal cord injury, multiple sclerosis cerebral palsy, stroke - rheumatologic disorders skeletal muscle spasm, pain - malignant hyperthermia - neuroleptic malignant syndrome

Peripherally Acting Muscle Relaxants

Botulinum toxin
Purified & attenuated form of toxin from C. botulinum Act on neuromuscular junction - inhibit acetylcholine release from presynaptic terminals muscle relaxation Act on autonomic nervous system - inhibit transmitter release from pre- & post-ganglionic cholinergic nerve ending Act on the nociceptor system - reduce inflammatory pain by inhibiting release of neuropeptides such as substance P and other neuromodulators

Peripherally Acting Muscle Relaxants

Botulinum toxin
Currently BTX is used for various conditions (1) focal dystonias : cervical dystonia, blepharospasm, laryngeal dystonia (2) nondystonic excessive muscle contractions : hemifacial spasm, spasticity, tics, tremors, stuttering (3) headaches : migraine, tension headache (4) myofascial pain (5) hyperhidrosis (6) genitourinary disorders : detrusor-sphinter dyssynergia (7) gastrointestinal disorder : achalasisa, constipation, esophageal sphincter spasm