MCMP 407 Spasmolytics Chronic neurologic diseases Cerebral Palsy, Multiple Sclerosis Acute Injury Spinal cord damage, muscle inflamation Goal of therapy: Reduce spasticity and pain, while retaining function

MCMP 407 Spasmolytics Benzodiazepines (Diazepam, etc.) l GABA A Receptors l CNS and Spinal Cord l Side Effects: Sedation Diazepam (Valium)

MCMP 407 Spasmolytics Baclofen (Lioresal l GABA B receptor agonist l Activation of K + channels l CNS and Spinal cord l (-)-Baclofen is the active isomer l Less sedation than BZDs l Intrathecal pumps now used in chronic conditions l Warning for severe withdrawal syndrome from intrathecal use  Altered mental status, hyperpyrexia, exaggerated spasticity, muscle rigidity, and rhabdomyolysis

MCMP 407 Spasmolytics  2 adrenergic receptor agonist l Congener of clonidine l Presynaptic inhibition of motor neurons l 1/10-1/50th potency as clonidine in lowering blood pressure l Side Effects: Drowsiness, hypotension, dry mouth Tizanidine (Zanaflex)

MCMP 407 Spasmolytics l Tricyclic structure l May act at level of brain stem l Strong antimuscarinic effects (sedation) l Ineffective in the treatment of chronic neurological disorders l Use: Relief of acute muscle spasm due to injury or strain Cyclobenzaprine (Flexeril)

MCMP 407 Atropine vs. Cyclobenzaprine

MCMP 407 Spasmolytics Other drugs similar to Cyclobenzaprine (Flexeril) v Chlorzoxazone (Paraflex, Parafon) v Orphenadrine (Norflex) v Carisprodol (Soma)

MCMP 407 Spasmolytics l Interferes with excitation- contraction coupling l Reduces release of Ca ++ from the sarcoplasmic reticulum l Blocks contraction Dantrolene Sodium (Dantrium) l Side Effects: Muscle weakness, sedation, rare hepatitis l Uses: Cerebral palsy, multiple sclerosis l Also Malignant Hyperthermia

MCMP 407 Action Potential Ca 2+ Motor neuron Na + ACH          Na + Skeletal Muscle ACHEsterase Neuromuscular Blockers

MCMP 407 Properties of neuromuscular blockers DrugElimination viaDuration of action (minutes) Short-acting MivacuriumPlasmaAChE10-20 Intermediate-acting AtracuriumSpontaneous20-35 VecuroniumHepatic and renal20-35 RocuroniumHepatic and renal20-35 Long-acting PancuroniumRenal60 SuccinylcholinePlasmaAChE5-10

MCMP 407 Clinical use of neuromuscular blockers  Muscle relaxation during surgical procedures  Endotracheal intubation  Maintain controlled ventillation

MCMP 407 Clinical problems associated with neuromuscular blockers v Potentiated by inhaled anesthetics (Isoflurane) v Potentiated by aminoglycosides and calcium channel blockers v Can block autonomic ganglia at higher doses v Respiratory paralysis