1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 25 Drugs for Muscle Spasm and Spasticity

2. 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drugs for Muscle Spasm and Spasticity  Two groups of drugs that cause skeletal muscle relaxation  One group for localized muscle spasm  Other group for spasticity  Most produce their effects through actions in the CNS (except dantrolene).  Groups are not interchangeable.

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drugs for Muscle Spasm and Spasticity  Muscle spasm: involuntary contraction of muscle or muscle group  Causes  Epilepsy  Hypocalcemia  Pain syndromes: adult and chronic  Trauma: localized skeletal muscle injury

4. 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy of Muscle Spasm  Treatment of spasm  Physical measures Immobilization of affected muscle Immobilization of affected muscle Cold compresses Cold compresses Whirlpool baths Whirlpool baths Physical therapy Physical therapy

5. 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy of Muscle Spasm  Treatment of spasm  Drug therapy  Analgesic anti-inflammatory (aspirin)  Centrally acting muscle relaxants Diazepam Diazepam Tizanidine Tizanidine

6. 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Centrally Acting Muscle Relaxants  Mechanism of action (MOA) unclear – may result from sedative properties of the drugs  Diazepam MOA through enhancing effects of GABA MOA through enhancing effects of GABA  Tizanidine MOA through agonist action at presynaptic alpha 2 receptors MOA through agonist action at presynaptic alpha 2 receptors

7. 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Centrally Acting Muscle Relaxants  Therapeutic use  Relieve local muscle spasm  Decrease local muscle pain  Increase range of motion  No studies to indicate superiority of one drug over another  Drug selection prescriber preference and patient response

8. 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Centrally Acting Muscle Relaxants  Adverse effects  Generalized CNS depression  Hepatic toxicity Tizanidine (Zanaflex) and metaxalone (Skelaxin) can cause damage. Tizanidine (Zanaflex) and metaxalone (Skelaxin) can cause damage. Chlorzoxazone (Paraflex) can cause hepatitis and necrosis. Chlorzoxazone (Paraflex) can cause hepatitis and necrosis.  Physical dependence Abstinence syndrome Abstinence syndrome

9. 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drugs for Spasticity  Spasticity  Movement disorders of CNS origin  Most common causes: multiple sclerosis and cerebral palsy  Characteristics include Heightened muscle tone Heightened muscle tone Spasm Spasm Loss of dexterity Loss of dexterity

10. 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Three Drugs for Spasticity  Baclofen (Lioresal)  Acts in the CNS  Diazepam (Valium)  Acts in the CNS  Dantrolene (Dantrium)  Acts directly on smooth muscle

11. 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Baclofen (Lioresal)  Mechanism  Acts in the spinal cord  Suppresses hyperactive reflexes  Mechanism unknown  May mimic the action of GABA on spinal neurons

12. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 25-1. Structural similarity between baclofen and gamma-aminobutyric acid (GABA).

13. 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Baclofen (Lioresal)  Therapeutic uses  Multiple sclerosis, spinal cord injury, cerebral palsy  NOT with stroke  Decreases flexor and extensor spasms  Suppresses resistance to passive movement  No direct effect on skeletal muscle

14. 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Baclofen (Lioresal)  Adverse effects  No antidote for overdose  Gradual withdrawal over 1 to 2 weeks Abrupt intrathecal withdrawal: risk for rhabdomyolysis Abrupt intrathecal withdrawal: risk for rhabdomyolysis  CNS depressant  GI symptoms (nausea, constipation)  Urinary retention

15. 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Diazepam (Valium)  Member of the benzodiazepine family (see Chapter 34)  The only one labeled to treat spasticity  Mechanism  Acts in the CNS  Mimics action of GABA  Adverse effect  Sedation

16. 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dantrolene (Dantrium)  Mechanism  Acts directly on skeletal muscle  Suppresses the release of calcium from the sarcoplasmic reticulum (SR)  Therapeutic uses  Spasticity associated with multiple sclerosis, cerebral palsy, spinal cord injury  Malignant hyperthermia Potentially fatal condition caused by succinylcholine and general anesthetics Potentially fatal condition caused by succinylcholine and general anesthetics

17. 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dantrolene (Dantrium)  Adverse effects  Hepatic toxicity  Muscle weakness  Drowsiness  Diarrhea  Acne-like rash