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Intrathecal baclofen

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A presentation for pharmacist about proper use of Intrathecal Baclofen

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Intrathecal baclofen

  1. 1. Trey Rumph Mercer University 4 th year Student
  2. 2. <ul><li>What is spasticity? </li></ul><ul><li>Current treatments for spasticity </li></ul><ul><li>How does Baclofen work? </li></ul><ul><li>How is Intrathecal Baclofen used in the clinical setting? </li></ul>
  3. 3. <ul><li>Modified Ashworth Scale </li></ul><ul><li>Penn’s Spasm Score </li></ul><ul><li>Spasticity </li></ul><ul><li>Dystonia </li></ul>
  4. 4. Score Ashworth Scale  (1964) Modified Ashworth Scale  Bohannon & Smith (1987) 0  (0) No increase in tone No increase in muscle tone 1  (1) Slight increase in tone giving a catch when the limb was moved in flexion or extension Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension. 1+ (2) Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the reminder (less than half) of the ROM (range of movement). 2  (3) More marked increase in tone but limb easily flexed. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved. 3  (4) Considerable increase in tone - passive movement difficult. Considerable increase in muscle tone passive, movement difficult. 4  (5) Limb rigid in flexion or extension. Affected part(s) rigid in flexion or extension.
  5. 5. Penn spasm frequency scale Score Spasm frequency score No spasms 0 No spasms Mild spasms at stimulation 1 One or fewer spasms per day Irregular strong spasms less than 1 time/[sol]/h 2 Between 1 and 5 spasms per day Spasms more often than 1 time/[sol]/h 3 Five to less than 10 spasms per day Spasms more than 10 times/[sol]/h 4 Ten or more spasms per day, or continuous contraction
  6. 6. <ul><li>Sustained stiff or rigid muscles with exaggerated deep tendon reflexes </li></ul>
  7. 7. <ul><li>Proposed Mechanisms </li></ul><ul><ul><li>Muscle spindle hyperactivity </li></ul></ul><ul><ul><li>Decreased pre-synaptic inhibition </li></ul></ul><ul><ul><li>Alteration in segmental reflex mechanisms </li></ul></ul><ul><ul><li>Impaired suprasegmental influence </li></ul></ul>
  8. 9. <ul><li>Movement disorder which causes involuntary contraction of one’s muscle/s </li></ul><ul><ul><li>Typically twisting and repetitive movements </li></ul></ul>
  9. 10. <ul><li>Types </li></ul><ul><ul><li>Focal —limited to one area of the body </li></ul></ul><ul><ul><li>Segmental —affecting 2 or more nearby or contiguous areas of the body </li></ul></ul><ul><ul><li>Multifocal —involving 2 or more distant regions of the body </li></ul></ul><ul><ul><li>Hemidystonia —affecting one half of the body </li></ul></ul><ul><ul><li>Generalized —leg involvement plus eventual involvement of another region or regions of the body </li></ul></ul>
  10. 11. <ul><li>Injectables* </li></ul><ul><li>Oral Antispasmodics* </li></ul><ul><li>Surgical Treatment </li></ul><ul><ul><li>Selective dorsal rhizotomy </li></ul></ul><ul><li>Orthopedic interventions </li></ul><ul><ul><li>Muscle-tendon surgery </li></ul></ul><ul><li>Physical Therapy </li></ul><ul><li>Constraint Therapy </li></ul><ul><li>Electrical Stimulation </li></ul>
  11. 12. <ul><li>Botulinum toxin (BTX A) injected into the affected muscle blocks the presynaptic release of acetylcholine from the motor endplates of the motorneural junction decreasing tone by limiting muscle contraction </li></ul><ul><ul><ul><li>**3-10 percent develop antibodies to the toxin and no longer will receive benefit from the medication </li></ul></ul></ul>
  12. 13. <ul><li>Treatment: </li></ul><ul><ul><li>Complete Baseline assessment </li></ul></ul><ul><ul><li>Dosing is based on body weight as well as the muscle being treated by the toxin </li></ul></ul><ul><ul><li>No reliable potency standard amongst the different preparations so each dosing scheme is unique to the manufacturer brand </li></ul></ul><ul><ul><li>Re-evaluate the patient six week post-treatment, effect typically last for 3 to 8 months  re-dose </li></ul></ul>
  13. 15. <ul><li>Zanaflex </li></ul><ul><ul><li>In the spinal cord : primary action is on polysynaptic pathways to reduce release of excitatory neurotransmitters and reduce the sensitivity of the post-synaptic neuron to excitatory neurotransmitters </li></ul></ul><ul><li>Dantrolene </li></ul><ul><ul><li>Inhibits release of calcium ions from the sarcoplasmic reticulum </li></ul></ul><ul><li>Benzodiazepines </li></ul><ul><ul><li>Increases presynaptic inhibition due to binding of the BZD receptors that are linked to the receptors for GABA located on the primary afferent fibers  increased affinity of GABA to its receptor </li></ul></ul><ul><li>Baclofen </li></ul><ul><ul><li>GABA analog </li></ul></ul><ul><ul><li>Oral availability is limited due to poor lipid solubility resulting in low levels in the CSF </li></ul></ul>
  14. 16. <ul><li>Pharmacology </li></ul><ul><ul><li>4-amino-3-(4-chlorophenyl)-butanoic acid </li></ul></ul><ul><ul><li>Oral baclofen is absorbed well via the GIT, but doesn’t cross the BBB (low lipophilicity) </li></ul></ul><ul><ul><ul><li>Oral dose: 30-60mg  CSF level: 12 to 96 μ cg </li></ul></ul></ul><ul><ul><ul><li>Onset 30min to 1hr </li></ul></ul></ul><ul><ul><ul><li>Peak: ~4hrs </li></ul></ul></ul><ul><ul><ul><li>DOA: ~8hrs </li></ul></ul></ul><ul><ul><ul><li>Renal clearance 10-85% </li></ul></ul></ul>
  15. 17. <ul><li>Baclofen given via intrathecal administration achieves much higher CSF concentrations </li></ul><ul><ul><ul><ul><ul><li>BLACK BOX WARNING : Don’t abruptly stop medication due to high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which in rare cases has advanced to rhabdomyolysis, multiple organ-system failure, and death </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Intrathecal dose: 400 μ cg  CSF level: 400 μ cg/ml </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Onset 30 min to 1hr </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Peak: ~4hrs </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>DOA: ~8hrs </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>CSF Clearance </li></ul></ul></ul></ul></ul>
  16. 18. <ul><li>Patient Selection </li></ul><ul><li>Pumps Implantation </li></ul><ul><li>Dosing Schemes </li></ul><ul><li>Side Effects </li></ul><ul><li>Complications </li></ul><ul><ul><li>Overdose </li></ul></ul><ul><ul><li>Baclofen Withdrawal </li></ul></ul><ul><li>Outcomes </li></ul>
  17. 19. <ul><li>Four Indications </li></ul><ul><ul><li>Spinal cord injuries or Familial paraparesis related spasticity </li></ul></ul><ul><ul><li>Secondary Dystonia (brain lesion) </li></ul></ul><ul><ul><li>Hemidystonia </li></ul></ul><ul><ul><li>Spastic hemiparesis </li></ul></ul>
  18. 20. <ul><li>Kroin, observed that CSF concentration varied along a gradient in the spinal canal. Drug concentrations at the foramen magnum were ¼ those in the lumbar region. </li></ul><ul><ul><li>T10-11: familial spastic paraparesis </li></ul></ul><ul><ul><li>C6-T2: spastic quadriparesis </li></ul></ul><ul><ul><li>C1-4: generalized secondary dystonia </li></ul></ul>
  19. 21. <ul><li>Screening </li></ul><ul><ul><li>“ virtually all patients with spasticity respond to bolus doses…” </li></ul></ul><ul><ul><li>“ The great majority of children who ‘do not respond’ to bolus doses have dystonia , which takes higher dose and often require continuous infusion” </li></ul></ul>
  20. 22. <ul><li>Test Doses (spasticity): </li></ul><ul><ul><li><40lbs  25 μ cg </li></ul></ul><ul><ul><li>> 40lbs  50 μ cg </li></ul></ul><ul><li>Test Dose (dystonia): </li></ul><ul><ul><li><7 years old, < 40lbs  50 to 100 μ cg bolus </li></ul></ul><ul><ul><li>> 7 years old, > 40 lbs  continuous infusions </li></ul></ul><ul><ul><ul><li>Begin @ 200 μ cg /day </li></ul></ul></ul><ul><ul><ul><li>Increase by 50 μ cg every 8 hours until desired effect is reached </li></ul></ul></ul><ul><ul><ul><ul><li>Look for the following: 1) dystonia improvement; 2) unacceptable side effects; 3) no significant response at 900 μ cg/day </li></ul></ul></ul></ul>
  21. 23. <ul><li>Dosing for Spasticity </li></ul><ul><ul><li>100 μ cg/day (a dose twice the test dose) </li></ul></ul><ul><ul><ul><li>Can adjust daily, often increasing 5-10% a day </li></ul></ul></ul><ul><li>Dosing for Dystonia </li></ul><ul><ul><li>200-300 μ cg/day </li></ul></ul><ul><ul><ul><li>Can adjust daily, often increasing 50 -100 μ cg/day </li></ul></ul></ul>
  22. 24. Source: Data on file at Medtronic.
  23. 25. <ul><li>Common Early Side Effects </li></ul><ul><ul><li>Hypotonia, somnolence, headache, convulsion, urinary retention, dizziness and nausea </li></ul></ul><ul><li>Common Chronic Side Effects </li></ul><ul><ul><li>Hypotonia, somnolence, nausea and vomiting, headache, urinary retention </li></ul></ul>
  24. 26. <ul><li>Three most common: </li></ul><ul><ul><li>Infections </li></ul></ul><ul><ul><li>Catheter Problems (breaks, kinks, migration) </li></ul></ul><ul><ul><li>CSF leaks </li></ul></ul>
  25. 27. <ul><li>Presentation </li></ul><ul><ul><li>Hypotonia, decreased alertness, depressed respiration, bradycardia and coma </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Turn off the pump, support oxygenation and respiration until the drug has metabolized </li></ul></ul><ul><ul><li>If significant overdose: CSF barbotage can speed up recovery </li></ul></ul>
  26. 28. <ul><li>Presentation </li></ul><ul><ul><li>Mild </li></ul></ul><ul><ul><ul><li>Characterized by pruritus (without exanthem), agitations, diaphoresis and increased tone </li></ul></ul></ul><ul><ul><li>Moderate </li></ul></ul><ul><ul><ul><li>Fever, tachycardia, spontaneous clonus and painful muscle spasms </li></ul></ul></ul><ul><ul><li>Severe </li></ul></ul><ul><ul><ul><li>Worsening of the following sx: seizures, hallucination, delirium, rhabdomyolysis and death </li></ul></ul></ul>
  27. 29. <ul><li>Treatment </li></ul><ul><ul><li>Administration of GABAergics </li></ul></ul><ul><ul><li>Enteral Baclofen: 10mg TID  30mg Q4h </li></ul></ul><ul><ul><ul><li>If NPO  IV Valium </li></ul></ul></ul><ul><li>Differential </li></ul><ul><ul><li>Malfunctioning Pump* </li></ul></ul><ul><ul><ul><li>Fluoroscopic study or Radionuclide instillation </li></ul></ul></ul><ul><ul><li>Tachyphylaxis to ITB (no reported cases) </li></ul></ul><ul><ul><ul><li>Give “meaningful” bolus: 50 - 150 μ cg through pump in shortest interval </li></ul></ul></ul>
  28. 30. Intrathecal Baclofen Therapy <ul><li>SynchroMed II (20ml, 40ml) </li></ul><ul><ul><ul><li>$11,000/unit </li></ul></ul></ul><ul><ul><li>Battery Life: 6-7 years </li></ul></ul><ul><ul><ul><li>20ml refill ~$425 </li></ul></ul></ul><ul><ul><ul><li>40ml Refill ~$850 </li></ul></ul></ul><ul><li>SynchroMed EL (10ml, 18ml) </li></ul><ul><ul><li>Battery Life: 3-7 years </li></ul></ul><ul><li>Intrathecal Test Dose </li></ul><ul><ul><li>$70 for the initial test bolus </li></ul></ul>
  29. 31. <ul><li>ITB has been proven efficacious in decreasing spasticity in the upper and lower extremities </li></ul><ul><li>ITB treats spasticity for at least 17 years and is effective for dystonia for at least 10 years </li></ul>
  30. 33. <ul><li>Albright, A. Leland, Ferson, Susan S. Intrathecal baclofen therapy in children. Neurosurgical FOCUS 2006 21:2, 1-6  </li></ul><ul><li>Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF: Long term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg 98:291-295, 2003 </li></ul><ul><li>Francesco Motta, M.D., Vincenzo Buonaguro, M.D., and Cecilia Stignani, P.T.. (2007) The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases.  Journal of Neurosurgery: Pediatrics   107 :1, 32-35 Online publication date: 1-Jul-2007. </li></ul><ul><li>Jagatsinh Y. Intrathecal baclofen: Its effect on symptoms and activities of daily living in severe spasticity due to spinal cord injuries: A pilot study. Indian J Orthop [serial online] 2009 [cited 2009 Dec 13];43:46-9. Available from:  http://www.ijoonline.com/text.asp?2009/43/1/46/45323 </li></ul><ul><li>Kroin JS, Ali A, York M, Penn RD: The distribution of medication along the spinal canal after chronic intrathecal administration. Neurosurgery 33:226-230, 1993 </li></ul>

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