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Intrathecal Delivery of Morphine

November 4, 2010 Jaimie M. Stewart In Collaboration with: Ying Hsu Advisor: Professor Andreas A. Linninger Laboratory for Product and Process Design Department of Bioengineering University of Illinois, Chicago, IL. Intrathecal Delivery of Morphine. Morphine. Potent opiate analgesic.

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Intrathecal Delivery of Morphine

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  1. November 4, 2010 Jaimie M. Stewart In Collaboration with: Ying Hsu Advisor: Professor Andreas A. Linninger Laboratory for Product and Process Design Department of Bioengineering University of Illinois, Chicago, IL Intrathecal Delivery of Morphine

  2. Morphine • Potent opiate analgesic. • Used to relieve severe pain. • Can be taken orally, rectally, subcutaneously, intravenously, intrathecally or epidurally. • Binds to μ-opioid receptors. • Located through out the brain and spinal cord.

  3. μ-opioid receptor locations

  4. μ-opioid receptor locations

  5. Toxicity of Morphine • Can be caused due to an allergic reaction or overdose. • Symptoms • Respiratory depression • Hypotension • Circulatory failure • Coma • Convulsions • Rhabdomylosis (Destruction of striated muscle fibers) • Renal failure

  6. Why Administer Morphine Intrathecally? • Morphine is subject to extensive first-pass metabolism. • If taken orally only 40–50% of the dose reaches the central nervous system. • Subcutaneous, intramuscular, and Intravenous injection administrations peak in the body from 20 to 30 minutes. • Morphine crosses the blood-brain barrier, but not easily. • This is due to poor lipid solubility, protein binding, fast conjoinment with glucuronic acid, and ionization.

  7. Case 1 • 5 cancer patients with sever, intractable pain in the lower half of the body. • Intrathecal administration (L5-S1) of 2 mg morphine in 2 forms: (1) isobaric (NaCl 0.9%) and (2) hyperbaric solution (7% dextrose). • CSF was collected at T10,then CSF morphine levels were determined by HPLC.

  8. Case 2 • Morphine was administered through a 25-gauge spinal needle at L3-L4 • Morphine was injected in 2ml saline solution followed by a 1 ml saline solution flush. • CSF morphine concentrations were determined by measuring CSF at the C1-2 level.

  9. Goals • Morphine infusion case study based on a clinical trial: • Morphine concentration field • Morphine delivery into the spinal cord • Therapeutic effect and toxicity

  10. Questions?

  11. References "MS-Contin (Morphine Sulfate Controlled-Release) Drug Information: User Reviews, Side Effects, Drug Interactions and Dosage at RxList." Web. 02 Nov. 2010. <http://www.rxlist.com/ms-contin-drug.htm#cp>. "Morphine Toxicity Symptoms, Diagnosis, Treatments and Causes - WrongDiagnosis.com." Wrong Diagnosis. Web. 02 Nov. 2010. <http://www.wrongdiagnosis.com/m/morphine_toxicity/intro.htm>. Caute, B., B. Monsarrat, C. Gouarderes, J.C. Verdie, Y. Lazorthes, J. Cros, and R. Bastide. "CSF Morphine Levels after Lumbar Intrathecal Administration of Isobaric and Hyperbaric Solutions for Cancer Pain." Pain 32.2 (1988): 141-46. Print Max, Mitchell B., Charles E. Inturrisi, Robert F. Kaiko, Patricia Y. Grabinski, Choh H. Li, and Kathleen M. Foley. "Clinical Pharmacology & Therapeutics - Abstract of Article: Epidural and Intrathecal Opiates: Cerebrospinal Fluid and Plasma Profiles in Patients with Chronic Cancer Pain." Nature Publishing Group : Science Journals, Jobs, and Information. Web. 02 Nov. 2010. <http://www.nature.com/clpt/journal/v38/n6/abs/clpt1985237a.html>. "Pain Processes - 1." Georgia Pain Physicians, P.C. Web. 03 Nov. 2010. <http://www.georgiapainphysicians.com/l2_edu_pharma_mod1_slides.htm>.

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