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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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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

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.


Opioid receptor locations

μ-opioid receptor locations


Opioid receptor locations1

μ-opioid receptor locations


Toxicity of morphine

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


Why administer morphine intrathecally

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.


Case 1

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.


Case 2

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.


Goals

Goals

  • Morphine infusion case study based on a clinical trial:

    • Morphine concentration field

    • Morphine delivery into the spinal cord

    • Therapeutic effect and toxicity


Questions

Questions?


References

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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