This book provides a unified and comprehensive compendium of issues related to the spinal delivery of drugs. The text, consisting of 34 chapters, begins with an extensive review of the early history, reflecting the development of the spinal cord as a route of spinal drug delivery. It then presents 4 principal divisions. In the first, the embryology, anatomy of the spinal canal, the spinal canal meninges and vasculature are reviewed in humans and non-human species. The second division considers the factors that define the redistribution of spinally delivered drugs and the movements of such drugs into the spinal parenchyma are considered in detail. The third section considers issues that relate to the preclinical development of drugs for spinal delivery. This division includes issues that pertain to preclinical models for drug safety evaluation, the nature of vehicles for spinal drugs and properties of materials for chronic spinal implantation. In addition, the nature of the inflammatory reactions that are observed with foreign bodies and toxicity are presented. The fourth division considers the several therapeutic targets towards which spinally delivered drugs are aimed. These include analgesics, anesthetics, antispasticity, antimetastatic and growth factors. In each case, the site and mechanisms of action and the several drug classes that are relevant are presented. The book seeks to address the broad categories of interest that are represented by the scientists who focus on the biology of spinal cord function, the toxicologist and chemist who develop and formulate drugs for human spinal therapeutic use and the clinicians who seek an in-depth review of spinal drug delivery.
List of contributors. Acknowledgements. Dedication. Introduction. 1. The history of spinal drug delivery: the evolution of lumbar puncture and spinal narcosis (D.C. Mackey). 2. Comparative spinal anatomy of vertebrates (R. Nieuwenhuys). 3. Spinal anatomy of experimental animals (T.F. Fletcher, S.A. Malkmus). 4. Gross anatomy of the human vertebral column (Q. Hogan). 5. Anatomy of DRG, intrathecal nerve roots, and epidural nerves with emphasis on mechanisms of neurotoxic injury (R.R. Myers, K. Olmarker). 6. The spinal meninges and their role in spinal drug movement (C.M. Bernards). 7. Anatomy and physiology of the spinal vasculature (M. Marsala). 8. Spinal cerebrospinal fluid chemistry and physiology (A.A. Artru). 9. Epidural and intrathecal drug movement (C.M. Bernards). 10. Structure of extracellular space and physiochemical properties of molecules governing drug movement in brain and spinal cord (C. Nicholson). 11. Spinal pharmacokinetics (S.L. Shafer, A. Shafer). 12. Reaction of intrathecal and epidural spaces to infection and inflammation (R.O. Weller). 13. Animal models of intrathecal and epidural drug delivery (T.L. Yaksh, S.A. Malkmus). 14. Human spinal drug delivery: methods and technology (M.S. Wallace). 15. General considerations in the formulation of drugs for spinal delivery (R.J.E. Grouls, E.H.M. Korsten, T.L. Yaksh). 16. Material properties and bioreactivity (D.E. Albert, M.A. Hintz). 17. General considerations in the characterization of drug action after spinal delivery (T.L. Yaksh). 18. Preclinical safety evaluation for spinal drugs (T.L. Yaksh, M.L. Rathbun, J.C. Provencher). 19. Clinical implementation of agents for spinal delivery (J.C. Eisenach). 20. Spinally delivered analgesic drugs (S.E. Abram). 21. Local anesthetics acting on the spinal cord (A. Gokin, G. Strichartz). 22. Intrathecal chemotherapy (L. Bomgaars, S.M. Blaney, D.G. Poplack). 23. Intrathecally delivered medications for spasticity and dystonia (J.M. Meythaler). 24. Spinal drug delivery: contrast media (V.M. Haughton). 25. Spinal delivery of neurotrophins and related molecules (C.P. LeBel). 26. Spinal drug delivery: cellular implants (J. Sagen). Subject index.
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