Neuraxial Opiods

Neuraxial Opiods - Neuraxial Opioids in Obstetrics Dmitry...

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Neuraxial Opioids in Obstetrics Dmitry Portnoy, MD Anesthesiology Department
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Objectives Description of known mechanisms of spinal opioids. Interaction with opioid receptors Distribution and redistribution of spinal opioids Properties that govern pharmacokinetics of spinal opioids Clinical application of spinal opioids. Specific drugs appropriate for spinal administration Sites and method of administration Recognition and treatment of side effects and complications.
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Historical Perspective 2000 b.c. opium used for pain relief in ancient China, Egypt, Rome and Greece. 1899 August Bier injected cocaine to produce spinal anesthesia. 1973 Pert and Snyder discovered specific opioid receptors of the spinal cord. 1979 Wang et al. reported the first clinical use of IT opioids. 1979 Behar et al. - epidural morphine in treatment of pain.
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The Physiology of Pain in Labor Pain during first stage of labor - visceral: Dilation of the cervix and distention of the lower uterine segment Dull, aching and poorly localized Slow conducting, visceral C fibers, enter spinal cord at T10 to L1 Can be blocked by spinal opioids alone Pain during second stage of labor – somatic: Distention of the pelvic floor, vagina and perineum Sharp, severe and well localized Rapidly conducting A-delta fibers, enter spinal cord at S2 to S4 Difficult to block with spinal opioids alone
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The Physiology of Pain in Labor
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Mechanism of Action Universal molecular mechanism of opioids: Binding to G-protein-coupled opioid receptor Inhibition of adenylate cyclase and voltage-gated Ca++ channels Decrease neuronal excitability, interruption of pain transmission Spinal effect – the substantia gelatinosa of the dorsal horn Highly selective nociceptive pathways Presynaptic receptor action – inhibition of substance P release Postsynaptic receptor action – modulation of pain transmission Supraspinal effect – inhibition of primary afferent transmission in the brainstem, thalamus and gray matter
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Mechanism of Action
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Mechanism of Action - Bioavailability Effect depends on affinity and ability to reach receptors Spinal and epidural opioids - same principle mechanism Penetration of neural tissue is the rate limiting step Factors affecting transmembrane movements of the opioids Molecular weight pK (the lower pK, the greater fraction of uncharged form at pH of 7.4) Protein binding Lipid solubility
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Mechanism of Action: Reaching Receptors Epidurally administered drugs must travel through: dura matter arachnoid matter CSF pia matter white matter gray matter dorsal horn Competing pathways Uptake into epidural epidural fat Uptake into systemic circulation
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Mechanism of Action: Meningeal Permeability Proposed mechanisms of movements spinal drugs : Diffusion through spinal meninges Preferential diffusion through spinal nerve root cuff
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This note was uploaded on 12/28/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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Neuraxial Opiods - Neuraxial Opioids in Obstetrics Dmitry...

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