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解热镇痛抗炎药 Antipyretic-analgesic and Anti-inflammatory Drugs

解热镇痛抗炎药 Antipyretic-analgesic and Anti-inflammatory Drugs. Pain Treatment. Analgesics Antipyretic-analgesic and anti-inflammatory drugs*. Pain. An unpleasant experience associated with actual or potential tissue damage. Pain Physiology. Neurochemistry. Ion Fluxes (H + / K + ).

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解热镇痛抗炎药 Antipyretic-analgesic and Anti-inflammatory Drugs

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  1. 解热镇痛抗炎药 Antipyretic-analgesic and Anti-inflammatory Drugs

  2. Pain Treatment • Analgesics • Antipyretic-analgesic and anti-inflammatory drugs*

  3. Pain An unpleasant experience associated with actual or potential tissue damage.

  4. Pain Physiology

  5. Neurochemistry Ion Fluxes (H+/ K+) Tissue Injury To brain Prostaglandins Bradykinin Leukotrienes Dorsal horn Sensitized Nociceptor Mast Cell Histamine Aspartate, Neurotensin, Glutamate, Substance P

  6. Pain Transmission Pain perception Enkephalin inter-neuron Descendingpathway Ascendingpathway Spinal cord Nociceptor

  7. Descending Pain Control Pathways Descending impulse Enkephalin Opioid receptor

  8. Opportunities for Pain Treatment • At the receptor • Along the nerve • At receptors in spinal column and brain

  9. Pain • Acute vs chronic • Nociceptive vs Neuropathic

  10. Acute vs. Chronic Pain Dorsal root ganglion To brain A-delta fibers: sharp,shooting pain C fibers: dull, aching, burning pain

  11. Nociceptive Pain Ascending pain pathway Spinal cord Tissue injury

  12. Neuropathic Pain Ascending pain pathway Nerve injury Spinal cord

  13. Principles of Pain Management • Gold standard: patient determines severity • Tradition: pain has been undertreated • Prevention or early treatment best • Pain kills • Pain is real • Balance pain relief with side effects of drugs

  14. Antipyretic-analgesic and Anti-inflammatory Drugs • Non-steroidal anti-inflammatory drugs, NSAIDs. • Aspirin-like drugs.

  15. COX Mechanism of NSAIDs phospholipid PLA2 NSAIDs Arachidonic acid, AA Leukotrienes, LTs Prostaglandin, PG PGE2 PGF2 PGI2 TXA2

  16. Salicylates Aspirin and NSAIDs • Anti-inflammatory • Inhibits cyclooxygenase pathway for breakdown of arachidonic acid to prostaglandins and thromboxane • Ibuprofen, Naprosyn & naproxen • COX-2 inhibitors

  17. Acetaminophen • Inhibits synthesis of prostaglandin in CNS but not in periphery. • No anti-inflammatory or anti-platelet effects but good for mild pain and to reduce fever • Adverse reactions rare. Overdose may cause liver disease esp in persons who regularly consume alcohol.

  18. Other Pain Management Drugs • Antidepressants in neuropathic pain • Ergotamine in migraine headache • Anticonvulsants in neuropathic pain or migrane headache • NMDA antagonists for neuropathic pain • Centrally acting alpha2 agonists such as clonidine • Anesthetics (lidocaine or bupivicaine) (ketamine) • Radiopharmaceuticals for cancer bone pain

  19. Ca++ Ca++ Nerve NMDA Memantine blocks the NMDA receptor. Phase II study: diabetic subjects with neuropathic pain experienced 29% less pain than placebo-treated subjects. N-methyl-D-aspartate (NMDA) receptor opens channel for Ca++influx. This can lead to nerve damage and pain.

  20. An Alpha 2 Agonist? Reuptake pump a R Post-synaptic cell NE NE NE Alpha 2 presynaptic receptor b R

  21. When stimulated, they inhibit nerve transmission. a R Post-synaptic cell NE Alpha 2 presynaptic receptor b R

  22. Clonidine given epidurally or orally blocks pain messages from neuropathic origin. a Post-synaptic cell NE Alpha 2 presynaptic receptor R

  23. A highly lipid soluble drug, what is the chance that epidurally-placed clonidine would get into the blood stream? a R Post-synaptic cell NE Alpha 2 presynaptic receptor b R

  24. What would the SNS blockade do to the blood pressure? a R Post-synaptic cell NE Alpha 2 presynaptic receptor b R

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