Opioid Analgesics - iMCP2 - 2020 post (1).pptx - Integrated Medicinal Chemistry and Pharmacology PSC 6311 Opioid Analgesics Agonists Mixed\/partial

Opioid Analgesics - iMCP2 - 2020 post (1).pptx - Integrated...

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Integrated Medicinal Chemistry and Pharmacology PSC 6311 Opioid Analgesics: Agonists, Mixed/partial Agonists, Antagonists, and Receptors Katzung, Basic and Clinical Pharmacology , 14 th ed.; Chapter 31 Foye’s, Principles of Medicinal Chemistry , 8 th ed.; Chapter 14 Foye’s, Principles of Medicinal Chemistry , 7 th ed.; Chapter 20 Goodman & Gilman’s The Pharmacological Basis of Therapeutics , 13 th ed.; Chapters 20 Karen S. Mark , Ph.D. ; Associate Professor Pharmaceutical Sciences Office: Room 275 email: [email protected] ph: 865-
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Peripheral nociception Lesion 1. Tissue/cell damage releases K+, ATP that are picked up by sensory neurons 2. Serotonin, bradykinins & prostaglandins infiltrate the tissue leading to inflammation 3. Prostaglandins sensitize nociceptors
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Lecture Objectives - I 1.Explain the pharmacological usefulness of opioid/opiate class of drugs2.List the opioid receptor sub-types and three main physiological effects that each elicit 3.Explain SAR relation of opioid receptor sub-types 4.Describe the structural similarities of endogenous and exogenous opioids/opiates 5.Differentiate between phenanthrene and phenylpiperidine class of opiate drugs 6.Explain pharmacodynamic effects of opioids at affected organ / tissue; which develop tolerance
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Lecture Objectives - II 7.Differentiate drug structures within phenanthrene sub-class 8.Describe opioid/opiates including MOA, potency, metabolism, side effects, DDIs 9.Explain which opioids are least likely to cross BBB and why; and, what is their clinical use.10.Compare and contrast the partial agonist/mixed agents and explain their use. 11.Describe symptoms of opiate overdose and how it is treated 12.Explain which agents have actions at additional sites
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Drugs Covered in this Section Codeine Morphine Hydrocodone Hydromorphone Oxycodone Hydrocodone Tramadol Tapentadol Naloxone Naltrexone Methadone Meperidine Fentanyl Alfentanil Sulfentanil Remifentanil Methylnaltrexone Loperamide Phenoxylate Dextromethorphan Buprenorphine Butorphanol Nalbuphine Pentazocine
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Descending PathwaysAscending PathwaysForce / traumaHeat Cold Chemicals “Nociceptors” on pain sensing neurons are stimulated by:
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Tissue Injury vs. Nerve Injury Nociception
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Synaptic inhibition: receptor pharmacology Opioids and most opiates are agonistsat pre-/post-synaptic opiate receptors (µ, κ, and δ) Modulates NT release (Glut, GABA, Ach, Dop, 5-Ht)Opiate receptors coupled to GiproteinsActivation of opioid receptors result in:1.All opioid receptors inhibit adenylate cyclase2.Downstream activation of PKC or PLCβ3.Post-synpatic open K+channelshyperpolarization 4.Pre-synaptic inhibit ѵ-g Ca2+channels (G-subunits) ; ß
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Opioid Neuronal Transmission Katzung; Fig. 31-1
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Endogeno us Opioids and Receptors Endogenous opioids synthesized by neuron soma body Opioid neuropeptides have inhibitory action on interneurons in spinal cord and CNS ascending pathway neurons block pain signal in spinal cord (dorsal horn) Opioid receptors form homodimers or heterodimers which changes pharmacological response of receptors MOR-DOR and KOR-DOR heterodimers have less
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