Presenter: Dr Deepika Karjigi
Budding Anaesthesiologist in AIIMS, Rishikesh
Opioids are a vital part of providing the analgesic component of anesthesia and often form the foundation for postoperative pain management.
□ Opioids suppress pain by targeting multiple sites throughout the nervous system including action in brain, spinal cord, and peripheral nervous systems.
□ An increased understanding of the molecular pharmacology of opioid receptors and opioid- induced cellular responses allows utilization of innovative techniques for analgesia.
□ Opioids also affect multiple organ systems, including the respiratory and cardiovascular systems, and can cause a variety of adverse effects. Proper dosing and monitoring may allow these adverse effects to be minimized.
The remarkable beneficial effects of opioids, as well as their toxic side effects and addictive potential, have been known for centuries. The term opioid refers broadly to all compounds related to opium. The word opium originates from opos, the Greek word for juice, the drug being derived from the juice of the opium poppy, Papaver somniferum. In contrast, the term opiate refers to natural products derived from the opium poppy and includes morphine, codeine, and thebaine.
The first undisputed reference to opium is found in the writings of Theophrastus in the third century B.C. During the Middle Ages, many of the uses of opium were appreci- ated. Opium contains more than 20 distinct alkaloids. In 1806, Sertürner reported the isolation of a pure substance in opium that he named morphine, after Morpheus, the Greek god of dreams. By the middle of the nineteenth century, the use of pure alkaloids rather than crude opium preparations began to spread throughout the medical world. Since then, there have been ongoing efforts to develop semisynthetic and synthetic opioid analgesics without the adverse side effects. Unfortunately, many of the synthetic opioids share side effects of natural opioids. The search for new opioid agonists led to the synthesis of opioid antagonists and compounds with mixed agonist/antagonist properties, which further expanded therapeutic options and provided important tools for exploring mechanisms of opioid actions. Although new methods of opioid administration, including patient-con- trolled analgesia (PCA) and computer-based infusion tech- niques, have been developed, opioids continue to act on common binding sites throughout the nervous system.
Classification of Opioid Compounds
Naturally occurring Morphine Codeine Papaverine Thebaine
Semisynthetic Heroin
Dihydromorphone, morphinone
Thebaine derivatives (e.g., etorphine, buprenorphine) Synthetic
Morphinan derivatives (e.g., levorphanol, butorphanol) Diphenylpropylamine derivatives (e.g., methadone) Benzomorphan derivatives (e.g., pentazocine) Phenylpiperidine derivatives (e.g., meperidine, fentanyl, sufentanil, alfentanil, remifentanil)
The opioid receptors belong to the G-protein-coupled receptor family. It has been demonstrated that activation of the opioid receptors leads to activation of the pertussis toxin-sensitive G proteins (Gi or Go or both). Expression of the cloned opioid receptors in cultured cells by transfection of the cloned cDNAs has facilitated analysis of the intra- cellular signal transduction mechanisms activated by the opioid receptors ).2 Adenylate cyclase is inhibited by opioid receptor activation, with a resulting reduction of the cellular cyclic adenosine monophosphate (AMP) content. Electrophysiologically, the voltage-gated Ca2+
The opioid receptors belong to the G-protein-coupled receptor family. It has been demonstrated that activation of the opioid receptors leads to activation of the pertussis toxin-sensitive G proteins (Gi or Go or both). Expression of the cloned opioid receptors in cultured cells by transfection of the cloned cDNAs has facilitated analysis of the intra- cellular signal transduction mechanisms activated by the opioid receptors (Fig. 24.6).2 Adenylate cyclase is inhibited by opioid receptor activation, with a resulting reduction of the cellular cyclic adenosine monophosphate (AMP) content. Electrophysiologically, the voltage-gated Ca2+ channel is inhibited and the inwardly rectifying potassium (K+) channels are activated by the opioid receptors. As a result, neuronal excitability is reduced by activation of the opioid receptors. However, the role of adenylate cyclase in opioid receptor activation is complex. For example, long- term tolerance to opioids has been thought to be associ- ated with superactivation of adenylyl cyclase activity, which is a counterregulatory response to the decrease in cyclic AMP levels seen after acute opioid administration.36 That this effect is prevented by pretreatment of cells with pertussis toxin demonstrates involvement of G proteins (Gi or Go or both).