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Pharmacology – OPIOIDS (explained )

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Opioids, sometimes known as narcotics, are a group of drugs that act on the central nervous system to produce morphine-like effects such as pain relief and euphoria. This pharmacology lecture covers topics such as nociceptive pain pathway, role of glutamate, substance P, and calcitonin gene-related peptide (CGRP) in pain processing, endogenous opioids (enkephalins, endorphins, dynorphins), NMDA, AMPA, NK-1, CGRP receptors, opioid receptors (mu, delta, kappa) mechanism of action and side effects of narcotic drugs, development of opioid tolerance and addiction, partial mu-receptor opioid agonist and antagonist. Drugs mentioned include; Morphine, Fentanyl, Hydrocodone, Hydromorphone, Methadone, Meperidine, Oxycodone, Oxymorphone, Buprenorphine, and Naloxone.

In this lecture we are going to cover the pharmacology of opioids so let’s get right into it opioids sometimes called narcotics or a group of drugs that act on the central nervous system to produce morphine-like effects such as pain relief and euphoria now in order to gain better understanding of their mechanism of action first we need to talk about the transmission

Of pain so pain begins at the nauseaceptors which are simply the branching ends of sensory neurons found within the peripheral nervous system these high threshold primary sensory neurons respond to damage to the body by transmitting the painful stimulus to the second order neurons in the dorsal horn of the spinal cord from there the signal is carried through the

Spinothalamic tract to the thalamus and then to the somatosensory cortex where pain is perceived now on a microscopic level the pain signal takes the form of a series of action potentials that fire repeatedly depending on the intensity of pain to enhance movement across the synaptic cleft transmitter chemicals are released from the presynaptic neurons including

Glutamate substance p and calcitonin gene-related peptide cgrp for short glutamate is one of the most important neurotransmitters for pain and can activate both nmda and empire receptors which permit influx of positively charged calcium and sodium ions respectively as you may recall the flow of positively charged ions into the neuron makes the neuron more

Likely to fire in this way glutamate excites the second order neurons in the dorsal horn which leads to propagation of a sharp localized pain signal substance p on the other hand binds to the neurochinen1 receptor nk1 for short which leads to intracellular signaling that involves activation of archedonic acid pathways nitric oxide synthesis and activation of

Nmda receptors nmd receptors are activated with substance p attaches to nk1 receptors and then gets incorporated into the cell activating protein kinase c this action removes the magnesium that under normal conditions is blocking nmda receptor this in turn allows glutamate to attach to the nmda receptor and thus permit the inflow of calcium ions ultimately

Causing the pain signal to increase and fire more frequently lastly the release cgrp binds to its receptor on second order neurons leading to changes in receptor expression and function and thereby altered neuronal activity this in turn contributes to the so-called central sensitization that is characterized by a lower threshold for evoking action potentials now

Fortunately for us our bodies can cope with certain amount of pain by releasing so-called endogenous opioids there are three major families of endogenous opioids the encephalins dinorphins and endorphins endogenous opioids exert their effects by binding to opiate receptors which are abundantly present in the central and peripheral nervous systems there are three

Major types of opiate receptors that is mu delta and kappa in general all three receptors differ in their cellular distribution their relative affinity for various opioid ligands and their contribution to specific opioid effects all opioid receptors are seven transmembrane spanning proteins that couple to inhibitory g-proteins and they are all present in high

Concentrations in the dorsal horn of the spinal cord activation of these receptors by an agonist such as the endogenous mu opioid peptide endorphin causes closing of the voltage-gated calcium channels on the presynaptic nerve terminals which in turn decreases the release of neurotransmitters such as glutamate substance p and calcitonin gene related peptide in

Addition to that activation of opioid receptors leads to opening of potassium channels allowing efflux of potassium ions which in turn results in hyperpolarization rendering neurons less sensitive to excitatory inputs now the majority of currently available opioid analgesics act primarily at the mu opioid receptors essentially mimicking the effects of endogenous

Opioid peptides however while naturally derived opioids can only reach a certain potency the synthetically produced opioids are refined and processed to be much more powerful the examples of synthetic opioid agonists are fentanyl hydrocodone hydromorphone methadone meperidine oxycodone and oxymorphone as a side note here it’s important to note that methadone is

Not only a potent mu receptor agonist but also a potent antagonist of the nmda receptor as well as norepinephrine and serotonin reuptake inhibitor these properties make methadone useful for treatment of both nosoceptive and neuropathic pain now in addition to producing analgesia activation of the opioid receptors in other parts of the body can bring about many

Side effects for example all opiates produce some degree of nausea which is due to direct stimulation of the chemoreceptor trigger zone in the medulla all opioid receptor agonists also produce a dose-dependent respiratory depression opioids primarily cause respiratory depression by reducing brainstem respiratory center responsiveness to carbon dioxide they also depress

Transcribed from video
Pharmacology – OPIOIDS (explained ) By EUROPEAN PHARMACYliveBroadcastDetails{isLiveNowfalsestartTimestamp2020-08-11T061849+0000endTimestamp2020-08-11T062653+0000}