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Opioid Analgesic
Types of drugs and effects
| Question | Answer |
|---|---|
| Nociceptive Pain | a defensive response to stimuli (e.g. mechanical, thermal or chemical) that activate nociceptor sensory units on nerve endings.Acute pain lasts only until the initiating stimulus, but ongoing tissue damage can produce chronic nociceptive pain. |
| Neuropathic Pain | occurs if chronic pain outlast the original trigger, becoming intractable because of persistent pathological change in the way that pain-carrying neuronal pathways function. E.g include phantom limb pain |
| Opioid Analgesics drugs | morphine, buprenorphine, codeine, diamorphine (heroin), dihydrocodeine, fentanyl, methadone, oxycodone, tramadol |
| Mechanism of action | Opioids produce their effects via specific receptors that are closely associated with the neuronal pathways that transmit pain from the periphery to the CNS. |
| The brain produces several endogenous opioid peptide neurotransmitters, most of which act via specific opioid receptors. These are? | Enkephalins or methionine (met-enkephalin); dynorphins A and B; β-endorphin endomorphins 1 and 2. |
| Name of opioid receptors | µ (mu) receptor (MOP receptor) κ (kappa) receptor (KOP receptor) δ (delta) receptor (DOP receptor) |
| Effects of Mu (µ) or MOP receptors | Analgesia (supraspinal µ1, spinal µ2) Respiratory depression (µ2) Constipation Euphoria Miosis Physical dependence Sedation Inhibition of gastrointestinal motility |
| Effects Kappa (κ) or KOP receptors | Analgesia (spinal, peripheral) Sedation Miosis Dysphoria Hallucinations |
| Effects Delta (δ) or DOP receptors | Analgesia (spinal) Respiratory depression Inhibition of GI motility Mood and emotional responses |
| Effects Nociceptin (NOP) receptors | Activation results in an anti-opioid effect (supraspinal), analgesia (spinal), immobility and impairment of learning |
| Where are opioid receptors found? | They are found on the presynaptic and postsynaptic membranes of neurons in CNS pain pathways, and the peripheral nervous system. The postsynaptic actions inhibit neuronal depolarization, and the presynaptic actions inhibit neurotransmitter release. |
| What proteins are the receptors coupled to? | To inhibitory G-proteins (Gi /G0 ). |
| Inhibition of adenylyl cyclase with reduced intracellular generation of cAMP due to opioid receptor activation will lead to? | reduces neurotransmitter release |
| Inhibition of voltage-gated Ca2+ channels in target neurons due to opioid receptor activation will lead to? | reduces neurotransmitter release |
| Activation of voltage-gated K+ channels due to opioid receptor activation will lead to? | hyperpolarizes the target cells, making them less responsive to depolarizing impulses |
| Opioid receptor activation phosphorylation of extracellular signal-regulated kinase (ERK) and other mitogen-activated protein (MAP) kinases | which may have actions on neural cell growth and proliferation; phosphorylation, desensitization and internalization of the opioid receptors, the extent of which varies among receptor ligands and underlie the development of opioid drug tolerance. |
| Morphine Pharmacological Actions on CNS | Analgesia: highly effective in most kinds of acute pain. They are less effective in treating neuropathic and other chronic pain states. Euphoria: is mediated through µ receptors, whereas κ receptor activation produces dysphoria and hallucinations. |
| Respiratory depression Due to morphine | mediated by µ receptors, occurs with normal analgesic dose of morphine, although in patients in severe pain the degree of respiratory depression produced may be less than anticipated. It is the commonest cause of death in acute opioid poisoning. |
| Pupillary constriction due to morphine | caused by µ and κ receptor-mediated stimulation of the oculomotor nucleus. Pinpoint pupils are an important diagnostic feature in opioid poisoning, because most other causes of coma and respiratory depression produce pupillary dilatation. |
| Effects on the GIT due to morphine | Opioids increase tone and reduce motility in many parts of the gastrointestinal system, resulting in constipation. |
| Methylnaltrexone bromide, alvimopan and naloxegol | are opioid antagonists that do not cross the BBB. They have been developed to reduce unwanted peripheral side effects of opioids, such as constipation, without significantly reducing analgesia or precipitating withdrawal in dependent individuals |
| Pethidine | is exceptional among alkaloids as it causes pupillary dilatation because it blocks muscarinic receptors. |
| Morphine releases histamine from mast cells (Pethidine and fentanyl do not produce this effect) | Local effects- urticaria, itching at site of the injection. Systemic effects-bronchoconstriction and hypotension. Hypotension, bradycardia occur with large doses of most opioids, due to activating the medulla, Morphine may contribute to the hypotension. |
| Actions of Morphine | analgesia ,euphoria and sedation,respiratory,depression,suppression of cough, nausea and vomiting, pupillary constriction,constipation histamine release Acute overdosage with morphine produces coma and respiratory depression |
| Diamorphine (heroin) | is inactive at opioid receptors but is rapidly cleaved in the brain to 6-acetylmorphine and morphine . Effects are the same as morphine |
| Codeine | converted to morphine but more slowly by liver metabolism. 20% less potent, more absorbed orally than morphine and is therefore used mainly as an oral analgesic for mild types of pain little or no euphoria and is rarely addictive antitussive activity |
| Dihydrocodeine | is pharmacologically very similar, having no substantial advantages or disadvantages over codeine. |
| Oxycodone | is used in the treatment of acute and chronic pain. |
| Fentanyl, alfentanil, sufentanil and remifentanil | highly potent derivatives,similar to morphine, with rapid onset and shorter duration of action, particularly remifentanil. Used extensively in anesthesia,can be given intrathecally. Fentanyl has minimal cardiovascular effects,does not release histamine. |
| Methadone | is orally active and pharmacologically similar to morphine. It is widely used as a means of treating heroin addiction. |
| Etorphine | is a morphine analogue with a potency more than 1000 times that of morphine, but otherwise very similar in its actions. |
| Pethidine (Meperidine): | similar to morphines effects, except causes restlessness rather than sedation. originally investigated for antimuscarinic but has opioid analgesic activity;residual antimuscarinic action responsible for side effects of dry mouth and blurring of vision. |
| Buprenorphine | is a partial agonist on µ-receptors that produces strong analgesia but there is a ceiling to its respiratory depressant effect. it is also used in the treatment of heroin addiction. |
| Meptazinol | Because of its short duration of action and lack of respiratory depression, it may have advantages for obstetric analgesia. |
| Loperamide | is a µ receptor agonist that is effectively extruded from the brain and therefore lacks analgesic activity. It inhibits peristalsis, and is used to control diarrhoea. |
| Pharmacokinetics of Opioids | Morphine is slowly, erratically absorbed, iv route- acute severe pain; oral-chronic pain. Oxycodone,a slow-release oral preparation. Codeine is well absorbed and normally given orally.Most morphine-like drugs undergo considerable first-pass metabolism. |
| Morphine poisoning (overdose) | Coma and respiratory depression, with characteristically constricted pupils. treated with naloxone intramuscularly or intravenously. Naloxone is less effective in reversing the effects of buprenorphine as agonist dissociates slowly from receptors |
| Opioid antagonists Naloxone (short acting) and Naltrexone (longer acting) | pure antagonists. block µ, δ and κ receptors. Naloxone rapidly reverses opioid-induced analgesia and respiratory depression, and is used mainly to treat opioid overdose or to improve breathing in newborn babies affected by opioids given to the mother. |
| Opioid antagonist Buprenorphine | (a partial agonist) can also precipitate withdrawal due to its antagonist action against higher efficacy opioid agonists |
| Opioid antagonists Alvimopan and naloxegol | are µ-receptor antagonists that do not cross the BBB. They block opioid-induced constipation, nausea and vomiting. |
| Opioid antagonist Pentazocine | Agonist-antagonist (κ agonist, weak μ-antagonist), Analgesic, less sedation and respiratory depression; less frequent constipation and vomiting |
Created by:
David wiid
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