Opioid Analgesics PDF

Opioid Analgesics This presentation will explore the world of opioid analgesics, exploring their classification, mechanisms of action, and pharmacological effects. We will examine the different types of opioids, their uses, and their potential risks and benefits.  Understanding Pain and Opio...

Opioid Analgesics This presentation will explore the world of opioid analgesics, exploring their classification, mechanisms of action, and pharmacological effects. We will examine the different types of opioids, their uses, and their potential risks and benefits.  Understanding Pain and Opioids Pain is a complex sensation arising from the peripheral and central nervous systems. Opioid analgesics are pain relievers derived from morphine or morphine-like compounds. These drugs effectively relieve all forms of pain but can induce tolerance, addiction, dependence, and CNS depression. Pain Perception Opioid Action Pain is subjective and relies on the patient's Opioids bind to specific receptors in the CNS, description. Clinicians must consider individual mimicking the action of endogenous experiences and perceptions. neurotransmitters like endorphin, enkephalins, and dynorphins)..  Classification of Opioids Opioids are classified based on their chemical structure and origin. This classification helps understand their potency, duration of action, and potential side effects. Natural Opioids Semisynthetic Opiates Morphine Diacetylmorphine (Heroin) Codeine Pholcodeine Synthetic Opioids Pethidine (Meperidine) Fentanyl Pentazocine Loperamide Tramadol Diphenoxylate Methadone  Opioid Agonists and Antagonists Opioid agonists bind to receptors and produce effects similar to endogenous opioids. Antagonists block the effects of agonists, reversing opioid overdose. Agonists Antagonists Strong: Meperidine, Morphine, Heroin, Naloxone Fentanyl, Methadone, Pethidine Narlorphine Partial: Buprenorphine, Meptazine, Naltrexone Pentazocine, Tramadol, Malbuphine Nalmefene Moderate: Propoxyphene, Codeine, Loperamide, Diphenoxylate Morphine: The Prototype Opioid Agonist Morphine is a major analgesic drug found in opium and serves as the prototype opioid agonist. Its pharmacological actions are similar to other opioids, with minor variations. Morphine acts on μ, κ, σ, and δ opioid receptors, primarily targeting the μ receptor. It exerts its effects by: 1 2 Enhanced Inhibitory Systems Decreased Neuronal Excitability Inhibits neurotransmitter release from Modulates GABA and glycine nerve terminals carrying pain signals. neurotransmitter activity. 3 Modulated Pain Perception Raises the threshold of neurons transmitting pain signals.  Pharmacological Actions of Morphine: CNS Effects Morphine exerts both stimulant and depressant effects on the central nervous system. Depressant Actions Antidiuretic Hormone Release: Stimulates the Analgesia: Relieves pain by raising the pain hypothalamus, leading to decreased urine output. threshold and altering pain perception. Euphoria: Produces a sense of contentment and well- Sedation: Drowsiness and clouding of mentation being, reducing fear and panic responses to pain. occur, especially at high doses. Stimulant Actions Respiratory Depression: Reduces responsiveness of Miosis: Constriction of the pupils, a the respiratory center to carbon dioxide, leading to characteristic of morphine use. decreased breathing. Emesis: Stimulates the chemoreceptor trigger Cough Suppression: Depresses the cough center zone, causing nausea and vomiting. in the medulla oblongata.  Pharmacological Actions of Morphine: Other Effects Morphine's effects extend beyond the CNS, influencing various bodily systems. GI Tract Cardiovascular Relieves diarrhea, increases Minimal effects on blood pressure intestinal tone, and causes and heart rate at low doses, but constipation. hypotension and bradycardia may occur at higher doses. Skin Hormonal Releases histamine, causing urticaria, sweating, and Prolonged use may lead to opioid- vasodilation. induced androgen deficiency.  Morphine's Effects on the Uterus Morphine can prolong the second stage of labor by transiently decreasing the strength, duration, and frequency of uterine contractions. The mechanism of this action is not fully understood. Morphine crosses the placenta and can lead to neonatal asphyxia. Therefore, its use during labor should be carefully considered and monitored. 1 Decreased Contractions 2 Prolonged Labor 3 Neonatal Asphyxia  Clinical Considerations for Opioid Use Opioids are powerful medications with significant potential benefits and risks. Their use requires careful consideration and monitoring. 1 Pain Management 2 Tolerance and Dependence Opioids are effective for managing acute Tolerance develops with repeated use, and chronic pain, but alternative requiring higher doses for the same effect. therapies should be explored when Dependence can lead to withdrawal possible. symptoms upon cessation. 3 Addiction 4 Overdose Opioid addiction is a complex disease Opioid overdose is a medical characterized by compulsive drug emergency that can be fatal. Naloxone seeking and use, despite negative is an antidote that can reverse the consequences. effects of opioid overdose. Pharmacokinetics of Opioids Absorption Metabolism Excretion Most opioids are absorbed from Metabolized in the liver by Excreted mainly in the urine. oral and parenteral routes. conjugation.  Therapeutic Uses of Opioids Analgesia 2 Diarrhea 3 Cough Suppression 1 Loperamide and Codeine and pholcodeine Relief of pain in trauma, diphenoxylate are used for suppress cough at lower post-operative, and cancer. diarrhea. doses than those needed for analgesia. 4 Pain Relief in Terminal Diseases 5 Anesthesia Opioids are used as pre-anesthetic medication Opioids provide pain relief for patients with to relieve pain and anxiety prior to general terminal diseases. anesthesia.  Contraindications of Opioids Impaired Hepatic and Renal Functions Head Injury Opioids are contraindicated in patients with Opioids are contraindicated in patients with impaired hepatic and renal functions. head injuries. Bronchial Asthma Hypotension Opioids are contraindicated in patients with Opioids are contraindicated in patients with bronchial asthma. hypotension. Emphysema During Delivery/Labor Opioids are contraindicated in patients with Opioids are contraindicated during delivery and labor. emphysema.  Side Effects of Opioids Respiratory Depression Nausea and Vomiting Opioids can cause respiratory Opioids can cause nausea and depression. vomiting. Tolerance and Addiction Constipation Opioids can lead to tolerance Opioids can cause constipation. and addiction.  Codeine  A naturally occurring opioid and a weak analgesic compared to morphine.  It is used for mild to moderate pain.  The analgesic actions of codeine are derived from its conversion to morphine by the CYP2D6 enzyme.  Codeine is commonly used in combination with acetaminophen for management of pain. The drug exhibits good antitussive activity at doses that do not cause analgesia.  Dextromethorphan is a synthetic cough depressant that has relatively no analgesic action and much lower potential for abuse in usual antitussive doses. It is preferred over codeine in most situations where cough suppression is needed.  TRAMADOL Tramadol is a centrally acting analgesic that binds to the μ opioid receptor. It undergoes extensive metabolism via CYP2D6, leading to an active metabolite, which has a much higher affinity for the mu receptor than the parent compound. It weakly inhibits reuptake of norepinephrine and serotonin. It is used to manage moderate to severe pain. Tramadol has less respiratory-depressant activity compared to morphine. Tramadol should be used with caution in patients with a history of seizures. As with other agents that bind the μ opioid receptor. Tramadol has been associated with misuse and abuse.  MEPERIDINE  A lower-potency synthetic opioid structurally unrelated to morphine.  It is used for acute pain and acts primarily as a κ agonist, with some μ agonist activity.  Meperidine is very lipophilic and has anticholinergic effects, resulting in an increased incidence of delirium compared with other opioids.  Meperidine has an active metabolite (normeperidine), which is potentially neurotoxic. Normeperidine is renally excreted, and in patients with renal insufficiency, accumulation of the metabolite may lead to delirium, hyperreflexia, myoclonus, and seizures.  Due to the short duration of action and the potential for toxicity, meperidine should only be used for short-term management of pain.  Meperidine should not be used in elderly patients or those with renal insufficiency, hepatic insufficiency, preexisting respiratory compromise, or concomitant or recent administration of MAOIs.  Fentanyl: A Potent Synthetic Opioid 1 Analgesic Potency Fentanyl is 100 times more potent than morphine. 2 Routes of Administration Administered IV, epidurally, or intrathecally. 3 Clinical Uses Used for anesthesia, acute pain management, and chronic severe pain. 4 Metabolism Metabolized by CYP3A4, and inhibitors of this enzyme can potentiate fentanyl's effects.  Opioid Antagonists: Reversing Overdose The opioid antagonists bind with high affinity to opioid receptors, but they fail to activate the receptor-mediated response. Administration of opioid antagonists produces no profound effects in individuals not taking opioids. In opioid-dependent patients, antagonists rapidly reverse the effect of agonists, such as morphine or any full μ agonist, and precipitate the symptoms of opioid withdrawal. Naloxone Is a competitive antagonist at μ, κ, and δ receptors, with a 10-fold higher affinity for mu than for kappa receptors. It rapidly displaces all receptor-bound opioid molecules and, therefore, can reverse the effects of morphine overdose, such as respiratory depression and coma within 1 to 2 minutes of IV administration. Naloxone can also be administered intramuscularly, subcutaneously, and intranasally, with a slightly longer onset of 2 to 5 minutes, however, little to no clinical effect is seen with oral naloxone due to extensive first-pass metabolism. Naloxone has a half-life of 30 to 81 minutes.  Opioid Antagonists: Reversing Overdose NALTREXONE Naltrexone has actions similar to those of naloxone, but it has a longer duration of action and can be given orally. A single oral dose of blocks the effect of injected heroin for up to 24 hours, Naltrexone has been reported to cause hepatotoxicity and monitoring of hepatic function is recommended.