Opioids: Pain Management & Treatment PDF

OPIOIDS PAIN  Pain is an unpleasant sensation (acute or chronic); and is a consequence of complex neurochemical processes in the peripheral and central nervous system.  Alleviation of pain depends on the specific type of pain (nociceptive, neuropathic, or central pain).  PAIN  For nocicepti...

OPIOIDS PAIN  Pain is an unpleasant sensation (acute or chronic); and is a consequence of complex neurochemical processes in the peripheral and central nervous system.  Alleviation of pain depends on the specific type of pain (nociceptive, neuropathic, or central pain).  PAIN  For nociceptive pain (mild to moderate arthritic pain), nonopioid analgesics such as nonsteroidal anti- inflammatory drugs (NSAIDs) are often effective.  For neuropathic pain responds best to anticonvulsants, tricyclic antidepressants (TCAs), or serotonin/norepinephrine reuptake inhibitors (SNRIs).  For severe acute pain or chronic malignant or nonmalignant pain, opioids can be considered as part of the treatment plan in select patients.  OPIOID All opioids act by binding to specific opioid receptors in the CNS to produce effects that mimic the action of endogenous peptide neurotransmitters (as endorphins, enkephalins, and dynorphins). Although the opioids have a broad range of effects, their primary use is to relieve intense pain, whether that pain results from surgery, injury, or chronic disease. The widespread availability of opioids has led to abuse of those agents with euphoric properties. Antagonists that reverse the actions of opioids are also clinically important for use in cases of overdose. OPIOID RECEPTORS The major effects of the opioids are mediated by three receptor families, which are commonly designated as: I. µ (mu) receptors, (the analgesic properties of the opioids are primarily mediated by the μ receptors that modulate responses to thermal, mechanical, and chemical nociception). II. κ (kappa) receptors, (in the dorsal horn of the spinal cords also contribute to analgesia by modulating the response to chemical and thermal nociception). III. δ (delta) receptors, (the enkephalins interact more selectively with δ receptors in the periphery).  OPIOID RECEPTORS All three opioid receptors are G protein–coupled receptor, Receptor stimulation inhibit adenylyl cyclase, leading to:  increase postsynaptic K+ efflux (hyperpolarization)  reducing presynaptic Ca2+ influx, leads to impeding neuronal firing and transmitter release. Chemical Classes of Opioid Agonists MORPHINE Morphine acts mainly at µ receptors with very high affinity. Acts also at κ receptors in the spinal cord. Inhibits the release of many excitatory transmitters from nerve terminals. MORPHINE Actions  Analgesia : (relief of pain without the loss of consciousness) by raising the pain threshold at the spinal cord level, and by altering the brain’s perception of pain.  Euphoria.  Respiratory depression: most common cause of death in opioid overdoses.  Depression of cough reflex (antitussive).  Miosis(pinpoint pupil) important for the diagnosis of morphine overdose. MORPHINE Actions  Emesis  GIT effects: antidiarrheal, cause constipation.  Increase intracranial pressure (because of CO2 retention).  Histamine release: causing urticarial / bronchoconstriction.  Hormonal actions: release GH / prolactin / ADH (antidiuretic hormone lead to urinary retention). MORPHINE Therapeutic uses: 1) Analgesia. 2) Treatment of diarrhea. 3) Relief of cough. 4) Treatment of acute pulmonary edema. MORPHINE Therapeutic uses: 1) Analgesia: it is very potent analgesic, used for moderate to severe pain , used as pre-anesthetic medication and for postoperative analgesic. 2) Treatment of diarrhea 3) Relief of cough 4) Treatment of acute pulmonary edema MORPHINE Therapeutic uses: 1) Analgesia 2) Treatment of diarrhea: cause constipation by decrease the motility and increase the tone of the intestinal circular smooth muscles and increase water reuptake. 3) Relief of cough 4) Treatment of acute pulmonary edema MORPHINE Therapeutic uses: 1) Analgesia 2) Treatment of diarrhea 3) Relief of cough: Codeine has greater antitussive action than morphine 4) Treatment of acute pulmonary edema MORPHINE Therapeutic uses: 1) Analgesia 2) Treatment of diarrhea 3) Relief of cough 4) Treatment of acute pulmonary edema: intravenous morphine dramatically relieves dyspnea caused by pulmonary edema associated with left ventricular failure, possibly via the vasodilatory effect. This, in effect, decreases cardiac preload and afterload, as well as anxiety of the patient. MORPHINE Pharmacokinetics:  Morphine has a significant first-pass metabolism in the liver.  Itis conjugated to Morphine-6-glucuronide , and morphine- 3-glucuronide.  Morphine-6-glucuronide is a very potent analgesic.  Morphine-3-glucuronide cause neuroexcitatory effects.  The conjugates are excreted primarily in urine.  Elderly, Neonates, and pregnant should avoid it. MORPHINE Adverse effects And Contraindications  Severe respiratory depression (result in death from acute opioid poisoning). And caution with resp. disorders  Nausea.  Constipation (OIC (opioid-induced constipation) as a result of the lack of fluid in the intestine leads to hardening of stool and decrease the motility and increase the tone of the intestinal circular smooth muscles. Morphine also increases the tone of the anal sphincter.).  Dysphoria (anxiety, depression, or unease).  Histamine-enhanced hypotension. MORPHINE Adverse effects And Contraindications  Potential for addiction.  Sedation.  Acute urinary retention (C/I with BPH (Benign prostatic- hyperplasia)).  Caution with bronchial asthma, liver failure, or impaired renal function. Tolerance And Physical Dependence:  Physical and psychological dependence readily occur with morphine with repeated use.  No tolerance develop to pupil-constricting and constipating effects.  Withdrawal produces a series of autonomic, motor, and psychological responses that can cause serious symptoms. Drug interactions The depressant actions of morphine are enhanced by coadministration with CNS depressant medications such as : Phenothiazines. Monoamine oxidase inhibitors (MAOIs), and Tricyclic antidepressant. MEPERIDINE (Pethidine) It is a synthetic opioid. Actions: Meperidine * increase the cardiac rate. * dilate the pupils (anticholinergic) Therapeutic uses: Analgesia (not for long-term use due to its active metabolite, normeperidine, which has significant neurotoxic properties). Meperidine :Adverse Effects  Anxiety, tremors, muscle twitches, and, convulsions (with large or repetitive doses because of cumulative normeperidine).  Dry mouth and blurred vision (anticholinergic action). Severe reactions (hyperthermia and convulsions) with patients taking MAOIs or dextromethorphan. Avoid in geriatric patients (impaired renal function/ accumulation of normeperidine).  Methadone It is a synthetic, orally effective opioid that has variable equi- analgesic potency compared to that of morphine, It induces less euphoria and has a longer duration of action. Mechanism of action: It causes:  Agonism to µ receptors.  Antagonist of the N-methyl-D-aspartate (NMDA) receptor- useful in the treatment of neurogenic pain.  Inhibit norepinephrine and serotonin reuptake. Methadone :Therapeutic uses Analgesic in nociceptive pain. Analgesic in neurogenic pain. Control withdrawal of dependent abusers from heroin and morphine (Oral methadone is administered as a substitute for the opioid of abuse, and the patient is then slowly weaned from methadone. The withdrawal syndrome with methadone is milder but more protracted (days to weeks) than that with other opioids). Fentanyl It is chemically related to meperidine. 100-folds the analgesic potency of morphine. Highly lipophilic and has a rapid onset and short duration of action (15–30 minutes). It is combined with local anesthetics to provide epidural analgesia for labor and postoperative pain. Eliminated through the urine. It causes pupillary constriction. Codeine It is a weak analgesic compared to morphine.  It should be used only for mild to moderate pain. The analgesic actions of codeine are derived from its conversion to morphine by the CYP450 enzyme system (demethylation). It is commonly used in combination with acetaminophen for management of pain. Codeine exhibits good antitussive activity at doses that do not cause analgesia. It has a lower potential for abuse (less potent analgesics). MIXED AGONIST-ANTAGONISTS AND PARTIAL AGONISTS Drugs that stimulate one receptor but block another. Their effects depend on previous exposure to opioids.  In individuals who have not received opioids (naïve patients), they show agonist activity and used to relive pain.  In the patient with opioid dependence, they may show primarily blocking effects (produce withdrawal symptoms). Like Pentazocine, Buprenorphine, and Nalbuphine. Buprenorphine Partial agonist, acting at the µ receptor. Acts like morphine in naïve patients, but precipitate withdrawal in morphine users.  A major use is in opiate detoxification (because it has shorter and less severe withdrawal symptoms compared to methadone. It causes little sedation, respiratory depression, or hypotension, even at high doses).  Other analgesics Tramadol Centrally acting analgesic that binds to the µ-opioid receptor. Metabolized via cytochrome P450 , leading to an active metabolite with higher affinity for µ receptor. It weakly inhibits reuptake of norepinephrine and serotonin. It is used to manage moderate pain. Its respiratory-depressant activity is less than that of morphine. Overdose or drug–drug interactions with medications, such as SSRIs, MAOIs, and tricyclic antidepressants, can lead to Naloxone Opioid antagonist Has a very high affinity to opioid receptors but fails to activate them. Used to reverse the coma and respiratory depression of opioid overdose. Half-life of 30 to 81 minutes Produces no pharmacologic effects in normal individuals, but it precipitates withdrawal symptoms in opioid abusers. Naltrexone Similar action to Naloxone but has a longer duration of action. Also beneficial in treating chronic alcoholism by an unknown mechanism.  Can lead to hepatotoxicity. THANK YOU