Opioid Analgesics PDF

# Opioid Analgesics ## Opioids - **Opiates:** Narcotic alkaloids derived from opium poppy or semi-synthetic derivatives with narcotic properties. Natural or not natural. - Representatives: Morphine, Opium, and Heroin - **Opioids:** Fully synthetic or semi-synthetic narcotic alkaloids that mimi...

# Opioid Analgesics ## Opioids - **Opiates:** Narcotic alkaloids derived from opium poppy or semi-synthetic derivatives with narcotic properties. Natural or not natural. - Representatives: Morphine, Opium, and Heroin - **Opioids:** Fully synthetic or semi-synthetic narcotic alkaloids that mimic the natural opiate alkaloid. - Not found in nature. ## OPIODS - Opioid analgesics are one of the oldest remedies for relief pain. - Opium is the dark brown gummy exudate obtained from the poppy capsule *(*Papaver somniferum*).* - Opium has been in use since 4000BC. ## CLASSIFICATION **Based on receptor occupation:** - **Agonists** - **Natural opium alkaloids** - Morphine, Codeine - **Synthetic opioids** - Pethidine, Methadone - **Antagonists** - Naloxone, Naltrexone - **Mixed agonist antagonists** - Pendazocine, Nalpurine, Butorphanol, Buprenorphine, Nalorphine **Opioids can also be classified depending on their sources as:** - **Natural opium alkaloids** - Morphine, Codeine, Noscapine - **Semisynthetic derivative** - Heroin, Oxymorphone, Pholcodeine - **Synthetic opioids** - Pethidine, Methadone, Loperamide Fentanyl ## MORPHINE - Morphine is the most important alkaloid of opium. Many new opioids with actions similar to morphine have been synthesized. ## Mechanism of Action - Morphine and other opioids produce their effects by acting on specific opioid receptors: mu(µ), kappa(k), and delta(δ). These receptors are present in the CNS and other tissues. - Stimulation of opioid receptors finally results in a decrease in the intracellular calcium, which in turn, decreases the release of neurotransmitters. - **In CNS:** mu(µ), kappa(k), and delta(δ) receptors - Stimulation of opioid receptors (Morphine) - Decrease the intracellular calcium level - Decrease the release of neurotransmitter - It decreases the visceral pain ## Pharmacological Action - **Analgesia:** Morphine is a potent analgesic and relieves pain without loss of consciousness. In higher doses, it relieves severe pain as that of biliary colic. - **Euphoria, sedation, and hypnosis:** Rapid IV inj of morphine produces a warm flushing of the skin and an immensely pleasurable sensation in the lower abdomen about 45 seconds. It also produces drowsiness, a calming effect, inability to concentrate, and indifference to surroundings. - **Respiration:** Morphine produces respiratory depression. It directly depresses the respiratory center in the brain stem. Death from morphine poisoning is almost always due to respiratory arrest. - **Cough center:** It directly depresses the cough center and thereby suppresses cough. Opioids should be used as antitussive only in the dry cough. - **Nausea and emesis:** Morphine directly stimulates the CTZ in the medulla causing nausea and vomiting. In higher doses, it depresses the vomiting center and hence there is no vomiting in poisoning. - **Pupils:** Morphine produces miosis resulting in a characteristic pinpoint pupil in high doses. - **Vagus:** Morphine stimulates the vagal center causing bradycardia. - **Cardiovascular system:** In therapeutic doses, morphine produces hypotension by: - Direct peripheral vasodilatation - Inhibition of baroreceptor reflexes. - In higher doses, it causes depression of the vasomotor center and histamine release, both contributing to a fall in BP. - **GIT:** Opioids decrease the motility of the gut. - **Stomach:** Gastric motility is decreased resulting in increased gastric emptying time. Gastric acid secretion is reduced. - **Intestine:** Morphine diminishes all secretions, delays digestion. ## PHARMACOKINETICS - Given orally, absorption of morphine is slow and incomplete. - Morphine undergoes first pass metabolism. - Morphine is absorbed well orally, metabolized in the liver, and excreted by the kidney. ## ADVERSE EFFECTS - Nausea, Vomiting - Respiratory Depression - Dysphoria (State of being unhappy) - Dizziness - Hypotension - Skin Rashes ## TOLERANCE - Tolerance is defined as the capacity of the body to endure or become less responsive to a substance. - Lethal dose of Morphine is 250 mg, an addict can tolerate morphine in gm. ## DEPENDENCE - Its ability to produce euphoria makes it a drug of addiction. - Opioids produce both psychological and physical dependence. ## MANAGEMENT OF ADDICTION - Morphine slowly withdrawn over several days and substituted by oral Methadone. Later on, methadone is gradually withdrawn. - **Acute Morphine Poisoning:** Symptoms include respiratory depression with shallow breathing, pinpoint pupils, hypotension, shock, coma, and death. ## Acute Morphine Poisoning Treatment 1. Positive Pressure Respiration 2. Maintenance of BP 3. Gastric lavage with potassium permanganate to remove unabsorbed drug. 4. Specific antidote is Naloxone 0.4 to 0.8 mg IV, repeated every 10 to 15 minutes. ## OTHER OPIOIDS - **Heroin:** It is converted to morphine in the body. It has higher lipid solubility. It gives Euphoric effects faster and greater. It is used as analgesics and banned in most countries. - **Codeine:** It is commonly used antitussives. It is also available with Paracetamol for analgesia,. - **Dextromethorphan:** It acts centrally to elevate the threshold for coughing. It is effective as codeine. - **Tramadol:** It is an effective analgesic; it is a weak opioid agonist. - **Pethidine:** It produces corneal anesthesia. It has anticholinergic effects; it causes dry mouth and blurring of vision. Dose - 25 - 100 mg IM. SC. Used as analgesics in visceral pain. Given as pre-anesthetic medications. Adverse effects - It is similar to morphine. ## OPIOIDS ANTAGONISTS - **Naloxone:** It is a pure antagonist; does not produce any significant action. It antagonizes the morphine action, especially respiratory depression, sedation, and precipitates morphine withdrawal syndrome. Given orally, it undergoes first pass metabolism; hence it is given IV. Dose - 0.4 mg IV. Uses - Drug of choice for Morphine overdose. It can also be used for the diagnosis of opioid dependence. ## MIXED AGONIST & ANTAGONIST - Pentazocine is similar to morphine. - 20 mg pentazocine is equal to 10 mg morphine. - Sedation and respiratory depression are less marked. - Doses - 50-100 mg oral, 30-50 mg IM. - Uses - Used as opioid analgesics, especially in post-operative and chronic pain. - Adverse Effect - Sedation, Sweating, Anxiety, Hallucination. ## General Considerations - Respirations should be monitored closely while patients are in opioids. - Watch for signs of tolerance in patients while they are using this drug for prolonged periods. - An antidote must be kept readily available for use in case of emergency. ## Common Side Effects of Opioids - Nausea and vomiting - Constipation - Itching - Sleepiness - Slowed breathing - Impaired motor skills, thinking, or judgment