Tiêu đề 24. ANALGESIC AND ANTI-INFLAMMATORY AGENTS.pdf ✅

PHARMD GURU Page 1 ANALGESICS: Analgesics are drugs that relieve pain without significantly altering consciousness. They relieve pain without affecting its cause. OPIOID ANALGESICS: Morphine is the most important alkaloid of opium – the dried juice obtained from the capsules of Papaver somniferum. Opium contains many other alkaloids, e.g. codeine, thebaine, papaverine, etc. The term ‘opiates’ refers to drugs derived from opium poppy, whereas ‘opioid analgesic’ applies to any substance (endogenous peptides or drugs), which produces morphine-like analgesia. CLASSIFICATION OF OPIOIDS: 1. Opioid agonists: (a) Natural opium alkaloids: Morphine, codeine, thebaine,* papaverine,* noscapine.* (b)Semisynthetic opiates: Heroin, pholcodine,* hydromorphone, oxymorphone. (c) Synthetic opioids: Pethidine, tramadol, tapentadol, methadone, dextropropoxyphene, fentanyl, alfentanil, sufentanil, remifentanil. 2. Opioid agonist–antagonists: Pentazocine, butorphanol, nalorphine, nalbuphine. 3. Partial μ-receptor agonist and κ-receptor antagonist: Buprenorphine. Note: *Have no analgesic activity. ANALGESIC AND ANTI-INFLAMMATORY AGENTS
PHARMD GURU Page 2 OPIOID RECEPTORS: The three main types of opioid receptors are μ (mu), κ (kappa) and δ (delta). These receptor-mediated effects are given below.  μ: Analgesia (spinal + supraspinal level), respiratory depression, dependence, sedation, euphoria, miosis, decrease in GI motility.  κ: Analgesia (spinal + supraspinal level), respiratory depression, dependence, dysphoria, psychotomimetic effect.  δ: Analgesia (spinal + supraspinal level), respiratory depression, proconvulsant action. 1)OPIOID AGONISTS: MORPHINE: MECHANISM OF ACTION: Morphine and other opioids produce their actions by interacting with various opioid receptors μ (mu), κ (kappa) and δ (delta). They are located at spinal, supraspinal (medulla, midbrain, limbic system and cortical areas) and peripheral nerves. Morphine is the prototype drug. PHARMACOLOGICAL ACTIONS OF MORPHINE: Morphine has mainly CNS-depressant effects but also has stimulant effects at certain sites in the CNS. 1. CNS: (a) The depressant effects: 1. Analgesic effect: Mediated mainly through μ-receptors at spinal and supraspinal sites (central action), it is the most important action of morphine. At the spinal level, it decreases release of excitatory neurotransmitters from primary pain afferents in substantia gelatinosa of dorsal horn. The excitability of neurons in dorsal horn is decreased. In the
PHARMD GURU Page 3 supraspinal level, it alters transmission of pain impulses. It is a very potent and efficacious analgesic. It causes sedation, drowsiness, euphoria, makes the person calm and raises the pain threshold. Perception of pain and reaction to it (fear, anxiety and apprehension) are altered by these drugs. Moderate doses of morphine relieve dull and continuous pain, whereas sharp, severe intermittent pain such as traumatic or visceral pain requires larger doses of morphine. Opioids also act peripherally to alter the sensitivity of small nerve endings in the skin to painful stimuli associated with tissue injury/inflammation. Therefore, morphine relieves ‘total pain’. 2. Euphoria (feeling of well-being): It is an important component of analgesic effect. Anxiety, fear, apprehension associated with painful illness or injury are reduced by opioids. 3. Sedation: Morphine, in therapeutic doses, causes drowsiness and decreases physical activity.
PHARMD GURU Page 4 4. Respiratory depression: It depresses respiration by a direct effect on the respiratory centre in the medulla; both rate and depth are reduced because it reduces sensitivity of respiratory centre to CO2. Respiratory depression is the commonest cause of death in acute opioid poisoning. 5. Cough suppression: It has a direct action on cough centre in the medulla. 6. Hypothermia: In high doses, morphine depresses temperature-regulating centre and produces hypothermia. (b) The stimulant effects: 1. Miosis: Morphine produces constriction of pupils due to stimulation of III cranial nerve nucleus. Some tolerance develops to this action. Pinpoint pupils are an important feature in acute morphine poisoning. Miosis is not seen on topical application of morphine to the eye. 2. Nausea and vomiting: It is due to direct stimulation of the CTZ in medulla. 5-HT3 antagonists are the drugs of choice to control opioidinduced nausea and vomiting. H1-blockers, such as cyclizine or prochlorperazine may also be used. 3. Vagal centre: It stimulates vagal centre in the medulla and can cause bradycardia. (c) Other effects: Physical and psychological dependence: Repeated use of opioids causes physical and psychological dependence. 2. CVS: Morphine produces vasodilatation and fall of BP