analgesics

• Analgesics


  Drugs used to relieve pain due to multiple causes
• Classification of Analgesics


  • Non-Opioid analgesics (used in mild to moderate pain, e.g. NSAIDs, Paracetamol)
  • Opioid analgesics (used in moderate to severe pain, e.g. Morphine, Synthetic Opioids)
• NSAIDs


  • Induce anti-inflammatory, analgesic and antipyretic effects
• Paracetamol


  Analgesic-antipyretic with no anti-inflammatory action
• Paracetamol mechanism of action


  Inhibits PG synthesis in CNS resulting in analgesic and antipyretic effects
• Paracetamol has no anti-inflammatory effect
• Paracetamol is given orally (500-1000mg 3 times daily) and is metabolized in the liver
• COX enzymes


  • COX-1 is constitutive and responsible for forming protective PGs in GIT and Kidney, as well as preventing premature closure of ductus arteriosus
  • COX-2 is inducible and formed during inflammation
• Mechanism of action of NSAIDs


  1. Acetyl Salicylic acid (Aspirin) induces irreversible inhibition of both COX-1 and COX-2 enzymes

  2. Celecoxib and Rofecoxib are selective COX-2 inhibitors
• Indications of NSAIDs


  • Rheumatic fever
  • Rheumatoid arthritis
  • Fever
  • Dental pain
  • Headache
  • Dysmenorrhea and Postpartum pain
  • Antiplatelet (Aspirin)
• Low dose Aspirin use


  • Prophylaxis against Transient Ischemic Attacks, Myocardial infarction and Unstable Angina
  • Cerebrovascular accident
• Aspirin doses


  • Anti-platelet effect: 75 – 150mg/day
  • Analgesic and Antipyretic: 300 mg, 1-2 tablets when necessary
• Ibuprofen


  • Effective and better tolerated (decreases incidence of side effects)
  • First choice in inflammatory joint disease
• Naproxen


  • More potent than Ibuprofen with moderate risk of side effects
  • Longer acting, given twice daily
• Piroxicam


  • Potent and long acting, given once daily
  • No accumulation in the elderly or in patients with renal impairment
• Diclofenac


  • Very potent, used in long-term treatment of chronic inflammatory musculoskeletal disorders
  • An ophthalmic solution is used for post-operative inflammation
• Indomethacin


  • Potent, but due to its serious adverse effects, has limited use
  • CNS: Dizziness, confusion, ataxia, severe headache (cerebral vasodilatation)
  • Salt and water retention and hyperkalemia
  • Aplastic anemia
• Common side effects of NSAIDs (particularly in the elderly)


  • Dyspepsia
  • Nausea
  • Vomiting
  • Gastritis
  • Ulceration with risk of hemorrhage (due to direct irritant effect on the mucosa and decreased protective PGs)
• Other side effects of NSAIDs


  • Renal damage (Analgesic nephropathy): due to decreased renal vasodilator PGs
  • Hypersensitivity reactions: Skin rash, Rhinitis, exacerbates asthmatic attacks in asthmatics patients
  • Interferes with uric acid excretion (Aspirin)
  • Reye's syndrome (Aspirin)
  • Increased bleeding tendency: Anti-platelet effect
• Anti-coagulants with Aspirin


  Increases the risk of GI bleeding. Binds to albumin and displaces other bound drugs, thereby potentiates Warfarin anticoagulant effect
• NSAIDs


  Reduces the effect of anti-hypertensive drugs
• Selective COX-2 inhibitors (Celecoxib and Rofecoxib)


  • Spare COX-1, hence have less GIT side effects
  • Celecoxib is structurally related to Sulphonamides, therefore its use might be associated with development of skin rash
• Analgesics


  Medications that relieve pain
• Descriptions of Pain


  • Categories of Pain by Duration
  • Categories of Pain by Type
• Acute Pain


  • Brief duration, goes away with healing, usually 6 months or less
  • Not necessarily more severe than chronic
  • May be sudden onset or slow in onset
  • Examples are broken bones, strep throat, and pain after surgery or injury
• Chronic Cancer Pain


  • Longstanding pain that persists beyond the recovery period or occurs along with a chronic health condition
  • Examples are cancer, arthritis
• Somatic Pain


  • Source is skin, muscle, and connective tissue
  • Examples are sprains, headaches, arthritis
  • Description is localized, sharp/dull, worse with movement or touch
• Visceral Pain


  • Source is internal organs
  • Examples are tumor growth, gastritis, chest pain
  • Description is not localized, constant and dull, less affected with movement
• Neuropathic Pain


  • Source is nerves
  • Examples are diabetic neuropathy, phantom limb pain, cancer spread to nerve plexis
  • Description is burning, stabbing, pins and needles, shock-like, shooting
• Treatment of Pain


  1. Use the lowest effective dose by the simplest route

  2. Start with the simplest single agent and maximize it's potential before adding other drugs

  3. Use scheduled, long-acting pain medications for constant or frequent pain, with prn, short-acting medication available for breakthrough

  4. Breakthrough pain is a sudden increase in pain that may occur in patients with chronic pain
• Adjuvant Analgesic


  • A medication whose primary indication is the management of a medical condition with secondary effects of analgesia
  • Examples are anticonvulsants, antidepressants, antihistamines, stimulants
• Opioid analgesics


  Drugs that mimic the effect of Morphine
• Sources of Opioid analgesics


  • Plant: Morphine, Codeine (natural products of Opium poppy)
  • Synthetic: Fentanyl, Methadone, Pethidine, Heroin
  • Endogenous: Endorphins, Encephalins and Dynorphins (Opiopeptides) released in the body, acting on Opioid receptors and producing Morphine-like effects
• Opioid receptors


  1. protein coupled receptors present in CNS and periphery (e.g. GIT)
• Mechanism of action of Opioids


  1. Opioids activate the receptors directly or through the release of endogenous opiopeptides

  2. This results in neuronal inhibition through: Inhibition of calcium entry decreasing release of excitatory neurotransmitters e.g. Substance-P

  3. Stimulation of potassium outflux resulting in hyperpolarization of neuronal membrane
• Mu receptors


  • Mediate most of the effects of opioids: Analgesia, Sedation, Euphoria, Dependence, Respiratory depression, inhibition of GIT motility
• Kappa receptors


  • Mediate spinal analgesia, sedation, and dysphoria
• Pharmacological actions of Opioids


  • Main effects: Analgesia, Sedation, Euphoria (sometimes dysphoria)
  • Inhibitory effects: Vasomotor centre, Respiratory depression, Inhibition of the cough centre, Inhibition of uterine muscle
  • Stimulatory effects: Stimulation of the oculomotor nucleus, Stimulation of CTZ, Increases smooth muscle tone but inhibit peristalsis, Stimulation of the release of ADH, Histamine release
• Tolerance develops to all effects except constipation and miosis
• Therapeutic uses of Opioids


  • Analgesics in: Acute pain (trauma), Chronic dull pain (visceral), Post-operative pain and Cancer pain, Anaesthesia (Morphine or Fentanyl)
  • Myocardial infarction and acute pulmonary edema (Morphine)
  • Antitussive (Codeine and Dextromethorphan)
  • Anti-diarrheal: Use Loperamide or Diphenoxylate because they are less addictive than Morphine