Pharmacology.

• Classification of opioids


  • Agonists
  • Partial agonists
  • Antagonists
• Agonists


  Interact with a receptor to produce maximal response
• Partial agonists


  Produce a partial functional response
• Antagonists


  Produce no functional response
• Pharmacokinetics of Opioids


  1. Absorption

  2. Distribution

  3. Metabolism

  4. Excretion
• Absorption


  • Opioids can be administered via various routes - Oral, Intravenous, intramuscular, transdermal
• Distribution


  • Once absorbed, Opioids circulate in the bloodstream, crossing cell membranes
  • Lipid soluble opioids can enter the brain easily
• Metabolism


  • Opioids are metabolized primarily in the liver by various enzymes (Cytochrome P450 System)
• Excretion


  • Metabolites and unchanged Opioids are excreted through the Kidneys in urine
• Pharmacodynamics of Opioids


  1. Mechanism of Action

  2. Receptor binding

  3. Physiological effects
• Mechanism of Action


  Opioids bind to Opioid receptors in the central and peripheral nervous system
• Receptor binding


  Opioids act as agonists by binding to the receptors, leading to downstream effects
• Physiological effects


  • Analgesia, sedation, respiratory depression, euphoria
• Opioids uses in pain management


  • Pain relief: reducing moderate to severe pain by binding to opioid receptors in the CNS
  • Quick onset action: rapid onset of action, fast relief
  • Potency: Opioids are the strongest/most effective analgesics available, effective in reducing severe pain
• Inappropriate use of opioids in pain management leads to Opioid misuse and addiction
• Genetic predisposition contributes to Opioid abuse
• Opioids and their Antagonists
• Four common medical conditions involving the gastrointestinal (GI) tract


  • Peptic ulcers
  • Gastroesophageal Reflux Disease (GERD)
  • Chemotherapy-Induced emesis
  • Diarrhea
  • Constipation
• Main causes of Peptic Ulcer Disease


  • H. Pylori
  • NSAIDs
  • Increased HCl secretion
• Treatment Approaches for Peptic Ulcer Disease


  1. Eradicating The H. Pylori

  2. Reducing HCl secretion

  3. Protect the gastric mucosa from damage (Misoprostol-Sucralfate)
• Antimicrobial Agents for Eradication of H. pylori


  • Triple Therapy: PPI +amoxicillin (Metronidazole in penicillin-allergic patients)+Clarithromycin
  • Quadruple Therapy: PPl+Bismuth Subsalicylate+ Metronidazole+ Tetracycline
• Factors regulating gastric acid secretion


  • Acetylcholine
  • Histamine
  • Gastrin
• CINV


  Chemotherapy-induced nausea and vomiting
• H2-Receptor Antagonists


  • Cimetidine
  • Ranitifine
  • Famotidine
  • Nizatidine
• CINV not only affects quality of life but can also lead to rejection of potentially curative chemotherapy
• Uncontrolled vomiting can produce dehydration, profound metabolic imbalances
• Proton Pump Inhibitors (PPIs)


  Bind to the H+/K+ase enzyme and suppress the secretion of hydrogen ions into the gastric lumen
• Emetic actions of chemotherapeutic agents


  • Chemotherapeutic agents can directly activate the Medullary Chemoreceptor Trigger Zone (CTZ) or Vomiting Center, Dopamine Receptor Type 2(DA2), and Serotonin Type 3 (5-HT3) play critical roles
  • The color or smell of chemotherapeutic drugs can activate higher brain centers and trigger emesis
  • Chemotherapeutic drugs can also act peripherally by causing cell damage in the GI tract and by releasing serotonin from the small intestine
• Available Proton Pump Inhibitors


  • Dexlansoprazole
  • Esomeprazole
  • Lansoprazole
  • Omeprazole
  • Pantoprazole
  • Rabeprazole
• Serotonin


  Activates 5-HT3 receptors leading to the emetic response
• Therapeutic uses of Proton Pump Inhibitors


  • Stress ulcer treatment
  • Prophylaxis
  • Erosive esophagitis
  • Active duodenal ulcer
• Antiemetic Drugs


  • Phenothiazines
  • 5-HT3 receptor blockers
  • Substituted benzamides
  • Butyrophenones
  • Benzodiazepines
  • Corticosteroids
• Antacids


  Weak bases that react with gastric acid to form water and salt, diminishing gastric acidity
• Phenothiazines


  • Blocks the dopamine receptors
  • Effective against low or moderately emetogenic chemotherapeutic agents (Fluorouacil-Doxorubicin)
• 1. HT3 receptor blockers


  • These agents selectively block 5-HT3 receptors in the periphery and the brain (CTZ)
  • Ondansetron
  • Granisetron
  • Administered as a single dose before chemotherapy (Intravenously or Orally)
• Antacid components


  • Aluminum hydroxide
  • Magnesium hydroxide
  • Calcium carbonate
  • Sodium bicarbonate
• Therapeutic uses of Antacids

  • Symptomatic relief of peptic ulcer disease and GERD
  • Promote healing of duodenal ulcers
• Substituted benzamides


  • Metoclopramide
  • Inhibits dopamine in the CTZ
  • Antidopaminergic side effects, including extrapyramidal symptoms, limit long-term high-dose use
• Butyrophenones


  • Act by blocking dopamine receptors
  • Droperidol
  • Haloperidol
• Sucralfate


  A complex of aluminium hydroxide and sulfated sucrose that binds to positively charged groups, creating a physical barrier