Pharmacotherapy of GIT Disorders - Antiemetics

Pharmacotherapy of GIT and Respiratory Disorders

• Course title: Pharmacotherapy of GIT and Respiratory Disorders
• Course code: RPB20403
• Instructor: Dr. Omar AH

Topic 1: Antiemetic Drugs

• Learning Outcomes:
  • Pathophysiology of vomiting
  • Receptor antagonists
  • Antipsychotic drugs
  • Metoclopramide & domperidone
  • Cannabinoids
  • Steroids & neurokinin antagonists

Definitions

• Nausea: The immediate need to vomit, associated with gastric stasis
• Retching: Making the sound and movement of vomiting before vomiting
• Vomiting: Forceful expulsion of gastric contents
• Peristalsis: Wave-like muscle contractions that move food through the digestive tract

Antiemetics

• Used to treat nausea and vomiting
• Uncontrolled vomiting can cause dehydration, electrolyte imbalance, and aspiration pneumonia

Etiology (Causes of Vomiting)

• Gastrointestinal (GI) Disorders:
  • Gastroenteritis (viral, bacterial, or parasitic infections of the GI tract)
  • Food poisoning (ingestion of contaminated food or water)
  • Indigestion (overeating, excessive alcohol consumption, oily or spicy food)
  • Peptic ulcers (erosions in stomach or small intestine lining)
  • Gastritis (inflammation of stomach lining)
  • Gastroparesis (delayed emptying of stomach)
  • Intestinal obstruction (blockage of intestines)
  • Appendicitis (inflammation of appendix)
  • GERD (gastroesophageal reflux disease)
• Other Conditions:
  • Motion sickness (disturbances of the middle ear)
  • Pregnancy (hormonal changes and increased pressure on the stomach)
  • Migraines (severe headaches)
  • Medications (side effects)
  • Neurological disorders (brain injuries, tumors, or infections)
  • Emotional distress (anxiety, stress, depression, sleep deprivation)
  • Toxic exposure (ingestion of poisons or toxins, or radiation exposure)
  • Metabolic disorders (liver or kidney disease)
  • Cancer
  • Surgery and pain

Vomiting Symptoms

• Sweating: Cold sweats
• Salivation: Increased production of saliva
• Dizziness: Feeling of lightheadedness or faintness
• Pale skin: Loss of color in the skin
• Headache: Pain in the head
• Abdominal cramps: Stomach pain
• Weakness: Fatigue or lack of energy
• Loss of appetite: Reduced interest in eating
• Dehydration: Fluid loss due to vomiting and diarrhea
• Weight loss: Decreased body weight due to inability to keep food down
• Tachycardia: Increased heart rate

Vomiting Treatment Strategies

• Pharmacological: Over-the-counter or prescription medications to stop vomiting
• Non-pharmacological:
  • Hydration: Drink fluids (water, clear broth, or sports drinks)
  • Bland diet: Consume bland foods (toast, crackers, applesauce) avoiding spicy, greasy, or acidic foods
  • Rest, relaxation and fresh air

Prevention of Vomiting

• Avoid foods and drinks that trigger vomiting
• Eat small, frequent meals (avoid overeating)
• Eat a balanced diet with plenty of fruits, vegetables, and whole grains
• Stay hydrated
• Get enough rest and sleep, and fresh air
• Avoid alcohol and caffeine
• Take medications for motion sickness when traveling
• Practice good food hygiene to prevent food poisoning
• Manage stress using relaxation techniques

Pathophysiology

• Vomiting is a protective reflex in response to toxins, irritants, or stimuli affecting the CTZ or the vomiting center
• The Vomiting center receives stimulatory signals from 4 pathways:
  • Chemoreceptor trigger zone (CTZ)
  • Vagal afferent neuron from GI system (Serotonin and Neurokinin receptors)
  • Central vestibular nuclei (inner ear)
  • Higher centers of the brain

Drugs associated with a high incidence of nausea & vomiting

(List of drugs and their associated symptoms)

The Vomiting Cascade

• Vomiting center stimulation
• Relaxation of the lower esophageal sphincter
• Contraction of diaphragm and abdominal muscles
• Increased intra-abdominal pressure
• Closed epiglottis
• Vomiting occurs

Receptor antagonist concept

• Drugs selectively bind to receptors in the vomiting center of the brainstem
• Block signaling pathways
• Inhibit stimulation of the GI tract, diaphragm, and abdominal muscles

Classes of Antiemetic drugs

(List of drug classes and associated examples)

Anticholinergics (Muscarinic receptor antagonist)

• Examples: Hyoscine, Scopolamine, Dicyclomine
• Mechanism: Act on muscarinic receptors in the visceral afferent pathways from the gut and labyrinth to the vomiting center
• Use: Motion sickness prophylaxis, not for chemotherapy.
• Side effects: Dry mouth, blurry vision, drowsiness

Histamine-1 (H1) receptor antagonists

• Examples: Promethazine, Meclizine, Cyclizine, Diphenhydramine, Dimenhydrinate.
• Use: Motion sickness, morning sickness, pregnancy nausea
• Side effects: Drowsiness, sedation, constipation, CNS depression, Headache, Dry mouth, urinary retention, blurry vision

Dopamine antagonists (D2-RA).

• Examples: Chlorpromazine, Haloperidol, Domperidone, Metoclopramide

• Use: Chemotherapy, radiation vomiting.

• Side effects: Sedation, hypotension, extra pyramidal effects, restlessness.

Serotonin (5-HT3) antagonists

• Examples: Ondansetron (Zofran), Granisetron, Palonosetron, Dolasetron.
• Use: Chemotherapy-induced vomiting, Post-operative vomiting
• Side effects: Headache, dizziness, GIT upset, constipation

Neurokinin 1 (NK1) receptor antagonists

• Examples: Aprepitant, fosaprepitant.
• Use: Chemotherapy-induced vomiting

Corticosteroids

• Examples: Dexamethasone, Methylprednisolone
• Use: acute emesis, often combined with other antiemetics
• Side effects: Hyperglycemia, hypertension, cataract, osteoporosis, increased Intraocular pressure

Adjuvant drugs (Prokinetics)

• Use: Enhance coordinated GIT propulsive motility, helping relieve nausea and vomiting.
• Examples: Metoclopramide, Domperidone

Benzodiazepines & barbituates

• Use: Reduce anticipatory vomiting related to anxiety

Summary of therapeutic choices (for motion sickness, morning sickness, chemotherapy)

• Provides specific drug options in each context noting the need to avoid certain drugs in early stages of pregnancy

Chemotherapy-induced vomiting

• Drugs: D2 receptor antagonists (Metoclopramide, Domperidone), 5HT3 receptor antagonists (Ondansetron), Adjunctive treatments (e.g. Benzodiazepines, Corticosteroids, Cannabinoids).
• Other induced vomiting: Cytotoxic drugs, GI disorders, radiation
• Postoperative vomiting
  • Drugs: Scopolamine, Metoclopramide, Domperidone, Prochlorperazine