Pharmacology of GI Drugs

Drugs and the Gastrointestinal Tract

• Drugs impact the gastrointestinal tract, affecting conditions like peptic ulceration, gastro-oesophageal reflux disease, diarrhoea, constipation & IBS and IBD.
• Learning resources include materials by James M. Ritter, Rod Flower, Graeme Henderson, Yoon Kong Loke, David MacEwan, Humphrey P. Rang, Bertram G. Katzung and Todd W. Vanderah.
• Key learning objectives include pharmacological management of various GI conditions, a list of main drug groups, descriptions of drug mechanism of action, identification of limitations of each drug.

Gastric Acid Secretion and Drug Targets

• Gastric acid secretion involves several cellular mechanisms with specific receptor targets.
• Different drugs such as histamine receptor antagonists, proton pump inhibitors, and antacids affect gastric acid secretion in different ways.

Proton Pump Inhibitors (PPIs)

• PPIs like Omeprazole and Esomeprazole irreversibly inhibit the H+/K+ ATPase (proton pump).
• Accumulation of the drug in the parietal cell is key to this mechanism.
• PPIs inhibit basal and stimulated acid secretion, with effects lasting 2-3 days after a single dose.

Histamine H2 Receptor Antagonists

• Cimetidine and Ranitidine, available over-the-counter in lower doses, competitively inhibit histamine H2 receptors.
• These drugs reduce histamine, gastrin and ACh-stimulated acid secretions by 70%.

Antacids

• Magnesium and Aluminum salts neutralize acidity by removing H+ ions by binding to them.
• This leads to different reactions and side effects. Sodium bicarbonate produces CO2 and thus will cause bloating and alkalosis, Mg(OH)2 produces diarrhea, and Al(OH)3 has constipation as a side effect.

Helicobacter pylori Infection

• Recommended first-line therapy usually involves a Proton Pump Inhibitor (PPI) plus a combination of antibiotics like Clarithromycin and Amoxicillin or Metronidazole.

Constipation and Diarrhoea

• Purgatives, osmotic laxatives, and stimulant laxatives are used to treat constipation and diarrhea. Docusate sodium is an example of a fecal softener. Biscodyl and other stimulant laxatives are administered to stimulate intestinal motility and excretion.

Constipation: CIC-2 Activator

• Lubiprostone is a selective chloride channel activator that increases intestinal motility and softens stool.

Oral Rehydration Therapy

• Oral rehydration therapy involves co-transport of glucose and sodium in the small intestine to restore fluids and electrolytes.

Anti-diarrhoeal Agents

• Codeine and Loperamide are mu opiod agonists prescribed to manage diarrhea, but may cause respiratory depression in small children and paralytic ileus.

Liver Ascites

• Liver ascites is fluid buildup in the peritoneal cavity due to liver disease or sinusoidal portal hypertension. Treatment involves sodium restriction and diuretics, primarily spironolactone.

Irritable Bowel Syndrome (IBS)

• IBS is a functional gastrointestinal disorder affecting ~20% of the population worldwide. IBS has a biopsychosocial basis, and three main subtypes (constipation-predominant, diarrhea-predominant, and mixed/alternating).
• Diagnosis is established using criteria such as the Rome criteria and the Manning criteria.
• Treatment approaches include fiber supplements, laxatives, anti-diarrhoeal medicines and a low-FODMAP diet.

Inflammatory Bowel Disease (IBD)

• IBD (including Ulcerative Colitis (UC), and Crohn's disease), can be understood as stemming from an inappropriate and continuing inflammatory response to microbes.
• Dysfunction of the epithelial barrier, innate immune cells, and adaptive T cells contribute to it. Differences in affected areas and presentation distinguish the two subtypes.
• Key symptoms for UC includes: Crampy abdominal pain, diarrhoea, urgency, tenesmus, weight loss, fever, and anaemia.
• Characteristics of Crohn's disease include: Crampy abdominal pain, diarrhoea, weight loss, fever, anaemia, obstruction, distension, vomiting and abscesses.
• Treatment management for IBD often involves several approaches such as medications (5-ASA, corticosteroids, mercaptopurine, ciclosporine, biologics) and surgery.

Explore the impact of various drugs on the gastrointestinal tract and their roles in managing conditions such as peptic ulcers and IBS. This quiz covers drug mechanisms, targets for gastric acid secretion, and key pharmacological treatments including proton pump inhibitors. Understand the limitations and pathways of these pharmacological agents in GI management.