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Topic 8

Part of the FMGE study roadmap. Botany topic pharma-008 of Botany.

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Gastrointestinal and Endocrine Pharmacology

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Gastrointestinal and Endocrine Pharmacology — Key Facts for FMGE Core concept: Acid-suppressing drugs (PPIs, H2 blockers, antacids) work by different mechanisms; antidiabetic drugs include insulin and oral hypoglycemics High-yield point: PPIs (omeprazole) are most effective for GERD and peptic ulcers; metformin is first-line for type 2 diabetes ⚡ Exam tip: Remember the ABCDE of acid suppression: Antacids (quick relief), H2 blockers, Cytoprotectives (sucralfate, misoprostol), PPIs (most potent), Triple therapy (H. pylori eradication)

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Gastrointestinal and Endocrine Pharmacology — FMGE Study Guide

Antacids

  • Neutralize gastric acid (increase pH from 1-2 to 3-4)
  • Components: Aluminum hydroxide (constipating), magnesium hydroxide (diarrheal), calcium carbonate (can cause rebound acid secretion), sodium bicarbonate
  • Onset: Rapid (minutes); short duration
  • Interactions: Decrease absorption of other drugs (give 2 hours apart)
  • Uses: Dyspepsia, GERD (symptom relief), peptic ulcer (adjunct)

H2 Receptor Antagonists

  • Examples: Cimetidine, ranitidine, famotidine, nizatidine
  • Mechanism: Block H2 receptors on parietal cells → ↓acid secretion
  • Effect: Reduce daytime, meal-stimulated, and nocturnal acid secretion
  • Onset: 1-3 hours; duration 6-10 hours
  • Cimetidine: Inhibits CYP450 → many drug interactions; also has anti-androgen effects (gynecomastia)
  • Uses: GERD, peptic ulcer, prevention of stress ulcers

Proton Pump Inhibitors (PPIs)

  • Examples: Omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
  • Mechanism: Irreversibly inhibit H-K-ATPase (proton pump) on parietal cells
  • Effect: Most potent acid suppression; inhibit both basal and stimulated acid secretion
  • Onset: 1-3 days for full effect; duration 3-4 days after stopping
  • Administration: Take 30-60 minutes before first meal (before pumps activate)
  • Uses: GERD, peptic ulcer, H. pylori eradication, NSAID-induced ulcer prevention, Zollinger-Ellison syndrome
  • Side effects: Hypomagnesemia, B12 deficiency (long-term), C. difficile infection, increased fracture risk
  • Note: C. difficile risk is higher with any acid suppression, not just PPIs

Cytoprotective Agents

Sucralfate:

  • Aluminum hydroxide sulfated sucrose → forms protective barrier over ulcer base
  • Requires acidic environment to polymerize
  • Side effects: Constipation, bezoar formation (in patients with gastric outlet obstruction)

Misoprostol:

  • PGE1 analog → ↑mucus and bicarbonate secretion, ↓acid secretion
  • Uses: Prevention of NSAID-induced gastric ulcers (especially in high-risk patients on NSAIDs for chronic conditions)
  • Side effects: Diarrhea, abdominal cramps, contraindicated in pregnancy (abortifacient)

Bismuth compounds (Pepto-Bismol, colloidal bismuth subcitrate):

  • Coats ulcer base, stimulates prostaglandin synthesis
  • Also has antimicrobial effect against H. pylori
  • Side effects: Black stools, black tongue

H. pylori Eradication

Triple therapy (7-14 days):

  • PPI + Clarithromycin + Amoxicillin (or Metronidazole)
  • Or Bismuth + Metronidazole + Tetracycline + PPI (quadruple therapy for resistant cases)
  • Follow-up: Urea breath test or stool antigen test to confirm eradication

Anti-Emetics

  • 5-HT3 antagonists (ondansetron, granisetron): Post-operative, chemo-induced nausea
  • D2 antagonists (metoclopramide, prochlorperazine, promethazine): Gastric emptying, vestibular causes; side effects: EPS, hyperprolactinemia
  • H1 antagonists (meclizine, dimenhydrinate): Motion sickness
  • NK1 antagonists (aprepitant): Chemo-induced nausea
  • Corticosteroids (dexamethasone): Adjunct for chemo-induced nausea

Laxatives

Bulk-forming (psyllium, methylcellulose): Increase stool bulk; safe for chronic use Osmotic (lactulose, sorbitol, magnesium hydroxide, polyethylene glycol): Draw water into lumen; lactulose also for hepatic encephalopathy (↓ammonia) Stimulant (bisacodyl, senna): Direct colonic stimulation; cause cramping Surfactant/stool softener (docusate sodium): Soften stool; less effective

Antidiabetic Drugs

Insulin

Types:

  • Rapid-acting (insulin lispro, aspart, glulisine): Onset 5-15 min, peak 1-2h, duration 3-4h
  • Short-acting (regular insulin): Onset 30min, peak 2-4h, duration 6-8h
  • Intermediate-acting (NPH): Onset 1-2h, peak 4-8h, duration 12-18h
  • Long-acting (glargine, detemir, degludec): Minimal peak; basal coverage; onset 1-2h, duration 24+ hours

Side effects:

  • Hypoglycemia (most common and dangerous)
  • Hypokalemia (insulin drives K into cells)
  • Lipodystrophy at injection site (rotate injection sites)
  • Weight gain

Oral Hypoglycemics

Biguanides - Metformin (First-line for Type 2 DM):

  • Mechanism: Activates AMP-kinase → ↓hepatic gluconeogenesis, ↑insulin sensitivity, ↓intestinal glucose absorption
  • Effects: ↓fasting glucose, ↓HbA1c (1-1.5%), ↓weight, improves lipid profile
  • Side effects: Lactic acidosis (rare but serious - contraindicated in renal failure, liver disease, sepsis), GI upset, vitamin B12 deficiency
  • No hypoglycemia when used alone (does not stimulate insulin secretion)

Sulfonylureas (Glipizide, Glyburide, Glimepride):

  • Mechanism: Close ATP-sensitive K+ channels on pancreatic beta cells → depolarization → insulin release
  • Side effects: Hypoglycemia (especially long-acting: glyburide), weight gain
  • Note: Glyburide has highest hypoglycemia risk among sulfonylureas

Thiazolidinediones (TZDs) (Pioglitazone, Rosiglitazone):

  • Mechanism: PPARγ agonist → ↑insulin sensitivity, ↑adipocyte differentiation
  • Side effects: Weight gain, fluid retention (edema), heart failure exacerbation, hepatotoxicity (troglitazone withdrawn), bone fractures
  • Pioglitazone: May protect against atherosclerosis

SGLT2 Inhibitors (Dapagliflozin, Empagliflozin, Canagliflozin):

  • Mechanism: Block glucose reabsorption in proximal tubule → glycosuria
  • Effects: ↓HbA1c, ↓weight, ↓BP (mild diuresis)
  • Side effects: Genital yeast infections, UTIs, dehydration, euglycemic diabetic ketoacidosis
  • Cardiovascular benefit: Empagliflozin and dapagliflozin shown to reduce HF hospitalizations and CV death in diabetic patients (and now used for HF even without diabetes)

DPP-4 Inhibitors (Sitagliptin, Saxagliptin, Linagliptin):

  • Mechanism: Inhibit dipeptidyl peptidase-4 → ↑GLP-1 levels → ↑glucose-dependent insulin secretion, ↓glucagon
  • Effects: Modest HbA1c reduction (0.5-0.8%)
  • Side effects: Pancreatitis (debated), heart failure (saxagliptin - FDA warning)
  • Weight neutral

GLP-1 Agonists (Exenatide, Liraglutide, Semaglutide, Dulaglutide):

  • Mechanism: Stimulate GLP-1 receptor → ↑glucose-dependent insulin secretion, ↓glucagon, ↓gastric emptying, ↑satiety
  • Effects: ↓HbA1c, ↓weight (significant), ↓cardiovascular events (liraglutide, semaglutide)
  • Side effects: Nausea/vomiting, pancreatitis, thyroid C-cell tumors (in rodents - contraindicated with family history of medullary thyroid carcinoma)
  • Note: Semaglutide also available as oral formulation

Alpha-glucosidase inhibitors (Acarbose, Miglitol):

  • Mechanism: Inhibit brush border α-glucosidases → delay carbohydrate digestion → ↓postprandial glucose
  • Side effects: Flatulence, abdominal discomfort, diarrhea (bacterial fermentation of undigested carbs)

Thyroid and Antithyroid Drugs

Thyroid Hormones

Levothyroxine (T4):

  • Drug of choice for hypothyroidism
  • Half-life 7 days; take in morning on empty stomach
  • Start low in elderly/cardiac patients; titrate slowly
  • Monitor TSH (goal: normal TSH in younger, slightly higher in elderly)

Antithyroid Drugs

Thionamides:

  • Propylthiouracil (PTU): Blocks thyroid peroxidase and peripheral T4→T3 conversion; used in first trimester pregnancy, thyroid storm
  • Methimazole: Blocks thyroid peroxidase; most commonly used; teratogenic (associated with aplasia cutis in first trimester - use PTU instead in T1)
  • Side effects: Agranulocytosis (fever, sore throat - must check WBC), hepatotoxicity (PTU - severe), rash

Iodine (KI/Lugol’s solution):

  • Blocks thyroid hormone release and synthesis (Wolff-Chaikoff effect)
  • Used for thyroid storm, preoperative thyroidectomy preparation
  • Note: “Escape” from Wolff-Chaikoff after 10-14 days → continued synthesis

Radioactive iodine (I-131):

  • Ablative therapy for hyperthyroidism and thyroid cancer
  • Contraindicated in pregnancy

Beta-blockers (propranolol):

  • Symptomatic relief (↓HR, ↓tremor) + inhibit peripheral T4→T3 conversion
  • Used in thyroid storm while definitive therapy takes effect

Corticosteroids

Glucocorticoids (hydrocortisone, prednisone, dexamethasone):

  • Uses: Inflammation, autoimmune diseases, asthma, adrenal insufficiency, shock
  • Side effects (chronic use): Cushing syndrome (moon face, buffalo hump, striae), osteoporosis, immunosuppression, hyperglycemia, adrenal suppression, cataracts, glaucoma

Mineralocorticoids (fludrocortisone):

  • Used in adrenal insufficiency (addison’s disease) with glucocorticoids

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