GIT 2

Question 1

What are the main learning objectives of GIT Pharmacology II?

Answer 1

At the end of this lecture, students should be able to:
1. Understand the basic and clinical pharmacology of drugs used in the treatment of:
- Nausea and Vomiting
- Diarrhoea
- Constipation
- Irritable Bowel Syndrome (IBS)
- Variceal Hemorrhage
- Gallstones
2. Provide safe, effective, and rational drug treatment for the above GI conditions.

Question 2

What is vomiting (emesis) and why is its suppression important?

Answer 2

Vomiting is a protective mechanism leading to expulsion of substances from the upper gastrointestinal tract. Suppression is important in:
- Chemotherapy
- Morning sickness of pregnancy
- Motion sickness
- Migraine
- Cardiac Ischemia
- Postoperative nausea and vomiting/General Anesthesia.

Question 3

List the common etiologies of nausea and vomiting.

Answer 3

Common causes include:
- GI infections
- Blood-borne molecules (toxins, peptides, drugs)
- Motion sickness/Morning sickness
- Labyrinthitis (vertigo)
- Chemotherapy/Radiotherapy
- Emergence from general anesthesia
- Migraine
- Acute pain
- Sensory and psychological stimulation.

Question 4

Name the 8 major classes of drugs used to treat nausea and vomiting.

Answer 4

1. Muscarinic receptor antagonists
2. Serotonin 5-HT3 receptor antagonists
3. H1 receptor antihistamines
4. Dopamine D2 receptor antagonists
5. Corticosteroids
6. Benzodiazepines
7. Neurokinin-1 (NK1) receptor antagonists
8. Cannabinoids

Question 5

Describe the mechanism of action of muscarinic receptor antagonists in treating nausea/vomiting.

Answer 5

MOA: They inhibit cholinergic stimulation of the vomiting center (VC) by impulses from the vestibular apparatus.
Example: Hyoscine (Scopolamine) - drug of choice for motion sickness.
Route: Transdermal patch is better tolerated due to severe anticholinergic side effects.
Side effects: Dizziness, dry mouth, sedation, confusion, urinary retention, cycloplegia, constipation.

Question 6

What are serotonin 5-HT3 receptor antagonists and their clinical use?

Answer 6

Examples: Ondansetron, Granisetron, Dolasetron, Palonosetron.
MOA: Central blockade of 5-HT3 receptors in the vomiting center (VC) and chemoreceptor trigger zone (CTZ), plus peripheral blockade on intestinal vagal and spinal afferent nerves.
Indication: Drug of choice for emesis mediated via vagal stimulation (postoperative and chemotherapy-induced vomiting).
Side effects: Constipation, dizziness, headache.

Question 7

How do H1 receptor antihistamines work against nausea/vomiting?

Answer 7

MOA: Central blockade of H1 histamine and M1 muscarinic receptors.
Examples: Promethazine, Cyclizine, Meclizine, Cinnarizine, Diphenhydramine.
Indications: Vomiting due to pregnancy, motion sickness, Meniere’s disease (Cinnarizine has additional anti-vertigo effect by inhibiting Ca2+ influx into vestibular sensory cells).
Side effects: Dizziness, dry mouth, sedation, confusion, urinary retention, cycloplegia.

Question 8

Explain the dual action of dopamine D2 receptor antagonists in GI pharmacology.

Answer 8

Examples: Metoclopramide, Domperidone (Cisapride is also mentioned but is a different class).
MOA:
1. Prokinetic effects: Increase esophageal peristaltic amplitude, increase LES pressure/tone, relax pyloric antrum and duodenal cap, enhance gastric emptying.
2. Antiemetic: Block D2 receptors in the CTZ.
No effect on small intestine and colonic motility.
Metoclopramide causes EPSEs (extrapyramidal side effects). Domperidone has fewer CNS side effects as it doesn’t readily cross BBB.

Question 9

What are the clinical uses of dopamine D2 receptor antagonists?

Answer 9

Uses:
- Nausea & vomiting (especially migraine-related)
- GERD (gastroesophageal reflux disease)
- Gastroparesis
- Non-ulcer dyspepsia
- Initiation of postpartum lactation
- Hiccup
Note: Prokinetics increase absorption of many drugs (aspirin, diazepam, sumatriptans).

Question 10

Describe the role of corticosteroids in nausea/vomiting management.

Answer 10

Examples: Dexamethasone, Methylprednisolone.
MOA: Exact antiemetic mechanism unknown, but they enhance efficacy of 5-HT3-receptor antagonists.
Use: Prevention of acute and delayed N&V in patients receiving emetogenic chemotherapy.
Typical regimen: Dexamethasone 8–20 mg IV before chemotherapy, followed by 8 mg OD orally for 2–5 days.

Question 11

What are NK1 receptor antagonists and how are they used?

Answer 11

Examples: Aprepitant (oral), Fosaprepitant (IV, converts to Aprepitant), Netupitant, Rolapitant.
MOA: Central blockade of NK1 receptors in the area postrema.
Pharmacokinetics: Aprepitant oral BA 65%, t½ 12h. Netupitant and Rolapitant have longer half-lives (90h, 180h) allowing single-dose administration. All metabolized by CYP3A4.
Combination therapy: NK1 antagonist + 5-HT3 antagonist + Dexamethasone prevents acute emesis in 80–90% of patients.

Question 12

How are benzodiazepines and cannabinoids used in nausea/vomiting?

Answer 12

Benzodiazepines (Lorazepam, Diazepam): Used before chemotherapy to reduce anticipatory vomiting or vomiting caused by anxiety.
Cannabinoids (Dronabinol/THC, Nabilone): Psychoactive agents used as appetite stimulants and antiemetics, but mechanism unclear. Now uncommonly used due to more effective agents available. Dronabinol undergoes significant first-pass metabolism.

Question 13

Summarize the choice of antiemetic drugs based on indication.

Answer 13

• General use/motion sickness: Muscarinic antagonists, H1 antihistamines, D2 antagonists
• Morning sickness of pregnancy: Promethazine (H1 antihistamine)
• Postoperative N&V/unresponsive cases: 5-HT3 antagonists
• Chemotherapy-induced N&V: Corticosteroids + 5-HT3 antagonists, or add Nabilone/Aprepitant

Question 14

Define diarrhea and state the first priority of therapy.

Answer 14

Diarrhea: Passage of 3 or more loose/liquid stools per day, or more frequent liquid passage than normal.
First priority: Preserve fluid and electrolyte balance.
Normal physiology: 7-8L secreted into GIT daily, 2-3L dietary fluid absorbed. Diarrhea results from imbalance between secretion and reabsorption of water.

Question 15

What are the four main mechanisms of diarrhea?

Answer 15

1. Osmotic Diarrhea
2. Secretory Diarrhea
3. Infectious Diarrhea
4. Drug-induced Diarrhea

Question 16

List common causes of acute diarrhea.

Answer 16

• Infectious agents: Enterotoxigenic E. coli, Vibrio cholerae, Campylobacter, Shigella, Salmonella
• Ingestion of toxins in contaminated food/drinks
• Medications: Broad-spectrum antibiotics, Metoclopramide, Quinidine, Clindamycin, etc.
• Rotavirus (common in children under five)

Question 17

Outline the general approach to drug treatment of diarrhea.

Answer 17

1. Treat underlying cause
2. Replace fluid & electrolyte imbalance (ORS & IVF)
3. Antidiarrheal drugs (symptomatic)
4. Antibacterial drugs (if evidence of infection)
5. Maintenance of adequate nutrition
6. Zinc therapy in children
   Key: Dehydration is most common cause of death. Mainstay is correction of dehydration, shock, and acidosis.

Question 18

Describe Oral Rehydration Therapy (ORT) and ORS composition.

Answer 18

ORT: Cornerstone of diarrhea management, advantageous for mild (5-7%) and moderate (7-10%) fluid loss.
WHO ORS composition per liter of water:
• Sodium chloride - 3.5 g
• Potassium chloride - 1.5 g
• Sodium citrate - 2.9 g
• Glucose - 20 g
IV rehydration recommended when fluid loss >10% of body weight.

Question 19

Explain the mechanism and use of antimotility drugs for diarrhea.

Answer 19

Examples: Loperamide (Imodium), Diphenoxylate (Lomotil).
MOA: Opioid agonists that do not cross BBB. Stimulate mu- and delta-receptors in intestines:
• Mu-receptor activation decreases peristalsis
• Delta-receptor activation contributes to antisecretory effects
Also increase anal sphincter tone and reduce central awareness for defecation.
Loperamide is 40-50x more potent than morphine as anti-motility drug, poor CNS penetration, t½ 11h.

Question 20

What is the dosing regimen and precautions for Loperamide?

Answer 20

Dosing: 4 mg initially, then 2 mg after each subsequent stool. Maximum 16 mg/day.
Precautions:
• Overdose may cause CNS depression (especially in children) and paralytic ileus
• Not recommended for infectious diarrhea without antibiotics (may prolong infection)
• Avoid in severe ulcerative colitis, pseudomembranous colitis

Question 21

List specific antibiotic therapies for different infectious diarrheas.

Answer 21

• Cholera: Tetracycline (TCN), Cotrimoxazole
• Salmonella infections (Typhoid fever): Ciprofloxacin, Ceftriaxone, Cotrimoxazole
• Shigellosis: Cotrimoxazole, Metronidazole, TCN, Chloramphenicol
• Amoebiasis/Giardiasis: Metronidazole
• Traveler’s diarrhea: Cotrimoxazole, Ciprofloxacin
• Rotavirus diarrhea: Self-limiting; ORT, IVF, Zinc, Vitamin A

Question 22

Describe Clostridium difficile diarrhea (CDD) and its treatment.

Answer 22

CDD: Ranges from offensive diarrhea to life-threatening pseudomembranous colitis.
Risk factors: Older age, recent antibiotic use, recent hospitalization (within 3 months), significant comorbidities.
Common causative antibiotics: Clindamycin, quinolones, cephalosporins, other β-lactams.
Treatment:
• Mild-moderate: Metronidazole PO for 7–14 days
• Severe/refractory/relapsed: Vancomycin (4-week tapering course)

Question 23

What is the role of zinc therapy in diarrhea?

Answer 23

Zinc supplementation:
• Reduces duration and severity of acute diarrhea
• Prevents subsequent episodes
WHO recommendation: All under-five children with acute diarrhea should receive:
• 20 mg/day for 10-14 days (≥6 months)
• 10 mg/day for infants <6 months
Reduces overall mortality from acute diarrhea by up to 50%.

Question 24

Describe Octreotide: mechanism and clinical uses.

Answer 24

Octreotide: Synthetic octapeptide similar to somatostatin.
MOA: Inhibits secretion of multiple hormones/transmitters (gastrin, CCK, glucagon, GH, insulin, secretin, VIP, 5-HT). Reduces intestinal fluid secretion, pancreatic secretion, slows GI motility, inhibits gallbladder contraction, reduces portal/splanchnic blood flow, inhibits some anterior pituitary hormones.
Clinical uses:
• Gastrointestinal neuroendocrine tumors (carcinoid, VIPoma) – reduces secretory diarrhea and systemic symptoms
• Pancreatic fistula
• Variceal hemorrhage (reduces portal blood flow)

Question 25

Define constipation and list its diagnostic criteria.

Answer 25

Constipation: Infrequent, hard-to-pass bowel motions. Formal criteria (≥2 present over 12 weeks): 1. Less than 3 stools per week 2. Straining (>25% of time) 3. Passage of hard stools 4. Incomplete evacuation 5. Sensation of anorectal blockage

Question 26

What are common causes of constipation?

Answer 26

• Lack of dietary fibre • Poor hydration • Lack of exercise • Certain drugs: Opioids, anticholinergics, muscle relaxants • Functional/mechanical intestinal obstruction

Question 27

Classify laxatives with examples.

Answer 27

1. Stool bulking agents: Dietary fibre (soluble: pectins, guar, ispaghula; insoluble: cellulose, hemicelluloses, lignin) 2. Osmotic laxatives: Lactulose 3. Stimulant laxatives: Bisacodyl, castor oil, senna, cascara, glycerol suppository 4. Faecal softeners/Emollients: Docusate sodium 5. Lubricants: Liquid paraffin

Question 28

Explain how dietary fibre works as a stool bulking agent.

Answer 28

Dietary fibre: Non-starch polysaccharides not digested by human enzymes. MOA: Increases volume and lowers viscosity of intestinal contents, producing soft bulky stool that encourages normal reflex bowel activity. Types: Soluble (pectins, guar, ispaghula) and insoluble (cellulose, hemicelluloses, lignin).

Question 29

Describe stimulant laxatives: mechanism and precautions.

Answer 29

Examples: Bisacodyl, senna, cascara, castor oil, glycerol suppository. MOA: Stimulate sensory nerve endings in colon, increase intestinal motility, reduce water/electrolyte reabsorption. Onset: Oral 6–10 hrs, suppository 1 hr. Indications: Radiological/surgical procedures. Disadvantages: Abdominal cramps, fluid/electrolyte imbalance, stimulates gravid uterus (contraindicated in pregnancy), contraindicated in children and intestinal obstruction.

Question 30

What is lactulose and how does it work?

Answer 30

Lactulose: Synthetic disaccharide osmotic laxative. MOA: Not digested/absorbed; acts as osmotic laxative by increasing bulkiness and reducing viscosity of intestinal contents. Additional benefit: Metabolized by colonic bacteria into lactic/acetic acids, which inhibit ammonia-producing organisms and reduce ammonia absorption (useful in hepatic encephalopathy). Tolerance may develop with prolonged use.

Question 31

Describe faecal softeners and lubricants.

Answer 31

Faecal softeners (Emollients): e.g., Docusate sodium. MOA: Lowers surface tension of bowel fluids, allowing faeces to retain more water. Useful for anal fissure and hemorrhoids. Lubricants: e.g., Liquid paraffin. MOA: Coats stool and intestinal walls, promoting easy passage. Useful where straining is avoided (hemorrhoids). Disadvantages: Not palatable, impairs fat-soluble vitamin absorption, perianal leakage.

Question 32

What are the risks of excessive laxative use?

Answer 32

• Severe water and electrolyte depletion • Hypokalemic paralysis • Renal failure (especially in elderly, diabetics, those with pre-existing renal impairment) • Long-term use: Decreased bowel tone, tolerance, dependency Management: Encourage high-fiber diet, increased fluid intake.

Question 33

List contraindications for laxative use.

Answer 33

• Undiagnosed abdominal pain • Inflammatory bowel disease • Intestinal obstruction • Hardened faeces in rectum (enema preferred)

Question 34

What is the choice of laxative based on desired stool consistency and onset?

Answer 34

• Soft formed stool (1-3 days): Bulk agents, softeners, lubricants • Semi-liquid stool (6-8 hrs): Bisacodyl (stimulant) • Watery stool (24-48 hrs): Lactulose (osmotic)

Question 35

Describe Ursodiol (ursodeoxycholic acid) for gallstone treatment.

Answer 35

Ursodiol: Naturally occurring bile acid. MOA: 1. Decreases cholesterol content of bile by lowering hepatic cholesterol secretion 2. Stabilizes hepatocyte canalicular membranes (reduces endogenous bile acid concentration/inhibits immune-mediated destruction) Pharmacokinetics: Absorbed, conjugated in liver, excreted in bile, extensive enterohepatic recirculation (t½ 100h). After long-term use, constitutes 30–50% of circulating bile acid pool.

Question 36

What are the clinical uses and dosing of Ursodiol?

Answer 36

Uses: 1. Dissolution of small cholesterol gallstones (<5-10 mm, non-calcified) in symptomatic patients unfit for surgery: 10 mg/kg/day orally for 12–24 months (up to 50% dissolution) 2. First-line drug for early primary biliary cirrhosis (PBC) 3. Prevention of gallstones in obese patients undergoing rapid weight loss Side effects: Well tolerated, no serious adverse effects.

Question 37

Explain the pathophysiology of portal hypertension and variceal hemorrhage.

Answer 37

Portal hypertension: Commonly due to chronic liver disease. Causes: 1. Increased splanchnic blood flow (due to low arteriolar resistance from increased vasodilators/decreased vascular sensitivity to vasoconstrictors) 2. Increased intrahepatic vascular resistance (due to fibrosis in spaces of Disse/hepatic veins + reversible vasoconstriction of sinusoids/venules) Result: Increased pressure in portal venous system leads to variceal formation and risk of hemorrhage.

Question 38

How does Octreotide help in variceal hemorrhage?

Answer 38

Octreotide in variceal hemorrhage: • Dose: 50 mcg/h IV • MOA: Reduces portal blood flow and variceal pressures (mechanism poorly understood; may involve inhibition of glucagon/other gut peptides altering mesenteric blood flow) • Efficacy: Probably effective in promoting initial hemostasis from bleeding esophageal varices • Duration: Administered for 3–5 days

Question 39

Describe the use of beta-blockers in variceal hemorrhage prophylaxis.

Answer 39

Drugs: Propranolol or Nadolol (nonselective β-blockers). MOA: • β1-antagonism: Reduces cardiac output • β2-antagonism: Induces splanchnic vasoconstriction (allowing unopposed α-adrenergic vasoconstriction) Use: Primary or secondary prophylaxis against variceal hemorrhage. Significantly reduce rate of recurrent bleeding in cirrhosis with portal hypertension. Note: Propranolol has extensive first-pass metabolism; systemic availability variable in cirrhosis.

Question 40

Name other drugs mentioned for variceal hemorrhage treatment.

Answer 40

• Vasopressin • Terlipressin (Details not expanded in slides, but these are vasoconstrictors that reduce portal pressure by causing splanchnic vasoconstriction.)

Question 41

Create a clinical scenario: A 45-year-old female on chemotherapy presents with severe nausea/vomiting. What antiemetic regimen would you choose?

Answer 41

For chemotherapy-induced N&V (emetogenic chemotherapy): • First-line: Combination therapy with Dexamethasone + 5-HT3 receptor antagonist (e.g., Ondansetron) • For enhanced prevention/add if inadequate: Add NK1 receptor antagonist (e.g., Aprepitant) • For anticipatory vomiting/anxiety: Add Benzodiazepine (e.g., Lorazepam) before chemotherapy • Alternative: Consider Cannabinoid (Nabilone) if others fail or for appetite stimulation.

Question 42

Create a clinical scenario: A 3-year-old child presents with acute watery diarrhea and mild dehydration. Outline management.

Answer 42

Management: 1. Assess dehydration severity (mild 5-7%) – ORT with WHO ORS 2. Zinc supplementation: 10 mg/day for 10-14 days (if <6 months) or 20 mg/day (if ≥6 months) 3. Continue breastfeeding/normal diet 4. Avoid antimotility drugs (Loperamide) in young children (risk of CNS depression) 5. If signs of infection (blood/mucus in stool, fever): Consider specific antibiotics after stool culture 6. Monitor for worsening dehydration (>10% loss needs IV rehydration)

Question 43

Create a clinical scenario: A 60-year-old male with cirrhosis presents with hematemesis. Suspect variceal hemorrhage. What acute drug management would you initiate?

Answer 43

Acute management: 1. Resuscitation: IV fluids, blood transfusion as needed 2. Vasoactive drug: Octreotide IV infusion 50 mcg/h for 3–5 days to reduce portal pressure and promote hemostasis 3. Antibiotic prophylaxis: To prevent bacterial infections (spontaneous bacterial peritonitis) 4. Endoscopic therapy: Band ligation or sclerotherapy ASAP 5. Prophylaxis for rebleeding: Start nonselective β-blocker (Propranolol or Nadolol) once stable, or consider Terlipressin/Vasopressin if available and indicated.

Question 44

Create a clinical scenario: A 50-year-old obese woman with symptomatic gallstones is not a surgical candidate. What pharmacological option exists?

Answer 44

Pharmacological option: Ursodiol (ursodeoxycholic acid). • Criteria: Small (<5-10 mm), non-calcified cholesterol gallstones • Dose: 10 mg/kg/day orally • Duration: 12–24 months • Success rate: Up to 50% dissolution • Monitoring: Regular ultrasound to assess stone dissolution • Additional: Advise weight loss management, low-fat diet

Question 45

Create a clinical scenario: A patient with opioid-induced constipation. What laxative strategy would you recommend?

Answer 45

For opioid-induced constipation: 1. First-line: Stimulant laxative (e.g., Bisacodyl) + stool softener (e.g., Docusate sodium) 2. Alternative: Osmotic laxative (Lactulose) if stimulants not tolerated 3. Prophylaxis: Start laxatives concurrently with opioids in chronic use 4. Non-pharmacological: Increase dietary fiber, fluid intake, physical activity 5. Avoid: Bulk-forming agents if poor fluid intake (risk of obstruction)

Question 46

Summarize the key differences between Loperamide and Diphenoxylate.

Answer 46

Loperamide: • More potent (40-50x morphine as anti-motility) • Poor CNS penetration, no abuse liability • Longer t½ (11 hrs) • OTC availability in many countries Diphenoxylate: • Often combined with Atropine (Lomotil) to discourage abuse • More central effects possible • Prescription usually required Both: Mu/delta opioid agonists, increase transit time, anal tone, antisecretory.

Question 47

What is the significance of the combination product Netupitant/Palonosetron?

Answer 47

Netupitant (300 mg) + Palonosetron (0.5 mg) combination: • Netupitant: NK1 receptor antagonist with long half-life (90h) • Palonosetron: 5-HT3 receptor antagonist with long half-life (40h) • Advantage: Single-dose administration for prevention of chemotherapy-induced N&V, especially delayed nausea • Simplified regimen, improves adherence

Question 48

How does Cinnarizine differ from other H1 antihistamines for vertigo?

Answer 48

Cinnarizine: • Additional mechanism: Inhibits Ca2+ influx from endolymph into vestibular sensory cells • Use: Specifically effective for vertigo (Meniere's disease, motion sickness) • Belongs to piperazine class of antihistamines • Also has vasodilatory effects (used in peripheral vascular disease)

Question 49

Explain the concept of "anticipatory vomiting" and its management.

Answer 49

Anticipatory vomiting: Nausea/vomiting that occurs before chemotherapy administration, triggered by anxiety/conditioning from previous cycles. Management: • Benzodiazepines: Lorazepam/Diazepam before chemotherapy to reduce anxiety • Behavioral techniques: Relaxation, desensitization • Optimal control of acute/delayed N&V in previous cycles to prevent conditioning

Question 50

Why is Metoclopramide contraindicated in intestinal obstruction?

Answer 50

Metoclopramide increases GI motility and tone. In intestinal obstruction: • Could exacerbate pain • Risk of perforation or worsening obstruction • Contraindicated in mechanical obstruction, GI hemorrhage, perforation • Use with caution in Parkinson's disease (can worsen symptoms due to D2 antagonism)

Question 51

What is the role of Vitamin A in rotavirus diarrhea?

Answer 51

Vitamin A supplementation: • Reduces severity and duration of diarrhea in children with vitamin A deficiency • Enhances immune function and mucosal integrity • WHO recommends in areas with vitamin A deficiency (along with ORT, zinc) • Dose: 200,000 IU for children >12 months, lower doses for infants

Question 52

Describe the "enterohepatic recirculation" of Ursodiol.

Answer 52

Enterohepatic recirculation of Ursodiol: 1. Oral absorption 2. Liver conjugation with glycine 3. Biliary excretion 4. Intestinal reabsorption (conjugated/unconjugated) 5. Small amount passes to colon: excreted or dehydroxylated to lithocholic acid (hepatotoxic) t½: 100 hours due to this recirculation.

Question 53

What is the difference between soluble and insoluble fibre?

Answer 53

Soluble fibre (pectins, guar, ispaghula): • Dissolves in water to form gel • Slows gastric emptying, may help lower cholesterol • Fermentable by colonic bacteria (prebiotic effect) Insoluble fibre (cellulose, hemicelluloses, lignin): • Does not dissolve in water • Adds bulk to stool, accelerates colonic transit • Less fermentable

Question 54

Why are bulk-forming laxatives contraindicated in intestinal obstruction?

Answer 54

Bulk-forming laxatives increase stool volume. In obstruction: • Could worsen blockage • Risk of impaction • May cause distension and pain • Ensure adequate fluid intake when using to prevent esophageal/bowel obstruction.

Question 55

How does Octreotide benefit pancreatic fistula?

Answer 55

Octreotide in pancreatic fistula: • Inhibits pancreatic exocrine secretion (reduces output from fistula) • Promotes fistula closure • Used as adjunct to NPO (nil per os), nutritional support, drainage • Dose: 100-200 mcg SC TID or IV infusion

Question 56

What is the "area postrema" and its role in vomiting?

Answer 56

Area postrema: • Located in the medulla oblongata, outside blood-brain barrier • Contains chemoreceptor trigger zone (CTZ) • Detects emetic toxins/drugs in blood and CSF • Rich in dopamine D2, serotonin 5-HT3, neurokinin NK1 receptors • Sends signals to vomiting center to initiate vomiting reflex.

Question 57

Explain the pathophysiology of chemotherapy-induced nausea/vomiting.

Answer 57

Chemotherapy-induced N&V involves multiple pathways: • Acute (within 24h): Mainly 5-HT release from enterochromaffin cells → vagal afferents → CTZ/VC • Delayed (24h-5 days): Involves substance P/NK1 receptors, corticosteroids help • Anticipatory (before chemo): Conditioned response, anxiety-mediated • Breakthrough/Refractory: Despite prophylaxis, needs rescue antiemetics.

Question 58

What is "dumping syndrome" and how is Octreotide used?

Answer 58

Dumping syndrome: Rapid gastric emptying post-gastrectomy, causing osmotic diarrhea, vasomotor symptoms. Octreotide use: • Inhibits insulin/other hormone release • Slows GI motility, transit • Reduces postprandial hypotension, diarrhea • Dose: 50-100 mcg SC before meals.

Question 59

Why is Lactulose used in hepatic encephalopathy?

Answer 59

Lactulose in hepatic encephalopathy: • Metabolized to lactic/acetic acids by colonic bacteria • Lowers colonic pH • Traps ammonia as ammonium ions (reduces absorption) • Acts as osmotic laxative to expel ammonia • Dosing titrated to produce 2-3 soft stools/day.

Question 60

What is the difference between primary and secondary prophylaxis for variceal hemorrhage?

Answer 60

Primary prophylaxis: Preventing first bleed in patients with varices but no prior hemorrhage. Use nonselective β-blockers or endoscopic variceal ligation. Secondary prophylaxis: Preventing rebleed after initial variceal hemorrhage. Use combination of β-blockers + endoscopic therapy ± Octreotide/Terlipressin acutely.

Question 61

How does Domperidone differ from Metoclopramide in side effect profile?

Answer 61

Domperidone vs Metoclopramide: • Domperidone does not cross BBB readily → fewer CNS side effects (no EPSEs, less drowsiness) • Metoclopramide crosses BBB → can cause EPSEs (dystonia, parkinsonism), restlessness, NMS • Both are D2 antagonists, prokinetic • Domperidone may increase QT interval (cardiac monitoring)

Question 62

What is "Osmotic diarrhea" and examples?

Answer 62

Osmotic diarrhea: Non-absorbable solutes in gut lumen draw water into intestine. Examples: • Lactose intolerance (lactose malabsorption) • Magnesium-containing antacids/laxatives • Sorbitol/mannitol (sugar alcohols) • Characteristic: Stops with fasting, stool osmotic gap >50 mOsm/kg.

Question 63

Describe "Secretory diarrhea" and common causes.

Answer 63

Secretory diarrhea: Increased intestinal secretion of water/electrolytes, continues despite fasting. Causes: • Bacterial enterotoxins (Vibrio cholerae, E. coli) • Hormone-secreting tumors (VIPoma, carcinoid) • Bile acid malabsorption • Laxative abuse (stimulant type) • Characteristic: Large volume, watery, persists fasting.

Question 64

What is "Traveler's diarrhea" and empiric treatment?

Answer 64

Traveler's diarrhea: Acute infectious diarrhea during/after travel, usually bacterial (ETEC, Campylobacter, Shigella). Empiric treatment: • Antibiotics: Ciprofloxacin 500 mg BID x 1-3 days or Azithromycin 500 mg OD x 1-3 days • Antimotility: Loperamide for symptom control (avoid if febrile/dysentery) • ORS for hydration • Prevention: Food/water precautions.

Question 65

How does Castor oil work as a stimulant laxative?

Answer 65

Castor oil: • Contains ricinoleic acid (hydrolyzed in small intestine) • MOA: Stimulates intestinal secretion and peristalsis via prostaglandin release and epithelial cell damage • Onset: 2-6 hours • Use: Pre-procedure bowel cleansing (largely replaced by PEG solutions) • Side effects: Cramping, electrolyte imbalance, malabsorption.

Question 66

What is "Pseudomembranous colitis" and hallmark feature?

Answer 66

Pseudomembranous colitis: Severe form of C. difficile infection. Hallmark: Yellow-white plaques (pseudomembranes) on colonic mucosa seen on endoscopy. Symptoms: Watery diarrhea, abdominal pain, fever, leukocytosis. Treatment: Oral Vancomycin or Fidaxomicin, IV Metronidazole if severe.

Question 67

Explain the "Rome IV criteria" for constipation.

Answer 67

Rome IV criteria for functional constipation (≥2 for ≥3 months): 1. Straining ≥25% of defecations 2. Lumpy/hard stools ≥25% 3. Sensation of incomplete evacuation ≥25% 4. Sensation of anorectal obstruction/blockage ≥25% 5. Manual maneuvers to facilitate defecations 6. <3 spontaneous bowel movements per week (Note: Slides used older 12-week criteria; Rome IV is standard.)

Question 68

What is "Irritable Bowel Syndrome (IBS)" and why is it not detailed in slides?

Answer 68

IBS: Functional GI disorder with abdominal pain and altered bowel habits (diarrhea-predominant IBS-D, constipation-predominant IBS-C, mixed). Not detailed in slides likely due to focus on specific drug classes. Treatment includes: • IBS-C: Fiber, laxatives, lubiprostone, linaclotide • IBS-D: Antispasmodics, loperamide, rifaximin, antidepressants • General: Diet (low FODMAP), stress management.

Question 69

Create a summary table: Anti-emetic classes and key indications.

Answer 69

Class | Examples | Key Indications --- | --- | --- Muscarinic antagonists | Hyoscine | Motion sickness 5-HT3 antagonists | Ondansetron | Post-op, chemo-induced N&V H1 antihistamines | Promethazine | Pregnancy, motion sickness D2 antagonists | Metoclopramide | Migraine, gastroparesis Corticosteroids | Dexamethasone | Chemo-induced (with 5-HT3) NK1 antagonists | Aprepitant | Chemo-induced (add-on) Benzodiazepines | Lorazepam | Anticipatory vomiting Cannabinoids | Dronabinol | Appetite/chemo N&V (last-line)

Question 70

Create a summary table: Laxative classes and onset.

Answer 70

Class | Examples | Onset | Notes --- | --- | --- | --- Bulking agents | Psyllium | 1-3 days | Need adequate water Osmotic | Lactulose | 24-48 hrs | Also for hepatic encephalopathy Stimulant | Bisacodyl | 6-10 hrs (oral) | Avoid in pregnancy Softener | Docusate | 1-3 days | For hemorrhoids/fissures Lubricant | Mineral oil | 6-8 hrs | Risk of lipid pneumonia if aspirated

Question 71

Create a summary table: Drugs for variceal hemorrhage.

Answer 71

Drug | Class | Use | Notes --- | --- | --- | --- Octreotide | Somatostatin analog | Acute bleed | IV 50 mcg/h x 3-5d Propranolol | Nonselective β-blocker | Prophylaxis | Reduces rebleeding risk Terlipressin | Vasopressin analog | Acute bleed | Vasoconstriction, limited availability Vasopressin | Vasoconstrictor | Acute bleed | More side effects (ischemia)

Question 72

Create a clinical scenario: A patient with carcinoid syndrome diarrhea. Which drug would be specific?

Answer 72

Carcinoid syndrome: Secretory diarrhea from neuroendocrine tumor (serotonin excess). Specific drug: Octreotide (somatostatin analog). MOA: Inhibits serotonin and other hormone secretion, reduces diarrhea and flushing. Dose: 100-200 mcg SC TID or depot monthly injection. Also consider: Telotristat (serotonin synthesis inhibitor) for inadequately controlled symptoms.