EBL W4 - Lower GI tract: Diarrhoea, constipation, and irritable bowel syndrome (IBS)

Question 1

types of laxatives

Answer 1

• bulk-forming
• stimulant
• osmotic
• stool softener

Question 2

Bulk forming laxative: examples, MOA, Key points

Answer 2

• Ispaghula husk (Fybogel), Methylcellulose
• Absorb water → swell → stimulate peristalsis
• Drink fluids; effect in 12–72 hrs; can cause bloating

Question 3

stimulant laxative: examples, MOA, Key points

Answer 3

• Senna, Bisacodyl
• Stimulate colonic nerves, ↑ motility - Short-term only; use at night; can cause cramps

Question 4

osmotic laxative: examples, MOA, Key points

Answer 4

• Lactulose, Polyethylene glycol (Macrogol), Magnesium hydroxide - Draw water into bowel
• Hydrate well; risk of bloating/diarrhoea

Question 5

stool softener laxatives: examples, MOA, Key points

Answer 5

• Docusate sodium, Glycerin, Liquid paraffin
• ↑ water/fat into stool
• Mild effect; not first-line; avoid long-term

Question 6

What’s senna

Answer 6

• plant-based treatment for constipation
• Licensed Herbal Medicine: Full MA, clinical trials, classified as GSL, P, or POM
• Traditional Herbal Remedy (THR): Based on 30+ years of traditional use; no clinical trial required

Question 7

Routes for herbal medicines to come to market

Answer 7

• Licensed Herbal Medicine: Full MA, clinical trials, classified as GSL, P, or POM
• Traditional Herbal Remedy (THR): Based on 30+ years of traditional use; no clinical trial required

Question 8

features of licensed herbal medicines

Answer 8

• Requires clinical trials
• Can claim “clinically proven”
• Stricter regulation

Question 9

features of traditional herbal remedies

Answer 9

• Based on traditional use
• Only “traditionally used”
• Easier market access

Question 10

role of starch in senna tablets

Answer 10

• Role: Disintegrant and binder
• Effect on Dissolution: Increases surface area → faster dissolution (per Noyes–Whitney equation)
  dm/dt =
• ↑ Surface Area (A): From tablet disintegration
• ↑ dm/dt: Faster drug release

Question 11

Loperamide – class, form mechanism

Answer 11

Class: Antimotility agent (µ-opioid agonist, peripheral only)

Form: Loperamide hydrochloride (2 mg capsule)

Mechanism: ↓ peristalsis, ↑ absorption of fluids/electrolytes

Question 12

loperamide: Lipinski’s rule

Answer 12

Violates (breaks) logP (>5), but generally bioavailable for gut-localised action

Question 13

loperamide: bioavailability factors

Answer 13

• Very low (~0.3%)
• Barriers:

CYP3A4, CYP2C8: Metabolise loperamide in liver/intestine
P-gp: Pumps loperamide out of enterocytes, prevents CNS entry

Therapeutic Benefit:
Low systemic absorption → acts locally in gut → avoids CNS opioid effects

Question 14

P-glycoprotein (ABCB1) Transporter: family, structure, function

Answer 14

Family: ABC transporter

Structure:

• 2 Transmembrane Domains (TMDs): Drug binding
• 2 Nucleotide Binding Domains (NBDs): ATP hydrolysis
• Extracellular loops + glycosylation: Stability, recognition

Function:

• Pumps drugs (e.g. loperamide) out of cells
• ↓ drug absorption, ↑ clearance

Question 15

NICE Guidelines (CG61): IBS Lifestyle Management

Answer 15

General Advice:

• Meals: Regular, no skipping
• Fluids: 8 cups/day (mainly water)
• Caffeine: ≤3 cups/day
• Fruit: ≤3 portions/day
• Avoid: Fizzy drinks, sorbitol, alcohol, bran
• Include: Soluble fibre (e.g. oats, linseeds)

Exercise & Mental Health:
- 30 min/day, 5x/week
- Relaxation and stress management

Probiotics:
- Try for 4 weeks at recommended dose