Pharmacological Basis For Treatment of GI Disorders I/II

Question 1

METOCLOPRAMIDE:
What does it do?

What is it used to treat?

Answer 1

• • Inhibits pre and postsynaptic dopamine (D2) and 5-HT3 receptors - inhibits vomiting:
  o Stimulation of D2 receptors in LOS and stomach = relaxation
  o Dopamine inhibits Ach release = relaxation

• Stimulate many 5-HT4 receptors to increase motility, and stimulates the inhibitory nitrogenic (NO) neurons = coordinated gastric motility

• Promotes gastric motility and emptying
o D2 receptor antagonist to increase Ach release and peristalsis of small bowel - Ach release increases intragastric pressure (due to increased LOS tone and tone of gastric contractions) - improves antroduodenal coordination to accelerate gastric emptying

• Used to treat GORD and Nausea from other conditions

Question 2

ANTISPASMODIC AGENTS:
What are they used to treat?

How do they work?

Give an example

Answer 2

• Irritable Bowel Syndrome (IBS), and Diverticular disease
• Reduce spasms of the bowel as they have relaxant action on the GIT
• Propantheline:
  • Muscarinic receptor antagonist - inhibit parasympathetic activity to reduce bowel spasm

Question 3

ANTACIDS:
What are they used to treat?

How do they work?

What can prolonged use of this drug help with?

Give an example

Answer 3

• GORD, Peptic ulcers
• Neutralise gastric acid - increase PH (pepsin activity stops at PH 5)
• Healing of duodenal ulcers
• Pepto-Bismol:
  • Protects gastric mucosa - forms a base over the ulcer, adsorbing pepsin and increasing bicarbonate/prostaglandin secretion
  • Toxic against H. Pylori - can be used to destroy it
  • Side effect is blackened stool and tongue

Question 4

H2 RECEPTOR ANTAGONISTS:
What are they used to treat?

How do they work?

What can happen if you stop treatment?

Answer 4

e. g. Ranitidine
- GORD, Peptic ulcer

• • Inhibit histamine, Ach, and gastrin-stimulated acid secretion - reduces pepsin secretion as a result
  • Decreases basal/food-stimulated acid secretion by 90% - promote ulcer healing
• Relapse

Question 5

PROSTOGLANDINS:
How do they work?

Why do NSAIDs lead to gastric bleeding?

Answer 5

• Stimulates HCO3- secretion, vasodilation in mucosa, ↓H+ secretion
• They inhibit Prostaglandin synthesis, leading to the mucosa being vulnerable to damage - ulceration, gastric bleeding

Question 6

PROTON PUMP INHIBITORS (PPIs):
What are they used to treat?

How do they work?

Answer 6

• GORD, Peptic ulcers
• • Drug of choice is hypersecretion occurs
  • Weak bases to irreversibly inhibit H/K ATPase on Parietal cells
  • Decreases basal/food stimulated Gastric acid secretion

Question 7

How is H.Pylori infection treated and managed?

Outline Metronidazole

Answer 7

• • Combination therapy - include PPIs and Antibiotics
  • Patient adhering to treatment is important to avoid antibiotic resistance

Metronidazole
• Disulfiram-like reaction if taken with alcohol - inhibits acetaldehyde dehydrogenase = build-up of acetaldehyde
• Don’t give this drug in first trimester of pregnancy

Question 8

Outline Constipation?

Answer 8

• Obstruction of the colon - subjective sensation of constipation
• Frequency of bowel opening depends on the individual
• Prolonged constriction can cause Headache, Loss of Appetite, Nausea,
Abdominal distension and pain
• Holding faecal matter = ↑Water loss and dryer faeces (more painful defecation)

Question 9

What causes constipation?

Answer 9

• Diet
• ↓Motility due to old age, inactivity, damage to enteric nervous system of colon
• Drugs

Question 10

How is constipation managed?

Answer 10

• Lifestyle changes
• ↑Fibre intake - bulk-forming laxative
• ↑Water intake if dehydrated

Question 11

What are Bulk Forming Laxatives? What are its side-effects?

What are Osmotic Laxatives? What are its side-effects?

Answer 11

• e.g. Methylcellulose
• Takes a few days to work
• Absorbs water in the gut lumen to increase stool solid content = promotion of peristalsis
• Side effects - Bloating, Flatulence
• • Works very quickly
  • Retain water in the gut lumen by osmosis
  • Increase small bowel motility
  • Side effects - Flatulence, Cramps, Diarrhoea, Vomiting

Question 12

What is Diarrhoea?

What causes it?

What do Anti-diarrhoeal agents do?

What is Loperamide?

Answer 12

• Frequent passage of watery stool - lots of fluid lost
• Due to infection, toxins, anxiety, drugs
• • Maintain body fluids and electrolytes
  • Identify causal organisms - treat with antibiotics
  • Modify secretion/absorption balance
• • μ-Opioid receptor agonist
  o Upon stimulation, it inhibits gastric emptying - ↑Sphincter tone, induces motor patterns, and blocks peristalsis
  • Selective to GIT - decreases passage of faeces and decreases duration of illness