GI Pharmacology

Question 1

Stomach diseases

Answer 1

GORD (gastroesophageal reflux disease)

Ulcers

Question 2

Panreas diseases

Answer 2

Pancreatitis

Question 3

Small Intestinal diseases

Answer 3

Celiac disease
Chrons disease
IBS (irritable bowel syndrome)
Leaky gut

Question 4

Rectum

Answer 4

Gas, bloating, constipation, diarrhoea

Question 5

Large intestinal disease

Answer 5

Chrons disease
IBS
Leaky gut

Question 6

Absorption process

Answer 6

Digest - break down
Absorbing nutrients - from intestine to blood stream
Elimination - Food not digested/absorbed

Question 7

Stomach pathophysiology

Answer 7

Chief cells - produce pepsinogen
Parietal cells - Produce HCl
Mucus/bicarbonate/water - lubricate stomach and protect from injury
Intrinsic factor (parietal cell) - increase cobalamin (vitamin B12) absorption
Neck cell - produce mucus and bicarbonate
ECL cell - histamine secretion
G cell - produce gastrin
D cell - secrete somatostatin
Breaks down food into chyme by reduction in particle size and mixing
Empties into the duodenum

Question 8

Regulation of gastric acid secretion

Answer 8

Carried out by the gastrin - ECL - parietal complex

1. Gastrin from G Cell produced
2. Acts on CCK2R on ECL cell which stimulates release of histamine
3. Histamine acts on H2R on parietal cell
4. Increases cAMP activating acid secretion by parietal cell
5. ACh released by vagus nerve acts on M3R which secretes gastric acid from parietal cell
6. Somatostatin act on SST2R which exert an inhibitory effect on parietal cell and G cell
7. Prostaglandin binds to EP2/3R on ECL exerting inhibitory effects

Question 9

Mechanisms that protect the stomach

Answer 9

Pepsin, H+ and HCl are prevented from digesting the wall by:

1. First line of defense is mucus
2. Bicarbonate (HCO3-) increases the pH to 7 to neautralise the wall
3. Prostaglandins keep blood vessels dilates for good blood flow into stomach which allows regeneration of the epithelium and also stimulate mucus + bicarbonate production

Question 10

GORD

Answer 10

Back flow of acid - with or without oesophagitis
Happens when there is low pressure or lower oesophageal sphincter causing the opening or if it doesn’t close properly
- Difficulty/pain when swallowing
- Pain in upper abdomen/chest/severe chest pain
- Feeling sick
- Acid taste in the mouth
- Bloated/indigestion/burning pain when swallowing
- Chronic cough/sore throat/voice change/gum problems and bad breath
- Symptoms worsen after a meal or night time
- Lifestyle - hot spicy foods, tight clothing, smoking, alcohol, overweight, pregnancy (pressure of womb into abdomen pushing stomach up), hiatal hernia

Question 11

Treatment options

Answer 11

Decrease damaging forces and re-inforce defensive forces

1. Drugs that inhibit/neutralise gastric acid secretion - Antacids, PPI’s, H2R’s and anticholinergic agents
2. Drugs that promote protection - Prostaglandin analogs and mucosal barrier fortifiers

Question 12

Antacids

Answer 12

Neutralise acid and prevent formation of pepsin

• Weak bases that react with HCl forming salt and water reducing gastric acid
• Help relieve symptoms i.e. after a heavy meal
• Not recommended for long term or chronic use

Question 13

Systematic antacids

Answer 13

SODIUM BICARBONATE AND SODIUM CITRATE

• Form CO2 and NaCl
• CO2 leads to gastric distention
• Unreacted alkali absorbed causes metabolic alkalosis
• NaCl absorption may exacerbate fluid retention

Question 14

Non-systematic antacids

Answer 14

MAGNESIUM HYDROXIDE, MAGNESIUM TRISILICATE, ALUMINIUM HYDROXIDE AND CALCIUM CARBONATE
- React slowly with HCl to form MgCl2 or AlCl2 and water
- No gas is generated (no belching and metabolic alkalosis)
- Unabsorbed Mg = osmotic diarrhoea
- Unabsorbed Al = constipation
Given together minimises effects

Question 15

H2R antagonists

Answer 15

CIMETIDINE, RANITIDINE, FAMOTIDINE
Competitively block histamine related gastric acid secretion
Suppress basal and meal stimulated acid secretion
Less potent than PPI
Side effect: diarrhoea, headache, myalgia, constipation, fatigue, confusion and hallucination

Question 16

Anticholinergic agents

Answer 16

PIRENZEPINE, TELENZEPINE
Competitively and selectively block ACh stimulated gastric acid secretion (M1 receptor on parietal cell)
Inhibit acid secretion and delay gastric emptying
Not commonly used due to low efficacy
Anti-cholinergic side effects - Dry mouth, blurred vision, dry eyes, constipation, urinary retension, dizziness, confusion and heart rhythm disturbance

Question 17

Proton pump inhibitors

Answer 17

OMEPRAZOLE, ESOMEPRAZOLE, LANSOPRAZOLE

• Irreversibly nhibit H+ K+ ATPase suppressing gastric acid secretion
• Block final step in gastric acid secretion (basal and stimulated)
• Highly bound to plasma proteins
• Metabolised in liver and secreted in urine
• Half-life of proton pump is greater than 18hrs so cells synthesis new ones to start producing acid again
• PPI administered when fasting i.e. 30 mins before a meal for greater absorption
• Half-life of PPI is short (1.5hrs) however acid secretion is supressed for 24 hrs as it takes 18hrs to synthesise new pumps
• Enteric coated/powder with sodium bicarbonate to prevent degradation

Question 18

Omeprazole as a pro-drug

Answer 18

1. Activated to sulfonamide at acidic pH in canaliculi

2. Sulfonamide binds to SH group of H+ pump and irreversibly inactivates it

Question 19

Side effects of PPI’s

Answer 19

Headache, diarrhoea, abdominal pain, skin rashes, arthralgia, decrease vitamin B12 absorption and increase rate of infection + fracture to bones

• Inhibit metabolism of phenytoin, warfarin and diazepam
• Decrease bioavailibity of itraconazole and iron salts

Question 20

Prostaglandin analogs

Answer 20

MISOPROSTOL
Reduce gastric acid secretion
Increase mucosa blood flow
Augment secretion of mucus and bicarbonate
Side effects: diarrhoea and abdominal cramps

Question 21

Mucosal barrier fortifiers

Answer 21

Form a complex gel with the mucus and create a protective coat
SUCRALFATE AND BISMUTH

Question 22

Sucralfate

Answer 22

Complex of AlOH and sulphated sucrose

• In acidic pH, polymerises to form sticky gel that adheres to the ulcer base and protects it for up to 6 hours
• Form barrier against acid - pepsin

Question 23

Bismuth

Answer 23

Bismuth salicylates and colloidal bismuth subcitrate

• React with proteins in base of ulcer and protect it from peptic digestion
• Stimulate secretion of PGE2, mucus and bicarbonate
• Antimicrobial against H.pylori
• Binds to enterotoxin in travelers diarrhoea

Question 24

H.pylori peptic ulcer combination therapy

Answer 24

Rapid healing, eradicates H.pylori infection and prevents relapse

1. Triple therapy
   - 7 days
   - Lansoprazole + Amoxicillin + Clarithromycin + Metronidazole
2. Quadruple Therapy
   - 10 days
   - Lansoprazole + Bismuth salicylate + 2 antibiotics

Question 25

Peptic ulcer with NSAID’s

Answer 25

1. Treat with PPI + continue or switch to misoprostol for maintenance therapy
2. Treat with PPI, switch non-selective to COX-2 selective inhibitor. Continuation of PPI in history of upper gastrointestinal bleeding further protects against recurrence
3. Switch to alternative therapy where PPI is inadequate i.e. H2R-antagonists