GI Pharmacology

Question 1

Proton pump inhibitors (omeprazole, lansoprazole)

Answer 1

• helps in GORD
• helps in h pylori infection
• pro drugs
• PPI are weak bases and accumulate in the acidic space of the secretory canaliculi
• oral PPI needs enteric coating to prevent premature activation in stomach
• bind covalently to gastric H+, K+ ATPase irreversibly and block function
• prolonged and nearly complete suppression of acid secretion
• needs de novo synthesis of pump enzyme to produce more acid

Interaction and side effects

• metabolized by CYP2C19 and CYP3A4
• liver failure will require smaller doses
• metabolite excreted by kidneys
• generally well tolerated but will cause headache, nausea, GI tract issues and abd pain
• leads to increased levels of gastrin because no drop in pH
• can cause parietal cell and ECL hyperplasia
• some concern that this could increase risk of gastric carcinoid tumours
• may decrease the effectiveness of Clopidogrel because both use CYP2C19
• increase risk of infections in hospital

Question 2

COX inhibitors

Answer 2

• provide some gastric protection

- but not good for CVS if given long term

Question 3

H2 receptor antagonists

Answer 3

• competitively and reversibly inhibits binding of histamine to H2 receptors
• indirectly blocks the effects of gastrin and ACh on the parietal cell
• activation of PKA helps change the shape of the parietal cell
• creating the canaliculi
• rapidly absorbed from the small interstine
• excreted by liver and kidney
• diarrhoea, constipation, muscle ache and fatigue
• reduced ketoconazole absorption (needs acidic environment)
• inhibits several CYP450 enzymes
• decreases metabolism of lidocaine, phenytoin and warfarin
• potentially resulting in toxic levels so is used less

Question 4

Prostaglandin analogues

Answer 4

• treatment for NSAID induced ulcers
• acts on PGE2
• affects a similar pathway to H2 RAs
• side effects: diarrhoea and abd pain which often result in non compliance
• contraindication: pregnant women because causes uterine contraction
• so can be used in post-Partum haemorrhage to stop bleeding
• can be used for abortion

Question 5

Antacids

Answer 5

-symptom relief for dyspepsia
-neutralize HCl
-reacts with acid to form water and salt
-perform a neutralizing reaction
Aluminum hydroxide
-constipation (AC)
-can bind phosphate resulting in low phosphate levels (weakness, malaise)
-in presence of renal failure can cause neurotoxicity
Magnesium hydroxide
-diarrhoea (MD)
-avoid in renal failure (leads to increase mg levels)
Sodium bicarbonate
-reacts with HCl to form water, CO2 and salt
-avoid in hypertension and fluid overload
Calcium carbonate
-reacts with HCl to form calcium chloride and CO2