Pharmacology: GORD drugs

Question 1

These 4 factors help stop ulceration (by autodigestion) of the stomach and duodenum:
- Mucus
- Bicarbonate
- Blood flow
- Prostaglandins

How?

Answer 1

Mucus traps bicarbonate ions - creating a 6-7 pH gel like protective layer
Blood flow maintains mucosal integrity.
Prostaglandins stimulate secretion of bicarbonates, promotes blood flow, suppresses gastric acid production

Question 2

Peptic ulcer disease
- What are the 2 types of ulcers it includes?
- MOA?

Answer 2

Peptic (stomach) and duodenal ulcers
Imbalance between defensive and aggressive factors –> tissue damage –> ulcer formation

Question 3

Gastro oesophageal reflux disease (GORD)
- MOA?
- Symptoms?

Answer 3

Back flow of stomach acid/duodenal contents into the oesophagus due to reduced contraction/tone of the lower oesophageal sphincter

Heart burn
Chest pain
Reflux
Dyspepsia (stomach pain)
Fullness, burping, bloating, nauseated

Question 4

Risk factors:
- Medicines: anticholinergics, peripheral calcium channel blockers
- Alcohol, smoking, coffee, greasy/rich food, over eating, stress

Answer 4

Yes

Question 5

Complications of GORD?

Answer 5

Oesophagitis
A severe form of which is Barrett’s oesophagitis - which can be pre cancerous

Question 6

Causative factors of GOD and PUD:
Increased acid:
- H pylori infection
- Increased gastric acid
- Increased pepsin
- Smoking (stimulates gastric acid production)
Decreased bases (duodenal bicarbonate)
Structural:
- Decreased mucosal blood flow
- Reduced thickness of mucus layer
- Alcohol
Drugs
- NSAIDs (reduced prostaglandins)

Answer 6

Yes

Question 7

Non pharmacological treatments for PUD and GORD?

Answer 7

Avoid alcohol, smoking, greasy/hot/spicy foods, weight loss, don’t eat just before bed

Administer NSAIDs with food or lower dosages to avoid ulcers

Question 8

What are the 2 drug classes?

Answer 8

Anti secretory agents
Cytoprotective agents and mucosal strengtheners

Question 9

What are the 3 types of anti secretory agents?

Answer 9

Proton pump inhibitors
H2 receptor antagonists
Anti muscarinic drugs

Question 10

Proton pump inhibitors
-MOA
- Is it a pro drug at neutral pH? What activates it?
- Is it the first line therapy in peptic ulcer disease?
- Does it have a variety of formulations? Eg. granules, tablets, capsules, IV injections

Answer 10

Irreversibly binds to H+/K+ ATPase pump, blocking HCl secretion by parietal cells. Only reversed when new proton pumps are synthesised
- Yes
- Yes. Low pH activates

Question 11

Proton pump inhibitors:
- ADRs?
- Can it interact with CYP450 enzymes?
- Can it impact the absorption of drugs that require an acidic environment to work?
- Examples?

Answer 11

Flatulence; but otherwise minimal
Yes
Yes
Esomeprazole, pantoprazole

Question 12

H2 receptor antagonists
- MOA?
- Do they interact with cytochrome P450 enzymes?
- Why are they disappearing from the market?

Answer 12

Reversible competitive inhibitors of H2 receptors on parietal cells –> downregulate H+/K+ ATPase –> lead to less HCl secretion
Yes
PPIs more effective, most popular H2 receptor antagonist contained carcinogens

Question 13

H2 receptor antagonist
- ADRs?
- Example?

Answer 13

Confusion, renal impairment
Nizatidine

Question 14

Anti muscarinic drugs
- MOA?
- Example?

Answer 14

Inhibits Ach receptors on parietal cells –> downregulate H+/K+ ATPase –> lead to less HCl secretion
Atropine

Question 15

4 types of cytoprotective agents and mucosal strengtheners?

Answer 15

Antacids
Prostaglandins
Bismuth
Sucralfate

Question 16

Antacids
- MOA?

Answer 16

Weak bases, which neutralise acids in the stomach.
Heps inactivate peptic enzymes

Question 17

Antacids:
They can come with additives. What is the role of
- Simethicone
- Alginates

Answer 17

Simethicone: reduces surface tension, thus bubble formation and reflux
Alginates: increases viscosity and adherence of mucus to protective gel layer

Question 18

Antacids:
- Can they interact with other drugs?
- Can they chelate?
- Is toxicity possible - especially in patients with renal impairment?

Answer 18

Yes
Yes
Yes

Question 19

What are the 2 types of antacids, and their ADRs?

Answer 19

Aluminium hydroxide: forms AlCl3 in the gut –> constipation, aluminium toxicity in renal disease
Magnesium hydroxide: forms MgCl2 in the gut –> diarrhoea, hypermagnesemia

Question 20

H pylori
- Is it gram positive or negative?
- What shape is it?
- Can it cause ulcers?
- Is it a class 1 carcinogen for gastric cancer?

Answer 20

Negative
Bacillus
Yes
Yes

Question 21

What is the preferred treatment for H pylori infections?

Answer 21

PPI + clarithromycin + amoxicillin

Question 22

If the patient is allergic to amoxicillin, what is the second line treatment?

Answer 22

PPI + clarithromycin + metronidazole

Question 23

Why are multiple drugs needed?
How long does it usually take to eradicate H pylori?
Does this regimen usually produce long term remission?

Answer 23

Otherwise resistance can develop
1-2 weeks
Yes