S11) Drugs Affecting Acid Secretion

Question 1

What are the defensive factors for gastric mucosa?

Answer 1

• Epithelial integrity
• Cell replication and restitution
• Mucous membrane barrier
• Vascular supply

Question 2

Which factors aggravate gastric mucosa?

Answer 2

• Acid
• Drugs
• Helicobacter pylori

Question 3

What are the stimulatory receptors on the basolateral membrane of a parietal cell?

Answer 3

• Acetylcholine
• Cholecystokinine B (CCK-B)
• Histamine 2 receptor (H₂)

Question 4

The proton pump is found on the canicular membrane of the parietal cell.

How does this pump work?

Answer 4

HK ATPase exchanges H⁺ for K⁺

Question 5

Briefly, describe some key features of proton pump inhibitor action

Answer 5

• Delayed action – not all pumps active at a time
• Max efficacy after 2-3 days
• Restoration of acid secretion requires de novo synthesis

Question 6

Briefly, illustrate the relationship between Helicobacter pylori and the following peptic ulcer disease:

• Gastric ulcer
• Duodenal ulcer

Answer 6

Question 7

Identify some common drugs which can be used to treat peptic disorders

Answer 7

• Antacids
• Alginates
• H₂RA
• PPI

Question 8

What medical advice is given to the patient in ‘step one’ for treating GORD?

Answer 8

• Weight loss
• Decrease alcohol
• Stop smoking
• Smaller meals / less acidic foods
• Antacids e.g. Gaviscon

Question 9

What treatment is given to the patient in ‘step two’ for treating GORD?

Answer 9

H₂ receptor antagonist e.g. ranitidine

Question 10

What treatment is given to the patient in ‘step three’ for treating GORD?

Answer 10

Proton pump inhibitors e.g. omeprazole, lansoprazole, esomeprazole

Question 11

What are the side effects of proton pump inhibitors?

Answer 11

• Diarrhoea
• Osteoporosis (with long term use)

Question 12

What investigation should one perform if a patient presents with any red flags for GORD?

Answer 12

Urgent upper GI endoscopy – ulcers, malignancy, hiatus hernia

Question 13

What is Helicobacter pylori?

Answer 13

• H.pylori is a gram negative bacteria found in the GI tract, which can cause gastric and duodenal inflammation / ulceration
• It is toxic to epithelial cells / degrades mucosal lining

→ gastritis, peptic ulcer and potentially gastric cancer

Question 14

How do we test for H.pylori?

Answer 14

• Carbon-13 urea breath test
• Stool antigen test

Question 15

How do we eradicate H.pylori?

Answer 15

Triple therapy for 1 week:

• Clarithromycin 500mg BD
• Amoxycillin 1g BD
• Lansoprazole 30mg BD

Question 16

describe some features of gastric and duodenal ulcers

Answer 16

→ epigastric pain so not accurate location

→ chronic ulcers can be asymptomatic

→ bleeding, perforation and scarring

→ early gastric emptying

→ after Heliobacter pylori, NSAIDS are most common cause

Question 17

what things are involved with acid secretion

Answer 17

→ actetylcholine activates protein kinase, releasing acid

→ histamine → increases Camp → PK activated

→ gastrin

→ inhibition of prostaglandins by NSAIDS (these can inhibit blood supply)

Question 18

Gaviscon

Answer 18

CLASS: Alginates and antacids

ROLE: buffers stomach acid

MOA: increase stomach acid viscosity and reduce acid reflux, foamy protective layer around stomach

TAKEN: alginic acid (sodium alginate and aluminium hydroxide)

ADVERSE EFFECTS: mg = diarrhoea, al = constipation

WARNING: renal failure, hyperglycemia

DRUG-DRUG: reduce absorption of drugs (alginate), increase urine alkalinity → aspirin excretion

Question 19

give two examples of PPI

Answer 19

→ lansoprazole

→ omeprazole

Question 20

PPIs MOA

Answer 20

MECHANISM: Inhibit H/K ATPase in gastric parietal cells in final stage of pathway so reduce acid secretion significantly

Question 21

PPIs adverse effects

Answer 21

GI disturbance, headache

Question 22

contradictions of PPIs

Answer 22

→ can mask gastro-oesophageal cancer

→ osteoporosis → risk of fractures

Question 23

drug reactions of PPIs

Answer 23

omeprazole is a CYP inhibitor

reduce effects of clopidogrel and increase effects of warfarin and phenytoin

Question 24

what other meds are PPIs often prescribed with

Answer 24

shortest effective duration at lowest dose

long NSAID or steroid

Question 25

give an example of a histamine receptor antagonist

Answer 25

Ranitidine

Question 26

MOA of H2 receptor antagonists

Answer 26

prevents activation of proton pumps, so only partially reduce acid secretion

Question 27

what are some side effects of H2 Receptor antagonists

Answer 27

diarrhoea and headache

Question 28

what are some contradictions of H2 receptor antagonists

Answer 28

mask symptoms of gastro-oesophageal cancer, renal impairment

Question 29

what are some drug interactions of H2 receptor antagonists

Answer 29

very few: reduce exposire to some anti-virals and protein kinase inhibitors

can be given lansoprazole

Question 30

what is the common treatment for infection of H pylori

Answer 30

→ one triple week therapy

PPI and two antibacterial agents

Lanzopramole + clarithromycin + amoxicillin

if allergic to antibiotics:

give metronidazole instead

Question 31

give an example of an amionsalicylate

Answer 31

mesalazine

Question 32

mesalazine

Answer 32

ROLE: used in first line treatment of Ulcerative colitis

Question 33

how do amionsalicylates work

Answer 33

→ acts locally on colonic mucosa

→ releases 5-aminosalsylic acid which reduces inflammation in mucosa

Question 34

adverse effects of amionsalicylates

Answer 34

GI disturbances, nausea and dyspepsia

Question 35

drug to drug reactions with amionslaicylates

Answer 35

enteric coated tablets may break down quicker in presence of Proton Pump Inhibitor