Drugs That Reduce Gastric Acid

Question 1

Stimulatory:
1. Histamine
2. Gastrin
3. Acetylcholine

Answer 1

Inhibitory:
1. PGE2
2. PGI2
3. Somatostatin

Question 2

Histamine:

Released by..
Increased by …
Acts how

Answer 2

 Released by enterochromaffin-like cells (ECL)  Further increased by gastrin and acetylcholine
 Histamine acts in a paracrine fashion on
parietal cell H2 receptors
 Increasing intracellular cAMP  Responsive to histamine concentrations below
threshold required for vascular H1
receptor activation

Question 3

CLINICAL INDICATIONS FOR REDUCING ACID SECRETION

Answer 3

-Peptic ulceration (both duodenal and gastric)
* H. Pylori infxn
- GORD
* gastric acid damages oesophagus
- Zollinger- Ellison syndrome
* rare gastrin- producing tumor
- NSAIDS
* COX-2 inhibitors may offer an advantage by causing less GI-related adverse effects

Question 4

THERAPEUTIC STRATEGIES

Answer 4

H2 receptor antagonists
 Proton pump inhibitors
 Antacids
 Alginates
 H. pylori eradication
 Cytoprotective agents

Question 5

HISTAMINE H2 RECEPTOR ANTAGONISTS
MoA

Answer 5

 Major breakthrough in the treatment of gastric ulcers
 Competitively inhibit histamine
actions at H2 receptors (reversible)
 Inhibit histamine- and gastrin-
stimulated acid secretion
 Decrease both basal and food-
stimulated acid secretion by 90% or more

Question 6

. HISTAMINE H2 RECEPTOR ANTAGONISTS
, Beneficial Effects

Answer 6

Promote healing of gastric and duodenal ulcers
-Relapses likely to follow after cessation of treatment

Question 7

Histamine receptor antagonists
Examples

Answer 7

Cimetidine, nizatidine, famoditine
Less effective than proton pump inhibitors (PPIs)

Question 8

Adverse effects

Answer 8

 Diarrhoea
 Dizziness
 Headache
 Hypergastrinaemia

Question 9

Cimetidine Adverse effects

Answer 9

 Gynaecomastia in men and rarely, a decrease in sexual function
 Probably caused by a modest affinity for androgen receptors
 CYP450 inhibitor
 Potentiates effects of a range of drugs e.g. oral anticoagulants and tricyclic antidepressants

Question 10

Clinical uses for Histamine receptor antagonist

Answer 10

• Peptic ulcer disease: treatment
and prevention of gastric and
duodenal ulcers (including
NSAID-associated ulcers)
• GORD and dyspepsia

Question 11

First line tx

Answer 11

Proton pump inhibitors

Question 12

PROTON PUMP INHIBITORS
Prototypical drug + other examples

Answer 12

Prototypical drug: Omeprazole

Other PPIs
 Esomeprazole
 Lansoprazole
 Pantoprazole
 Rabeprazole

Question 13

PPI MoA

Answer 13

—Irreversibly inhibits the proton pump
• Basal and stimulated gastric acid secretion are reduced
— Weak base
• Accumulates in the acid environment of the canaliculi of the stimulated parietal cell where it is activated
• Administration: 30 minutes before food
• Specific effect on parietal cells

Question 14

Adverse effects are uncommon

Answer 14

• Headache
• Diarrhoea
• Rebound hypergastrinemia (problem when stopping tx)
• Hypomagnesemia
• Increased bone fracture risk
• Increased susceptibility to infections (e.g.
  C difficile)

Question 15

CLINICAL USES
Of PPI

Answer 15

• Peptic ulcer disease: treatment and
prevention of gastric and duodenal
ulcers (including NSAID-associated
ulcers)
• Treatment of GORD and dyspepsia
• As part of H. pylori triple/quadruple
eradication therapy
• Reduction of gastric acid secretion in
Zollinger-Ellison Syndrome

Question 16

Antacids INDICATIONS+MoA

Answer 16

 Treat the symptoms of excessive gastric acid secretion
 Directly neutralize acid
 May produce healing of duodenal ulcers
 Calcium salts induce gastrin secretion

Question 17

Antacids CI, careful

Answer 17

 Some preparations contain high concentrations of sodium
 Should not be given to patients on a sodium-restricted diet
 May cause changes in acidity and thus pharmacokinetic interactions with other drugs
 Recommended to take them at least 2 hours apart from other drugs

Question 18

Antacids commonly used

Answer 18

 Magnesium (Mg) salts cause diarrhea
 Aluminum (Al) salts cause constipation
 Mixtures of Mg/Al can preserve normal bowel function

Question 19

Antacids examples

Answer 19

1. Aluminium hydroxide
2. Calcium carbonate
3. Magnesium hydroxide

Question 20

Aluminium hydroxide AE

Answer 20

• Constipation
• Hypophosphatemia
• Muscle weakness
• Osteodystrophy

Question 21

Calcium carbonate AE

Answer 21

• Hypercalcaemia
(milk alkali syndrome)
• Rebound acidity
• Chelate and decrease effectiveness of
other drugs

Question 22

Magnesium hydroxide

Answer 22

• Diarrhoea hydroxide
• Hyporeflexia • Hypotension • Cardiac arrest

Question 23

Aliginates MoA

Answer 23

 Sometimes combined with
antacids

 May increase viscosity and
adherence of mucus to the oesophageal mucosa
 Forming a protective barrier

Question 24

Alginates Clinical uses

Answer 24

• Most often taken as compound
preparations containing an alginate with
one or more antacids for:
• GORD: for symptomatic relief of
heartburn
• Dyspepsia: for short-term relief of
indigestion

Question 25

TREATMENT OF HELICOBACTOR PYLORI INFECTION

Answer 25

 Causative factor in gastric and duodenal ulcers H. pylori eradication  Rapid and long-term healing of ulcers  Routine practice to test for the organism  If positive 1- or 2-week regimen of ‘triple therapy’ •PPI + 2 antibiotics: Amoxicillin (or metronidazole) and clarithromycin • Other combinations are also used  Bismuth-containing preparations sometimes added • Quadruple therapy (in patients with macrolide resistance): PPI; Bismuth; Metronidazole; Tetracycline  Quadruple therapy may alternatively include 3 antibiotics + PPI

Question 26

-DRUGS THAT PROTECT THE MUCOSA

Answer 26

-Cytoprotective agents -Bismuth chelate

Question 27

Cytoprotective agents MoA

Answer 27

 Enhance endogenous mucosal protection mechanisms and/or  Provide a physical barrier over the surface of the ulcer

Question 28

Bismuth chelate MoA

Answer 28

 Adjunct in H. pylori treatment  Toxic effects on the bacillus  May also prevent its adherence to the mucosa or inhibit its bacterial proteolytic enzymes  May also have other mucosa-protecting actions

Question 29

Bismuth chelate Clinical use

Answer 29

''Clinical Use: widely used as an over-the-counter remedy for mild GI symptoms and in quadruple therapy for H.pylori eradication

Question 30

Bismuth AE

Answer 30

 Nausea  Vomiting  Blackening of the tongue and faeces  In renal impairment may cause encephalopathy • Salicylate component Therefore, pts with aspirin allergy shouldn’t take this

Question 31

MISOPROSTOL clinical uses

Answer 31

 Stable analogue of PGE 1  Promotes the healing of ulcers  Prevents gastric damage due to chronic use of NSAIDs —- Now PPIs used More 3rd line

Question 32

MISOPROSTOL MoA

Answer 32

 Exerts a direct action on the ECL cell  Possibly on parietal cells as well  Inhibits basal and stimulated secretion of gastric acid  Increases mucosal blood flow  Augments the secretion of mucus and bicarbonate

Question 33

MISOPROSTOL AE

Answer 33

 Diarrhea  Abdominal cramps  Uterine contractions can also occur -Should not be given during pregnancy for this indication (Given to induce abortion)

Question 34

GERD (Mild/ intermittent)

Answer 34

1st line - Antacids, H2RA Alternative - PPIs

Question 35

GERD (severe)

Answer 35

1st line - PPIs Alternative - H2 RA (step down)

Question 36

Pregnancy

Answer 36

1. Antacids 2. H2RA, PPIs

Question 37

H. Pylori eradication

Answer 37

1. Triple therapy (Amoxicillin or metronidazole Clarithromycin; PPI) 2. Quadruple therapy (in pts. W/ macrolide resistance): PPI; bismuth; metronidazole; tetracycline

Question 38

NSAID prophylaxis

Answer 38

1. PPIs 2. MISOPROSTOL, H2RA

Question 39

Zollinger Ellison Syndrome

Answer 39

1. PPIS 2. Somatostatin analogues