GI 1 - Drugs reducing gastric acid Flashcards
Drugs used in the reduction of Gatric acid secreting in the GI tract
1) H2 receptor antagonists (2nd line)
2) Proton pump inhibitors (1st line)
3) Antacids
4) Alginates
5) H. pylori eradication
6) Cytoprotective agents
MoA of HISTAMINE H2 RECEPTOR
ANTAGONISTS
- 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
Histamine H2 receptor antagnoists examples
Cimetidine (not preferred) , nizatidine, famotidine
* -tidine
Clinical uses of H2 receptor Antagonists
2nd line in the tx of Gastric/duodenal Ulcers
*less effective than PPIs
AE of H2 receptor Antagonists
Unwanted effects are rare:
Diarrhoea
Dizziness
Headache
Hypergastrinaemia
*Cimetidine –> CYP450 inhibitor
- Gynaecomastia and decrease in sexual function
MoA of PPIs
Weak base that protonats parietal cells -> decreases gastric acid secretion
Irreversibly inhibits the H+ pump
PPIs Examples
Omeprazole,
Esomeprazole,
Lansoprazole
Pantoprazole
Rabeprazole
* -prazole
Clinical uses of PPIs?
1st line
* 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
Administration of PPIs?
30 minutes before food
AE of PPIs?
Headache
Diarrhoea
Rebound hypergastrinemia (esp after stopping tx)
Hypomagnesemia
Increased bone fracture risk ( ↓ Ca+2 absorption)
Increased susceptibility to infections (e.g.
C difficile)
* ↑ susceptibiltiy -> ↓ gastrin -> ↑ pH -> ↑ risk of infection
Antacids Exmaples
Magnesium salts, Aluminum salts, calcium bicarbonate
AE of Magensium salts
1) Diarrhoea
2) hyporeflexia,
3) hypotension,
4) cardiac arrest.
AE of (Al) salts?
1) Constipation
2) hypophosphatemia,
3) muscle weakness,
4) osteodystrophy (abnormal changes in the growth and formation of bone)
AE of calcium bicarbonate
1) Hypercalcaemia,
2) rebound acidity,
3) chelate and decreases effectivness of other drugs
MoA of Mg/Al salts vs Calcium salts?
Mg/Al salts: Directly neutralize acid
Calcium salts: induce gastrin secretion
Administration of Mg/Al salts
should be given 2h apart from other drugs
* since they may cause changed in acidity and thus pharmacokinetic interaction w/ other drugs (E.g,. reduced the absorption of beta-blockers in HF patients when taken at the same time)
Contraindications of Mg/Al salts
- patients on a sodium restrited diet
- interaction w/ other drugs, therefore take them at least 2h apart from other drugs
Clinical uses of Alginates
Used in combo w/ Antacids
- GORD: for symptomatic relief of heartburn
- Dyspepsia: for short-term relief of indigestion
MoA of Alginates
- May increase viscosity and adherence of mucus to the
oesophageal mucosa (prevent reflux) - Forming a protective barrier
————- : causative factor in gastric and duodenal ulcers
H.Pylori infection
Treatment approach in the eradication of H.pylori
*Rapid and long-term healing of ulcers
If positive 1- or 2-week regimen of ‘triple therapy’ –> PPI + 2 antibiotics: Amoxicillin (or metronidazole) and clarithromycin ( a macrolide)
In resistant patients: quadruple therapy in (patients with macrolide resistance) (PPIs + Bismuth; metronidazole, tetracycline)
MoA of Cytoprotective agents
- Enhance endogenous mucosal protection mechanisms and/or
- provide a physical barrier over the surface of the ulcer
Clinical uses of Bismuth chelate
- Qurduple therpay in the eradication of H.pylori
- over-the-counter remedy for mild GI symptoms
AE of Bismuth chelate
1) Nausea,
2) vomit,
3) blackening of tongue and
faeces.
*stool is sticky and smells very bad
Contraindications of Bismuth Chelate
1) In renal impairment may cause encephalopathy
2) Asprine allergy
What type of drug is Misoprostol?
PGE1 analogue,
–> exerts direct action on the ECL cells and maybe also on parietal cells
MoA of Misoprostol
Inhibits gastric acid secretion,
increases blood flow and thus increases secretion
of mucus and bicarbonates
Clinical uses of Misoprostol?
3rd line tx option
- Promotes healing of ulcers and used to
- prevent damage due to chronic use of NSAIDs.
(Now PPIs are used)
AE of Misoprostol
1) Diarrhoea,
2) abdominal cramps,
3) uterine contractions (contraindicated in pregnancy)
Contraindiactions of Misoprostol?
PREGNANCY (uterine contraction)
