Drugs To Treat Disorders Of Acid Secretion Flashcards
(36 cards)
What are the main 3 classes of drugs used to treat disorders of acid secretion?
- Antacids + alginates
- Histamine H2-receptor antagonists (old gold standard)
- Proton pump inhibitors (new gold standard)
What is an antacid?
Any substance, generally a base, which counteracts stomach acidity by buffering gastric acid thereby, raising the gastric pH
What are some examples of antacids?
Aluminium hydroxide + magnesium hydroxide (Maalox)
Calcium carbonate + magnesium carbonate (Rennie)
What is an alginate?
Anionic polysaccharide that forms a viscous gel upon binding water so they increase viscosity of stomach contents forming a ‘raft’ that floats on the surface of stomach contents protecting the oesophageal mucosa from acid reflux + reducing symptoms of reflux
How are alginates often taken?
In combination with antacids for use in reflux oesophagitis
What are some examples of alginates?
Sodium alginate
Sodium bicarbonate
Calcium carbonate (Gaviscon combines all 3)
What do histamine-H2 receptor antagonists do?
Competitively inhibit histamine action at H2 receptor on parietal cells by binding the receptor, blocking it + preventing histamine from binding to stimulate acid secretion inhibiting acid secretion by about 90%
What is one benefit of taking histamine H2-receptor antagonists?
The drugs are specific as the H2 receptor is not really expressed anywhere other than parietal cells
What are some examples of histamine H2-receptor antagonists?
Cimetidine (Tagamet)
Ranitidine (Zantac)
What is one downside to taking Cimetidine?
It inhibits many cytochrome P450 enzymes weakly so has a few side effects as a result
What are some examples of proton pump inhibitors (PPIs)?
Omeprazole (Losec, Prilosec + Zegerid)
Lansoprazole (Prevacid, Zoton + Inhibitol)
Why are proton pump inhibitors (PPIs) better at treating acid secretion disorders than histamine H2-receptor antagonists?
Histamine H2-receptor antagonists only block the proportion of acid secretion stimulated by histamine whereas PPIs are uniquely targeting the actual proton pump which stops H+ secretion irreversibly
What do proton pump inhibitors (PPIs) do?
- From the circulation, the lipophilic pro-drug traverses the parietal cell + enters the canaliculus
- Become trapped + accumulate in the secretory canaliculi of parietal cells
- Activated in acid environment (inactive at neutral pH) - very specific in being directed to the site of action
- Binds + IRREVERSIBLY inhibits the H+/K+ ATPase pump - the terminal step in the acid secretory pathway
- For acid secretion to resume, new pump molecules must be synthesized via protein synthesis (2-3 days)
How is omeprazole administered? Why?
In capsules containing enteric-coated granules because it degrades rapidly at low pH
What is the half-life (T1/2) of proton pump inhibitors (PPIs)?
1 hour
Increases doses of proton pump inhibitors (PPIs) give ______ __ __ in plasma concentration.
Disproportionately higher increases
What conditions require drug treatment of acid secretion?
Reflux oesophagitis
Peptic ulcer from NSAIDs or H. Pylori infection
What is reflux oesophagitis?
Inflammation of the lower oesophagus produced by persistent episodes of reflux (GORD) where the liquid content of the stomach regurgitates into the oesophagus
What are symptoms of reflux oesophagitis?
Heartburn
Regurgitation of food into mouth
Haematemesis (vomiting blood as a result of ulceration)
What are the complications of reflux oesophagitis?
Oesophageal ulceration
Peptic stricture
Barrett’s oesophagus (in a small proportion of patients)
How is reflux oesophagitis often treated?
- Antacids + alginates: OTC so self-medicated before consultation or prescribed in mild cases
- H2- receptor antagonists: available OTC used to self-medicate if antacids/alginates fail
- PPIs: prescribed drugs of choice for all but mild cases
What causes a peptic ulcer?
Persistent irritation/gastritis
What types of peptic ulceration exist?
Benign
Deep
Where do more peptic ulcers arise than in the stomach?
Duodenum
