Drugs To Treat Disorders Of Acid Secretion Flashcards
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
What do prostaglandins E2 and I2 do?
Stimulate gastric mucus + HCO3- production
Inhibit gastric acid production
What are some examples of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Ibuprofen
Aspirin
Naproxen
Why would a patient have to be on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) long-term?
Long-term pain or inflammation management
What do Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) do?
Inhibit COX, which is the enzyme that converts arachidonic acid to PGs I2 + E2 so they inhibit PG formation thereby impairing the renewal of the gastric mucosal barrier impairing gastroprotection -> gastric erosions causing or worsening ulcers
When trying to avoid the adverse effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), what should be considered?
Alternative drug? E.G. Ibuprofen is lower risk than Naproxen
Lowest dose + shortest duration
Avoid concomitant NSAIDs
Frequent review of need for NSAIDs
Co-prescription of PPI in patients at increased risk of adverse effects + requiring NSAIDs
What is Helicobacter Pylori (H. Pylori)?
A spiral-shaped gram -ve bacterium ingested by mouth, which damages stomach + duodenal tissue
How does Helicobacter Pylori (H. Pylori) damage the gut?
Penetrates gastric mucus barrier/cells facilitating acid + protease penetration
Produces + secretes urease which breaks down urea into CO2 + NH3 (ammonia):
- NH3 neutralises gastric acid
- NH3, other bacterial products + acid damage epithelial cells
What percentage of peptic ulcers are causes by Helicobacter Pylori (H. Pylori)?
80%
What is the treatment of Helicobacter Pylori (H. Pylori)?
Eradication regime involves a combination of antibiotics + a PPI -> produces long-term remission of peptic ulcers
What is achlorhydria/hypochlorhydria?
Absence/deficiency of HCl in gastric juice
What are some causes of under-secretion of gastric acid?
Iatrogenic (caused by drugs)
Atrophy of gastric mucosa in older adults
What are the consequences of under-secretion of gastric acid?
Impaired ability to digest + absorb certain nutrients such as iron + the B vitamins
Increased vulnerability of GI tract to bacterial infection
