F2. Pharmacological treatment of the upper GI tract Flashcards
Hydrochloric acid is produced by what kind of cells and secreted into where?
Hydrochloric acid is produced by parietal cells in the stomach and secreted into their canaliculi.
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How is gastric acid secretion regulated?
Directly or indirectly control parietal cell acid output via:
1.Acetylcholine(astimulatoryneurotransmitter).
2.Histamine(astimulatorylocalhormone).
3.Gastrin(astimulatorypeptidehormone).
4.ProstaglandinsE2andI2(inhibitorylocalhormones). 5. Somatostatin(aninhibitorypeptidehormone)
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What is dyspepsia?
a group of symptoms that arise from the upper gastrointestinal tract, such as heartburn, abdominal pain or discomfort, fullness, bloating, early satiety, belching and nausea.
what are the different types of dyspepsia?
-Non-ulcer dyspepsia.
-Gastro-Oesophageal reflux disease (GORD).
-Gastritis.
-Peptic Ulcer Disease.
-Zollinger-Ellison Syndrome.
what is Gastro-Oesophageal Reflux Disease (GORD)
Stomach acid continuously refluxes into the oesophagus causing pain, heartburn, and inflammation.
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what is GORD caused and exacerbated by?
-Increased intra-abdominal pressure (obesity, pregnancy, big meals, tight clothing);
-Reduced lower esophageal sphincter (LES) tone
(hiatus hernia, tricyclic, opioids, calcium channel blockers and anticholinergic drugs).
What is gastritis?
Inflammation of the gastric mucosa.
causes of gastritis?
-Alcohol.
-Smoking.
-Prolonged use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).
-Infection (H. Pylori).
what is peptic ulcer disease?
A lesion extending through the mucosa and submucosa into deeper structures of the wall of the GI tract.
-Breakdown of the mucosal barrier (mucus and HCO3–).
-Increased secretion of H+ or pepsin
Describe gastric ulcers
Commonly found on the lesser curvature between the corpus and antrum of the stomach.
Describe duodenal ulcers
The most common ulcers, develops in the first part of the small intestine.
main causes of peptic ulcer disease?
-Helicobacter pylori: 70% gastric, 90% duodenal.
-NSAID therapy: interference with the synthesis of cytoprotective prostanoids via COX1 inhibition.
what is Zollinger-Ellison Syndrome?
Rare condition caused by gastrin-secreting pancreatic adenomas that lead to multiple ulcers in the stomach and duodenum.
what are the goals of treatment for dyspepsia?
symptomatic relief and cure
Describe symptomatic relief
Lifestyle changes:
-Avoidance of causative drugs.
-Avoidance of causative foods.
-Smoking cessation.
-GORD – propping up bed, removing belts!
-Neutralizing acid.
-Suppression of acid release or activity.
-Mucosal protection.
Describe cure
-Suppression of acid release to allow natural
healing.
-Eradication of H. pylori infection. Latter goal reduces the chance of developing gastric carcinomas, as H. pylori is regarded as a carcinogen.
what are antacids?
Weak bases able to partially neutralize gastric acid and inhibit pepsin activity both directly and by increasing pH, thus protecting the stomach mucosa.
what are systemic antacids?
Systemic Antacids are absorbed into the systemic circulation. They have a cationic group that does not form insoluble basic compounds with HCO3–. Thus, the HCO3–can be absorbed producing a metabolic alkalosis.
what are non-systemic antiacids?
Non-Systemic Antacids are not absorbed into the systemic circulation. Their anionic group neutralizes the H+ ions in gastric acid. This releases their cationic group which combines with HCO3–from the pancreas to form an insoluble basic compound that is excreted in faeces.
Describe non- systemic antiacids- Magnesium Hydroxide (Milk of Magnesia)
-Mg2+ salts act as both antacids and laxative agents.
-The laxative effect is lessened by concomitant use with calcium carbonate or aluminum hydroxide.
Describe non- systemic antiacids- Aluminium Hydroxide
Reacts with hydrochloric acid to form aluminum chloride. This in turn reacts with intestinal secretions to produce insoluble salts, especially phosphate.
Could cause constipation, osteomalacia (by interfering with PO43– absorption).
Describe systemic antiacid- sodium bicarbonate
Reacts with acid and relieves pain within minutes.
It is absorbed and causes a metabolic alkalosis.
It can release sufficient carbon dioxide in the stomach to cause discomfort and belching.
Severe distention of the stomach by CO2 gas may be dangerous if a gastric ulcer that could perforate is present.
Describe systemic antiacid- calcium carbonate
Acts by neutralizing hydrochloric acid in gastric secretions. It also inhibits the action of pepsin by increasing the pH and via adsorption. Cytoprotective effects may occur through increases in bicarbonate ion (HCO3-) and prostaglandins. Neutralization of hydrochloric acid results in the formation of calcium chloride, carbon dioxide and water.
Describe antiacids with alginic acid
-Alginic Acid works by forming a protective layer that floats on top of the contents of your stomach, and this stops stomach acid escaping up into your food pipe
-All proprietary preparations combine alginic acid with an antacid.
Which drugs are proton pump inhibitors?
-Omeprazole
-Esomeprazole
-Lansoprazole
-Pantoprazole
how does gastric secretion regulation work?
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How do proton pump inhibitors work?
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What are proton pump inhibitors?
-Lipophilic weak bases that diffuse into the parietal cell canaliculi, where they become protonated and concentrated more than 1000-fold.
-There they undergo conversion to compounds that irreversibly inactivate the parietal cell H+/K+ ATPase.
-Although half-life is about 1 h, a single daily dose affects acid secretion for 2–3 days.
PPIs Adverse Effects?
-Headache and diarrhoea (both sometimes severe) and rashes.
-Acid-suppression with proton pump inhibitors is associated with increased risk of Clostridium difficile diarrhoea, due to alteration of gut microbiota, particularly in patients who are immunosuppressed or have been receiving antibiotics.
-Proton pump inhibitors may decrease the oral bio-availability of vitamin B12 and certain drugs that require acidity for their gastrointestinal absorption (e.g., digoxin, ketoconazole).
-Proton pump inhibitors should be used with caution in patients with liver disease, or in women who are pregnant or breastfeeding.
Describe Histamine H2 Antagonists
Pharmacologic blockade of histamine H2 receptors (Reduced c-AMP).
what four H2 Antagonist available OTC?
Cimetidine (the prototype) Ranitidine
Famotidine
Nizatidine
How do Histamine H2 Antagonists work?
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How do Histamine H2 Antagonists affect the ulcers?
-Duodenal Ulcer: reduce nocturnal acid secretion, accelerate healing, and prevent recurrences.
-Gastric Ulcer: also effective in accelerating healing and preventing recurrences.
-Intravenous H2 blockers are useful in preventing gastric erosions and haemorrhage in intensive care units.
Describe Helicobacter pylori Eradication
Eradication is the most effective treatment for long term cure of ulcers with low relapse rates.
Describe ‘triple therapy’ for Helicobacter pylori Eradication
2 antibiotics:
Clarithromycin.
Amoxicillin.
Metronidazole.
plus
-PPI and/or H2 antagonist.
NB: Triple Therapy for 1 week then PPI alone.
Describe ‘quadruple therapy’ for Helicobacter pylori Eradication
-Bismuth sub citrate potassium. § Metronidazole.
-Tetracycline.
-Omeprazole.
NB: Very effective, especially when there is antibiotic resistance.
Describe the ulcerogenic effects of NSAIDs (& Oral Steroids)
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How to minimise GI damage of NSAIDs
-Prophylaxis with PPI.
-H2 antagonists less or ineffective.
-Famotidine has been shown to be effective.
-Give in combination with misoprostol - a stable PGE1 analogue - acts on prostanoid
receptors to inhibit gastric H+ secretion.
-‘Take with food’ ~ probably ineffective.
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