Gastrointestinal Pharmacotherapy Flashcards
Physiologic Mechanisms of Gastric acid secretion
- What chemicals regulate gastric acid secretion?
- How does gastric acid secretion come about?
- How is the stomach able to protect itself from gastric acid erosion?
Gastric Acid Secretion and Regulation
1. Neuronal (ACh, Gastrin-releasing peptide)
2. Paracrine (Histamine)
3. Endocrine (Gastrin)
Parietal cells in stomach secrete Hydrogen cations
1. Receptor on parietal cells are activated
2. cAMP and Ca2+ dependent pathways activate proton pumps (H+/K+ ATPase)
3. H+ and K+ exchange across parietal cell membrane
Gastric defences against acid like the secretion of mucus layer which trap secreted bicarbonate at the cell surface.
What is acid reflux (GERD)?
Acid reflux is when the acid that is normally in your stomach backs up into the esophagus. The esophagus is the tube that carries food from your mouth to your stomach.
When acid reflux causes bothersome symptoms or damage, doctors call it “gastroesophageal reflux disease” or “GERD.”
What are the symptoms of acid reflux?
The most common symptoms are:
●Heartburn, which is a burning feeling in the chest
●Regurgitation, which is when acid and undigested food flow back into your throat or mouth
Other symptoms might include:
●Stomach or chest pain
●Trouble swallowing
●Having a raspy voice or a sore throat
●Unexplained cough
●Nausea or vomiting
Is there anything I can do on my own to feel better for GERD?
Yes. You might feel better if you:
●Lose weight (if you are overweight)
●Raise the head of your bed by 6 to 8 inches – You can do this by putting blocks of wood or rubber under 2 legs of the bed or a foam wedge under the mattress.
●Avoid foods that make your symptoms worse – For some people these include coffee, chocolate, alcohol, peppermint, and fatty foods
●Stop smoking, if you smoke
●Avoid late meals – Lying down with a full stomach can make reflux worse. Try to plan meals for at least 2 to 3 hours before bedtime.
●Avoid tight clothing – Some people feel better if they wear comfortable clothing that does not squeeze the stomach area.
How is acid reflux treated?
Mild Symptoms
- Antacids (Only for short time)
- H2RAs are stronger and last longer
Frequent and More Severe Symptoms
- PPIs
When should I see a doctor or nurse about my acid reflux?
Should consult:
- Long lasting / severe / uncontrolled symptoms
Should seek medical attention right away:
●Have trouble swallowing, or feel as though food gets “stuck” on the way down
●Lose weight when you are not trying to
●Have chest pain
●Choke when you eat
●Vomit blood or have bowel movements that are black tarry stools
Peptic Ulcer Definition and Types
Open sores in the upper part of the digestive tract that can cause stomach pain or stomach upset, and that can lead to internal bleeding
- Gastric Ulcer
- Duodenal Ulcer
Peptic Ulcer Pathophysiology and Causes
Pathophysiology:
- When excess acid causing erosion of the lining.
- When the protective layer of mucus on the lining is broken down (making it more susceptible)
Causes:
- Helicobacter pylori - Increase acid, cause inflammation, break down mucus layer
- NSAIDs - Cause changes in protective mucus layer
- Others - Genetics, smoking, alcohol, food, stress
What are some Peptic Ulcer Symptoms?
●Upper abdominal pain or discomfort (often a burning or hunger-like feeling)
●Feeling full quickly when eating
●Stomach pain, belching, or feeling bloated after eating
●Heartburn or acid reflux
●Nausea
●Vomiting (in severe cases, there may be blood in the vomit)
●Blood in the stools (which may cause stool to appear black or tar-like)
How is peptic ulcer diagnosed?
- Upper endoscopy
- H Pylori testing (Breath or stool sample)
How is peptic ulcer treated?
Treat according to cause:
(1) H Pylori
- Bismuth Quadruple Therapy (10-14 days, Penicillin Allergy): PPI BD, Bismuth BD, Metronidazole TDS, Tetracycline QDS
- Clarithromycin Triple Therapy (14 days, No Penicillin Allergy): PPI BD, Amoxicillin BD, Clarithromycin BD
(2) NSAIDs
- 8-week regimen of H2RA or PPI
- Options for NSAID use:
a) Continued but PPI must be 12-week regimen
b) Reduce NSAID dose
c) Switch to paracetamol or selective COX-2 inhibitors
MOA of H2RAs
Competitively, reversibly blocks histamine stimulation of gastric acid secretion by reducing cAMP – attenuate protein kinases stimulation on H+K+ ATPase (proton pump)
Why are H2RAs taken at night?
To achieve 90% inhibition.
H2RAs are highly effective in inhibiting fasting and nocturnal secretion (histamine dependent)
Meal-stimulated acid secretion is dependent on gastrin, ACh and histamine, so it is less effective here
Dosing for H2RAs
Ranitidine
- 150 mg tab ON
- 50 mg q6-8h IM or IV
Famotidine
- 40 mg tab ON
- 20 mg q12h IV
MOA of PPIs
Prodrug:
- Destroyed by gastric pH (enteric coated)
- Molecular conversion to active thiophilic sulfonamide cation in acidic canaliculi of parietal cell
Irreversibly blocks H+ K+ ATPase (Proton Pump), i.e. the final step in gastric acid secretion – antagonizes all stimulants of gastric secretion
Takes 3-4 days for full inhibition
Takes 4-5 days after drug withdrawal to return to pre-treatment proton pump levels
