L20 - GI Drugs Flashcards
What is the function of the GI tract?
- ingestion
- motility
- secretion
- digestion
- absorption
What is the neurological control of the GI tract?
- CNS
- enteric NS
What are the hormones that play a role in the GIT?
- acetylcholine (ACh)
acts through muscarinic receptors to induce motility and secretion - serotonin (5HT)
released in response to stress and food and triggers gastric motility (peristalsis) - dopamine
produced by muscle and epithelial cells + inhibits neurotransmitter release to decrease motility - histamine
acts through H1 receptors in brain (induces nausea) or H2 receptors in gut (induces gastric acid secretion)
What cells are involved in gastric acid secretion?
- parietal cells produce HCl
- chief cells produce pepsinogen which is converted to pepsin (protease)
What are the protective mucosal factors in the stomach?
- prostaglandins (COX1)
- mucus
- bicarbonate
- mucosal blood flow
What are the aggressive factors in the stomach that promote disease?
- acid
- pepsin
- NSAIDs
- helibacter pylori
What are gastric disorders characterised by? What disorders can this lead to?
characterised either by:
- hypersecretion of gastric acid
- lack of mucous secretion
common disorders:
- gastroesophageal reflux disorder (GORD)
- peptic ulcers
What is GORD? What is it caused by?
- gastroesophageal reflux disorder
- caused by reflux of gastric acid into the oesophagus = heartburn
If unresolved, what can GORD develop into?
- erosive inflammation in the oesophagus
- adenocarcinoma (cancer which forms in mucous-secreting glands)
What are the treatment options for GORD?
increase gastric pH
- antacids
- H2 (histamine) receptor antagonist
- proton pump inhibitor (ulcers) (preferred for mild-severe gastric-acid related diseases)
protect gastric mucosa
- coating agents
What are antacids and their mechanism of action?
- weak bases (CaCO3, Mg(OH)2, Al2(OH)3)
- neutralise acid to form water and salt
- thus raises gastric pH
DOES NOT PREVENT OVERPRODUCTION OF ACID
When are antacids used?
used for mild cases of GORD
What are the adverse effects of antacids?
- excessive use can result in kidney stones with calcium salts
adverse effects rare and depend on the salt used:
- Al + Ca = constipation
- Mg = diarrhoea
- CaCO3 = produces gas and belching
What are H2 (histamine) antagonists? What is their mechanism of action?
HISTAMINE ANTAGONISTS IMPORTANT
- H2 receptors are GsPCR
the receptors increase cAMP and PKA which activates proton pump (H+/K+ ATPase) = increases gastric acid secretion
the receptor modulates histamine, gastrin and ACh induced acid secretion via pre-synpatic receptors - histamine antagonists are competitive antagonists that prevent the receptor activation
What is are the 4 histamine antagonists?
HISTAMINE ANTAGONISTS IMPORTANT
- cimetidine (bold)
- ranitidine, famotidine, nizatidine
When are histamine H2 antagonists used?
HISTAMINE ANTAGONISTS IMPORTANT
use in the treatment of mild peptic ulcers and mild GORD
- not directly affecting acid production
What are the adverse effects of histamine H2 antagonists?
HISTAMINE ANTAGONISTS IMPORTANT
usually rare and minor side effects
- dizziness
- headache
- diarrhoea
- muscular pain
abrupt withdrawal can result in transient increase in gastric acid secretion due to upregulation of H2 receptors as compensation for receptor activity inhibition
= relapse of peptic ulcer or GORD
Where can peptic ulcers occur?
- stomach
- duodenum
- lower oesophagus
What are the risk factors of peptic ulcers?
Helicobacter pylori is a major causative factor also include: - smoking - excessive alcohol - genetic factors - NSAID use - physical and emotional stress they somehow turn down the protective mechanism in the stomach lining
What are the symptoms of peptic ulcers?
- abdominal pain made worse by food (time to pain depends on location of ulcer)
- nausea/vomiting
- loss of appetite and weight loss
- blood in faeces due to bleeding
Why does Helicobacter pylori cause peptic ulcers?
- eats away at mucosal layer
- expose endothelial cells to acid = ulcer
diagnosed by endoscopic biopsy
What are the treatment options for peptic ulcers due to H. pylori?
first-line treatment
- broad spectrum antibiotics (amoxycillin)
other:
- proton pump inhibitor (omeprazole)
for treatment of symptoms - increase pH by inhibiting gastric acid secretion
What is the mechanism of action for proton pump inhibitors? How are they different to histamine antagonists?
- bind to gastric proton pump (H+/K+ ATPase) and inactivates
- cf. histamine antagonists: more potent because both basal and stimulated acid secretion is inhibited
What are the benefits of proton pump inhibitors?
- rapidly absorbed from the small intestine
- short plasma half-life ~2 hours
- have prolonged duration of effect due to covalent binding to H+/K+ ATPase pump = convenient once daily dosing
once PPIs bind to pump it stays for the life of the cell ~2-3 days
What are the adverse effects and interaction associated with proton pump inhibitors?
they are generally well tolerated but more likely to have side effects than with histamine antagonists minor adverse effects: - headache - abdominal pain - nausea
interactions:
- PPIs metabolised before excretion so caution needed for patients with hepatic disease because less effective
- Oemprazole inhibits CYP2C19 = decreases metabolism of other drugs associated with that enzyme
- interacts with absorption of drugs that require acidic environment of stomach (e.g. aspirin)
