Gastrointestinal pharmacology Flashcards
Histamine H2 receptor antagonists
Used to reduce stomach acidity.
MOA: they inhibit histamine action at all H2 receptors. This inhibits histamine- and gastrin-stimulated gastric secretion, also reducing pepsin secretion by reducing the volume of gastric juice:
Side-effects: rare.
Proton pump inhibitors
Used to reduce stomach acidity.
MOA: Irreversibly binds to a cysteine residue in the H+/K+ ATPase. This creates a prolonged and irreversible action that only ends once new proton pumps are synthesized after ca. 18 hours.
They are administered as prodrugs, requiring activation by the acidic environment; the only place in the body where it is acidic enough is the stomach. When ingesting the drug, you need to consume food after around 30-40 minutes to drop the pH in the stomach or else the prodrug won’t be converted to active form and will just be filtered in kidneys.
Side effects: rare.
Antacids (aluminum, hydroxide, magnesium)
These are the easiest way to neutralize stomach pH. They are not effective for gastric ulcer treatment, though may have some applicability for duodenal ulclers.
MOA: salt of magnesium and aluminum raise the pH of the stomach contents.
Side-effects: magnesium salts cause diarrhea and aluminum salts cause constipation. Taken together, these effects cancel out.
Misoprostol (drug increasing mucosal protection)
Usage: promotes healing of ulcers or used to prevent gastric damage from chronic NSAID use.
MOA: prostaglandin E1 analogue. Exerts the same protective effects as prostaglandin, namely reducing acid secretion by acting on ECL cells, stimulating mucus and bicarbonate secretion, and increasing mucosal blood flow- Most of the effects are involved in increasing mucosal protection, but it also has an acid-reducing effect.
Side-effects: diarrhea, abdominal cramps, uterine contractions.
Sucralfate (drug increasing mucosal protection)
MOA: this is a complex of aluminum hydroxide and sulfated sucrose that releases aluminum in the presence of acid. The residual complex carries a negative charge, allowing it to bind to glycoproteins in the mucous, forming a protective barrier by stabilizing the mucous and forming a complex gel, reducing mucous degradation by pepsin and reducing H+ diffusion.
Side effects: reduces absorption of a number of other drugs. Constipation, vomiting.
How can NSAIDs cause peptic ulcers?
The enzyme Cox1 is responsible for the synthesis of prostaglandins. These have a protective effect on the stomach mucosa. NSAIDs are Cox-inhibitors that are often more specific for Cox-1 (due to myocardial infarction effect of Cox-2 specific inhibition), therefore they reduce prostaglandin activity in the stomach, reducing mucosal protection and increasing acid secretion, and increasing peptic ulcer risk. NSAIDs will affect COX1 and COX2. COX2 inhibition will reduce inflammation, but COX1 inhibition also reduces homeostatic function and doesn’t allow the formation of protective mucus barrier, prostaglandin activity, etc.
H1 receptor antagonist (antiemetic drug)
Usage: nausea and vomiting prevention, including against motion sickness and stomach irritation.
MOA: antagonists for H1 receptors in the vestibular nuclei, and they also have some affinity for muscarinic receptors.
Side effects: drowsiness and sedation.
Muscarinic receptor antagonists (antiemetic drug)
Usage: used as prophylaxis (to prevent) for motion sickness.
MOA: antagonist for muscarinic receptors in vestibular nuclei and vomiting centre.
Side effects: drowsiness and sedation, though less sedation than H1 receptor antagonists.
5-HT3 receptor antagonists (antiemetic drug)
Usage: prevention and treatment of vomiting, and nausea to a lesser extent. Often used in connection with chemotherapy, surgery, or radiation therapy.
MOA: antagonists for 5-HT3 receptors in the chemoreceptor trigger zone.
Side effects: headache and GI tract upset.
Osmotic laxatives (for constipation)
Mechanism: poorly absorbed solutes that increase the osmolarity of the intestinal lumen contents, creating an osmotic load that traps more fluid in the GI lumen, accelerating passage through the intestines by softening intestinal content, increasing volume of intestinal content, and increasing reflex motility
Side effects: abdominal cramps
Stimulant laxatives (for constipation)
Mechanism: Increase water and electrolyte secretion by the mucosa. Also increase peristalsis by increasing contraction of intestinal lumen.
Side effects: abdominal cramps
5-ASA-mesalazine (mesalamine) (for inflammatory bowel disease)
Mechanism: acts locally in the gut to block prostaglandin synthesis by inhibiting COX, inhibit lipoxygenase and scavenge free radicals to reduce oxidative stress, interfere with cytokine production to reduce inflammation, and decrease NF-kB activity to reduce immune activity.
Antibodies against TNF-alfa (for inflammatory bowel disease)
These reduce TNF-α mediated inflammation by binding, reducing Th1 and Th2-cell effects in the GI tract. They bind both soluble and receptor-bound TNF-α to inhibit their activity. Examples include infliximab and adalimumab.
