Foregut Pharmacology Flashcards
PPIs: MOA
Ex: Omeprazole (all end in “-azole”)
MOA: • Irreversibly bind proton pump • To function: pump needs to be active • Slow onset of action (hours) but long lasting (up to 12 hours) • Available OTC in full strength
PPIs: uses
Heal ulcers
• H. pylori treatment: 2 weeks of PPI + (amoxicillin, clarithromycin OR amoxicillin, metro); and 8 weeks of ulcer therapy
• Must always document eradication
• Need to visually document gastric ulcer healing
- Erosive esophagitis & erosive gastritis/duodenitis
- Treat gastrinoma (Zollinge Ellison)
PPIs: adverse effects
- Increase risk of C. difficile, GI infections, pulmonary infections
- Decreased Ca2+ absorption, osteoporosis risk, low magnesium
- Interacts with clopidegrel (anti-platelet medication)
- May cause abdominal pain, diarrhea
H2-Histamine Receptor antagonists: MOA
Ex: Ranitidine, Cimetidine, Famotidien, Nizatidine (end in “-idines”)
MOA: • Blocks histamine signaling pathway = reversibly competes with histamine for H2-receptor binding on parietal cells • Faster onset (15-20 min) • But less potent effect • Available at ½ and full strength OTC
H2-Histamine Receptor antagonists: Uses
- Strong enough to heal ulcers
- Most effective in suppressing nocturnal acid secretion
- Dyspepsia, heartburn, treating uncomplicated GERD
H2-Histamine Receptor antagonists: adverse effects
- Low incidence
- Diarrhea, headache, drowsiness, fatigue, muscular pain, constipation, less commonly CNS effects
Cimetidine:
• Interacts with anticoagulation
• Can cause gynecomastia in me and galactorrha in women
Prostaglandins: MOA
Ex: Misoprostol
MOA:
• Synthetic analog of PGE1
• Binds EP3 receptor on parietal cells → inhibits acid production
• Also = stimulates mucin and bicarbonate secretion; improves mucosal blood flow → cytoprotective effects
Prostaglandins: uses
• When taken together, protects stomach from NSAIDs
Prostaglandins: adverse effects
- Diarrhea (up to 30% of patients)
* Contraindicated in women of child-bearing age or during pregnancy → fetal loss
Sucralfate: MOA
o The “super antacid”
MOA:
• An octasulfate of sucrose with aluminum hydroxide added
• Cross-links into viscous, sticky liquid → Sticks to inflamed areas
• Binds to both HCL and bile salts
• Also = cytoprotective → stimulates PG and epidermal growth factor (EGF) production
• Need to take 4x/day for full effect
Sucralfate: adverse effects
- Constipation
- Aluminum poisoning if in renal failure
- Viscous layer can inhibit absorption of other drugs
Antacids: types
- Aluminum = can constipate
- Magnesium = can cause diarrhea
- Calcium carbonate (Tums)
Antacids: MOA
- Neutralizes acid
- Fast!
- Bind both HCl and bile salts
Antacids: Adverse effects
- Alter gastric and urinary pH → altered rates of dissolution and absorption of other drugs (Need to take antacids 2 hours before other drugs)
- NaHCO3- = can cause alkalosis
- Bicarbonate and carbonate-containing antacids = release CO2 → belching, occasional nausea, abdominal distension, flatulence
- Mg2+ = laxative
Describe the mechanism that accounts for the difference between the adverse effects of NSAIDs (both COX-1 and COX-2) on the gastrointestinal tract.
NSAIDs = inhibit prostaglandins
Selective COX-2 inhibitors
o Less upper GI toxicity (in short term use NOT taking with aspirin)
o If take with aspirin = same incidence of ulcers as with non-selective NSAIDs
Metoclopramide: MOA
Facilitates Ach release from enteric neurons
• Suppresses inhibitory interneurons that use 5-HT
• Blocks dopamine recptors
Result: coordinated contractions = enhance transit and improves gastric emptying
Metoclopramide: adverse effects
o In elderly: confusion at high doses
o Black box warning: Parkinson’s like and tardive dyskinesia (may be irreversible)
Erythromycin
o Resembles GI messenger motilin → increases stomach emptying
o Only works at low dose
o Works best in IV form
o Side effect: tachphylaxis (diminished drug response = so limited utility)
List 5 classes of antiemetics and the mechanisms responsible for their actions.
5-HT3-receptor antagonists
Dopamine-receptor antagonists
Antihistamines – H1-histamine receptor blockers
Anticholinergics:
Dronabinol (delta-9-THC)
Anti-emetics: 5-HT3-receptor antagonists
o Ondansetron
o Unclear if work at central or peripheral sites (or both)
o Highest 5-HT3 receptor concentrations in nucleus tractus solitarius (of vagus nerve) and chemoreceptor trigger zone
o Very well tolerated
o Adverse effects: constipation, diarrhea, headache, light-headedness
Anti-emetics: Dopamine-receptor antagonists
o The phenothiazines: prochlorperazine (Compazine)
o Block D2-dopamine receptors in chemoreceptor trigger zone
Anti-emetics: Antihistamines – H1-histamine receptor blockers
o Promethazine (Phenergan)
o Act on vestibular afferents and within brainstem
o Used: motion sickness and post-op emesis
Anti-emetics: Anticholinergics:
o Scopolamine
o Prevent and treat motion sickness
o No role in chemotherapy-associated nausea
Anti-emetics: Dronabinol (delta-9-THC)
o For cancer chemotherapy and refractory cases
o Adverse effects: tachycardia, conjunctival injection
o High doses can cause Cannabinoid induced cyclic vomiting syndrome
