Peptic ulcer diseases
UlcersGERDZollinger-Ellison (ZE) syndromeStress-related mucosal injury Heartburn (pyrosis)
95% of ulcers are caused by....
H. Pylori or use of NSAIDs (e.g. ASA)
MOA of antacids
They are bases that contain Na+, Ca+, Al+, or Mg+ that NEUTRALIZE acid secreted in the stomach and offer subsequent mucosa protection. Since the pH is maintained at ~5, the activity of pepsin is inhibited—> decreased tissue injury.
What do antacids not do?
They DO NOT prevent acid production (only neutralize it) and they do not coat the ulcers or GI mucosa
Buffered antacids
AKA: Alka-SeltzerMix of aspirin (headache), sodium bicarbonate and citric acid (decrease stomach acidity)Note buffered comes with the base and citric acid.
Fast but short antacids (efficacy, side effects)
NaHCO3 (sodium bicarbonate) and Calcium carbonate (CaCO3)NaHCO3: High efficacyCaCO3: moderate efficacy SE: systemic alkalosis and fluid retention
Medium onset antacids (efficacy and Side effects)
Mg(OH2): high efficacy, SE= hypermagnesemia—> diarrheaAl(OH2): High efficacy.-SE: Aluminum toxicity—> constipationMix of Al/Mg: SE: decreased constipation and diarrhea
Drug interactions of Fast and medium onset antacids
Decrease absorption of acidic drugs (e.g. digoxin)Form insoluble chelates (eg. Tetracyclines)
Contraindications for fast and medium onset antacids
Renal failure.
Mucosal protectant drugs (name them)
Bismuth subsalicylateSucralfateMisoprostol
Clinical uses for mucosal protectants
Used for stomach, duodenal, and esophageal ulcersLess efficient than H2 antagonists and PPIs
Natural protective factors of the mucosa
Bicarbonate, mucus, Prostaglandins, blood flow, and regenerative processes
Clinical use and MOA of Bismuth Subsalicylate
Relieves heartburn, nausea and diarrheaMOA:-Salicylate: decreases net fluid secretion and stool frequency (antidiarrhetic) and inhibits prostaglandins (increased risk of GI bleed)-Bismuth: Antibacterial activity (important for tx of H. Pylori) and forms a protectant coat over the ulcer
MOA of sucralfate
Prevents ulcers produced by NSAIDsMOA/Effects:-Sulfate-Al-sucrose complex forms a protective layer in the ulcer site—> preventing acid exposure and promotes faster healing-Inhibits pepsin—> decreased tissue injury-Binds bile salts: protects the stomach lining from injury caused by bile acids-stimulates PG secretion—> rapid restitution and preservation of the gastric mucosa-Suppresses H. Pylori infection
Clinical uses and MOA of misoprostol
Prevention and treatment of peptic ulcers produced by NSAIDsMOA: 1. Protects mucosa by increasing bicarbonate/mucus secretion In the stomach and duodenum2. Reduces acid production in the stomach3. NOT FIRST LINE THERAPY due to adverse-effect profile (can induce labor)
Bismuth subsalicylate Pharmacokinetics, side effects, drug interactions, and contraindications
PK: local effect, fecal excretionSE: black stools, GI bleeding in excessDI: decreased absorption of tetracyclines, interaction with NSAIDSContraindications: GI bleeding, ulcers
Sucralfate (PK, SE, DI, CI)
PK: local effect, minimal liver and GI metabolism—> fecal excretionSE: constipation and hypophosphatemia DI: Chelates with -azole anti fungal, cimetidine, and digoxinCI: hyopophosphatemia, renal dysfunction
Misoprostol (PK, SE, DI, CI)
PK: activated to misoprostol acidSE: miscarriage and birth defectsDI: noneCI: Pregnancy
H2 antagonist drugs (3)
Cimetidine, famotidine, Nizatidine -DINE. After you eat H-too much at the DINEr, you need an antacid.
Clinical uses of H2 antagonists
Zollinger-Ellison syndromeGERDAdjunct tx for H. Pyloriused when other tx's fail
MOA of H2 antagonists
Inhibit H2 receptors—> both meal and basal acid secretions decrease. FYI:-Normal physiology: Food—> increased gastrin—> increases histamine—> binds H2 receptor on parietal cells—> increased HCL.
H2 antagonist PK, SE, DI, and CI
PK: highest efficiency and longest duration (12 hrs), liver metabolismSE: -common: stomach upset, headache-Long-term (and/or high dose): CIMETIDINE inhibits DHT from binding to androgen receptors—> gynecomastia, impotence (men), and galactorrhea in women. DI:-H2 antagonists prevent PPI activity, take them 4 hours apart-Decrease absorption of acidic drugs (azoles)—> decrease their efficacy-Cimetidine (only) inhibits CYP450-> decreased metabolism of different drugs—> side effects of those drugs. CI: lactation (only Nizatidine)
HE HAS PREPARED A STUDYGUIDE
...
PPIs name them (5)
Omeprazole (racemic mix)Esomeprazole (S(-)-omeprazole)LansoprazoleRabeprazolePantoprazole-PRAZOLE
Clinical use of PPIs
Most efficient for treating GERDSimilar effectiveness as H2 antagonists for peptic ulcersZollinger-Ellison syndrome (needs higher dose)
MOA of PPIs
Covalently attach and inhibit the H+/K+-ATPase which decreases HCL production from the parietal cells.
Pharmocokinetics of PPIs
HALF-LIFE hours but DURATION for days (GOOD TQ!!)Rabeprazole: highest/fastest activityR(+)-omeprazole (inactive)—> (2C19) esomeprazole (active): therefore, lower efficacy in "poor metabolizes
SEs of PPIs
Common: headache (more than H2 blockers), stomach upsetLonger the use, higher the risk of increased gastrin secretion—> gastric mucosal hyperplasia.
Drug interactions of PPIs
PH dependent drugs and vitamins:-decreases absorption of acidic drugs, vitamin b12, and Ca/Mg (increases risk of osteoporosis) pH independent:Omeprazole/esomeprazole (only): inhibit metabolism (2c19,2d6, 3A4) of several drugs
Contraindications for PPIs
Hepatic dysfunction (liver metabolism)
Treatment for H. Pylori infection
80-95% have ulcers Multidrug therapy1. H2 blocker OR PPI (6-8weeks)2. Two or more antibiotics OR bismuth (2 weeks)Remission rates are higher after eradication of H. Pylori infection
Combined Drugs (PPI+ antibiotics)
Lansoprazole (or omeprazole) + amoxicillin and Clarithromycin Omeprazole + amoxicillin and rifabutinFor RESISTANT H. Pylori (change to clarithromycin and metronidazole)
Side effects and contraindications of Clarithromycin
SE: GI upset, rash, overuse—> resistanceCI: hypersensitivity
SE and CI for amoxicillin
GI upset, rashRenal impairment (since renal secretion)Lactation
SE and DI of Flagyl (metronidazole)
Headache, nausea, metallic taste, overuse—> resistanceCV disease, or low levels of neutrophils
Tetracycline SE and DI
GI upset, photosensitivity, stained teethPregnancy, lactation, children <8yrs
Rifabutin SE and DI
Diarrhea nausea, headacheActive tuberculosis