Drugs for peptic ulcer disease Flashcards
Rank potency of gastric drugs from highest to lowest
- Proton pump inhibitors
- H2 receptor antagonist
- Antacids - neutralise acidity with base
Types of antacids
NaHCO3
CaCO3
Mg(OH)2
Al(OH)3
Antacids MOA
- weak base, neutralise gastric acid
- reduce gastric acidity, DOES NOT prevent gastric acid production
potency
- NaHCO3 > CaCO3 > Mg(OH)2 > Al(OH)3
Indication for antacid
- non prescription remedy for HEART BURN, DYSPEPSIA
- large, frequent doses required
Why do some antacids contain simethicone
simethicone: anti-foaming agent
- ease release of gas (CO2) within GI tract via burping/ flatulence
Na+, Ca2+ antacids adverse effects
- Na+ antacids: fluid retention, hypertension, CHF
- Ca2+ antacids: hypercalcemia, rebound acid secretion (after discontinuing medicine)
common to both:
- metabolic alkalosis
HCO3-, CO3- antacids adverse effects
- belching, flatulence from CO2 gas formation
Mg2+, Al3+ antacids adverse effects
- Mg2+ antacids: osmotic diarrhoea
- Al3+ antacids: constipation
antacids contraindication
- avoid LT use in RENAL INSUFFICIENCY
- do not take within 2 HOURS of other medication
H2 receptor antagonist examples
FAMOTIDINE (most potent), ranitidine, cimetidine (least potent)
H2 receptor antagonists MOA
- competitive inhibitor of H2 receptors, suppress acid secretion by PARIETAL cells
H2 receptor antagonist efficacy
- inhibit 60-70% of total gastric acid secretion
- inhibit NOCTURNAL acid secretion
- little effect on meal induced acid secretion (meals trigger acid secretion from other mediators - gastrin, AChE)
when is the most appropriate time to take famotidine
- at night before sleeping -> inhibit NOCTURNAL acid secretion
therapeutic index of H2 antagonists
- high therapeutic index -> relatively safe
H2 antagonists adverse effects
famotidine & ranitidine:
- headache, nausea, dry mouth
- (RARE, severe): tachycardia, blood dyscrasia, blurred vision, musculoskeletal pain
cimetidine:
- headache, nausea, diarrhea
- ANTI ANDROGENIC -> gynaecomastia (men); galactorrhoea (women)
PPI (proton pump inhibitor) examples
Omeprazole, Esomeprazole (S-isomer of omeprazole)
omeprazole MOA
- inhibit H+/K+/ATPase (proton pump) in PARIETAL cells
- IRREVERSIBLE block
- some antimicrobial activity (against H pylori, but insufficient)
why do PPI contain enteric coating
- protect against activation by stomach acidity before absorption (active drug very poorly absorbed)
how is PPI activated
- enteric coating protects drug from stomach -> prodrug is released and absorbed in small intestines
- prodrug has good bioavailability in blood -> eventually enters PARIETAL CELL CANALICULUS -> protonated & activated
- drug forms IRREVERSIBLE covalent disulfide bonds with proton pump in parietal cell
can PPI be taken with food?
NO. bioavailability is decreased 50% by food
- give on EMPTY stomach (usually 1 hr before breakfast)
Why must meals be taken 1 hour after PPI (and not longer?)
- PPIs inhibit active pumps (not resting pumps) -> pumps active when food is present in stomach
- PPIs have SHORT t1/2 (1-2hr) -> must give food soon after ingestion so PPI is still present in bloodstream to take effect
PPI dosage
irreversible blockage -> 24hours block -> ONCE DAILY
PPI adverse effects
- headache, nausea, flatulence, diarrhoea, dizziness, rash
- increase risk of C. difficile infection
- hypomagnesemia
(RARE): acute interstitial nephritis, chronic kidney disease, SLE
Gastric mucosal protection drug examples
- Sucralfate
- Bismuth compounds
- Misoprostol
gastric mucosal protection drug indications
- PREEXISTING peptic ulcers (cannot be treated by gastric acid secretion drugs)
sucralfate MOA
- Negatively charged sucrose sulphate binds to positively
charged proteins at ulcer crater forming a viscous,
tenacious gel -> prevents further acid attack
– Stimulates mucosal PG -> increase bicarbonate and mucus secretion
sucralfate systemic effects
- highly insoluble -> NO systemic effects
how is sucralfate administered
- on empty stomach (1hr before food) -> prevent binding to +ve charges on food
sucralfate adverse effects
- constipation (contain Al(OH)3)
- impair absorption of other drugs
bismuth compounds MOA
- forms a protective layer protecting ulcers from acid and pepsin
– stimulates mucus and bicarbonate secretion
– directly anti-microbial activity against H. pylori
bismuth compounds adverse effects
- harmless blackening of stool, reversible blackening of tongue
- ONLY short term use (prolonged use -> bismuth toxicity, encephlopathy)
- AVOID in renal insufficiency
Misoprostol MOA
- PGE1 analogue (mimic endogenous PG)
- Binds to PGE2 receptors (EP1-4)
– Low dose (cytoprotective): promotes bicarbonate and
mucus secretion, enhances mucosal blood flow
– High dose (antisecretory): inhibits gastric acid secretion
Indications of misoprostol
- prevent NSAID induced peptic ulcers
Misoprostol adverse effects
- Abdominal pain
– Diarrhoea
– Abortion (uterine contraction)
– Bone pain and hyperostosis (excessive bone growth)
what is the triple therapy for H pylori infection
- clarithromycin
- amoxicillin or metronidazole
- PPI (omeprazole/ esomeprazole)
(2 antibiotics + 1 PPI), 7-14 days
why are 2 antibiotics used in triple therapy against H pylori
- H pylori becomes resistant to metronidazole & clarithromycin when given alone
PPI MOA in triple therapy
- increase gastric acid pH (H pylori multiplies better at higher pH)
- antibiotics work best when H pylori is MULTIPLYING
after completion of triple therapy, PPI is continued to ensure complete healing:
– 4-8 weeks for duodenal ulcers
– 8-12 weeks for gastric ulcers
administration of antibiotic in triple therapy
- twice a day
- with/ after food within 1 hour (reduce GI effects)
administration of PPI
- twice a day
- after 2 hours fasting, + 30min-1hr before food
second line quadruple therapy drugs
– 1 Bismuth + 2 antibiotics + 1 PPI or H2 antagonist (10-14 days
