git - drugs for peptic ulcer disease Flashcards
3 classes of agents that reduce gastric acid
ranked from strongest to weakest
PPIs > H2 antagonists > antacid
moa of antacids
neutralise gastric acid to salt and water
rank antacids according to rate of neutralisation
NaHCO3 > CaCO3 > Mg(OH)2 > Al(OH)3
indications for antacids
- heartburn
- dyspepsia
what is antacids usually combined with and why?
simethicone (anti-foaming agent) → coalesces bubbles and reduces bloating → reduce gastric distention, belching or flatulence
adverse effects of antacids
- Na+: fluid retention, HTN, avoid in chronic HF
- Ca2+: hypercalcemia, rebound acid secretion
- Na+, Ca2+: metab alkalosis, milk-alkali syndrome
- HCO3-/CO32-: gastric distention, belching, flatulence
- Mg2+: osmotic diarrhoea
- Al3+: constipation
caution of use for antacids
- avoid LT use in pts w renal insufficiency
- do not take within 2h of other meds (affect absorption of other meds)
why are Mg2+ and Al3+ usually formulated tgt in antacids?
minimise impact on bowel func (Mg2+ cause diarrhoea, Al3+ cause constipation → effects cancel out)
name 3 H2 antagonists, ranked in terms of potency
famotidine > ranitidine > cimetidine
moa of H2 antagonists
- comp inhibitor of H2 receptors on parietal cells → suppresses acid secretion
- effective at inhibiting nocturnal acid secretion (due to histamine)
- modest effect on meal-induced acid secretion (due to gastrin, ACh)
when should H2 antagonists be taken for max efficacy
at night before sleeping
adverse effects of famotidine and ranitidine
- headache, nausea, dry mouth
- rarely: tachycardia, blood dyscrasia, blurred vision, MSK pain
adverse effects of cimetidine
- headache, nausea, diarrhoea, constipation, fatigue
- mental confusion in critically ill pts/pts w renal/hepatic dysfunc
- inhibits estradiol metab, increases serum prolactin
- gynaecomastia and impotence (men)
- galactorrhoea (women)
name 2 PPIs
- omeprazole (mix of S and R isomers)
- esomeprazole (S-isomer of omeprazole)
moa of PPIs
- inactive pro-drugs → absorbed in intestines → activated in parietal cell canaliculi → forms covalent disulphide bonds w proton pumps → irreversibly blocks proton pumps in parietal cells → most potent inhibitor
- some anti-microbial activity against H. pylori
dosing of PPIs
- give on empty stomach, 1h before meal
- given once a day (doa: 24h)
- 3-4 days to fully inhibit acid secretion
adverse effects of PPIs
- headaches, nausea, flatulence, diarrhoea, dizziness, rash
- C diff infection
- intestinal colonisation w MDR org
- hypomagnesaemia
- risk of microscopic colitis
- rare: CKD, lupus
name 1 PCAB
vonoprazan
moa of PCABs
inhibits H+/K+ ATPase at parietal cells by blocking K+ binding
advantages of PCABs over PPIs
- elimination independent of CYP enzymes
- more acid resistant
- bioavailability not reduced by food
- better for severe erosive oesophagitis
3 eg of mucosal protective agents
- sucralfate
- bismuth compounds
- misoprostol
moa of sucralfate
- breaks down to sucrose sulphate (-vely charged) → binds +vely charged proteins at ulcer crater → forms tenacious gel that prevents further acid attack
- stimulates mucosal prostaglandin → bicarb and mucus secretion
dosing of sucralfate
empty stomach, 1h before meals
use of sucralfate
prevention of stress-related bleeding in critically ill pts
adverse effects of sucralfate
- constipation
- binds to +ve charges of other drugs and impair their absorption
moa of bismuth
- form protective layer, protecting ulcer from acid and pepsin
- stimulates mucus and bicarb secretion
- direct anti-microbial activity against H. pylori
adverse effects of bismuth
- harmless blackening of stools and reversible darkening of tongue
- prolonged use → encephalopathy
- use only for short periods
- avoid in pts w renal insuff
moa of misoprostol
- synthetic PGE1 analogue → binds to PGE2 receptors
- low dose: promotes bicarb and mucus secretion, enhances mucosal blood flow
- high dose: inhibits gastric acid secretion
indication for misoprostol
prevention of NSAID-induced peptic ulcers
adverse effects of misoprostol
- abdominal pain
- diarrhoea
- abortion
- bone pain and hyperostosis
list the drugs used in triple-therapy for H. pylori eradication
- clarithromycin
- amoxicillin/metronidazole
- PPI (eg. omeprazole)
triple therapy administered for 7-14 days
mech of PPI in triple therapy
- antimicrobial properties
- raises intragastric pH
- reduce symptoms of PUD
- lowers min inhibitory conc of abx against H. pylori
how long should PPI be continued for complete healing
4-8 wks for duodenal ulcers, 8-12 wks for gastric ulcers
adverse effects of triple therapy
diarrhoea, nausea, vomiting
list drugs used in quadruple therapy
- bismuth
- PPI/H2 antagonist
- metronidazole
- tetracycline
