anti-ulcer drugs Flashcards
what is a peptic ulcer?
area of damage to inner lining of stomach (gastric ulcer) or upper part of the duodenum (duodenal ulcer)
how can these ulcers be distinguished?
- based on timing of symptoms
- gastric ulcer: pain at mealtimes when acid secreted
- duodenal ulcer: pain relieved by a meal as pyloric sphincter closes (pain starts after 2 hours)
which ulcers are more common?
duodenal: gastric = 4:1
what are the protective factors of GI barrier? What do they do?
- lubricate food and protect mucosal surfaces
- mucus from gastric mucosa creates GI mucosal barrier
- HCO3- ions are trapped in mucous, generate protective pH at 7 at mucosal surface
what do locally produced prostaglandins do?
- stimulate mucus and bicarbonate production
- inhibit gastric acid secretion
- facilitate a good blood supply to stomach
what are some factors that convert the food into chyme and damage the mucosal barrier?
- parietal cells: acid secretion from parietal cells of oxyntic glands in gastric mucosa
- chief cells: pesinogens which erode mucous layer
what are the factors that contribute to mucosal damage?
- inc. acid or dec. HCO3-
- dec. thickness of mucosal layer
- inc. in pepsin type 1
- dec. mucosal blood flow
- infections w/ H. pylori
- risk factors: genetic, stress, diet
what are the 5 classes if drugs used to treat ulcers? what do each of them do?
- antibiotics: eradicate H. pylori
- inhibitors of gastric acid scretion: prevent gastric acid production
- cytoprotective drugs: promote healing
- antacids: neutralize gastric acid
- triple therapy
how many ulcers are infected with H. pylori?
- 100% of duodenal
- 80-90% gastric
what are the risk factors for acquiring H. pylori?
- socioeconomic conditions
- contact w/ animals and contaminated faeces
what is the triple therapy treatment?
- clarithromycin, amoxicillin, proton pump inhibitor
1. antibiotics: more than 1 type as there is some small resistance
2. drugs that reduce gastric acid secretion
3. drugs that promote healing
what are the 3 inhibitors of gastric acid secretion?
- proton pump inhibitors e.g. Omeprazole
- H2 receptor antagonists e.g. Rantidine
- Anti-muscarinics
describe the production of gastric acid
- presence/ smell of food can trigger acid production
- in fundus, there are acid secreting parietal cells
- PNS can act on H-cells to stimulate histamine production
- in antrum, amino acids can trigger g-cells to secrete gastrin
- gastrin triggers more histamine release/ more acid production
how do inhibitors of gastric acid secretion work?
- acid is produced by H/K exchanger
- histamine then acts on H2 receptors on parietal cells
- triggers activation of these exchangers via cAMP pathway
- superficial epithelial cells provide protective bicarbonate secretion
- mixes with mucus to protect
what is the MoA of proton pump inhibitors?
- inhibits basal and stimulates gastric acid secretion
- irreversible inhibitor of H/K ATPase exchanger
- becomes inactive at neutral pH
where do proton pump inhibitors accumulate? Why?
at canaliculi as it is a weak base
give an example of a proton pump inhibitor
omeprazole
what are the uses of PPIs?
- peptic ulcers resistant to H2-receptor antagonists
- triple therapy component
- GERD and oesophagitis
- prophylaxis of peptic ulcers in intensive care
what are the pharmacokinetics of PPIs?
- oral
- administered in an enteric coating
what are the side effects of PPIs?
- side effects rare due to short term use
- long term + high dose –> enteric infections (C. diff), community acquired pneumonia
what is the MoA of H2 receptor antagonists?
- inhibits gastric acid secretion by parietal cells by around 60%
- less effective than PPIs
- competitive H2 receptor antagonists
what are the pharmacokinetics and side effects of these?
- oral, well absorbed
- rare side effects = headaches, dizziness
are anti-muscarinic drugs used?
- little use as anti-ulcer drug
- more effective in combo therapies
what do cytoprotective drugs do? name examples
- enhance mucosal protection
- build physical barrier over ulcer
e. g. Sucralfate, Misoprostol
what is the MoA of sucralfate?
- in an acid environment, needs a strong -ve charge
- binds to +ve groups in large molecules
- forms gel-like complexes
- this coats and protects ulcer
- limits H+ diffusion and pepsin degradation pf mucus
- inc. prostaglandin, mucus and HCO3- production
- dec. number of H pylori
what is the structure of Sucralfate?
- polymer containing Al(OH)3 and sucrose octa-sulphate
what are the side effects of sucrafate?
- most orally administered
- sucralfate remains in GIT
- causes constipation or reduced absorption of other drugs e.g. digoxin, antibiotics
what is bismuth chelate/ pepto-bismol?
acts like sucralfate
used in triple therapy
what is misoprostal?
- prostaglandin analogue
- orally active
- mimics action of prostaglandins to maintain mucosal barrier
why is misoprostal co-prescribed with NSAIDs when used chronically?
- NSAIDs block COX enzymes needed for prostaglandin synthesis from arachidonic acid
what are the side effects of misoprostol?
- diarrhoea
- abdo cramps
- uterine contractions
what are ant acids? what is the speed of action?
- salts of Na, Al, Mg
- sodium bicarbonate has rapid effects
- aluminium hydroxide and magnesium trisilicate have slower actions
what is the MoA of antacids?
- neutralise acid
- raise gastric pH
- reduce pepsin activity
- oral admin
what are the problems with triple therapy?
- compliance
- antibiotic resistance
- adverse response to alcohol (metronidazole)
what drugs are included in the triple therapy?
- antibiotics
- inhibitors of gastric acid secretion
- cyto-protective agents
- reduces rate of peptic ulcer relapse rate
what OTC medication can be used for GORD?
antacids
H2 antagonists
what do patients experience with GORD?
heart burn
what does chronic GORD lead to?
- barrett’s oesophagus
what drugs can be used to treat chronic GORD?
PPIs
H2 antagonists
