Lecture 19 – GI Pharmacology Flashcards
peptic ulceration involves
gastric and uodenal ulcers
symptoms of peptic ulcerations are not
a reliable guide to ulcer location e.g. epigastric pain
chronic ulcers cna be
asymptomatic
adverse events of peptic ulceration
- Bleeding, perforation, scarring and possible obstruction
acid and peptic ulceration
- Acid essential for ulceration and inability of normal [acid] to inhibit further acid is a significant factor
risk factors of peptic ulcers
- Early gastric emptying also risk factor
- Helicobacter pylori is a major risk factor
- NSAIDs most common cause after H. pylori
Smoking and alcohol delay healing
How is acid produced by parietal cells
- Apical membrane has H+/K ATPase pump, K+ and Cl- pumps
- On the basal membranes HCO3-/Cl- antiport
- Carbonic anhydrase produces H2CO3 from water and carbon dioxide
- This dissociates to form HCO3- and H+
- H+ is pumped out of the cell on the apical membrane in exchange for potassium which comes into the cell
- Potassium conc of the lumen is replenished by the K+ transporter
- The chloride channel allows Cl- to move out of the cell into the lumen and combine with H+ à HCL
- Meanwhile the Cl- conc of the cell is maintained by the HCO3-/Cl- antiport on the basal membrane
- Influx of HCO3- into bloodstream= ALKALINE TIDE
drugs used to treat peptic ulceration
- Alginates and antacids
- PPIs
- H2 receptor antagonists
- aminosalicylates
name a drug undee the class Alginates and antacids
gaviscon
gaviscon is a compound of
- Alginic acid (sodium alginate) +
- Antacid (aluminium hydroxide/magnesium carbonate)
alginates and antacids (gaviscon) Uses
Protect the oesophageal mucosa from acid reflux
Mode of action of gaviscon
- Antacids- buffer stomach acid
- Alginic acid (seaweeds)- increase stomach content viscosity and reduce reflux
Adverse drug response of gaviscon
- Magnesium salts can cause diarrhoea
- Aluminium salts can cause constipation
Contraindication gaviscon
- Na+ and K+ containing preparations should be used with caution in renal failure
- High [sucrose] in some preparations- hyperglycaemia in DM
Drug-drug interactions gaviscon
- Can reduce absorption of many drugs so doses should be separated
- Increased urine alkalinity can increase aspirin excretion
name 2 proton pump inhibitors
- Lansoprazole
- Omeprazole
uses of PPis
Uses (often prescribed alongside long term NSAID or steroid)
- Relive acid reflux symptoms and GERD
- Duodenal or stomach ulcers
- Treat damage to lower oesophagus caused by acid reflux
Mode of action of PPis
- Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
- Final stage in pathway therefore very significant reduction in acid secretion
Adverse drug response PPIs
- GI disturbances- abdominal pain, constipation, diarrhoea
- Headache, dizziness
- Drowsiness/confusion
Contraindication PPIs
- BEWARE: can mask symptoms of gastro-oesophageal cancer
- Osteoporosis – fracture risk
Drug-drug interactions
- Omeprazole is CYP inhibitor- reduced clopidogrel action
- PPIs can increase effects of warfarin and phenytoin- need to monitor
- Should be given shortest effective duration at lowest effective dose
name a h2 receptor antagonist
ranitidine
Uses of ranitidine (H2 receptor antagonist)
- Indigestion
- Heart burn
- Acid reflux
- Protect the oesophageal mucosa from acid reflux
Mode of action raniditine
- Local histamine release contributes to proton pump activation
- H2 receptor antagonists inhibit H2 receptors reducing this local histamine release –> therefore only partial reducing in acid secretion
Adverse drug response ranitidine
Generally well tolerated- diarrhoea, headache
Drug-drug interactions ranitidine
Few DDIS
cureent large scale recall of most ranitidine due to
possible carcinogenic contaiminantion
- iansoprazole typically first alternative upon pt review
Helicobacter pylori and peptic ulceration
- major risk fact
- gram negative bacteria
- infection: H. pyrlori infects lower part of the stomach antrum
- inflammation: inflammation of gastric mucosa (gastritis)- often asymptomatic
- ulcer: gastric inflammation may lead to duodenal or gastric ulcer
- complications: bleeding ulcer and perforated ulcer
% of people in UK infected
10-15% (infection from childhood)
consider H. pylori for all pts with
- duodenal or gastric ulcers not associated with NSAID or unresponsive to lifestyle PPI and antacids
confirmation of H.pylori infection
- Urea breath test
- Gastric urea= C12 isotopes (99%) and C13 isotopes= 1%
- Pts ingest urea with enriched C13
- H. pyrloi should convert this to ammonia and CO2
- Can detect C13 in exhaled CO2
- Stool antigen test
- Endoscopy with biopsy
treatment of H pylori
- One week triple therapy
- PPI + two antibacterial agents
- Lansoprazole + clarithromycin + amoxicillin OR
- Lansoprazole + clarithromycin + metronidazole (where allergic to amoxicillin )
- Some evidence of local metronidazole resistance
- Compliance with full course important for effectiveness and minimise risk of bacterial resistance
name a drug under the class aminosalicylates
mesalazine (enteric coated tablet)
mesalazine uses
first line treatment in UC
Mode of action mesalazine
- Release of 5-aminosalsylic acid
- Topical anti-inflammatory action at the colon (enteric coated tablets limit gastric breakdown)
- Mesalazine has no role in rheumatoid arthritis (no systemic effect)
- Sulfasalazine has more side effects so used infrequently for UC but sulfa group good for rheumatoid arthritis
Adverse drug response mesalazine
- GI disturbance- nausea, dyspepsia
- Leukopenia- rare
Contraindication mesalazine
Salicylates like aspirin- similar hypersensitivity
Drug-drug interactions mesalazine
Enteric coated tablets may break down quicker in presence of PPI (because of increase pH)
