Pharmacology of upper/lower GI tract drug treatment Flashcards
How is acid secreted in the stomach?
Gastric parietal cells- action of acetylcholine, histamine +gastrin (+ prod) and PGE2(-) influencing action of H+/K+ ATPase pump
What is a peptic ulcer?
Defect in gastric/ duodenal mucosa, caused by imbalance in peptic acid secretion / gastroduodenal mucosal defence.
Principles of PUD therapy
Pain relief (non NSAID), ulcer healing and prevention of relapse/ complications (investigate at risk of gastric carcinoma (smoking obesity etc)
What aetiological factors are indicated in PUD?
H. pylori infections, NSAIDS, aspirin/ ccsteroids, bisphosphonates(gastroporous), nicotine, alcohol, caffeine, psych stress and hypersecretory states (rare)
Antacids as treatment for PUD
raise gastric pH reducing proteolytic activity- commonly Al/Mg salts
Sodium bicarbonate fast acting; v well absorbed, can cause metabolic alkalosis, na+/h2o retention and renal stones
Proton pump inhibitors: OmePRAZOLE M.O etc
Targeted irreversible proton pump inhibition
Clinical indications e.g dyspepsia, PUD and reflux oesophagitis
Very effective and well tolerated, watch for masking red flag symptoms
Common and important adverse reactions of omePRAZOLE
GI disturbances, e.g nausea (^ADH), vomiting etc
Important ADR’s: inc. risk of C.Diff, hyponatraemia, hypomagnesaemia ( muscle fatigue weakness), Hep, interstitial nephritis, blood disorders e.g leucopenia
^ risk of CA/ HA pneumonia/ CKD?
OmePRAZOLE- interactions
Warfarin- O.praz and esomeprazole weak CYP450 enzyme inhibitors, ^ anticoagulant effect
Clopidogrel (hepatic prodrug)- ^^^, reduce antiplatelet effect
H2 receptor antagonists
CimeTIDINE- competitive antagonist at h2 receptor in GP cells
2nd line agent for PUD + R.oesophagitis
Adverse effects- diarrhoea, confusion, gynaecomastia
Interactions- POTENT CYP450 dependent metabolism
Why does h.pylori cause peptic ulceration?
gram negative bacteria which secretes inflammatory proteins/ toxins and produces urease- nh4 and co2 produced, undermines muc. system
Tested by C-13 urea breath test and upper GI endoscopy w/ biopsy + rapid urease test
Helicobacter eradication regimens
PPI/ H2RA, clarithromycin and amoxicillin (metronidazole if pen allergy)
1 week triple threapy, continue PPI for 3 weeks if problematic ulcer
Diff antibiotic if 2nd course needed
NSAID ulceration
withdrawal, high risk prescribe PPI/ H2RA
H.pylori patients need eradication therapy and those with NSAID induced ulcer > PPI
When to do urgent upper GI endoscopy?
Acute bleeding suspected/ chronic bleeding ( fe def anaemia), weight loss, dysphagia, persistent vomiting
Anyone with unexplained, peristent dyspepsia (esp over 55)
Constipation treatment
Non-pharmacological interventions- ^ fluid intake, improve mobility, fibre intake, stopping constipating drugs and excluding underlying pathology
Causes of constipation?
drugs: especially opiods and antimuscarinics (antidepressants)
Local pain e.g anal fissure, benign colorectal disease (diverticular disease e.g), endocrine/metabolic (hypercalcaemia, hypothyroidism, DM) malignancy (colorectal, ovarian + uterine tumours)
