Pharmacology of Upper and Lower GIT Drug Treatment Flashcards
What is the drug target in the gastric mucosa
Parietal cells gastric acid secretion
What is the physiological control of gastric acid secretion ( 4 controls)
- vagal nerve works through ACH to give a positive signal by H/K ATPase proton pump to stimulate acid secretion
- histamine stimulates acid secretion via histamine 2 receptor
- gastrin responds to dietary intake to stimulate acid secretion
- Prostaglandin decreases secretion
What is a peptic ulcer
- defect in the gastric or duodenal mucosa
- caused by imbalance in peptic acid secretion and gastroduodenal mucosal defence
- acids higher than mucosal defines can cope with
Principles of PUD therapy
1- Relief of pain ( epigastric pain )
2- Ulcer healing
3- Prevention of relapse and complications
4- everyone at increased risk of gastric carcinoma must be investigated since treatment could mask symptoms (ex: elderly, smokers, alcoholics)
What is the treatment for PUD ( 5 steps )
1- remove irritants : especially NSAIDS , helicobacter pylori infection 2- Antacids : alkali based salts 3- proton pump inhibitors 4- H2 receptor antagonists 5- Antibiotics for helicobactor pylori
How NSAIDs effect acid secretion
- NSAIDs act on COX 1 &2
- COX 1 housekeeps prostaglandin formation and the prostaglandin signal that’s used to reduce acid signal
- COX 2 causes inflammation
Drugs that can cause PUD (8)
- NSAIDs
- aspirin
- corticosteroids
- bisphosphonates ( mucosal toxic)
- Nicotine ( smoking )
- alcohol
- caffeine
- severe physiological stress
- Hypersecretory states ( gastronomes )
Describe role of antacids, and the common ones used for PUD treatment
- increase gastric PH and reduce proteolytic activity
- can’t something too alkali or too easily absorbed because will get into blood
- aluminium and magnesium salts combinations are used
Why is sodium bicarbonate not used to treat PUD
- easily absorbed and therefore will not stay in GIT
- will go into blood and can cause metabolic alkalosis , sodium and water retention and renal stones
Why is milk not good for PUD
- temporary pain relief but contains a lot of fat and sugar which stimulates gastrin
- gastrin increases acid secretion which makes situation worse
Why are antacids sometimes not used fo PUD treatment
- parietal cells are still releasing acid so the problem is not being fixed
- antacids just react with acids so they’re not longterm treatment
What is the first line treatment for significant ongoing dyspepsia or PUD , give examples
- proton pump inhibitors
- Omeprazole
- Lansoprazole
- Pantoprazole
- Esomeprazole
What is PPIs mode of action
- Targeted irreversible proton pump inhibition
- Inhibit the H/K ATPase proton pump = decrease acid secretion
- used for dyspepsia , PUD , GORD
Why to be careful of PPIs
- can mask gastric cancer because effect are so good
Common ADRs of PPIs
- causes slight change to normal GIT function
- nausea , vomiting , abdominal pain , flatulence, diarrhoea, constipation , headache
Important ADRs of PPIs (5)
- clostridium difficile
- Hypomagnesaemia : if magnesium is low then patient feels weak
- Hyponatraemia : if PPI is helping with nausea it will decrease hyponatraemia risk
- Hepatitis
- pneumonia
PPIs drug interactions
- warfarin : omeprazole and esomeprazole are weak CYP450 enzyme inhibitor so metabolism of warfarin will decrease , warfarin effect will fo up
- clopidogrel ( hepatic pro-drugs ) : omeprazole and esomeprazole are weak CYP450 enzyme inhibitor so anti platelet effect will not be activated
Describe RAHS
- rebound acid hypertension syndrome
- when PPIs switch of acid secretion irreversible a reaction can occur 2-3 months after PPIs are stopped
- recommended to only use PPIs for 8 weeks
What is the second line treatment for PUD, give examples
- Histamine 2 receptor antagonists
- ex: cimetidine and ranitidine
- blocks histamine 2 signal decreasing gastric acid secretion
Cimetidine mode of action and ADRs
- competitive antagonist of H2 receptor in gastric parietal cells
- ADRs: diarrhoea , confusion , gynaecomastia
Cimetidine drug interactions
- potent inhibitor of cytochrome P450
- messes with all drugs that are hepatic ally processed by CYP450
Why is Ranitidine better than Cimetidine
- did not cause gynaecomastia and was only a mild inhibitor of CYP450
What is Helicobacter pylori , why does it cause PUD
- gram negative bacillus
- stays in gastric mucosae secreting inflammatory proteins and toxins
- produced urease which converted urea to ammonia and CO2
How to find H pylori
- detected by carbon 13 urea breath test
- takes urea tablet and if there is a spike of CO2 in breath after that’s urease working
