CPT2: GI 5 (PPI,H2RA, Antacids) Flashcards
1
Q
Examples of PPIs
A
2
Q
- What forms are the PPIs available in?
- Which are affected by food and which are not?
- What counselling advice should therefore be givne?
A
- Available as gastro-resistant capsules, orodispersible and IV formulations
- Food affects the bioavailability of lansoprazole and esomeprazole – these should be taken 30mins- 1 hour before food.
- Omeprazole, pantoprazole and rabeprazole are not affected by food.
3
Q
What is the mechanism of action of PPIs?
A
They irreversbilily bind to H/K/ATPase and inhibit its action
4
Q
Describe the pharmacokinetics of PPIs
A
- PPIs are acid labile and so must be in a gastro-resistant formulation to transit through the stomach and be absorbed in the small intestine.
- Converted to active form in the acidic environment surrounding the parietal cell and bind to the proton pump. (prodrug)
- New proton pumps have to be synthesised to regain maximal acid secretion.
- Hepatic metabolism to inactive metabolites, renal/biliary elimination
5
Q
When should PPIs be taken?
What are their half lifes and DOA like?
A
- Only effective when parietal cells are active and secreting gastric acid. Therefore they should be taken before food.
- Half lives are short (1-2hrs) and DOA long as they irreversibliy bind and it takes around 24hrs to synthesise new PPs
- Most effective when take 1 hour before a meal (food stimulates acid secretion)
- Lansoprazole must be taken at last 30 mins before food as food reduces lansoprazole bioavailability
- Dose reduction unnecessary in poor renal function
6
Q
What drug interactions need to be considered when taking PPIs?
A
Drug Interactions
Omeprazole/esomeprazole inhibits CYP2C19:
- Clopidogrel?
- Warfarin?
- Diazepam?
PPIs increase gastric pH which interferes with the solubility of medicines that require acidic pH
- Epclusa (Hepatitis C)
- Itraconazole capsules
- Erlotinib (EGFR inhibitor for lung/pancreatic cancer)
Cumulative effect with medicines that cause low Na+ and Mg2+
7
Q
Common side effects of PPIs
A
- Abdominal pain
- constipation
- diarrhoea
- headache
8
Q
Severe but rare side effects
A
- Electrolyte disturbance – Na+ and Mg2+
- Subacute lupus erythematosus
- Rebound acid hypersecretion
- Acid secretion can have negative feedback on gastrin production – if PPIs are used this feedback pathway is altered leading to a rise in gastrin that may explain hypersecretion when a PPI is stopped.
- Osteoporotic fractures
- Reduced Ca2+ absorption
- Interstitial nephritis
- Inflammation of nephrons of kidneys
9
Q
What microorganism is associated with PPIs?
Describe the characteristics, symptoms it causes and why it causes this.
What should you do?
A
Clostridioides difficile
- Gram positive anaerobic bacteria
- Spore forming, toxin producing
- Healthcare associated infection
- Faecal-oral route of transmission
- Disturbance of normal bowel flora
- Severe diarrhoea (therefore dehydration and spread), pseudomembranous colitis
- Risk groups: elderly, hospitalised patients, immunosuppressed,
- Higher risk if on ‘4C antibiotics’ and PPIs
- co-amoxiclav, ciprofloxacin, clindamycin, cephalosporins
STOP PPI, REVIEW ANTIBIOTICS
10
Q
What are antacids and how do they work?
How does alignate containing antacids work?
A
Antacids
- Neutralise gastric acid, increasing gastric pH. Either salts of magnesium or aluminium. Magnesium causes diarrhoea & aluminium causes constipation, so a mixture of both is used.
- Rennies, Tums, Mucogel, Maalox/Maalox plus (with simeticone –antifoaming agent, aids with bloating)
Alginate containing antacids
- Increase the viscosity and adherence of mucus to the oesophageal mucosa forming a protective barrier. Forms a ‘raft’ on the surface of the gastric contents, preventing reflux into the oesophagus.
- Gaviscon advance, Peptac
11
Q
What are considerations when using Antacids
A
Considerations:
- Sodium content
- Kidney disease, heart failure, hypertentsion need low Na+ diet
- Lots of these meds have high H+
- effect on pH
- Increase pH - some medicines require low pH for absorption
- chelation of medicines
- Metals in prep bind to other meds
- (iron, tetracyclines, bisphosphonates, fluoroquinolones)
12
Q
H2RA drugs
A
Ranitidine
- 75mg OD – OTC dose
- 150mg OD/BD or 300mg OD/BD
- Discovery of contaminant - N-nitrosodimethylamine (NDMA) – linked to gastric cancer
- No new patients to be started on ranitidine, existing patients to be switched to PPI/other H2RA
Cimetidine
- 400mg BD up to 400mg QDS
- Cytochrome inhibitor (CYP3A4, CYP2D6, CYP1A2) – warfarin, diltiazem, phenytoin, theophylline
- Antiandrogen effect – gynecomastia, loss of libido, erectile dysfunction
Famotidine
- 20mg – 40mg daily
- Side effects:
- Common - Constipation/diarrhoea, headache, fatigue,
13
Q
How are these drugs excreted?
Half life and time to reach peak conc
In renal dysfunction dose change?
A
- Ranitidine – renal elimination as unmetabolized drug
- Cimetidine –hepatic metabolism and then renal excretion
- Famotidine - hepatic metabolism and then renal excretion
- Half life roughly 3 hours
- Time to peak concentration 1-3 hours
- Reduce dose in renal dysfunction
14
Q
Mechanism of H2RA
Why is PPI better?
A
- Reversible inhibition (competitive) of the histamine-2 receptor on the gastric parietal cell
- Parietal cell has other stimulating factors (gastrin, acetylcholine) which makes PPIs more effective.
- Useful to treat nocturnal symptoms (histamine rise at night)
- Inferior to PPIs for ulcer healing/oesophagitis/H.pylori eradication
15
Q
Summary
A
- PPIs are the 1st choice for GORD, H.pylori eradication and ulcer healing. Irreversible inhibitors of H/K/ATPase pump in parietal cells.
- H2RA can be used as an alterative to PPI, nocturnal symptoms or symptomatic control of dyspepsia. Reversible inhibitors of histamine-2 receptor on parietal cells.
- Antacid/alginates can be used for short term symptomatic control of dyspepsia and heartburn
- Remember lifestyle advice and medicine review
