S10 L1 GI pharmacology Flashcards
What GI pathology can arise from inappropriate acid secretion?
Gastric and duodenal ulcers
What is the problem with gastric and duodenal ulcers?
Symptoms not reliable - guide is epigastric pain
Chronic ulcers are asymptomatic
Bleeding, perforation, scarring and possible obstruction is possible
What are the risk factors for ulceration?
- Acid is essential for ulceration- inability to switch off acid secretion is a major risk factor
- Early gastric emptying can be a risk factor- ↓pH of contents into duodenum causes damage
- Helicobacter pylori
- NSAIDs - anti-inflammatory → inhibit protective mechanisms of acid secretion by inhibiting PGE2 and reducing mucosal blood supply - disrupts the hydrogen carbonate levels in the mucosa
- Smoking and alcohol delay healing
What medications can be used to inhibit GI pathology?
- Alginates and antacids
- Proton pump inhibitors
- H2 receptor antagonists
- Aminosalicylates
What are alginates and antacids?
Antacids- buffer stomach acid
Alginic acid- increases stomach content viscosity and reduce reflex
Often taken as compound preparations → sodium alginate and aluminium hydroxide/magnesium carbonate
What is an example of an alginate and antacid?
Gaviscon
What are the adverse effects of alginate and antacids?
Magnesium salts → diarrhoea
Aluminium salts → constipation
Taken together balance each other out
What are the contraindications of alginates and antacids?
Na+ and K+ containing preparation should be used with caution in renal failure
High [sucrose] in some preparations - hyperglycaemia in DM
What are the important drug drug interactions of alginates and antacids?
Reduce absorption of many drugs so doses should be separated- disrupts the bioavailability of other drugs
↑urine alkalinity = ↑aspirin excretion
What are proton pump inhibitors?
Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
Final stage it the pathway so very significant reduction effect
Shortest effective duration at lowest effective dose
Often prescribed alongside long term NSAID or steroid
What are examples of proton pump inhibitors?
‘-prazole’
Lansoprazole
Omeprazole
What are the adverse effects of the proton pump inhibitors?
GI disturbances - abdominal pain, constipation diarrhoea
Headache, dizziness
Drowsiness/confusion
What are the contraindications of proton pump inhibitors?
Mask symptoms of gastro-oesophageal cancer
Osteoporosis- fracture risk
What are the important drug-drug interactions of proton pump inhibitors?
Omeprazole CYP inhibitors- (specific action of omeprazole not all PPIs)- reduced clopidogrel action - prevents conversion to active metabolites
PPIs can increase effects of warfarin and phenytoin - monitor
What are the H2 receptor antagonists?
Inhibition of H2 receptors- local histamine release contributes to proton pump activation (secreted from enteroendocrine cells- act on H2 receptor on parietal cells)
Only partial reduction in acid secretion (other routes to activate parietal cells)
What are the adverse effects of H2 receptor antagonists?
Generally well tolerated
Diarrhoea and headaches possible
What are the contraindications of H2 receptor antagonists?
Mask the symptoms of gastro-oesophageal cancers, renal impairment
What are the important drug-drug interactions of H2 receptors antagonists?
Few DDI
Reduced exposure to some antivirals and protein kinase inhibitors
What is an example of the H2 receptor antagonists?
Ranitidine
- Current large scale recall on most products due to possible carcinogenic contaminant
What is helicobacter pylori?
Gram negative bacteria
Colonises the gastric mucosa
When should helicobacter pylori infection be considered?
Patients with duodenal or gastric ulcers
Not associated with NSAIDs or unresponsive to lifestyle PPI and antacids
How is H.Pylori infection confirmed?
Urea breath test
- Urea labelled with C13 isotope given to patients
- H.Pylori have own urease enzymes converts urea to CO2 with C13
- Patient breathes it out can be detected on test
How it H.Pylori infection treated?
One week triple therapy
PPI and two antibacterial agents
Lansoprazole + clarithromycin + amoxicillin
Lansoprazole + clarithromycin + metronidazole (if allergic to amoxicillin, some local resistance to metronidazole in leic)
Full compliance with course important for effectiveness and minimise risk of bacterial resistance
What are the aminosalicylates?
Anti-inflammatory drug
First line treatment for ulcerative colitis
Release of 5-aminosalicylic acid
Topical action at colon- enteric coated to prevent/limit breakdown within the stomach
What is an example of the aminosalicylate?
‘-salazine’
Mesalazine - no role in RA
Sulfasalazine - more side effects so used infrequently for UC but sulfa group good for RA
What are the adverse effects of aminosalicylates?
GI disturbances - nausea, dyspepsia
Leukopenia - rare
What are the contraindications of aminosalicylates?
Salicylates like aspirin - pt with aspirin hypersensitivity show caution with prescribing of aminoalicylates
What are the important drug drug interactions?
Enteric coated tablets may breakdown quicker in presence of PPI because of ↑pH - so interferes with the enteric coat
