Lecture 33 Flashcards
(31 cards)
What are the two main group of drugs that inhibit gastric acid secretion?
1) H2 receptor antagonist (burimamide).
2) Proton pump inhibitors.
What is histamine involved in?
Both acid secretion and allergic reaction.
Describe the H1 receptor?
On smooth muscle and endothelial cells. Involved in allergy.
N.B. Anti-histamines are H1 receptor antagonists.
Describe H2 receptor?
On parietal cells. Involved in gastric acid.
Describe H2 receptor antagonists?
- These compete with histamine (agonist) for the binding site i.e. competitive antagonist.
- These can be “overcome” by strong agonist effect.
- Increasing doses - less additive effect.
- Rapid action (within 30 minutes), duration is 6-8 hours.
- Tolerance (tachyphylaxis): first does is most effective.
What are the problems with H2 antagonists?
1) Not effective for many patients with heartburn.
2) Unable to heal moderate-severe reflex oesophagitis.
3) Need for multiple doses - four times per day for severe symptoms.
4) Maximum acid suppression - 50%.
5) Ok for peptic ulcer (given as sing;e night-time dose) but recurrence on stopping.
Describe proton pumps?
They’re located on the gastric parietal cells and are responsible for acid secretion.
Describe proton pump inhibitors?
1) Omeprazole is absorbed into the blood -> parietal cell.
2) Passes across parietal cell to canaliculi.
3) In canaliculi, converted to active sulphonamide in presence of acid.
4) Reacts with sulphydryl group of cysteine (amino acid) at proton pump.
What do proton pump inhibitors do?
They provide irreversible blockage of activated proton pump.
What is the duration of omeprazole?
Long duration - only need to take it once daily or twice as some duration is
Can inhibition be overcome in omeprazole?
Blockage cannot be overridden by increased stimulation from histamine, gastrin or ACh.
>90% acid suppression in most people.
What are the potential problems with long-term acid suppression?
1) Bacterial overgrowth of the stomach.
2) Malabsorption - acid helpful for absorption B12, Fe and Ca.
3) Potential formation of carcinogenic compounds.
4) acid required to sterilise food - small risk of enteric infections.
5) ECL hyperplasia secondary to high gastrin (compensatory response).
What are the practical tips for H2 Receptor antagonists?
1) They’re good for “if required” dosing because of rapid onset and good first does effect.
2) Most effective in reducing nocturnal acid secretion.
3) Not as good for todd-stimulated acid-secretion.
What are the practical tips for proton pump inhibitors?
1) Several days for maximal effect.
2) Good for maintenance treatment.
3) Prevention of degradation by gastric acid (enteric coated).
4) A meal to stimulate proton pumps - give 30 minutes before meal.
What are the use of proton pump inhibitors?
1) Gastro-oesophageal reflux disease.
2) Not required as much for ulcer disease.
3) Required in ulcer disease causes by non-steroidal anti-inflammatory drugs (NSAIDs).
4) Useful for acute ulcer bleeding:
- Possible mechanism: decreases activity of pepsin when pH>5.
- Pepsin may dissolve fibrin clot in a vessel in the ulcer base.
Describe the effect of the gut on drug delivery?
1) Acid degradation - some drugs may need to be enteric coated/delayed release.
2) Acid enhanced absorption - itraconazole.
3) Effect of rate of gastric emptying - matching insulin and meals.
4) Hepatic enzyme function - cytochrome p450 pathway.
5) Enterohepatic circulation/biliary secretion.
Describe Case 1?
- 50yo man with chronic pancreatitis from long history of excessive alcohol.
- Develops steatorrhoea.
- Diagnosed with fat malabsorption from pancreatic exocrine insufficiency.
- Plan is to have supplement pancreatic enzymes.
What are the problems with replacing pancreatic enzymes in chronic pancreatitis?
1) Large volume of enzyme required to replace normal function.
2) degradation by gastric acid.
3) Need for neutral pH in the duodenum.
4) Release in the proximal small bowel.
What are the partial solutions with replacing pancreatic enzymes in chronic pancreatitis?
1) enteric coated capsules - problems with size and delayed release.
2) Non-enteric coated but also giving a proton pump inhibitor.
Describe Case 2?
- 20yo man with bloody diarrhoea for 6 months, presents for colonoscopy.
- Diagnosed with mild ulcerative colitis affecting left and transverse colon.
- Plan is to start 5-aminosalicylic acid.
What are the problems with giving anti-inflammatory medication (5-aminosalicytic acid 5-ASA) to the inflamed part of the SI or LI?
1) 5-ASA is the active drug used to treat IBD but is degraded by gastric acid.
2) 5-ASA needs to be delivered in highest concentration to areas of inflammation - mostly colon and terminal ileum.
What are the possible solutions for giving anti-inflammatory medication (5-aminosalicytic acid 5-ASA) to the inflamed part of the SI or LI?
1) Join two 5-ASA molecules together with an ago bond - needs colonic bacteria to cleave bond.
2) Enteric coated - resists gastric breakdown.
3) pH-dependent release (neutral/alkaline pH).
4) Time-dependent release.
What is sulphasalazine?
Made up of two 5-ASA linked to sulphapyridine, allows to travel to colon before being degraded by bacteria.
Uses colonic bacteria to be released at appropriate site.
What are the limitations of sulphasalazine?
1) Adverse effects (hypersensitivity or intolerance in 20% of patients) - caused by “sulphur” part (sulphapyridine).
2) Only acts in colonic disease.
3) Higher doses may be more effective but cause severe adverse effects in most patients.
