Gastro-Intestinal Pharmacology and Therapeutics Flashcards
Drugs affecting acid in lumen
Antacids (partially neutralise acid) and alcohol (stimulates gastric secretion therefore
increasing acid)
Antacids
These are given for symptomatic relief, there is little evidence to suggest they heal ulcers.
They act by neutralising the acid in the stomach. They are best given when the symptoms occur and at bedtime.
If they are taken on an empty stomach, the effects last 20-40 mins, if taken after meals the effects can last 2-3 hours
Magnesium
Salts include hydroxide, trisilicate, carbonate. Relatively insoluble in water so it needs to be a suspension. The main side effect is diarrhoea. Use with caution in renal
impairment (in elderly patients)
Aluminium
Salt is hydroxide. Relatively insoluble in water. Main side effect is constipation. It can also be used to treat hyperphosphataemia so it is CI in
hyPOphosphataemia and porphyria (rare metabolic disease)
Calcium carbonate
More soluble. “Milk-alkali syndrome” is hypercalcaemia caused by excess consumption of milk and calcium containing antacids. Can induce acid rebound at
higher doses. Side effects include constipation
Sodium bicarbonate
Rapid but short action, it is soluble. Can lead to fluid retention, aggravation of hypertension, metabolic alkalosis. Can also cause belching which some
people find helpful
Bismuth
Not recommended because absorbed bismuth can cause encephalopathy
Dimeticone (simeticone)
Used as an anti-foaming agent to relieve flatulence, it can be used alongside antacids
Alginates
These are rafting agents that can be used in combination with antacids.
Carbon dioxide liberated by reaction between acid and carbonate/bicarbonate, this carbon dioxide reacts with alginate to form a stable foam which floats on the top of the stomach contents, it prevents stomach contents and especially the oesophagus
Drug interactions involving antacids
- Decreased rate and extent of absorption of tetracyclines, biphosphonates, ketoconazole
- Decreased effect of enteric coated tablets e.g. colpermin, diclofenac ec
- Decreases action of some drugs like sucralfate
Acid secretion in the stomach
The parietal cell found in the gastric gland has three receptors that cause the stimulation of
acid production in response to:
- Gastrin
- Acetylcholine
- Histamine
Acid secretion is dependent on H+/K+ ATPase pump which pumps protons against their concentration gradient.
H2 receptor antagonists
Inhibit acid secretion produced by histamine, gastrin and acetylcholine by competitively blocking the H2 receptors.
Cimetidine original product but limited by side effects including gynaecomastia and drug interactions, newer agents include ranitidine, famotidine which have few side effects, reduces acid secretion by 70% (not enough for some patients)
Proton Pump Inhibitors (PPI)
Irreversibly inhibit the proton pump only in actively secreting cells, reduces acid secretion by
90%. PPIs are prodrugs, converted in acidic pH to the active drug, they are given as enteric coated preparations to prevent conversion in the stomach lumen.
PPIs include omeprazole, lansoprazole, pantoprazole. Use in caution with liver disease and may
cause diarrhoea, DDI with clopidogrel
Misoprostol
A synthetic prostaglandin analgoue which inhibits acid production by activating Gi, which stimulates mucus and bicarbonate production.
CI in women of child
bearing age because it also effects the uterus and cervix - can induce abortion.
Side effects include diarrhoea and vaginal bleeding
Sucralfate
A sulphated disaccharide aluminium hydroxide complex, in acidic environments it releases aluminium which binds to the surface of ulcers (protective
coating). It also directly inhibits pepsin and binds bile salts. It is only used occasionally in intensive care
Gastric secretion
Increased by - anger, hostility, food in stomach, alcohol, caffeine, hypoglycaemia
Decreased by - fats, carbohydrates, acid in duodenum
Motility
Increased by - excitement, carbohydrate rich food
Decreased by - fats, cutting the vagus nerve
Dopamine Receptors -
Dopamine D2 receptors in enterochromaffin-like cells (ECL Cells) inhibit gastric emptying
Metoclopramide
Antagonist at peripheral dopamine receptors which results in stimulation of plain muscle in the stomach and upper GI tract, this drug is used to enhance
gastric emptying and intestinal transit.
Can give rise to acute dystonic reactions in young women, which are face muscle spasms resulting in gurning facial expression (neurological)
Domperidone
Similar to metoclopramide but lacks cholinergic activity and doesn’t cross the blood brain barrier in significant amounts
Drugs which relax lower oesophageal sphincter
Anticholinergics, tricyclic antidepressants, phenothiazines, nitrates, progestins,
theophylline, nicotine patches, CCBs, levodopa
Drugs which increase lower oesophageal sphincter tone
Anticholinesterases, metoclopramide, succinylcholine, pancuronium, histamine, antacids
Drugs which injure oesophageal mucosa
Tetracyclines, bisphosphonates (alendronate) - these drugs require counselling (stand up/sit upright for 30 mins after taking)
Drugs associated with oesophageal strictures (restriction)
Potassium chloride SR, quinidine SR, NSAIDs
Drug induced oesophageal problems
More common in the elderly, especially if there is a pre-existing oesophageal disease. It is more likely if medication is taken whilst lying down
