Gastro Flashcards
Magnesium trisillicate and aluminium hydroxide
Class: antacid
MOA: neutralise gastric acid
Magnesium salts do this quicker than aluminium
Both have prolonged effect if taken after food, produce quick symptom relief, poorly absorbed from the gut
Use: dyspepsia, GORD
Side effects: constipation (aluminium), diarrhoea (magnesium), systemic alkalosis (large doses), may contribute to metabolic bone disease and encephalopathy in advanced renal failure
Drug interactions: aluminium salts can bind to NSAIDs and tetracyclines in the gut and reduce their absorption
Ranitidine and cimetidine
MOA: histamine H2 receptor antagonist, reducing basal acid secretion and pepsin production
Absorption is almost complete, first-pass metabolism, eliminated unchanged by the kidney, 1/2 life = 1-4 hours
Side effects: diarrhoea, GI disturbance, headache, dizziness, tiredness, rash
Drug interactions: cimetidine inhibits hepatic P450 isoenzymes, increasing plasma conc and actions of drugs (warfarin, phenytoin, theophylline)
Use: dyspepsia, GORD, peptic ulceration, prophylaxis of NSAID peptic ulceration
Lansoprazole
Omeprazole
Class: PPI
MOA: inhibit gastric acid secretion by blocking the H+/Na+ ATP pump of the parietal cells
Prodrugs (unstable in acid), given orally as enteric-coated formulations, some are available IV, eliminated by hepatic metabolism, short plasma 1/2 life (1-2 hour) but have irreversible MOA
Side effects: GI upset, headache, omeprazole inhibits CYP2C9 and CYP2C19 in the liver (decreases metabolism and increases clinical effects of warfarin, phenytoin)
Use: dyspepsia, GORD, oesophagitis, peptic ulceration, prophylaxis of NSAID peptic ulceration, H.pylori eradication
Codeine phosphate
Class: opioid
MOA: bind to u-receptors in neurons in the submucosal neural plexus of the intestinal wall, enhances segmental contractions in the colon and inhibits propulsive movements of the SI and colon, prolonging transit time
Short 1/2 life (<5 hour)
Use: diarrhoea
Side effects: constipation, nausea, sedation, confusion, hallucinations, flushing/sweating, dry mouth, difficulty with micturition, hypotension
Loperamide
Class: opioid
Use: diarrhoea
MOA: bind to u-receptors in neurons in the submucosal neural plexus of the intestinal wall, enhances segmental contractions in the colon and inhibits propulsive movements of the SI and colon, prolonging transit time
More rapid onset of action, 1/2 life = 11 hours, more selective for the gut than other opioids, also has additional antimuscarinic activity (inhibits peristalsis)
Side effects: constipation, nausea, sedation, confusion, hallucinations, flushing/sweating, dry mouth, difficulty with micturition, hypotension
Bulk forming laxatives
E.g. isphaghula husk, methylcellulose
MOA: hydrophilic action (causing water retention in gut lumen which expands and softens faeces), proliferation of colonic bacteria (increases faecal bulk), stimulation of colonic mucosal receptors by the increased bulk (promoting peristalsis)
Take 24 h after ingestion to work, needs fluid intake (minimise risk of obstruction, lubricates colon)
Useful to establish a regular bowel habit in chronic constipation, diverticular disease and IBS
Avoid is the colon is atonic or faecal impaction
Side effects: sensation of bloating, flatulence, abdo pain
Osmotic laxatives
E.g. lactulose
This is a disaccharide of fructose and galactose (these are released by bacterial action in the colon normally) which are fermented and the products of this are osmotically active. They also lower intestinal pH which inhibits proliferation of ammonia-producing bacteria.
Useful in treating hepatic encephalopathy
Side effects: flatulence, abdo cramps
Can take >24 hours to act
Irritant and stimulant laxatives
E.g. Senna, sodium picosulfate
MOA: stimulate local reflexes through myenteric nerve plexuses in the gut (enhances gut motility and increases water and electrolyte transfer)
Stimulant laxatives are more useful for severe forms of constipation, but tolerance is common with regular use. they stimulate defecation after 6-12 hours.
Senna - most gentle action, given orally, hydrolysed by colonic bacteria
Sodium picosulfate: powerful irritant, given orally, often for bowel prep for surgery/colonoscopy, acts in <6 hour
Mesalazine and sulfasalazine
Class: aminosalicylates
MOA: deliver 5-ASA to the lumen of the colon, the precise mechanism is unclear but may involve inhibiting leucocyte chemotaxis by reducing cytokine formation, reducing free radical generation, inhibiting lipid inflammatory mediators
First-line prophylaxis of mild-moderate UC and highly effective for reducing relapse rates, less effective in acute exacerbations
Partially absorbed from the gut intact, but most reaches the colon where it undergoes reduction by gut bacteria; products are absorbed fro the colon and metabolised in the liver
1/2 life = 5-20 hours
Enteric coated or modified-release formulation, may be given rectally for distal disease
Adverse effects (15%): nausea, vomiting, diarrhoea, abdo pain, headache, rashes, blood dycrasias (agranulocytosis, thrombocytopenia), cough, insomnia, fever, oligospermia
Corticosteroids
E.g. hydrocortisone, prednisolone, budesonide
Use: induce remission in active IBD
May be topical (enema, suppositories) for localised rectal disease, or oral or parenteral (severe/extensive disease)
Hyoscine (Buscopan)
Use: IBS
Mebeverine and peppermint oil
Antispasmodic agents
MOA: direct SM relaxant properties, relieving gut spasm and assoc. pain
Oral absorption of mebeverine is rapid and undergoes first-pass metabolism
Side effects: perianal irritation (peppermint oil), headache, allergic reactions
Use: IBS
Hyoscine (Buscopan)
Antimuscarinic
Incomplete oral absorption, hepatic metabolism, 1/2 life = 8 hours
Use: IBS, motion sickness, surgical premedication
Nystatin
Polyene
MOA: bind to ergosterol in the cell wall of fungi, forming aqueous pores which promote leakage of IC ions and disrupt active transport mechanisms
Can be fungistatic or fungicidal
Effective for infections with Candida species
Resistance is rare
Used topically (too toxic for systemic use, not absorbed by GIT)
Fluconazole
Triazoles
MOA: alter fungal cell membrane fluidity by inhibiting ergosterol synthesis, reducing membrane-assoc. enzymes and increasing cell wall permeability
Used for candidiasis and for cryptococcal infection
Resistance is rare
Oral absorption is good, IV formulations are also available
Metabolised in the liver, long 1/2 life (6-30 hours)
Can penetrate into CSF (useful for cryptococcal meningitis)
Side effects: nausea, abdo pain, diarrhoea, headache, dizziness, abnormalities of liver function, hepatitis, cholestasis, rashes
