GIT pharm

• List two types of anti secretory agents

  -H2-receptor antagonists

  -proton pump inhibitors
• List the 4 types of cytoprotective agents and mucosal strengtheners

  sucralfate

  prostaglandins

  bismuth

  antacids
• Histamine receptor antagonists

  Reversible competitive inhibitors of H2 receptor

  Promote healing of duodenal ulcers

  Relapse on withdrawal
• Proton pump inhibitors MOA

  Block acid secretion by irreversibly inactivating hydrogen-potassium(H+/K+) ATPase proton pump at the parietal cell surface

  As they irreversibly inhibit proton pumps, acid secretion resumes only after synthesis of new molecules
• At a neutral ph, PPIs are inactive, they can only be activated in an acidic environment
• PPIs accumulate in the canaliculi(small channel/duct) of parietal cell
• What are the most effective drugs in anti-ulcer therapy?

  PPI

  Esomeprazole(inc. Nexium)

  Omeprazole(inc. Meprazol)

  Pantoprazole(inc. Somac)

  Rabeprazole(inc. Pariet)
• Pharmacokinetics of PPIs

  Administered as capsules containing enteric coated granules to make sure they reach site of action

  Administered 1 hr before meals(to give time to reach caniculi + bind to pump)

  DONT coadminister with other acid suppressing agents
• Adverse effects of PPIs

  Extreme safe drugs(headache, skin rashes, dizziness)

  Inhibit CYP450(warfarin, phenytoin, theophylline, etc...)
• What is sucralfate?

  Mucosal protective agents

  Complex of aluminium hydroxide and surfaced sucrose
• MOA of sucralfate

  Viscous at acid pH and adheres to surface of ulcers, to act as a barrier to aggressive luminal factors(eg acid, pepsin, bile salts)

  Stimulates mucosal protecting mechanisms(mucus, bicarbonate, prostoglandinins)
• When to take sucralfate?

  Taken on empty stomach 1 hr before meals(4/day)

  Antacids & meals should not be taken within 30 min of sucralfate as they may raise the gastric pH and alter the physicochemical properties of sucralfate
• Adverse effects of sucralfate

  constipation(~15%), inhibit absorption of some drugs(eg theophylline, tetracycline, digoxin & amitriptyline)
• Prostaglandin analogues


  misoprostol(inc, Cytotec)- PGE1 analogue comparable ulcer healing efficacy with H2 receptor antagonists only in patients using NSAIDs with high risk of ulcer
• Side effects of prostaglandin analogues

  Pain endings sensitised so pain often worsens initially

  Diarrhoea, nausea, headache and dizziness

  Uterine contractions(bc of prostaglandins), contraindicated in pregnancy
• Bismuth chelate


  Colloidal bismuth, not first line(used in combination therapy)
• MOA of bismuth chelate

  Coats ulcer base

  Forms precipitate which binds to proteins on surface of ulcers at acidic pH providing barrier to aggressive factors in gastric juice

  Enhance PG synthesis, stimulates mucus & bicarbonate secretion(as per sulcralfate)
• Side effects of bismuth chelate


  May cause blackening of stools & tongue

  Not used for long periods-bismuth toxicity(could damage kidneys & CNS)

  Not be taken with meals, antacids or other meds bc needs acidic pH
• MOA of antacids


  Weak bases that neutralise acid(ie raise gastric pH)

  Also inhibit formation of pepsin(as pepsinogen converted to pepsin at acidic pH)

  More effective against duodenal ulcer(than gastric)
• Antacids


  Over the counter drug form symptomatic relief of indigestion

  Contains=

  aluminium hydroxide (forms AlCl3 in gut)

  magnesium hydroxide (forms MgCl2 in gut)

  Adverse effects of constipation and diarrhoea respectively
• Helicobacter pylori


  Gram-ve bacteria

  Major cause of gastric & duodenal ulcers

  Classified as class 1 carcinogen for gastric cancer
• Triple therapy of H. Pylori


  PPI (Esomeprazole) + amoxicillin + clarithromycin (‘triple therapy’)

  • First-line treatment

  • Eradication results of >80% with best triple regimens (7-14 days)
• Quadruple therapy of h.pylori

  • PPI (Esomeprazole) + bismuth + metronidazole + tetracycline (‘quadruple therapy’)

  • Not commonly used

  • Second-line treatment: typical used in patients that suffer from clarithromycin resistance
• List the drugs that treat constipation/diarrhoea

  Lactulose

  Senna

  Loperamide
• List drugs used to treat nausea & vomiting


  promenthazine

  hyoscine

  ondansetron

  metoclopramide
• Potential causes of constipation

  -pregnancy

  -post surgery

  -drug-induced(ie side effect), opiods, antacids, Ca+ channel blockers

  -lack of dietary fibre

  -IBS

  -dehydration
• Action of purgatives

  Pro-kinetic agents

  Increase transit of food through intestines

  Used to relieve constipation or clear bowel prior to surgery/examination
• Types of purgatives

  Laxatives

  Faecal softeners

  Stimulant purgatives
• MOA of laxatives


  Bulk laxatives - poorly digested compounds (e.g. methylcellulose, psyllium) often occurring in natural foods

  • Polysaccharide polymers not broken down by normal digestive processes in upper GIT

  • Form bulky hydrated (retain water) mass in GIT lumen promoting peristalsis
• Examples of laxatives


  Metamucil, citrucel
• Osmotic laxatives


  Poorly absorbed solutes, include salts and sugars

  Draw water into the gut to accelerate transfer of contents through small intestine

  Sugars broken down by bacteria in GIT creating acidic metabolites which attract water(also produce gas)

  Eg Movicol
• Stimulant laxatives


  aloe, senna, cascara-plant derived bisacodyl(CorrectolTM, DulcolaxTM)-p.o. or suppository glycerol suppositories

  Increase electrolyte (and water) secretion by mucosa

  Increase peristalsis(stimulate enteric nerves)
• Faecal softeners


  Docusate sodium(eg ColoxylTM), glycerin suppository

  Surfactant, Surface Active Agent-reduces surface tension of water(ie detergent-like effect) which produces softer faeces

  Weak laxative effects
• Who should take faecal softeners as opposed to other drugs for constipation?


  Useful in patients where 'straining' should be avoided, eg after child birth, surgery

  Goof first therapy option for children ie coloxyl oral drops
• Drugs that increase GIT motility, without purgation

  D2 receptor antagonists eg domperidone, metoclopramide
• MOA of D2 receptor antagonist


  • Stimulation of D2 receptors inhibits cholinergic smooth muscle activation

  • D2 receptor antagonists prevent this from occurring

  • Increase lower oesophageal sphincter pressure, enhance

  gastric emptying

  • Very little effect on colonic motility

  • May also block D2 in chemoreceptor trigger zone
• Definition of diarrhoea


  Defined by frequency and 'looseness' of bowel movement

  Can be acute or chronic

  Frequent passage of liquid faeces

  Defence mechanism for rapidly ridding the gut of poisonous/irritating substances

  Globally: one of the major causes of death in malnourished infants
• Causes of diarrhoea

  • viral gastroenteritis
  • 'food poisoning' (bacterial)
  • drug-induced
• Treatment of diarrhoea


  • Maintenance of fluid and electrolyte balance

  (replace Na+, water, etc) - primary (and often only) treatment

  • In ileum, Na+ and glucose are co-transported.

  Therefore, glucose ‘drinks’ enhance Na+ (and water) absorption

  • Use of anti-infective agents (if necessary) (e.g. bacterial - antibiotics

  • “traveller’s diarrhoea” – E. coli

  • Cholera vaccine (killed whole cell oral vaccine) • Use of antidiarrhoeal agents
• Anti diarrhoeal agents


  Opioids eg loperamide, (codeine)

  -Doesn't cross BBB; no CNS effects

  -relatively selective for GIT

  -decreases activity of myenteric plexus