14 Gastrointestinal tract drugs Flashcards
14.01 H2 ANTAGONIST
Ranitidine, famotidine, cimetidine, nizatidine - actions
inhibit gastric acid secretion
inhibit the action of histamine released from mast cell-like cells in the gastric mucosa
partially inhibit acid secretion stimulated by gastrin or vagal stimulation
14.01 H2 ANTAGONIST
Ranitidine, famotidine, cimetidine, nizatidine - MOA
selective, reversible, competitive antagonism of histamine H2 receptors on parietal cells
14.01 H2 ANTAGONIST
Ranitidine, famotidine, cimetidine, nizatidine - abs/distrib/elim
given orally, rapidly absorbed
mainly renal excretion
14.01 H2 ANTAGONIST
Ranitidine, famotidine, cimetidine, nizatidine - clinical use
gastric and duodenal ulcers
gastro-oesophageal reflux disease
NSAID-induced ulcers (with discontinuation of NSAID)
14.01 H2 ANTAGONIST
Ranitidine, famotidine, cimetidine, nizatidine - adverse effects
uncommon
headache, GIT disturbances
anti-androgenic effects with cimetidine but not other H2 blockers: gynaecomastia in men, galactorrhoea in women
14.02 PROTON PUMP INHIBITORS
Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole - actions
inhibit gastric acid secretion
14.02 PROTON PUMP INHIBITORS
Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole - MOA
bind irreversibly to the H+/K+-ATPase (proton pump) in the gastric parietal cells to inhibit H+ transport
omeprazole (like other PPIs) is a prodrug - the acidic conditions in the parietal cell canaliculi convert the drug to the active form
14.02 PROTON PUMP INHIBITORS
Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole - abs/distrib/elim
given orally or IV but needs to be enteric coated to avoid deactivation by gastric acid before absorption
mainly eliminated by liver metabolism
14.02 PROTON PUMP INHIBITORS
Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole - clinical use
peptic and duodenal ulcers
gastro-oesophageal reflux disease
Zollinger-Ellison syndrome
as part of the triple therapy for Helicobacter pylori-dependent ulcers
treatment of NSAID-associated ulcers
PPIs are more effective than H2 antagonists
14.02 PROTON PUMP INHIBITORS
Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole - adverse effects
generally safe
occasionally: headache, abdominal pain, diarrhoea, GI infections
rarely: hypomagnesaemia, fractures
14.03 MUCOSAL PROTECTANTS
Sucralfate, bismuth subsalicylate, tripotassium dicitratobismuthate - actions
local protective or healing action at GI mucosa
antibacterial effects
14.03 MUCOSAL PROTECTANTS
Sucralfate, bismuth subsalicylate, tripotassium dicitratobismuthate - MOA
these agents coat the ulcer/mucosa to protect against the action of acid and pepsin and may increase mucus and bicarbonate secretion
bismuth has antibacterial action against Helicobacter pylori
14.03 MUCOSAL PROTECTANTS
Sucralfate, bismuth subsalicylate, tripotassium dicitratobismuthate - abs/distrib/elim
very little of oral dose is absorbed into the systemic circulation
14.03 MUCOSAL PROTECTANTS
Sucralfate, bismuth subsalicylate, tripotassium dicitratobismuthate - clinical use
(I) indigestion and gastric or duodenal ulcers, bismuth is additionally used for eradication of H. pylori
(II) binds enterotoxins in treatment of diarrhoea (including travellers)
14.03 MUCOSAL PROTECTANTS
Sucralfate, bismuth subsalicylate, tripotassium dicitratobismuthate - adverse effects
sucralfate: constipation, formation of solid complexes (bezoars) in stomach
bismuth: nausea, vomiting, black stools
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - actions
neutralise acid to raise pH in gut lumen
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - MOA
antacids are weak bases that neutralise the HCl secreted in the stomach
the elevated pH also usefully reduces the activity of pepsin
stimulate prostaglandin synthesis
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - abs/distrib/elim
aluminium and magnesium hydroxides are poorly absorbed from the gut (no systemic actions)
NaHCO3 and CaCO3 are absorbed and may have significant systemic actions
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - clinical use
short-term symptom relief for duodenal ulcers
gastro-oesophageal reflux disease
need to be taken 5-7 times daily
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - adverse effects
Al(OH)3 causes constipation
Mg(OH)2 has a strong laxative action (osmotic purgative)
NaHCO3 and CaCO3 release CO2, which causes belching and also metabolic alkalosis
CaCO3 causes hypercalcaemia
14.04 ANTACIDS
Aluminium or magnesium hydroxide, sodium bicarbonate, calcium carbonate - special points
calcium and aluminium salts complex with orally administered tetracyclines to prevent their absorption
14.05 PROSTAGLANDIN E AGONIST
Misoprostol - actions
promotes gastric ulcer healing
combats the ulcerogenic action of NSAIDs
14.05 PROSTAGLANDIN E AGONIST
Misoprostol - MOA
activates prostaglandin receptors (EP3 subtype) to inhibit acid secretion
effects via Gi-mediated inhibition of adenylate cyclase
also stimulates mucus and bicarbonate secretion
14.05 PROSTAGLANDIN E AGONIST
Misoprostol - abs/distrib/elim
given orally, well absorbed
rapidly hydrolysed to free acid (active moiety)
half-life 30-40 min
14.05 PROSTAGLANDIN E AGONIST
Misoprostol - clinical use
gastric ulcers, particularly those caused by NSAIDs and where the NSAIDs cannot be withdrawn
also used for induction of labour
14.05 PROSTAGLANDIN E AGONIST
Misoprostol - adverse effects
diarrhoea, abdominal cramps
should be avoided in pregnancy because of contractile action on uterus
14.06 5-HT3 ANTAGONISTS - ANTIEMETICS
Ondansetron, granisetron, dolasetron, tropisetron - actions
antiemetic
14.06 5HT3 ANTAGONISTS - ANTIEMETICS
Ondansetron, granisetron, dolasetron, tropisetron - MOA
reversible competitive antagonism at 5-HT3 receptors in the chemoreceptor trigger zone and at the sensory endings of vagal afferents in the GIT
14.06 5HT3 ANTAGONISTS - ANTIEMETICS
Ondansetron, granisetron, dolasetron, tropisetron - abs/distrib/elim
given orally or IV (if vomiting)
half-life 4-6h
metabolised by cytochrome P450 system in liver
14.06 5HT3 ANTAGONISTS - ANTIEMETICS
Ondansetron, granisetron, dolasetron, tropisetron - clinical use
main agents for nausea and vomiting due to cytotoxic, anticancer drugs
often given prophylactically before starting chemotherapy
nausea and vomiting arising postoperatively or after radiation treatment
limited effectiveness in motion sickness
14.06 5HT3 ANTAGONISTS - ANTIEMETICS
Ondansetron, granisetron, dolasetron, tropisetron - adverse effects
well tolerated
headache, GIT upsets
14.07 OTHER ANTIEMETICS
Anticholinergics
hyoscine acts on the vestibular nuclei and vomiting centre
used for motion sickness
15.07 OTHER ANTIEMETICS
Antihistamines
e.g. promethazine, cyclizine and cinnarizine
antiemetic action is due to blocking H1 receptors in the vestibular nuclei and vomiting centre
14.07 OTHER ANTIEMETICS
Dexamethasone
mechanism of antiemetic action is not established
generally used in combination with other antiemetics during surgery or chemotherapy
14.07 OTHER ANTIEMETICS
Cannabinoids
action via CB1 receptors
used for nausea and vomiting associated with cancer chemotherapy
dronabinol is the main active ingredient (tetrahydrocannabinol) of cannabis, nabilone is a synthetic analogue
14.07 OTHER ANTIEMETICS
Neurokinin 1 (NK1) receptor antagonists
aprepitant blocks substance P receptors in the vomiting centre
adjunct for treatment of chemotherapy-induced and postoperative nausea and vomiting
orally active
14.08 OSMOTIC LAXATIVES
Lactulose, macrogols, magnesium sulfate - actions
increase osmotic load
include magnesium salts, disaccharides (lactulose) and ethylene glycol polymers (macrogols)
14.08 OSMOTIC LAXATIVES
Lactulose, macrogols, magnesium sulfate - MOA
poorly absorbed, these agents raise the osmotic load within the gut lumen
this causes ingested water to be retained and water to be withdrawn from the bloodstream
the increased fluid volume promotes movement along the gut
14.08 OSMOTIC LAXATIVES
Lactulose, macrogols, magnesium sulfate - abs/distrib/elim
given orally
not absorbed
14.08 OSMOTIC LAXATIVES
Lactulose, macrogols, magnesium sulfate - clinical use
constipation (lactulose and macrogols)
bowel cleansing prior to surgery or examination (MgSO4)
the effects of lactulose develop after 2-3 days
14.08 OSMOTIC LAXATIVES
Lactulose, macrogols, magnesium sulfate - adverse effects
abdominal cramps, flatulence
few systemic actions because of low absorption
14.09 BULK LAXATIVES
Methylcellulose, ispaghula husk, sterculia, bran - actions
purgative
14.09 BULK LAXATIVES
Methylcellulose, ispaghula husk, sterculia, bran - MOA
these agents (polysaccharide polymers) are poorly absorbed and, being hygroscopic, form a soft faecal mass which distends the gut to promote peristalsis
14.09 BULK LAXATIVES
Methylcellulose, ispaghula husk, sterculia, bran - abs/distrib/elim
given orally
not absorbed
14.09 BULK LAXATIVES
Methylcellulose, ispaghula husk, sterculia, bran - clinical use
constipation
used if increasing dietary fibre has not helped
beneficial in various bowel disorders (e.g. haemorrhoids, irritable bowel syndrome)
maintain fluid intake to prevent intestinal obstruction
14.09 BULK LAXATIVES
Methylcellulose, ispaghula husk, sterculia, bran - adverse effects
flatulence
few systemic actions because of low absorption
obstruction
14.10 STIMULANT LAXATIVES
Bisacodyl, senna, glycerol - actions
laxative
14.10 STIMULANT LAXATIVES
Bisacodyl, senna, glycerol - MOA
active metabolite of bisacodyl stimulates peristalsis by irritation of mucosa and/or an effect on the enteric nervous system
also increases fluid volume by promoting net fluid secretion into the lumen
14.10 STIMULANT LAXATIVES
Bisacodyl, senna, glycerol - abs/distrib/elim
given orally or rectal
half-life 16h
senna is activated in the colon by bacteria
14.10 STIMULANT LAXATIVES
Bisacodyl, senna, glycerol - clinical use
chronic constipation
bowel cleansing prior to surgery/investigation
action of bisacodyl is more rapid rectally (30 min) than orally (6h)
14.10 STIMULANT LAXATIVES
Bisacodyl, senna, glycerol - adverse effects
abdominal cramps
tolerance to action with atony of the colon if used excessively
14.11 FAECAL SOFTENERS
Docusate, liquid paraffin, arachis oil - actions
soften/lubricate the stool to allow easier passage along the gut and defaecation
14.11 FAECAL SOFTENERS
Docusate, liquid paraffin, arachis oil - MOA
surfactant with emulsifying action
docusate has weak stimulant action
14.11 FAECAL SOFTENERS
Docusate, liquid paraffin, arachis oil - abs/distrib/elim
docusate is given orally or rectally, arachis oil rectally
14.11 FAECAL SOFTENERS
Docusate, liquid paraffin, arachis oil - clinical use
constipation
haemorrhoids
14.11 FAECAL SOFTENERS
Docusate, liquid paraffin, arachis oil - adverse effects
well tolerated, possible abdominal cramping
liquid paraffin may impair the absorption of fat-soluble vitamins, and is seldom used nowadays
14.12 OTHER DRUGS FOR CONSTIPATION
Prucalopride
selective 5-HT4 receptor agonist
marked prokinetic properties
used in chronic constipation when other types of laxatives have failed
14.12 OTHER DRUGS FOR CONSTIPATION
Lubiprostone
activates the CIC-2 chloride channel in the apical membrane of the gastrointestinal epithelium
promotes chloride and fluid secretion into the lumen, which softens the stool and improves gut motility
14.12 OTHER DRUGS FOR CONSTIPATION
Linaclotide
acts on guanylate cyclase-C receptor at the gut epithelium
greater secretion of intestinal fluid, chloride and bicarbonate ions, and more rapid intestinal transit
14.12 OTHER DRUGS FOR CONSTIPATION
Naloxegol
similar to naloxone but does not penetrate the CNS
acts as a µ-opioid receptor antagonist to counteract opioid-induced constipation
14.13 ANTIDIARRHOEAL AGENTS
Loperamide (similar: diphenoxylate, codeine) - actions
reduces gut motility and secretions
the slower transit time allows for more fluid absorption and more solid stools
14.13 ANTIDIARRHOEAL AGENTS
Loperamide (similar: diphenoxylate, codeine) - MOA
agonist action at µ-opioid receptors in the myenteric plexus of the gut inhibits peristalsis
effects can be reversed by naloxone
loperamide and diphenoxylate (not codeine) achieve low concentrations in the CNS, so have few central effects (including analgesia and addiction)
14.13 ANTIDIARRHOEAL AGENTS
Loperamide (similar: diphenoxylate, codeine) - abs/distrib/elim
given orally
metabolised by hepatic cytochrome P450 system
diphenoxylate is hydrolysed to an active metabolite
14.13 ANTIDIARRHOEAL AGENTS
Loperamide (similar: diphenoxylate, codeine) - clinical use
acute diarrhoea
chronic diarrhoea associated with inflammatory bowel disease
diphenoxylate is commonly administered in a combined preparation with atropine
14.13 ANTIDIARRHOEAL AGENTS
Loperamide (similar: diphenoxylate, codeine) - adverse effects
drowsiness, nausea
constipation, abdominal cramps
CNS depression may occur in overdose
14.14 OTHER DRUGS THAT REDUCE GI MOTILITY
Eluxadoline
mixed opioid receptor agonist-antagonist acting on enteric neurons
improves stool consistency and slows the transit time
used in irritable bowel syndrome with predominant diarrhoea symptoms
14.14 OTHER DRUGS THAT REDUCE GI MOTILITY
Racecadotril
prodrug of thiorphan
inhibits enkephalinase, which reduces the breakdown of enkephalins and alleviates excessive intestinal secretion
used in conjunction with rehydration therapy for acute diarrhoea
