L21. Pharmacology of the GIT Flashcards
Antacids Mechanism of Action
Neutralises gastric acid content in the lumen without impacting production or secretion of acid
- often in combination with PPI or H2 antagonists
Antacid example 1
ANTACID
Magnesium hydroxide
Magnesium salts have a laxative effect (non-absorbable ion)
Antacid example 2
ANTACID
Gaviscon
Mixture with sodium bicarbonate to make it fizzy
Can cause alkalosis
Risk of the rebound hyperacidity effect due to feedback pathways
Antidiarrhoeal major class
ANTI-DIARRHOEAL
Opioid Anti-diarrhoeals
Activate mu opioid receptors in the gut wall leading to decreased motility and increased fluid absorption (inhibit ACh release)
Very potent
Traveller’s diarrhoea
Adverse effect: abdominal pain, bloating, vomiting and nausea, constipation
Example of antidiarrhoeal
Loperamide
- last derivation of morphine
Most commonly used and doesn’t cross the BBB doesn’t have the the analgesic effects of opioids.
Two other less commonly used antidiarrhoeals
Direct spasmolytics: mebeverine
Muscarinic receptor antagonists: hyoscine butylbromide
What are the two broad classes of anti-emetics?
Anti-nausea and vomiting:
Target the Vomiting centre: H2 and M receptor antagonists
Reflex anti-emetics:
Target the Chemoreceptor Trigger Zone: D2 and 5HT3 and NK1 receptor antagonists
Mechanism of action of the anti-histamines (H1)?
ANTI-EMETIC
First generation anti-histamines (cross the blood brain barrier and thus have sedative effects)
Blocks H1 receptors in the brain and prevents signalling pathways from the vomiting centre
Adverse effects: psychomotor impairment, dizziness, confusion, headache, blurred vision, dry eyes, constipation
Example of anti-histamine
Promethazine
Mechanism of action of the muscarine receptor antagonists
ANTI-EMETIC
Inhibits muscarinic signalling from the vomiting centre
May cause tachycardia
Adverse effects (inhibition of SLUD) - dry mouth, dry eyes, urinary retention and constipation, confusion
Example of muscarinic antagonist
Hyoscine hydrobromide
Dopamine D2 receptor antagonist mechanism of action
ANTI-EMETIC
Blockage of dopamine receptors in the CNS, basal ganglia and in the gut (facilitate gastric emptying)
However leads to severe extra-parametal side effects including dysphonia and parkinson’s-like symptoms
Example of D2 receptor antagonist that enter the CNS
Metoclopromide
Prochloroperazine
Examples of D2 receptor antagonists that don’t enter the CNS
Domperidone
Mechanism of action of Serotonin 5HT3 receptor antagonists
ANTI-EMETICS
Very effective especially with cytotoxic drug and chemotherapy related nausea and vomiting
Inhibit serotonin receptors in the CTZ and has less side effects as the dopamine receptors: constipation, headaches
Often used in combination with the D2 and NK1 antagonists
Example of serotonin 5HT3 receptor antagonist
ANTI-EMETIC
Ondasetron
Mechanism of action of neurokinin 1 antagonists
Prevents the neurokinin-1 receptor (receptor for substance P) at the CTZ
Never used alone, always in combination
Example of NK1 receptor antagonist
ANTI-EMETIC (add on drug)
Aprepitant
Mechanism of action of anti flatulence drugs
Defoaming polymers that alters surface tension on small air bubbles allowing them to coalesce into larger bubbles that are easier to pass
Used in mixtures with antacids
Example of drugs targeting flatulence
Simethicone
Mechanism of action of the proton pump inhibitors (PPI)
GASTRIC ULCERS
Irreversible inactive that pump system suppressing acid secretion (restoration only occurs upon synthesis of new pumps)
Headache, nausea, vomiting, diarrhoea, abdominal pain, constipation and flatulence
Indications of PPIs
Peptic ulcer disease, GORD, dyspepsia, H.pylori infection, NSAID adverse effects
Examples of PPIs [3]
Esomeprazole
Omperazole
Pantomeprazole
Mechanism of action of histamine D2 receptor antagonists
GASTRIC ULCERS
Competitive blockage of H2 receptor antagonists in the gut (basal membrane of parietal cells)
Leads to decreased activation of cAMP and decreased activity of the pump leading to decreased acid secretion
Often used in combination with PPI and anti-inflammatory drugs
Low side effects: hypotension, headache, confusion, diarrhoea or constipation
What are examples of histamine D2 receptor antagonists? [2]
Ranitidine
Cimetidine
What are the different types of laxatives? [5]
- Bulking agents
- Stool softeners
- Osmotic laxatives
- Stimulant laxatives
- Glycerol
Mechanism of action of bulking agents
LAXATIVE
Increase fibre content and increases water retention of intestinal contents increasing reflex bowel action for peristaltic activity
Must be taken with lots of fluid
Adverse: flatulence, bloating, abdominal discomfort, intestinal obstruction, hypersensitivity reactions (rare)
Examples of bulking agents
LAXATIVE
Bran
Psyllium
Mechanism of action of stool softeners
LAXATIVE
Detergent action to enhance the mixing of water into the faeces (emulsifying effect)
Can increase intestinal fluid secretion
abdominal cramps, diarrhoea, nausea, rash
Example of stool softener
Docusate
liquid paraffin
What is docusate often combined with for treatment with opioid drugs to prevent constipation
Docusate + Senna (stimulant laxative)
What are the different classes of osmotic laxatives? [5]
- Saline laxatives
- Disaccharide
- Polyols
- Macrogols
- Glycerol
General mechanism of action of the osmotic laxatives?
Most contain an non-absorbable component (metal ions, sugars, large macropolymers) that exert an osmotic effect on the gut to force water out
All are contraindicated in intestinal obstruction
Saline laxative example
Magnesium sulphate (epsom salts)
Disaccharide example
Lactulose
Polyols example
Sorbitol (artificial sweetener in confectionary)
Macrogol uses
Bowel preparations - often combined with electrolytes
Mechanism of action of stimulant laxatives
LAXATIVE
Direct stimulation of nerve endings in colonic mucosa to increase intestinal motility
can also cause accumulation of water and electrolytes in the lumen by reduction of net reabsorption
Example of a stimulant laxative
SENNA
Example of another laxative class (acts on mu opioid receptors)
Methylnaltrexone
Peripherally acts on mu opioid receptors to block action in the gut
Cytoprotective drug for ulcers
Sucralfate
Forms protective barrier at the ulcer site resistant to acid, pepsin and bile
Use of spasmolytics in ulcers: MOA and example
MUSCARINIC RECEPTOR ANTAGONIST
Hyoscine butylbromide
Reduces gut motility (anti-slud) = buscopam
Not absorbed so only has periperal effects
Use of prostaglandin E analogues in ulcers: MOA and example
Mimics endogenous PG
Increases mucosal secretion, mucosal blood flow and decreases acid secretion
Misoprostol
