S2: Pharmacological Basis for Treatment of GI Disorders I Flashcards
What food and ion also stimulate gastrin release?
Milk and Ca2+ containing solutions stimulate gastrin release in the stomach. So do not use Ca2+-containing salts to control acid secretion.
What is gastrin?
A peptide hormone that is secreted by the gastric mucosa and duodenum, it stimulates gastric secretion, blood flow and gastric motility. There is evidence that the parietal cells express gastric receptors.
- Released from G cells
How do PGE2 and PGI2 affect acid, bicarbonate and mucus secretion?
Inhibit acid secretion, important in increasing mucus secretion, bicarb secretion and blood flow.
How does dopamine affect the gut?
- Dopamine has a direct relaxant effect on the gut by activating D2 receptors in the lower oesophageal sphincter and stomach (fundus and antrum).
- Dopamine also inhibits the release of Ach (so would prevent contraction of gut smooth muscle).
- If you want to increase motility you want to stop dopamine’s effects.
Describe the effects of Metoclopramide
Metoclopramide is useful for gastrointestinal reflux
- Metoclopramide stimulates gastric motility and accelerates gastric emptying.
It decreases postprandial fundus relaxation and increases antral contractions.
Increased Ach will increase LOS and gastric tone.
Can metoclopramide be used for paralytic ileus?
No
It can cause symptoms such as moderate, diffuse abdominal discomfort e.g. abdominal distension, nausea/vomiting especially after meals
Paralytic ileus: Obstruction of the intestine due to paralysisof the intestinal muscles.
Explain the mechanism of Metoclopramide
Metoclopramide promotes gut motility by inhibition of presynaptic and postsynaptic D2 receptors, so it inhibits dopamine effects.
It also stimulates 5-HT4 receptors and there is also antagonism of presynaptic inhibitory muscarinic receptors for Ach (-ve feedback), thus it means there will be increased Ach release.
It can also stimulate Ach release from enteric neurones.
It also stimulates presynaptic excitatory 5-HT4 and inhibitory nitregeric neurones causes coordinated gastric motility.
Where is metoclopromide effects limited to?
Its prokinetic effects are to a large extent limited to the proximal gut
Clinical uses of metoclopromide
- Symptoms of gastriparesis
- Promotes gastric emptying
- Anti-emetic effects via central pathways
Metoclopramide can also be used in other areas, it appears to be quite useful in nausea. It has also been shown to help reduce pain.
Give an example of an Antispasmodic Agents
Meberverine
What do Antispasmodic Agents do?
These reduce spasm in the bowel and have a relaxant action on the GIT (relax smooth muscle in the GIT).
- Propantheline has antimuscarinic effects (which will help relaxation)
- Muscarinic receptor antagonists inhibit parasympathetic activity which reduces spasm in the bowel.
What may Antispasmodic Agents be used for?
Antispasmodic agents may be useful in irritable bowel syndrome and diverticular disease
3 goals for pharmacological intervention in gastric ulcers
- Reduce acid secretion with H2 receptor antagonists
- Neutralise secreted acid with antacids
- Attempt to eradicate H.pylori
How does inhibition of acid secretion help peptic ulcers?
What conditions can drugs that inhibit or neutralise acid secretion treat?
Inhibition of acid secretion removes the constant irritation of the epithelium and allows the ulcer to heal.
- Peptic ulcers
- Reflux oesophagitis (acid can damage the oesophagus)
- Zollinger-Ellison syndrome (gastrin-producing tumour)
How is H.pylori a risk factor for peptic ulcer?
It causes chronic gastritis that leads to an duodenal ulcer.
Mechanisms of antacids
The general mechanism of antacids are that they neutralise gastric acid. They increase the pH of gastric acid (peptic activity stops at pH 5).
The antacids form a raft on top of the acidic chyme also which reduces the amount of acidic chyme that refluxes into and damages the oesophagus.
How do antacids affect duodenal and gastric ulcers?
Prolonged dosing can lead to healing of duodenal ulcers, however they seem to be less effective for gastric ulcers.
What does Bismuth chelate do (an antacid do)?
- Protects gastric mucosa
- Forms a base over the crater of the ulcer and sticks to pepsin (adsorbs it) and stops it from working
- It also increases HCO3- and PG secretion and on top of this is toxic against H. pylori, so is used in combination with the triple therapy to eradicate it
- Promote bicarbonate secretion
- Enhances local synthesis of PGs
Side effects of Bismuth chelate
It blackens the stool and tongue
If a patient has renal impairment [bismuth chelate]blood may rise causing encephalopathy
- Nausea
- Vomiting.
How do prostaglandins protect the stomach mucosa?
- Inhibit mucus secretion
- Increasing bicarbonate secretion
- Increasing blood flow by vasodilating
- Reduce H+ secretion by antagonising acid release
Why do NSAIDs (e.g. aspirin) cause gastric bleeding?
They inhibit PG synthesis which protects the stomach mucosa and thromboxane A2 (involve in healing)
Selective COX-2 inhibitors are much more stomach friendly causing less bleeding
Warnings when taking metronidazole
- We must advise the patient to adhere to treatment and also be aware that sometimes there is resistance to metronidazole.
- They also cannot drink alcohol if they take metronidazole as it results in disulfiram like reaction, the patient will feel severely ill and may stop taking the drug.
- Disulfiram inhibits aldehyde dehydrogenase causing a build up of acetylaldehyde resulting in unpleasant flushing and nausea
do serotin diagram
fdds before u print lol hopefully u figured it out!!!
Triple combination therapy for H.Pylori
We need to use a combination therapy against H. pylori (drugs that will inhibit acid secretion and KILL the bacteria)
e.g.
Omeprazole (PPI) , amoxicillin, metronidazole
