Pharmacological Basis for Treatment of GI Disorders
The major mechanism(s) by which metoclopramide stimulates gastric
motility and the emptying of the stomach in patients in which it is
delayed
Two conditions in which metoclopramide may be used
The mechanism of action of two spasmolytics which are used to treat
spasms of the smooth muscle of the lower bowel (which are
responsible for some types of 'colicky' pain)
The mechanism of action of two pharmacological treatments for
heartburn or gastroesophageal reflux disease
Advice that you might give a patient with heartburn or G.O.R.D
The pharmacological effect and identify the site of action of two drugs
acting on histamine2 receptors
The pharmacological effect and identify the site of action of one drug
acting on the 'proton pump' (H+ / K+ATPase)
The mechanism of action of two different types of laxative agent
The mechanism of action of one anti-diarrhoeal agent
Recap Gastrointestinal Tract
There is hormonal control of the gut, this includes endocrine secretions which release
substances into the GIT (peptides e.g. gastrin).
Paracrine secretions which are regulatory peptides released by cells in the GIT wall (e.g.
histamine).
Some of the paracrine secretions function also as neurotransmitters e.g. CCK.
There are areas of the GIT which are of pharmacological importance as if there is
dysregulation of the way the gut functions (more specifically secretions) then this can
cause harm.
So one is gastric acid secretion, as 2.5L of gastric juice is secreted/day.
If acid is fluxed out by vomiting this can cause damage (such as ulcers if not cleared).
Gut motility is also very important, because stasis of the gut increases the likelihood of
reflux and also reduces ability of clearance of acid from oesophagus. In intestine could
result in constipation.
Another important component is bile formation and excretion, as if it is not functioning
properly can lead to things like gallstones or malnutrition.
Recap: How acid secretion is regulated in the GIT?
Stimuli that act on parietal cells include ->
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.
, The release of gastrin is controlled by neurotransmitters and other mediators e.g. Milk
and Ca2+ containing solutions stimulate gastrin release in the stomach. So do not use
Ca2+-containing salts to control acid secretion.
Ach -> A neurotransmitter that stimulates muscarinic Ach receptors on parietal cells
and on histamine containing cells (and G-cells)
Histamine -> A local hormone that acts on H2 receptors on parietal cells and mast cells.
Its release can be increase by gastrin and Ach
PGE2 and PGI2 -> Inhibit acid secretion, important in increasing mucus secretion, bicarb
secretion and blood flow.
Effects of Metoclopramide on Gastric Motility and the Emptying
Too much stasis of gastric juice could cause damage.
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.
Metoclopramide is useful for gastrointestinal reflux (in keeping things down) but is
useless in paralytic ileus (can cause symptoms such as moderate, diffuse abdominal
discomfort e.g. abdominal distension, nausea/vomiting especially after meals)
Metoclopramide stimulates gastric motility and accelerates gastric emptying.
Metoclopramide promotes gut motility by inhibition of presynaptic and postsynaptic D 2
receptors, so it inhibits dopamine effects.
The major mechanism(s) by which metoclopramide stimulates gastric
motility and the emptying of the stomach in patients in which it is
delayed
Two conditions in which metoclopramide may be used
The mechanism of action of two spasmolytics which are used to treat
spasms of the smooth muscle of the lower bowel (which are
responsible for some types of 'colicky' pain)
The mechanism of action of two pharmacological treatments for
heartburn or gastroesophageal reflux disease
Advice that you might give a patient with heartburn or G.O.R.D
The pharmacological effect and identify the site of action of two drugs
acting on histamine2 receptors
The pharmacological effect and identify the site of action of one drug
acting on the 'proton pump' (H+ / K+ATPase)
The mechanism of action of two different types of laxative agent
The mechanism of action of one anti-diarrhoeal agent
Recap Gastrointestinal Tract
There is hormonal control of the gut, this includes endocrine secretions which release
substances into the GIT (peptides e.g. gastrin).
Paracrine secretions which are regulatory peptides released by cells in the GIT wall (e.g.
histamine).
Some of the paracrine secretions function also as neurotransmitters e.g. CCK.
There are areas of the GIT which are of pharmacological importance as if there is
dysregulation of the way the gut functions (more specifically secretions) then this can
cause harm.
So one is gastric acid secretion, as 2.5L of gastric juice is secreted/day.
If acid is fluxed out by vomiting this can cause damage (such as ulcers if not cleared).
Gut motility is also very important, because stasis of the gut increases the likelihood of
reflux and also reduces ability of clearance of acid from oesophagus. In intestine could
result in constipation.
Another important component is bile formation and excretion, as if it is not functioning
properly can lead to things like gallstones or malnutrition.
Recap: How acid secretion is regulated in the GIT?
Stimuli that act on parietal cells include ->
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.
, The release of gastrin is controlled by neurotransmitters and other mediators e.g. Milk
and Ca2+ containing solutions stimulate gastrin release in the stomach. So do not use
Ca2+-containing salts to control acid secretion.
Ach -> A neurotransmitter that stimulates muscarinic Ach receptors on parietal cells
and on histamine containing cells (and G-cells)
Histamine -> A local hormone that acts on H2 receptors on parietal cells and mast cells.
Its release can be increase by gastrin and Ach
PGE2 and PGI2 -> Inhibit acid secretion, important in increasing mucus secretion, bicarb
secretion and blood flow.
Effects of Metoclopramide on Gastric Motility and the Emptying
Too much stasis of gastric juice could cause damage.
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.
Metoclopramide is useful for gastrointestinal reflux (in keeping things down) but is
useless in paralytic ileus (can cause symptoms such as moderate, diffuse abdominal
discomfort e.g. abdominal distension, nausea/vomiting especially after meals)
Metoclopramide stimulates gastric motility and accelerates gastric emptying.
Metoclopramide promotes gut motility by inhibition of presynaptic and postsynaptic D 2
receptors, so it inhibits dopamine effects.
