Pharmacological Basis For Treament Of GI Disorders Flashcards
List some areas of GIT importance.
gastric acid secretion
vomiting
gut motility
bile formation and excretion
What are two types of anti-secretory agents?
H2 receptor antagonists and proton pump inhibitors.
What are the clinical uses of H2 receptor antagonists?
They inhibit histamine-, ACh- and gastrin-stimulated acid secretion on parietal cells.
They reduce gastric acid secretion and, as a consequence, reduce pepsin secretion.
They promote the healing of duodenal ulcers.
List some examples of H2 receptor antagonists.
Ranitidine
Cimetidine
Famotidine
Nizartidine
What are some side effects of H2 receptor antagonists?
They’re generally rare, but there may be:
diarrhoea
muscle cramps
transient rashes
hypergastrinaemia
Cimetidine, in particular, can cause gynaecomastia (man-boobs) in men (also decreased sexual function, but this is rare).
Cimetidine also inhibits P450 enzymes, meaning it decreases the metabolism of a number of drugs broken down by P450 enzymes (eg. anticoagulants, tricyclic antidepressants)
How do proton pump inhibitors work?
They are weak bases; they’re inactive at a neutral pH.
They irreversibly inhibit the H+/K+-ATPase pump. This means that there is less H+ in the cell to combine to make HCl.
Thus, it decreases basal and food-stimulated gastric acid secretion.
List examples of proton pump inhibitors.
Omeprazole
Lanzoprazole
Pantoprazole
Rabeprazole
What are the clinical uses of proton pump inhibitors?
They are used against:
peptic ulcers
reflux oesophagitis
as a component of therapy against H. Pylori
can also be used in the treatment of Zollinger-Ellison syndrome (overproduction of gastric acid)
What are some side effects of proton pump inhibitors?
headaches
diarrhoea
mental confusion
rashes
somnolence (strong desire to sleep)
impotence
gynaecomastia
dizziness
Prostaglandins are gastroprotective.
How do they work?
increase mucous secretion
stimulate bicarbonate secretion
promotes vasodilation
negatively regulates parietal cells, so reduces H+ secretion
Why do NSAIDs (eg. aspirin) cause gastric bleeding?
They cause gastric bleeding because they inhibit prostaglandin synthesis (meaning there is less gastric protection) and Thromboxane A2 synthesis (which is involved in healing).
It would be better to use selective COX-2 inhibitors (such as celecoxib, rofecoxib) as they cause less bleeding.
What effect does dopamine have on 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.
Thus, if you want to increase motility, you want to stop dopamine’s effects.
By which three mechanisms does metoclopramide promote gut motility?
inhibition of pre- and post-synaptic D2 receptors
stimulation of presynaptic, excitatory 5-HT4 receptors
antagonism of presynaptic inhibition of muscarinic receptors
What does metoclopramide promote the release of?
It promotes the release of ACh, which results in the following:
increases LOS tone and gastric tone
increases intragastric pressure
improved antroduodenal coordination and accelerated gastric emptying
Describe antispandmodic agents (what they work, examples, clinical uses).
They decrease spasms in the bowel. They have relaxant actions on the GIT (relax the smooth muscle in the GIT).
Examples include:
propantheline (antimuscarinic agent)
dicloxerine (dicyclomine)
mebeverine
They may be useful in irritable bowel syndrome and diverticular disease.
What are the goals of pharmacological intervention in gastric ulcers?
reduce acid secretion with H2 receptor antagonists
neutralise secreted acid with antacids
attempt to eradicate H.pylori (if applicable)
Inhibition of acid secretion removes the constant irritation and allows the ulcer to heal.
What is the general mechanism of antacids?
neutralise gastric acid
increase the pH of gastric acid (peptic activity stops at pH 5)
prolonges dosing can lead to healing of duodenal ulcers (less effective for gastric ulcers)
What are some examples of antacids?
sodium alginate (eg. Galviscon)
sodium bicarbonate
calcium carbonate
How does bismuth chelate work (and what is its prominent side effect)?
It protects the gastric mucosa:
forms a base over the crater of the ulcer
adsorbs pepsin
increased HCO3- and PG secretion
it’s toxic against H.pylori, and used as part of a triple therapy to eradicate it
The side effect is that it blackens the stool and tongue.
How would you treat an H.pylori infection?
To treat it, we would use a combination therapy of at least three drugs (PPI and antibiotics):
omeprazole, amoxicillin, and metronidazole
[omeprazole, clarythromycin, and amoxicillin] or [tetracycline, metronidazole, and bismuth chelates]
lansoprazole, clarythromycin, tinidazole, and bismuth chelates
To the patient, we would advise them to:
adhere to the treatment
watch out for resistance to metronidazole (you can’t take it with alcohol)
What are some consequences of constipation as a result of rectal distention?
headache
loss of appetite
nausea
abdominal distention and stomach pain
What are some causes of constipation?
decreased motility of the large intestine
old age
damage to the enteric system of the colon
List some factors that can improve colonic motility.
increased fibre, cellulose and complex polysaccharides
bran, some fruits and vegetables with high fibre
laxatives (beware that excessive use can lead to decreased responsiveness)
mineral oil, as it lubricates the faeces
castor oil, as it stimulates the motility of the colon
What are some alarm signs and symptoms of someone with chronic constipation?
acute onset of constipation in older individuals
weight loss (10 lbs)
blood in the stool
anaemia
family history of colon cancer or IBD
