L30 GASTROINTESTINAL DRUGS

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L30 GASTROINTESTINAL DRUGS AND
NAUSEA Objectives ? name and describe the drugs
that - treat gastric acidity conditions
arising from excess acidity - control nausea
and vomiting
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References

• Bryant et al., pp 536 - 546
• L 17 - antimuscarinics
• L 14 - dopamine antagonists

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GIT Most drugs affect either motility or
secretion GASTRIC ACIDITY protein digestion -
HCl - pepsinogen ? pepsin Peptic ulcer
- mucosa of the stomach and/or upper intestine
is directly exposed to HCl and pepsin. Peptic
Ulcer Disease (PUD) Excess acid production ?
gastro-oesophageal reflux disease (GORD)
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Factors that damage the mucosa HCl
secretion pepsin activity and secretion Helicoba
cter pylori Factor that protect the
mucosa HCO3- secretion mucous
secretion prostaglandin production.
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Control of these Factors Vagus nerve - ACh
stimulates M1-receptors ? stimulates
histamine release Gastrin - hormone - stimulus
for release amino acids, peptides,
stretch. stimulates histamine
release Histamine - stimulates H2-receptors
parietal cells contains proton pump creates and
pumps HCl into stomach
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Control of these Factors (cont) Prostaglandins
inhibit secretion of HCl, gastrin
pepsinogen stimulate secretion of mucous
HCO3- Stress, Smoking, Alcohol, NSAIDs ? acid
production, ? prostaglandin synthesis
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GOALS FOR TREATMENT OF PEPTIC ULCERS 1. Relief
from pain 2. Promote healing of the GIT
lining 3. Prevent recurrence
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1. ANTACIDS ? pH of stomach (chemical effect) 1.
? pain caused by acid 2. when pH is above 4 - 5,
pepsin is inactive. main ones Magnesium
carbonate, Aluminium hydroxide Mg salts cause
diarrhoea Al salts cause constipation ? these
drugs are usually administered together.
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2. CYTOPROTECTIVE AGENTS Form gel-like
protective coating over the damaged mucosa
coating is resistant to acid and
pepsin Bismuth forms protective coating and
assists eradication of H. pylori
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3. H2-Antagonists Ranitidine, Cimetidine,
Famotidine competitive antagonists at
H2-receptor ? ? volume of acid ? ? H ? ?
release of pepsin effect maintained during
fasting and sleeping effective for treating PUD
and GORD
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4. Proton Pump Inhibitors Omeprazole,
lanoprazole, pantoprazole irreversibly blocks
proton pump in parietal cells. should only be
used for short term administration (no HCl
interferes with digestion and prevents defence
against orally acquired infections) used to
treat ulcers resistant to H2-antagonists assists
eradication of H. pylori
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5. Prostaglandin Analogues Misoprostol ?
secretion of HCl, gastrin, pepsinogen ? secretion
of mucous, HCO3- (useful in smokers, heavy
alcohol drinkers and patients administered
NSAIDs) Cannot be used in women of childbearing
age.
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6. Antibiotics Clarithromycin, Amoxycillin
Metronidazole Bismuth standard triple therapy
Two of the antibiotics proton pump inhibitor
for 1 week. Or Two of the above antibiotics with
bismuth for 2 weeks
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NAUSEA AND VOMITING
Sensory motion, pain, sight
Memory anticipation
higher centres
Emetic centre
vomiting
(M1, H1)
CTZ
(D, 5-HT3)
drugs, chemicals
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ANTIEMETICS Antiemetics act on emetic centre, CTZ
or stomach administered in anticipation (oral,
transdermal) injection / suppository if vomiting
has commenced 1. Antimuscurinics Hyoscine acts
on M1 receptors in semicircular canals on
emetic centre produce dry mouth, blurred vision
etc.
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2. Antihistamines Promethazine,
Dimenhydrinate act on semicircular canals on
emetic centre most effective also have
antimuscurinic activity may cause drowsiness 3.
Dopamine Antagonists Prochlorperazine,
Metoclopramide, Domperidone act in CTZ used
mainly to treat cancer chemotherapy induced
nausea
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4. 5-HT3 Antagonists Ondansetron, Dolasetron,
Tropisetron blocks 5-HT3 receptors in CTZ and
peripherally very powerful used to prevent
cancer chemotherapy induced nausea may cause
dizziness, headache and nausea
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Dopamine and 5-HT antagonists only control nausea
induced by actions on the CTZ and do NOT block
motion sickness Benzodiazepines (anticipatory
nausea) Corticosteroids (chemotherapy-induced
nausea)
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Drugs you need to know

• Magnesium carbonate
• Aluminium hydroxide
• Bismuth
• Ranitidine
• Omeprazole

• Hyoscine
• (Promethazine)
• (Prochlorperazine)
• Ondansetron