Review of Pharmacology - 9E (2015)

Gastrointestinal Tract
Anti Emetic Drugs
Vomiting (emesis) occurs due to stimulation of vomiting centre (VC) in lateral medullary
reticular formation. It receives input from GI mucosa, chemoreceptor trigger zone (CTZ) and
vestibular apparatus.
• Irritation of GI mucosa by drugs or irritants leads to release of serotonin that
stimulates VC via 5HT 3
receptors.
• CTZ is rich in dopamine (D 2
) and serotonin (5HT 3
) and neurokinin (NK 1
) receptor.
• Motion sickness occurs due to stimulation of vestibular apparatus and cerebellum.
These structures result in stimulation of VC by activating M 1
and H 1
receptors.
• By stimulation of H 1
receptors, histamine plays a permissive role in all types of
vomiting.
Drugs For Motion Sickness
• Hyoscine is used as i.m. injection or transdermal patch (applied behind pinna) for
prophylaxis of motion sickness. It has no role in treatment, once the vomiting
starts.
• Antihistaminics like promethazine, diphenhydramine, cyclizine or meclizine can
also be used for prophylaxis.
• Cinnarizine (antihistaminic with anticholinergic and antiserotonergic properties) is
used for treatment of vertigo.
Drugs for Morning Sickness
General Gastrointestinal Pharmacology Tract
• Combination of doxylamine (antihistaminic) with pyridoxine (Vit B 6
) in high dose
is safest anti-emetic drug in pregnancy
• D 2
blockers although effective should not be used due to their teratogenic potential
Drugs for Chemotherapy and Radiation therapy Induced Vomiting
• 5 HT 3
blockers like ondansetron, granisetron, dolasetron, palonosetron and
ramosetron are DOC for this condition.
• Palonosetron is most potent 5 HT 3
blocker. Dolasetron may prolong QT interval.
• Palonosetron has longest t 1/2
whereas ondansetron has shortest t 1/2
.
• Efficacy of these drugs increases if used along with antihistaminics, D 2
blockers or
dexamethasone.
• These drugs are also effective in hyperemesis of pregnancy and post operative nausea.
• D 2
blockers like metoclopramide and domperidone can also be used
• Vomiting due to cisplatin (most emetogenic anti cancer drug) can occur within 24
hours or it may be delayed (after 2 days). DOC for the former condition is 5HT3
blocker whereas for the latter condition, DOC is aprepitant (substance P antagonist).
Palonosetron may also be effective in delayed emesis.
• Aprepitant is a highly selective NK1 receptor antagonist, orally active, and enter the
Combination of doxylamine (antihistaminic)
with pyridoxine (Vit
B6) in high dose is safest antiemetic
drug in pregnancy
5 HT 3
blockers like ondansetron,
granisetron, dolasetron, palonosetron
and ramosetron are DOC
for chemotherapy induced vomiting.
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