The document discusses Ondansetron tablets and syrup, which contain the active ingredient Ondansetron used to treat nausea and vomiting. It provides details on the physiology and mechanisms of vomiting, including the role of serotonin and dopamine receptors. It describes the indications, pharmacokinetics, safety profile and dosing of Ondansetron as an antiemetic for conditions like chemotherapy-induced nausea and vomiting, postoperative nausea and vomiting, and hyperemesis gravidarum.
8. • Physiology of Emesis:
Vomiting Centre
Pharynx
Liver
Cerebral Cortex
CTZ
GUT
Vomiting
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9. • Emesis is a reflex phenomenon. It is a
complex process involving several organ
systems. It is controlled by vomiting centre
(VC) in the brain. the centre receives
inputs from gastrointestinal tract, liver,
vestibular apparatus and the CTZ.
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10. • The CTZ responds to any chemical stimuli
(due to drugs or toxins) which in turn
activates VC. the main pathway from the
gut to the VC is via the vagus nerve.
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11. Role of serotonin in emesis
• Recent research has emphasized the importance of
serotonin (5- HT) receptors (specifically the 5-HT3
receptor ) in controlling emesis.
• Until recently dopamine (D3) receptors were considered
the most important.
• But it was found that the dopamine receptor antagonist
metoclopramide, when given in high doses, was also a
serotonin receptor antagonist.
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12. • Probably the blockade of this serotonin receptor is responsible
for its antiemetic effect. Simultaneoulsy 5-HT3 receptors were
identified in brain and gastrointestinal tract.
• 5-HT3 receptors are densely located in areas known to be
involved in the emetic reflex.
• There are 5- HT3 receptors on vagal afferent terminals which
innervate the gastrointestinal mucosa and on the same vagal
afferent nerves located in the brain stem
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13. • mechanism of serotonin (5- HT) in chemotherapy induced vomiting
Chemotherapy and
Radiation therapy
Act on rapidly dividing
cells of the gut mucosa
Cell damage, cell death
Release of 5-HT
Activation of 5-HT3 receptors
Chemoreceptor Trigger Zone
Vomiting
Centre
Vomiting
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14. central mechanism of serotonin in
chemotherapy induced vomiting?
• The direct action of cytotoxic drugs or the
peripheral activationof vagal afferents
causes 5-HT
• to be released from these neurons. This
then activates 5-HT3 receptors located
withn the vomiting centre.
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15. • The Vagus Nerve is a Cranial Nerve (Number X) that starts in the medulla
oblongata of the brainstem and travels downward to various organs of the
body.
• It has been called the "wandering nerve" because of the many areas that it
innervates. The Vagus Nerve has two major components, efferent fibers
and afferent fibers.
Efferent fibers are those that travel away from the origin of the nerve, the
central nervous system (CNS).
• Vagus Nerve efferents from the brainstem to organs like the lungs, heart,
and those of the gastrointestinal tract. These fibers send signals that assist
in the control of those and other organs. These efferent fibers make up
about 10% of the Vagus Nerve.
The afferent fibers carry sensory information from the organs back to the
brainstem which is part of the central nervous system (CNS).
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18. • Post-operative nausea and emesis continue to
be frequent occurrence even when conventional
antiemetic therapies are used prophylactically.
• No single mechanism can be invoked to explain
post-operative nausea or emesis.
• The frequency of post-operative emesis is
influenced by factors such as the patient’s age
and sex, type of surgery, duration of the surgical
procedure, anesthetic technique and the
patient’s ambulatory status.
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19. • ANTIEMETIC DRUGS
• Antiemetic in common use are blockers of
one or more of neurotransmitters. The
main antiemetics used in the treatment of
radiotherapy and chemotherapy induced
emesis are given
• Metoclopramide , Haloperidol, Droperidol ,
Domperidone
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20. • Metaclopramide
• Metaclopramide is a widely used anti- emetic.
• The anti- emetic action of metaclopramide involved is the
antagonism of dopamine receptors.
• Metoclopramide also possessed weak 5- HT3 receptor
antagonistic activity in high doses.
• It is this activity which is responsible for its antiemetic
effect in cancer chemotherapy.
• Faster gastric emptyingby increasing peristalsis.
• Increases lower Esophageal sphinter pressure thus
preventing eophageal reflux.
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21. • extrapyramidal effects of metaclopramide?
• Metaclopramide, the dopamine antagonist anti-
emetic agent (which is widely used in high doses
in preventing cancer chemotherapy induced
nausea and vomiting) causes extrapyramidal
reactions.
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22. EPS
• These are restlessness, involuntary
shaking of the limbs, totricollis (spasms of
neck), rolling movements of the eyeballs
agitation, foot tapping, inability to sit still,
tremors, unstable gait.
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24. • Receptor
• a molecule that recognizes specifically a second small
molecule whose binding brings about the regulation of a
cellular process…in the unbound state a receptor is
functionally silent
• protein molecule usually found embedded within the
plasma membrane surface of a cell that receives chemical
signals from outside the cell
• Agonist
Drug or any substance that produce stimulation of
receptor
• Antagonist
That block the stimulation of agonist
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25. What are 5- HT3 receptor antagonists?
• What are 5- HT3 receptor antagonists?
• It is clear that 5-HT (serotonin) is the principal
neurotransmitter of chemotherapy and radiotherapy
induced emesis and it exerts its reaction by acting on the
5- HT3 receptor subtype.
• Therefore, there are a number of 5- HT3 receptor
antagonists which have been developed. These
compounds are Ondansetron, Tropisetron, Granisetron,
Pancopride and Zacopride.
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26. 5- HT3 Antagonist
• These brings about their acting by
inhibiting the 5- HT3 receptors.
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27. • Indications:
• Chemotherapy and radiotherapy induced nausea and vomiting.
• Inpost operative nausea and vomiting
– as prophylaxis
– -rescue therapy.
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28. • Hyperemesis gravidarum
• Nausea and vomiting are common in pregnancy, occurring in
70-85% of all gravid women.
• Hyperemesis gravidarum is a severe and intractable form of
nausea and vomiting in pregnancy.
• It may result in weight loss; nutritional deficiencies; and
abnormalities in fluids, electrolyte levels, and acid-base
balance.
• The peak incidence is at 8-12 weeks of pregnancy, and
symptoms usually resolve by week 20 in all but 10% of
patients. Uncomplicated nausea and vomiting of pregnancy is
generally associated with a lower rate of miscarriage, but
hyperemesis gravidarum may affect the health and well-being
of both the pregnant woman and the fetus.)
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Manager-MPD)
29. • Pharmacokinetics: Oral bioavailability of Ondansetron
is 60-70% due to first pass metabolism. It is hydroxylated
by CYP1A2, CYP2S6 and CYP1A3 but no clinically
significant drug interactions have been noted. It is
eliminated in the urine and faeces, mostly as
metabolites; t1/2 being 3-5 hours and duration of action
4-12 hours.
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30. • Drug Interactions:
• Ondansetron can be safely
coadministered with cytotoxic drugs,
corticosteroids, anaesthetics and
antibiotics.
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31. • Safety profile:
• ONDA is safe and well tolerated. Main
side effects are headache, flushing or
warmth in the head or epigastrium.
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32. • Dose:
• PostOperative: Adult: 16 mg taken 1 hr
before anaesthesia followed by doses of 8
mg at 8 hr interval.
• Highly Emetogenic Chemotherapy: Days
2-5: 8 mg orally twice daily for upto 5 days.
• Emetogenic Chemo/Radiotherapy: Days
2-5: 8 mg orally twice daily for upto 5 days
• Children: 4 mg orally twice daily
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33. • chemotherapy induced nausea and
vomiting
• Nausea and vomiting usually begin within the
first 4 hours after administration of
chemotherapeutic agents, peaking at 4-10
hours and generally subsiding by 12-24
hours(acute emesis) .
• However, emesis starting from 24 hours and
lasting for 2-5 days may occur with high dose
cisplastin and cyclophosphamide. (delayed
emesis)
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35. • Pregnancy:
• Category B
• Reproduction studies have been
performed in rats and mice.
• It was not found to be mutagenic .
• No evidence of impaired fertility or harm to
the fetus.
• There are, however, no adequate and well
controlled studies in pregnant women.
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36. • Dose
• 8 kg to 15 kg: 2 mg
• 15 kg to 30 kg: 4 mg
• Greater than 30 kg: 6 mg to 8 mg
• Adult: 4-16 mg twice a day
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37. PREGNANCY SAFETY INDEX.
Category A:
Controlled studies in
women fail to
demonstrate a risk to
the foetus ; and the
possibility of foetal
harm remains remote.
Eg: Folic
acid,Electrolyte, Vit. B
complex, C,D,E
Category B: Either
animal reproduction
studies have not
demonstrated a foetal
risk but there are no
controlled studies in
pregnant women.
Calcium,
Cephalosporins
Pantoprazole,Paraceta
mol
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38. Category C
Either studies in animals have revealed
adverse effect in the foetus but there are no
controlled studies in women.
Omeprazole, Salbutamol
Category D
There is positive evidence of
human foetal risk, but the
benefits from use in pregnant
women may be acceptable
despite the risk.
Tetracycline, Lorazepam
Category X
Demonstrated fetal abnormalities
in human and animals.
Contraindicated in women who
are or may become pregnant.
Norgestrel, Warfarin, Nimesulide,
Northisterone, Thalidomide
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