Antiemetics

Antiemetics
Causes of Vomiting
Nausea and vomiting may be manifestations
of many conditions and may occur due to
stimulation of vomiting center that respond to
inputs from:
 Chemoreceptor trigger zone (CTZ) stimulation

 Disturbance of vestibular system
 Higher cortical centers stimulation (CNS)
 The periphery (Pharynx, GIT) via sensory nerves
1. Chemoreceptor trigger zone stimulation
 CTZ is an area of medulla that communicate
with vomiting center to initiate vomiting.
 CTZ is physiologically outside BBB.
 CTZ Contains opioid receptors, D2
receptors & 5 HT3 receptors, Substance P
 stimulated by:
 Drugs (opioids, general anesthetics),
 Chemicals and toxins in blood, CSF.
 Radiation.
2. The periphery via sensory nerves
GIT irritation, myocardial infarction, renal or
biliay stones.
3. Disturbance of vestibular system
by motion sickness
4. Higher cortical centers stimulation:
emotional factors, nauseating smells or sights.
Receptors Associated with Nausea and Vomiting
Pathophysiology of Emesis
chemotherapy Cerebral cortex

Opioids Smell
Anesthetics Sight Anticipatory emesis
Thought
Chemoreceptor Vestibular
Trigger Zone Vomiting Centre
nuclei
(medulla) Motion
(CTZ) sickness Muscarinic
Muscarinic, 5 HT3 &
Histaminic H1
(Outside BBB) Histaminic H1
5 HT3
Chemo & radio therapy
Dopamine D2 Gastroenteritis
Opioid receptors
Pharynx & GIT
Substance p
5 HT3 receptors
Chemical transmitters & receptors
involved in vomiting include:
 Ach (Muscarinic receptors)

 Dopamine (D2)
 Histamine (Histaminergic receptors H1)
 Serotonin (5 -HT3)
 Substance P (Neurokinin receptors, NK1)
 Opioid (Opioid receptors)
Classification of Antiemetic Drugs
1. 5-HT3 antagonists
2. D2 receptor antagonists
3. NK1 antagonists
4. H1-receptor antagonists
5. Muscarinic receptor antagonists
6. Cannabinoids
7. Glucocorticoids
5-HT3 antagonists
 Drugs as Ondansetron, Granisetron
 Orally or parenterally
 Potent antiemetic effects
 Block 5-HT3 receptor in vomiting center, CTZ
and 5HT3 receptors on intestinal vagal
afferents.
Uses of 5-HT3 antagonists
 First choice for prevention of:
– Chemotherapy-induced nausea and vomiting
(CINV) especially cisplatin.
– Post-radiation NV& Post-operative NV
– Their effects is increased by combination
with corticosteroids and NK1 antagonists.
Side effects
o Well tolerated
o mild headache, dizziness and constipation
o minor ECG abnormalities (QT prolongation)
D2 receptor antagonists
 block D2 dopamine receptors in the CTZ
 Two types exist:
1) Prokinetics drugs
2) Neuroleptics (antipsychotics)
Uses of D2 receptor antagonists

 are among the most commonly used drug for
nausea and vomiting of non-specific causes.
 Effective against vomiting due to drugs,
 gastroenteritis, post-operative, toxins,
uremia, radiation.
1) Prokinetics drugs
 Drugs as metoclopramide, domperidone
 Both are prokinetic agents due to their 5 HT4
agonistic activity.
 used in GERD (gastroesophageal reflux
disease), gastroparesis.
 Used as antiemetics (blocking D2 receptors)
 Metoclopramide crosses BBB but
domperidone cannot (both have antiemetic
effects as CTZ is outside BBB).
Side effects (only for metoclopramide):
 Dyskinesia (extra-pyramidal side effects) ,
 Galactorrhea, menstrual disorders,

impotence.
 Sedation, postural hypotension.
Neuroleptics (Antipsychotics)
 Chlorpromazine (CPZ), droperidol
 used for postoperative vomiting and
chemotherapy-induced nausea & vomiting.
 Side effects: extrapyramidal symptoms

sedation, postural hypotension
Neurokinin1 (NK1) receptor antagonists
Aprepitant
 Is a substance P antagonists that acts by
blocking neurokinin 1 receptors.
 Orally
 Used in prevention of acute and delayed
chemotherapy-induced nausea and vomiting
and for prevention of postoperative nausea
and vomiting.
 Usually combined with 5-HT3 antagonists
and corticosteroids.
Neurokinin receptor
antagonists
.Aprepitant is the only drug on the market 
Mechanism of action: blockade of substance

P/neurokinin-1 receptors located on
a) Nucleus of tractus solitarius (likely the main site
of action)
b) Visceral afferent nerves- In this way it is likely
that it can prevent both peripheral and central
.stimulation of the vomiting center
Neurokinin-1 [NK1] receptors mediate most of

.)central and peripheral effects of substance P
Adverse effects -Sleepiness (20%), 
.diarrhea (10%)
Therapeutic uses 
Chemotherapy-induced nausea and- 
vomiting (drug of first choice)
.Postoperative nausea and vomiting
H1-receptor antagonists
 Effective for motion sickness, morning
sickness in pregnancy
 Drugs as
– Diphenhydramine
– Meclizine - Cyclizine
– Promethazine: severe morning sickness of
pregnancy (if only essential).
Side effects:
– prominent sedation, hypotension,
anticholinergic effects (dry mouth, dilated
pupils, urinary retention, constipation.
Muscarinic receptor antagonists
 Hyoscine (scopolamine)
 Orally, injection, patches
 Used as transdermal patches in motion
sickness (applied behind the external ear).
 Not in chemotherapy-induced vomiting
 Side effects: tachycardia, blurred vision,
dry mouth, constipation, urinary retention
(atropine-like actions).
Cannabinoids
 Nabilone, dronabinol
 mechanism of action not understood.
 act at central cannabinoid receptors.
 Used in vomiting due to cytotoxic
anticancer drugs (adjuvant therapy).

 Not commonly used.
Side effects: euphoria, dysphoria, sedation,

hallucination.
Glucocorticoids
 Dexamethasone - methylprednisolone
 Used in chemotherapy-induced vomiting
 combined with 5-HT3 antagonists or NK1
receptor antagonists.
Glucocorticoids
 Side effects:
– Hyperglycemia
– Hypertension
– Cataract
– Osteoporosis
– Increased intraocular pressure
– Increased susceptibility to infection
– Increased appetite & obesity
Summary
The choice of antiemetic depends on the etiology
Motion sickness
Muscarinic antagonists
Antihistaminics
Vomiting with pregnancy (morning sickness)

avoid all drugs in the first trimester
Pyridoxine (B6)
.Promethazine ( late pregnancy)
Drug- induced vomiting (CTZ)
Dopamine antagonists
Post operative nausea & vomiting
Dopamine antagonists
HT3 antagonists-5
NK1 antagonists
.Vomiting due to cytotoxic drugs
HT3 antagonists-5
NK1 antagonists
D2- antagonists
Glucocorticoids
Cannabinoids
Thank you
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Antiemetics

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Antiemetics

 Chemoreceptor trigger zone (CTZ) stimulation

chemotherapy Cerebral cortex

 Ach (Muscarinic receptors)

Uses of D2 receptor antagonists

 Galactorrhea, menstrual disorders,

 Side effects: extrapyramidal symptoms

Mechanism of action: blockade of substance

Neurokinin-1 [NK1] receptors mediate most of

anticancer drugs (adjuvant therapy).

Side effects: euphoria, dysphoria, sedation,

Vomiting with pregnancy (morning sickness)

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