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Anti-Emetics: B. Dian Novita, DR., Mked

The document discusses various classes of anti-emetic agents, including their mechanisms of action, indications, and side effects. Dopamine receptor antagonists like metoclopramide and domperidone relieve nausea by blocking dopamine receptors. Serotonin 5-HT3 receptor antagonists such as ondansetron, granisetron, and dolasetron are effective for chemotherapy-induced and postoperative nausea and vomiting. Phenothiazines, butyrophenones, antihistamines, anticholinergics, and cannabinoids are also discussed as classes of anti-emetic medications.

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73 views

Anti-Emetics: B. Dian Novita, DR., Mked

The document discusses various classes of anti-emetic agents, including their mechanisms of action, indications, and side effects. Dopamine receptor antagonists like metoclopramide and domperidone relieve nausea by blocking dopamine receptors. Serotonin 5-HT3 receptor antagonists such as ondansetron, granisetron, and dolasetron are effective for chemotherapy-induced and postoperative nausea and vomiting. Phenothiazines, butyrophenones, antihistamines, anticholinergics, and cannabinoids are also discussed as classes of anti-emetic medications.

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We take content rights seriously. If you suspect this is your content, claim it here.
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You are on page 1/ 9

09/08/2016

Anti-emetics

B. Dian Novita, dr., MKed.


diannovitakrisdianto@yahoo.co.id

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09/08/2016

General Classification of
Anti-emetic Agents

Dopamine (DA) Receptor


Antagonists
 Presents in significant amounts in the GI tract
 Effect : motility↓ (lower esophageal sphincter &
intragastric pressures↓)  as suppression result of
ACh release from myenteric motor neurons&
mediated by D2 dopaminergic receptors.
 DA receptor antagonists are effective as prokinetic
agents; they have the additional advantage of
relieving nausea and vomiting by antagonism of DA
receptors in the chemoreceptor trigger zone.
Examples of such agents are metoclopramide and
domperidone.

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Metoclopramide ...1
 one of the oldest true prokinetic agents
 m.o.a : complex and involve 5-HT4 receptor agonism, vagal
and central 5-HT3 antagonism, sensitization of muscarinic
receptors on smooth muscle with results in coordinated
contractions that enhance transit. Its effects are confined
largely to the upper digestive tract  increases lower
esophageal sphincter tone and stimulates antral and small
intestinal contractions.
 metoclopramide has no clinically significant effects on large-
bowel motility
 rapidly after oral ingestion, undergoes sulfation & glucuronide
conjugation by the liver, excretion : urine, with a t1/2 of 4-6
hours. Peak concentrations occur within 1 hour after a single
oral dose; the duration of action is 1-2 hours.

Metoclopramide …2
Therapeutic Use :
 gastroesophageal reflux disease (to produce symptomatic
relief of, but not healing of, esophagitis), combines with
proton pump inhibitors or histamine H2 receptor antagonists.
Metoclopramide is caused gastroparesis
 diagnostic procedures such as intestinal intubation or
contrast radiography of the GI tract
 postoperative ileus persistent hiccups

Metoclopramide crosses BBB (w/extra pyramidal effect :


dystonias (i.v); parkinsonian-like symptoms in several weeks
 tx with anticholinergic or AH1 drugs & discontinuation of
metoclopramide (reversible); tardive dyskinesia also can
occur with chronic treatment (months to years) )

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09/08/2016

Domperidone (D2 Receptor


Antagonists)
 Domperidone predominantly antagonizes the D2 receptor
without major involvement of other receptors.
 has modest prokinetic activity in doses of 10-20 mg three
times a day.
 Although it does not readily cross the blood-brain barrier to
cause extrapyramidal side effects, domperidone exerts
effects in the parts of the CNS that lack this barrier, such as
those regulating emesis, temperature, and prolactin release.
 Domperidone does not appear to have any significant effects
on lower GI motility.

Serotonin Receptor
Antagonists...1
 5-HT  important role in the normal motor & secretory
function of the gut (>90% of the total 5-HT in the body
exists in the GI tract)
 The enterochromaffin cell (cell in the epithelium lining the
mucosa of the gut)produces most of this 5-HT and rapidly
releases 5-HT in response to chemical and mechanical
stimulation (e.g., food boluses; noxious agents such as
cisplatin; certain microbial toxins; adrenergic, cholinergic,
and purinergic receptor agonists).
 5-HT triggers the peristaltic reflex by stimulating intrinsic
sensory neurons in the myenteric plexus (via 5-HT1p and 5-
HT4 receptors),& extrinsic vagal and spinal sensory
neurons (via 5-HT3 receptors).

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Serotonin 5 HT3 Antagonists …2


 High first pass metabolism
 Excreted by liver & kidney
 No dose reduction in renal insufficiency but needed in
hepatic insufficiency
 Given once or twice daily – orally or intravenously.
 The availability of serotonergic prokinetic drugs has in
recent years been restricted because of serious adverse
cardiac events
 E.g : Tegaserod maleate (discontinued 2007), Cisapride
(restricted)
 5-HT4 agonist (prucalopride) : symptomatic treatment of
chronic constipation in women in whom laxatives fail to
provide adequate relief

Serotonin 5 HT3 Antagonists …3

• can be administrated once a day


•absorbed well from the GI tract.
• Ondansetron is extensively liver metabolized by
CYP1A2, CYP2D6, and CYP3A4, followed by glucuronide
or sulfate conjugation

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 Granisetron is liver metabolized predominantly,


involve the CYP3A family, as it is inhibited by
ketoconazole.
 Dolasetron is converted rapidly by plasma
carbonyl reductase to its active metabolite,
hydrodolasetron.

Indications
 Chemotherapy induced nausea & vomiting – given
30 min. before chemotherapy.
 Postoperative & postradiation nausea & vomiting

Adverse Effects
 Excellent safety profile

 Headache & constipation

 All three drugs cause prolongation of QT interval,


but more pronounced with dolasetron.

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09/08/2016

Phenothiazines & Butyrophenones


 Phenothiazines :

Prochlorperazine
Promethazine
 Phenothiazines are antipsychotics with potent
antiemetic property due to D2 antagonism.
 Butyrophenone :
Droperidol
 Droperidol used for post-op. nausea & vomiting,
but cause QT prolongation.

H1 Antihistaminics

 Most effective drugs for motion sickness


 Drugs available
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness

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Anticholinergics

 Scopolamine – used as transdermal patch for


motion sickness

Cannabinoids

 Dronabinol – used as adjuvant in chemotherapy


induced vomiting.It is a psychoactive substance
 Nabilone

Receptor Specificity of
Anti-emetic Agents

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09/08/2016

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