Antiemetic drugs Antiemesis Drugs used for emesis

1. ِ‫ن‬ ٰ‫م‬ْ‫ح‬َّ‫الر‬ ِ‫هللا‬ ِ‫م‬ ْ‫س‬ِ‫ب‬
ِ‫م‬ْ‫ي‬ِ‫ح‬َّ‫الر‬

2. Emesis & Anti Emetic
Drugs
Presented By: - Hassaan Mughal & Labeed Ahmed Presented To: - Dr Mashkoor & Dr Misbah

3.  Emesis is a medical term that means vomiting.
 Vomiting is the forceful expulsion of the contents of the gastrointestinal system out through the mouth
 The stomach itself does not actively expel its contents during vomiting. The stomach, esophagus, and
their relevant sphincters are all in fact relaxed during vomiting.
 Most of the force that expels the contents arises from the contraction of the diaphragm, which is the
major respiratory muscle, and the abdominal muscles, which are the muscles involved in active
expiration
Emesis
Nausea
 Nausea is an unpleasant sensation of wanting
to vomit
 Nausea is the feeling discomfort, and
generally occurs before the actual vomiting
 Retching is a strong involuntary effort to vomit, and usually
follows nausea. During retching, the abdominal muscles, chest
wall and diaphragm all contract without any expulsion of gastric
contents.
Retching

4. Causes of Nausea & vomiting
Irritation of the stomach and duodenum
Infectious causes
Pregnancy
Central nervous system (CNS) Disorder
Chemotherapy and radiotherapy
Drug/treatment induced
Labyrinth causes
Tactile/touch stimulation
Post-operative
Psychological induced
Increased intracranial pressure

5. Symptoms Of Emesis
 Profuse salivation
 Sweating
 fainting
 Elevated heart rate
 lightheadedness
 Nausea & retching movements
Consequences Of Emesis
 Dehydration
 Starvation, malnutrition and vitamin deficiency
 Aspiration pneumonia
 Electrolyte depletion
 Metabolic alkalosis

6. Pathophysiology of
Emesis
1. CTZ (Chemoreceptor trigger zone)
2. Pharynx & GIT (gastrointestinal tract)
3. Vestibular nuclei
4. Cerebral cortex
 Bilateral vomiting centers in the reticular formation of the medulla integrate signals from a large number of
outlying sources and their excitement is ultimately what triggers vomiting. Electric stimulation of these centers
induces vomiting
1. Vomiting center
2. CTZ (Chemoreceptor trigger zone)
 The vomiting centers receive afferent signals from at least four major sources

7. Vomiting
Center
Vestibular Nuclei
Vomiting Reflex
Cerebral Cortex
(higher cortical centers)
Pharynx & GIT
Chemoreceptor Trigger Zone
GIT & Abdominal &
Pharyngeal
Respiratory Center Salivary Center
Muscarinic, 5 HT3 &
Histamine H1
 5 HT3
 Dopamine D2
 NK1 receptors
 Muscarinic M1
 Histamine H1
 5 HT3 Receptor
 GABA
 Histamine H1

8. Center Structures Receptor
Chemoreceptor Trigger
Zone
The area postrema 5 HT3
D2
Vomiting Center The area postrema M1
5 HT3
Vestibular Nuclei Nucleus of tractus
solitarius
M1
H1
GIT Vegal nerve ending 5 HT3

11.  Motion sickness is due to labyrinth stimulation
 codeine, morphine, pethidine, induce pathways cause nausea and vomiting through a
number of different possible mechanisms
 such as
 Cytotoxic drugs cause stimulation of 5-HT3 receptors peripherally and possibly centrally on the CTZ
 This in turn will cause the release of the aforementioned chemical transmitters dopamine and 5HT, which trigger
the vomiting centre
 Ex: - Cisplatin, Doxorubicin etc
Stimulation for vomiting
 Motion sickness
 Opioid medications
 Chemotherapy
 Chemoreceptor Trigger Zone
 Pharynx & GIT
 Vestibular Nuclei

12. Stimulation for vomiting
Pain, sight, smell, taste, emotion
Motion sickness
Opioid medications
Chemotherapy
Hormonal changes during pregnancy
Throat/stomach

14.  Muscarinic M1 receptors (Ach)
 Histamine H1 receptors
 Serotonin 5 HT3 receptors
 Dopamine D2 receptors
 Opioid receptors
 NK1 receptors (Substance P)
Types of Receptor

15. Pharmacology Of Emesis
 Group of antiemetic drugs
 5 HT3 receptors blocker
 D2 receptors antagonist
 Dolasetron
 Ondansetron
 Granisetron
 Phenothiazine
 Butyrophenones
 Substituted benzamides
 Prochlorperazine
 Droperidol
 Metoclopramide

16.  H1 receptors antagonist
 Anti Muscarinic
 Neurokinin receptor antagonist
 Diphenhydramine
 Meclizine
 Promethazine
 cyclizing
 Scopolamine
 Dexamethasone
 Methylprednisolone
 Dronabinol
 Nabilone
 Aprepitant
 Netupitant
 Rolapitant
 Corticosteroids
 Cannabinoid
Other Drugs

17. Pharmacology Of
Emesis
Antiemetic
5 HT3 Blocker
Dolasetron
D2 receptors
Blocker
Prochlorperazine
H1 receptors
antagonist
Diphenhydramine
Antimuscarinics
Scopolamine
Corticosteroids
Dexamethasone
Cannabinoids
Dronabinol
Neurokinin
receptor
Antagonist
Aprepitant

18. 5HT3 Blocker
 5-HT3 blocker drugs are Dolasetron, ondansetron, granisetron, palonosetron
 5-HT3 blocker drugs block both the central & peripheral receptors
 Central 5-HT3 receptor found in the CNS especially in chemoreceptive area of vomiting and vomiting
center.
 Peripheral 5-HT3 receptor present on enteric nerves system & sensory (intestinal vagal afferents pathway)
 These drugs can be administered prior to chemotherapy & are effective against all grades of emetogenic
therapy
 High first pass metabolism
 Excreted by kidney

19. Clinical Application
Chemotherapy
Postoperative
Post radiation
Adverse Effects
Excellent safety profile
Headache dizziness
Constipation
Possible arrhythmias
All of the drugs cause prolongation of QT
interval

20. D2 Receptors Antagonist
 Phenothiazine (Prochlorperazine)
 Substituted benzamides (Metoclopramide)
 Butyrophenones (Droperidol)
 Inhibits CTZ dopamine receptor
 Less effective against emetogenic chemotherapeutic agent (low to moderate)
 Inhibits vomiting dopamine receptor or Central dopaminergic blockade
 Often used for sedation in surgery & endoscopy also used for postoperative nausea & vomiting
 Common adverse effect QT prolongation, Headaches, Gynecomastia, Galactorrhea
 Inhibits CTZ dopamine receptor
 More/highly effective against emetogenic chemotherapeutic agents
 Useful in case of vomiting caused by by uraemia, radiation, viral gastroenteritis
 Adverse effect extrapyramidal symptoms, anxiety, Gynecomastia

21. H1 Receptors Antagonist
 H1 Receptors blocker drugs blocks H1 receptors in nucleus of solitaries
 H1 Receptors blocker drugs most effective drugs for motion sickness
 There are two generations of H1 Receptors blocker drugs
1. First generation
2. Second generation
First generation Second generation
 Diphenhydramine (older/earliest)
 Cyclizing (Prototypes)
 Meclizine
 Meclizine
 Promethazine
Used
 Prevention of motion sickness=cyclizing
 Morning sickness of pregnancy=Doxylamine
 Management of CTZ induce vomiting=Diphenhydramine
 Loratadine
 Fexofenadine
 Cetirizine
 Less seductive
 Far less lipid soluble
 More effective
Used

22. H1 Receptors Antagonist
 H1 receptors blocker best given before histamine release occur
 H1 receptors blocker drugs closely resembles muscarinic & Alpha-adrenoceptor blocker first generation
drugs tend to stimulate these receptor too along with histamine
 Metabolism extensively in liver
 Half life 1st generation=4-12 hours & 2nd generation=12-24 hours
Adverse effect Cause
Blurred vision
Sedation
Dry mouth
Urinary retention
Muscarinic receptor blockage
Orthostatic hypotension
arrhythmias
Alpha-adrenoceptor blockage

23. Anti Muscarinic
 Scopolamine block the M1 receptor present on Vestibular Nuclei or Vomiting center
 Scopolamine has many uses including the prevention of motion sickness
 Scopolamine prevents nausea and vomiting due to motion sickness
 Scopolamine also may work directly on the vomiting center. Scopolamine must be taken before the onset
of motion sickness to be effective.
 Used as transdermal patch for motion sickness

24. Neurokinin Receptor Antagonist
 Aprepitant
 Netupitant
 Rolapitant
 These drugs block the action of substance P on the vomiting center
 These drugs used for the management of CTZ induce vomiting
 These drugs can be given after chemotherapy compare to those 5-HT3 used
as CTZ induce vomiting prophylaxis
 These drugs undergo hepatic metabolism and effect(inhibit) the CYP enzyme
system which effect the metabolism of other drugs
 Adverse effect are diarrhea, abdominal pain, hiccups.

25. Corticosteroids
 Dexamethasone , Methylprednisolone both are effective in prophylaxis
 Corticosteroids are effective as prophylaxis against CINV, but the mechanisms underlying this effect
are still unknown
 Study showed that it decreased cisplatin-induced 5-HT release from peripheral blood mononuclear
cells
 Its ability to decrease 5-HT release is consistent with the fact that emesis is associated with increased
levels of this indoleamine(serotonin derivative) in the gut and brain stem
 Uses Post radiation and chemotherapy induced nausea and vomiting & hyperemesis gravidarum

26. Cannabinoid
 Any of a group of closely related compounds which include cannabinol and the active constituents of
cannabis.
 The mechanism of the antiemetic action of clinically useful cannabinoids is presently unknown.
 Studies clearly show that (Dronabinol) or Delta-9- tetrahydrocannabinol (delta9-THC) and its synthetic
analog nabilone , demonstrate significant antiemetic efficacy
 Pretreatment with either delta9-THC block the ability of the chemotherapeutic agent, cisplatin, to
produce emesis

27. Adverse effects
Euphoria or dysphoria, sedation and hallucinations
tachycardia
orthostatic hypotension
palpitation
restless, insomnia and irritability

28. BCQs
 Which of the following group is H1 receptor blocker
A. Dolasetron, ondansetron, granisetron
B. Aprepitant, netupitant, rolapitant
C. Prazosin, terazosin, doxazosin
D. Promethazine, cyclizing, diphenhydramine
 Receptor present of vomiting center
A. M1,5-HT3 & H1
B. M1,D2 & H1
C. 5-HT3 & NK1
D. M1,5-HT3 & NK1

29.  Which of the following group prolong QT
A. Cannabinoid
B. D2 Receptors
C. Neurokinin Receptor Antagonist
D. Antimuscarinics
A. Pons
B. Thalamus
C. Medulla
D. Spinal cord
 Bilateral vomiting centers present?
 A 45 year old female with lung cancer presents reporting excessive vomiting history of the patient show that she
is been taking chemotherapy from last 2 weeks which of following drug is the best choice in this case?
A. Aprepitant
B. Promethazine
C. Cyclizing
D. Dolasetron

30. Thank You