Emetics and Antiemetics drugs. Pharmacology

1. EMETICS & ANTI-EMETICS
(Pharmacology & Therapeutics-1)
Lecture By
Dr. Syed Baqir Raza Naqvi
(BSc, Pharm-D, M. Phil-Pharmacology)
Nazar College of Pharmacy
DAKSON Institute of Health Sciences, Islamabad
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2. WHAT IS VOMITING ?
It is the forceful expulsion of the contents of the stomach
through stomach by anti peristaltic movements.
The vomiting reflex is stimulated by two centers in the
medulla
1 . Vomiting center
2 . Chemoreceptor trigger zone(CTZ)
2

3. Is emesis beneficial ?
 Vomiting is considered to be a protective reflex of
the body to expel toxic substances in the stomach and
gut.
 Antiemetic drugs are often necessary to suppress
vomiting, especially if there’s severe dehydration.
Why anti-emetics ?
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4. Consequences of vomiting
 Severe vomiting may result in :
 Dehydration
 Acid-base imbalance
 Electrolyte depletion
 Aspiration pneumonia
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5. 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:
 Higher cortical centers stimulation (CNS)
 Chemoreceptor trigger zone (CTZ) stimulation
 Disturbance of vestibular system
 The periphery (Pharynx, GIT) via sensory nerves
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6. 1. Stimulation of chemoreceptor trigger
zone (CTZ)
 CTZ is an area of medulla that communicate
with vomiting center to initiate vomiting.
 CTZ is physiologically outside BBB.
 CTZ contains D2 receptors, 5 HT3 receptors
& opioid receptors.
 Stimulated by;
 Emetogenic drugs (opioids, general
anesthetics, digitalis).
 chemicals and toxins (blood, CSF).
 Radiation.
 Uremia 6

7. 2. The periphery via sensory nerves
 GIT irritation
 myocardial infarction
 renal or biliary stones
3. Disturbance of vestibular system:
 motion sickness (H1 & M1 receptors)
4. Higher cortical centers stimulation:
 Emotional factors
 Nauseating smells or sights 7

8. Common types of vomiting
 1. Vomiting in Pregnancy (In 1st trimester~ secretions of placental
hormones~ CTZ stimulations)
 2. Vomiting due to Uremia (Buildup of toxins in blood. It occurs
when the kidneys stop filtering toxins out through urine ~ increased level of urea in
blood ~ CTZ stimulations)
 3. Vomiting due to disease state (Pyloric stenosis* Constriction of
pyloric end of stomach~ delayed passage of food from stomach to intestine)
 4. Post operative vomiting (After surgery because of anesthetics)
 5. Vomiting due to motion sickness (Over stimulation of labyrinth
( middle ear)~ CTZ stimulations)
 6. Vomiting due to radiations 8

9. 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)
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10. Receptors Associated with Nausea and
Vomiting
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11. Vomiting Centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nuclei
Motion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
chemotherapy
Opioids
Anesthetics
Muscarinic, 5 HT3
5 HT3 receptors
5 HT3
Dopamine D2
Opioid receptors
Substance p
Muscarinic
Histaminic H1
Pathophysiology of Emesis
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12. 12
Emetics

13. Emetics
Those agents
which causes
emesis or
vomiting are
called emetics.
Contra indications
 Morphine poisoning
 Children
 Unconscious patient
 Corrosive and caustic
poisoning (Acid, Alkali
poisoning)
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14. Centrally acting
emetics
 Pilocarpine
 Apo morphine
 Pilocarpine
 Cardio active
glycosides (Digoxin)
 Ergot alkaloids
Locally acting
emetics
 Mustard (‫)سرسوں‬
 Common salt
 Heavy metals
 Ipecacuanha
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Classification of Emetics

15. 1. Apo morphine
 A synthetic agent, chemically related to morphine.
 Stimulating action on CTZ center and induce vomiting
 It is given subcutaneously (s.c.) 4mg and vomiting starts
within few minutes
 It is agonist to D2 receptors present in CTZ.
Contraindications
Contraindicated in Asthma. It has CNS depressant and
respiratory depressant actions.
Not given orally. 15
A). Centrally acting emetics

16. 2. Pilocarpine:
 Stimulates CTZ center because it is a cholinergic alkaloid
and may be given parenteraly and causes vomiting.
3. Cardio glycosides:
 Vomiting is a side effect of cardiac glycosides especially
digoxin because it has stimulating action on CTZ.
4. Ergot alkaloids:
 They also stimulate CTZ and induce vomiting.
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Centrally acting emetics (Cont.)

17. 17
B). Locally acting emetics
1. (‫)سرسوں‬

18. 2. Concentrated solution of NaCl
 Traditionally used to induce vomiting, given orally and irritates the
gastric mucosa which leads to initiation of vomiting reflexes and
causes contraction of pyloric end of stomach resulting in vomiting.
3. Solution of heavy metals
 1% Copper Sulphate solution (orally). Copper is irritant in nature
which irritates gastric mucosa.
 These are not used currently bcz of heavy metals poisoning due to
accumulation in liver.
4. Ipecacuanha (Ipecac Syrup)
 It contains an alkaloid (cephaline & emetine) which is irritant in
nature and irritates gastric mucosa when given orally.
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Locally acting emetics

19. Different Brands of Emetics
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20. 20
Anti-Emetics

21. ANTIEMETICS
Antiemetic's are those
agents/drugs which counter act or
stop the nausea and vomiting.
These two symptoms are very
common and can be caused by
many different conditions,
therapies, procedures, and
medications (such as opioids).
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22. Classification of Antiemetic Drugs
1. 5-HT3 antagonists
2. D2 receptor antagonists
3. H1-receptor antagonists
4. Muscarinic receptor antagonists
5. Glucocorticoids
6. NK1 antagonists (SP)
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23. Classification of anti-Emetics
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24. 24

25. 25

26. General Mechanism of antiemetic's
 Anti emetics work on the neural pathways involved with vomiting by
blocking specific receptors that respond to neurotransmitter molecules,
such as serotonin, dopamine and histamine. Most of these are central
receptors found in the vomiting center of the brainstem, while peripheral
receptors are found in the vagus nerve.
 When the gastrointestinal tract senses a threat, it sends information to
the peripheral receptors, which in turn convey the information to the
central receptors in the vomiting center. In response, the vomiting center
triggers nausea and vomiting by stimulating the gastrointestinal tract,
abdominal muscles, and the diaphragm.
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27. 27

28. Classification of ANTI EMETIC DRUGS
1. Prokinetics
Metoclopramide, Domperidone
2. Antimuscarinics/Anticholinergics
Hyocine, Meclozine
3. Antihistamines
Cyclizine, Promethazine (phenergan)
4. Neuroleptics
Chlorpromazine, Prochlorpromazine
5. 5-HT3 antagonists
Ondansetron, Granisetron
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29. 1. Serotonin (5-HT3) antagonists
 Drugs as
 Ondansetron (Rx~ Zofran, ONSET)
 Granisetron
 R/A: Orally or parenteral,
 Have long duration of action
 The most potent antiemetic drugs
 MOA: Act by blocking 5-HT3 receptor centrally (in
vomiting center, CTZ) and peripherally (5-HT3 receptors
on GI vagal afferents). 29

30. Uses of 5-HT3
antagonists
 First choice for prevention of
moderate to severe emesis:
 Chemotherapy-induced nausea and
vomiting (CINV) especially
because of Cisplatin.
 Post-radiation NV& Post-operative
NV.
 Their effects is augmented by
combination with corticosteroids
and NK1 antagonists.
Dosage forms
Injectable: 2 mg/ml
Tablet: 4, 8, 24 mg,
Oral solutions: 4mg/5ml
Half life: 3-4 hours and could be extended to
6-8 hours in the elderly.
Dose in adults: 8mg, frequency: 8 hours/Orally
Dose in Paeds: 4mg, Route: IV-infusion
Side effects
Headache, dizziness and constipation
minor ECG abnormalities
May be excreted in milk.
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31. 2. D2 receptor antagonists
Block D2 dopamine receptors in the CTZ
Two types exist
1. Neuroleptics (anti psychotics)
 Chlorpromazine (CPZ)
 used for postoperative vomiting and chemotherapy-induced emesis.
Adverse effects
 In CNS: Sedation, drowsiness, fatigue
 In CVS: Hypotension
 Mild teratogenic effects (can harm the fetus during pregnancy)
 In Endocrine system: gynecomastia, decreased libido,
 Urticaria, Amenorrhea.
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32. D2 receptor antagonists
2. Prokinetics drugs
 Metoclopramide: oral, i.v
 Domperidone: oral (prokinetic agents increased GI
motility & gastric emptying)
The mechanisms of action of metoclopramide involve
 Peripheral and central 5-HT3 antagonism,
 Possible sensitization of muscarinic receptors on smooth
muscle,
 Dopamine receptor antagonism. 32

33. Metoclopramide crosses BBB but domperidone cannot.
(both have antiemetic effects as CTZ is outside BBB).
Adverse effects (only for metoclopramide):
 Tardive dyskinesia ( Uncontrolled stiff, jerky
movements of face and body. You might blink your
eyes, stick out your tongue or wave your arms
without meaning) also can occur with chronic
treatment (months to years) and may be
irreversible.
 Galactorrhea, menstrual disorders,
 Sedation, drowsiness
Uses
Gastro esophageal reflux disease
(GERD)
Gastro-paresis (impaired gastric
emptying after surgery).
Acute Migraine Treatment in Adults in
combination with aspirin
 Metoclopramide should be used
with caution in Parkinson's
disease since, as a dopamine
antagonist.
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34. Domperidone
Brand name: Motilium
Mechanism; It provide relief from nausea by blocking D2 receptor
In CTZ and GIT symptoms by blocking D2 receptors in GUT.
It is used to treat nausea and vomiting and certain gastrointestinal
problems like gastroparesis (delayed gastric emptying).
It raises the level of prolactin in the human body and is used to
induce and promote breast milk production.
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35. Adverse effects:
Dry mouth, Abdominal
cramps, Diarrhea, rashes.
Hyperprolactinemia
(the symptoms may include breast
enlargement, galactorrhea, breast
pain/tenderness, gynecomastia,
and menstrual irregularities).
Uses:
• Nausea and vomiting
associated with acute migraine
• Gastroparesis
• Domperidone, results in
increased prolactin secretion,
and thus promotes lactation as
a galactagogue.
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36. 3. Neurokinin-1 (NK1) receptor
antagonist
Rx: Aprepitant
 Acts centrally as substance P
antagonist by blocking neurokinin-1
receptors.
 Orally administered
 Usually combined with 5-HT3
antagonists and corticosteroids in
prevention of chemotherapy-induced
nausea and vomiting and post-
operative NV.
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37. 4. H1-receptor antagonists
Include drugs as
 diphenhydramine, promethazine
 meclizine, cyclizine
Used for
 Motion sickness
 Morning sickness in pregnancy
 Promethazine: severe morning sickness of pregnancy
(if only essential).
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38. Adverse effects:
Prominent sedation
Hypotension
Anticholinergic effects or
atropine like actions (dry
mouth, dilated pupils, urinary
retention, constipation).
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39. 5. Muscarinic receptor antagonists
Hyoscine (scopolamine) (Rx~ Buscopan)
Routes of Administrations: Oral, injection, patches
Used as transdermal patches (applied behind the external ear) in motion sickness.
Reduce impulses from vestibular apparatus
Not in chemotherapy-induced vomiting
Side effects:
Sedation, Tachycardia, blurred vision, dry mouth,
constipation, urinary retention (Atropine-like
actions).
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40. Dexamethasone-methylprednisolone
Used in chemotherapy induced vomiting.
combined with 5-HT3 antagonists or NK1 receptor antagonists.
Adverse effects:
Hyperglycemia, Hypertension, Cataract, Osteoporosis,
Increased intraocular pressure,
Increased susceptibility to infection,
Increased appetite & obesity
6. Glucocorticoids
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41. Thank you !
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