pharmacology of emetics and anti emetics

1. Emetics
&
M. Lakshmi Santha, M.Pharm ,
ASN Pharmacy College,
Tenali

2.  Emesis, or vomiting, is a physiologic response to the
presence of irritating and potentially harmful substances in
the gut or bloodstream.
 Also known as Vomiting, it is defined as the process of
evacuation or elimination of gastric content.
 Emetics are the drugs which cause the vomiting. It is must
be important to use when poison is known to have been
swallowed.
 Nausea and vomiting are feared and frequently very
distressing symptoms that have multiple triggers including
drugs, motion, pregnancy, fear, vestibular disease, migraine
and gastrointestinal pathology.
 Postoperative nausea and vomiting (PONV) is one of the
most common cause of after anaesthesia.

4.  In the medulla oblongata, vomiting center are situated, that
region is known as Area postrema. In the area
postrema Chemoreceptor Trigger Zone (CTZ) and Nucleus
Tractus Soliterius (NTS) is also present.
 The vomiting centre receives afferent impulses from the
chemoreceptor trigger zone (CTZ), vestibular apparatus,
cardiovascular and abdominal afferents (via the vagus
nerve), peripheral pain pathways and the limbic cortex.
 The CTZ rich in dopamine (D2 ) and serotonin (5-
hydroxytryptamine, 5-HT3 ) receptors.
 Drugs (e.g. opioids) and neurotransmitters (e.g. dopamine,
noradrenaline, acetylcholine, 5-HT) can stimulate the CTZ.

5.  Motion sickness is primarily a central nervous system
response mediated by the vestibular apparatus.
 Acetylcholine and histamine receptors are found in the
vestibular centre.
 The limbic system is associated with expression of
mood, emotions and feelings, as well as memory recall.
 Anxiety, fear and other emotions may play a role at this
site in the perception of nausea and vomiting.
 Noxious substances in the gut can activate vagal
afferent pathways to the solitary tract nucleus, which
projects to the vomiting center, as well as pathways to
the nerve tracts that stimulate the CTZ.
 The D2, 5-HT3, and neurokinin 1 (NK1) receptors also
have a major role in these pathways.

6.  Emetic drug or vomiting drug are those drug which is
responsible for the vomiting. Emetic drugs
1. Centrally acting drugs: Apomorphine
2. Peripherally acting drugs: Mustard, hypertonic Nacl sol
3. Both Centrally and Peripherally acting drugs: Ipecacuanha
Apomorphine : Apomorphine is the synthetic derivative of
the morphine.
 It acts as a dopaminergic agonist on CTZ. Apomorphine
drug is injected in IM or SC in a dose of 6mg.
 Apomorphine drug are starting vomiting in 5 min. and it
should not use in a respiratory depressant patient.

7. Ipecacuanha : is a part of the dried root of Cephaelis
Ipecacuanha contains emetine.
 It acts by irritating gastric mucosa and as well as through
CTZ. That drug is used as a syrup ipeca.
 The dose of Ipecacuanha in an adult is 15-30ml, in
children 10-15ml and 5ml in the infant. It takes 15 min or
more for the action.

8. • Antiemetic drugs are those drugs which is
responsible for the prevention of the vomiting.
• The treatment of nausea and vomiting aims to
antagonise the afferent supply to the vomiting
centre.
• classified according to the receptor at which they
act:
 dopamine antagonists
 anticholinergics
 antihistamines
 serotonin antagonists
 miscellaneous.

9. • Anticholinergic Drug
– Hyoscine
– Dicyclomine
• H1 Antihistaminics
– Promethadine
– Diphenhydramine
– Cinnarizine
– Cyclizine
– Doxylamine
• Neuroleptics (D2
Antagonists)
– Droperidol
– Prochlorperidol
– Chlorpromazine
• Prokinetic Drug
– Domperidone
– Cisapride
– Mosapride
– Metochlopramide
• 5-HT3 Antagonist
– Granisteron
– Ondansteron
– Dolasetron
– Palonosetron
• Neuro kinine -1antagonists
– Aprepitant

10. Anticholinergic Drugs
It acts as the blockage of conduction nerve impulse around
the cholinergic link in the pathway vestibular apparatus to
the vomiting center.
Muscarinic receptor antagonist found in autonomic ganglia
and the neuromuscular junction.
Hyoscine is an ester of tropic acid and scopine.
It is used in the prophylaxis of motion sickness and, when
administered together with an IM opioid, has been shown
to reduce PONV.
In addition, hyoscine decreases muscle tone (anti-
spasmodic) and gut secretions, which may contribute to its
antiemetic effect.
is presented as a clear solution for IV, IM and subcutaneous
(SC) injection. It can also be administered orally and via
transdermal patch

11. • Dose- Hyoscine is used 0.2-0.4mg as oral or intramuscular.
And Dicyclomine are used 10-20mg oral.
• Use- Hyoscine is mostly used in motion sickness. But it
also produces sedation and anticholinergic side effect.
And Dicyclomine is used for motion sickness and morning
sickness.
• H1- Antihistaminic Drugs
• block the H1 receptor in the area postrema part of medulla
oblongata and as well as block muscarinic receptor in
the CNS. Dose- 20-25mg oral.
• Use- mainly used in the motion sickness and small amount
in morning sickness. radiotherapy-induced emesis.
• Side effects include tachycardia, drowsiness, blurred vision
and pain on injection.
• a clear, colourless solution for IV or IM injection.

12. Dopamine D2 Receptor Antagonists
• All of the D2 receptor antagonists appear to act on the CTZ
to inhibit stimulation of the vomiting center,
• they may also inhibit afferent impulses from the gut by
antagonizing receptors in the solitary tract nucleus.
• Metoclopramide: on GIT acts by
a) Dopamine receptor antagonism
b) 5-HT4-receptor agonism
c) Vagal and central 5-HT3-antagonism
d) Sensitization of muscarinic receptors on smooth
muscle
e) Antiemetic action

13. Therapeutic Use:
• It is used in nausea and vomiting that often accompanies GI
dysmotility syndromes.
• It is prescribed in Gastro esophageal reflux disease
(symptomatic relief but not healing of esophagitis)
• It is also prescribed in Gastro paresis where it improves
gastric emptying.
• Used in diagnostic procedures such as intestinal intubation
or contrast radiography of the GI tract.
• Metoclopramide also used in Postoperative ileus
• Administration: M
1. Oral (rapid absorption)
2. I.M. in cases of nausea and vomiting
3. I.V. infusion in chemotherapy-induced vomiting

14. Adverse Effects:
• Extra pyramidal effects
• Tardive dyskinesia: Repetitive, involuntary, movements
(usually involve the face) like tongue projection, lip
smacking, tightening of the lips and rapid eye blinking.
• It occurs with chronic treatment (months to years) and
may be irreversible.
• Akathisia –Restlessness and inability to sit still
• Dystonias-Muscular spasms of neck
• Parkinsonian like symptoms . Galactorrhea
Domperidone: : It acts on dopamine D2 receptor in CTZ
which is outside BBB.
• It enhance GIT propulsive motility of the upper digestive
tract where it increases lower esophageal sphincter tone
and stimulates antral and small intestinal contractions.

15. Adverse effects: No extra pyramidal side effects because it
can not cross the blood-brain barrier.
• Galactorrhea-By inhibiting dopamine-mediated inhibition
of the release of prolactin.
Serotonin Antagonists
• Ondansetron: was the first selective 5-HT3 receptor
antagonist to be developed for the treatment of cancer
chemotherapy–induced nausea and vomiting.
• Significantly reduces cisplatin induced episodes of emesis.
• Anticancer drugs stimulates 5-HT3 at small intestine, also
stimulate the CTZ that activates the vomiting center in the
medulla.
• Competitively block 5-HT3 receptors located on visceral
afferent nerves in the gastrointestinal tract, in the solitary
tract nucleus, and in the CTZ.

16. • Ondansetron can be administered orally or intravenously,
palonosetron are only given intravenously.
• the prevention and treatment of postoperative emesis
nausea and vomiting caused by radiation therapy.
• Additive or synergistic effect in combination with 5-HT3
antagonists, and dexamethasone is often employed in
combination with a 5-HT3 antagonist for preventing
chemotherapy-induced emesis.
• Adverse Effects and Interactions:
• IV dolasetron-prolongation of the QT interval of the
electrocardiogram, polymorphic ventricular tachycardia.
• headache, constipation, and diarrhea, hypertension and
elevated hepatic enzyme levels.
• ondansetron resulted in an anaphylactoid reaction
consisting of bronchospasm, angioedema, hypotension,
and urticaria.

17. Neurokinin-1 Receptor Antagonists
Aprepitant
• Substance P is released from vagal afferent fibers in the solitary tract,
where it activates NK1 receptors and thereby produces emesis.
• Aprepitant is a nonpeptide NK1 receptor antagonist that prevents
emesis.
• intended to be used in combination with a 5-HT3 antagonist (e.g.,
ondansetron) and dexamethasone to prevent acute and delayed nausea
and vomiting occurring with highly emetogenic cancer chemotherapy.
• Other Antiemetics
• Scopolamine is a muscarinic receptor antagonist that is
similar to atropine and is primarily used to prevent motion sickness.
• Dronabinol, an oral formulation of Δ9-tetrahydrocannabinol, is approved
for the treatment of cancer chemotherapy– induced emesis.
• Serotonin antagonist plus dexamethasone and aprepitant for preventing
acute emesis caused by highly emetogenic drugs such as cisplatin,
dacarbazine, and cyclophosphamide