KK Anti emetic drugs

This powerpoint presentation deals with what is emesis how is emesis caused and what are the anti emetic drugs used with their detailed pharmacology.

1. ANTI EMETIC DRUGS
OR
ANTIEMETICS
PREPARED BY
KESHARI KUMAR SRIWASTAWA
M. PHARM (PHARMACOLOGY) , 1
ST
YEAR
(2
ND
SEM)

2. WHAT IS EMESIS?
It is defined as the involuntary, forceful
expulsion of contents of the stomach
through the mouth and sometimes through
the nose.
It is also known as vomiting, puking, barfing
or throwing up.
Nauseais a feeling of discomfort or sickness
in the stomach that may lead to an urge to
vomit.

3. CAUSES OF EMESIS
Motion sickness or sea sickness
Early stages of pregnancy (nausea occurs in
almost 50%-90% of all pregnancies,
vomiting occurs in 25%- 55%)
Medication induced vomiting
Intense pain
Emotional stress
Gall bladder disease
Food poisoning
Reaction to certain smells or odours.

4. HOW DOES EMESIS OCCUR?
Emesis (vomiting) occurs due to the activation of
vomiting centre (VC) present in the medullary
reticular formation. It receives input from GI mucosa,
chemoreceptor trigger zone (CTZ) and vestibular
apparatus.
The main neurotransmitters involved in the control of
vomiting are acetylcholine, histamine, 5-HTand
dopamine.

Irritation of GI mucosa by drugs or irritants leads to
release of serotonin that stimulates VC by 5-HT
3
receptors.

5. Stimuli are relayed into the VC from the peripheral
axis ( i.e. Gastric mucosa and other parts of GIT)
Sensory stimuli also arise within the CNS itself i.e
cerbral cortex and vestibular apparatus.
Motion sickness occurs due to the stimulation of
vestibular apparatus and cerbellum. These structures
result in stimulation of VC by activationg M1 and H1
receptors.
By stmulation of H1 receptors histamine plays a
permissive role in all type of emesis.
Lack of BBB at CTZ allows it to be directly stimulated
by blood borne drugs and toxic substances.

8. CLASSIFICATION

9. SITES OF ACTION

10. 1. ANTICHOLINERGICS
Scopolamine ( Hyoscine or Devil’s breath )
1.Natural or synthetically prepared tropane alkaloid
2.Non specific muscarinic antagonist
3.Drug of choice for motion sickness.
4.It is used as IM injection or transdermal patch (applied behind pinna) in the
prophylaxis of motion sickness
5.It has no role in treatment once vomiting starts.
6.MOA–Blocks the afferent impulses from the vestibular apparatus in the VC by
its anticholinergic action .
7.Its sedative effect also contributes to its antiemetic action.
8.When given by injection its effect begins after 20minutes and lasts upto 8
hours.
9.Other routes of administration– Oral, eye drops, SC, sublingual , rectal , buccal
and transmucosal.
10.Pharmacokinetics–A–Unergoes first pass metabolism
M-Liver
E-2.6 %excreted unchanged in urine ,
Elimination half life 0f 4.5 hours
E

11. 2. NEUROLEPTICS (D2BLOCKERS)
It is divided into 2 classes-
(i)Phenothiazines-
Chlorpromazine , Prochlorperazine, Trifluoperazine ,
Metoclopramide, Thiethyl perazine(used only as antiemetic)
(ii) Butyrophenone derivatives –
Haloperidol, Domperidone,
Droperidoletc.
1)These drugs apart from blocking the D2 receptors also block
the M1 and H1 receptors in the CTZ.
2)Most commonly used drug is Prochlorperazine.
3)These drugs are not much effective in motion sickness.
4)Metoclopramide and Domperidone produces prokinetic effect
due to blocking the peripheral D2 receptors and activating the
muscarinic receptor in GIT.

12. Metoclopramidecrosses the BBB therefore causes
extrapyramidal side effects which are :Acute
dystonia and Tardive dyskinesia. It also produces
some other side effects like gynecomastia,
galactorrhea and long term parkinsonism.
Domperidonepoorly crosses the BBB and hence does
not cause extrapyramidal side effects.
Metoclopramideis also a 5HT 4agonist and prolactin
releaser.
Moreover Metoclopramidehas been found to be safe
in pregnancy.
Metoclopramide has an oral bioavailibility of 65%-
95%and excreted 70-85% in urine and 2% in faeces
with an elimination half life of 5-6 hours.

13. 3. ANTIHISTAMICS (H1 RECEPTOR BLOCKER)
Thse drugs block the H1receptors in the CTZ and NTS.
Drugs like Promethazine,Cyclizine,Meclizine,and
Diphenhydramine are used in the prophylaxis of motion
sickness.
Cinnarizine(antiemetic with antihistaminic and
anticholinergic property) is used in the treatment of vertigo.
Centrally acting antihistaminics like Diphenhydramine,
Dimenhydrinate, Promethazineetc are also used in the
treatment of parkinsonism.
Promethazine can be administered via a rectal suppository, IV
injection,oral tablet or oral suspension for adults and children
for over 2 years of age.
Mirtazepine is a antidepressant that also has antiemetic effect
is also a potent H1blocker.

14. 4. PROKINETIC AGENTS
They are also called as gastroprokinetic or gastrokinetic or
propulsive agents.
These agents increase the GI motility by increasing the
frequency or strength of contractions without disrupting the
rhythm and hasten the gastric emptying time.
Cisapride and Zipapride are structurally similar to
metoclopramide but deprived of the D2 blocking property.
Metoclopramideacclerates the absorption of diazepambut
decreases the absorption of digoxin.

Metoclopramide has 2important actions –Central and
Peripheral.

15. 5HT4
agonist
5HT3antagonist
in the GIT
Increases Ach secretion from the myenteric motor neurons
D2-Antagonist
Metoclopramide
PROKINETIC EFFECT OF METOCLOPRAMIDE
ON UPPER GIT

16. Increase in tone
of lower
oesophagal
sphincter (LES)
Increase in tone
and amplitude
of antral
contractions
Increase of
peristalsis of small
intestine
Relaxation of
Pyloric
Sphincter
Effects of
metoclopramide
on the upper GI
tract

17. 5. 5HT3RECEPTORANTAGONIST
Ondansetronis the prototype drug with the shortest half life.
These classes of drugs shows 2 kinds of actions –
(I) Central action –Blocks 5-HT3receptors in CTZ and NTS
(II) Peripheral action –Blocks 5-HT3 receptors in vagal afferents in the
gut.
•They are the DOC for chemotherapy and radiation therapy induced
vomiting.
•Palonosetronis the most potent in this class and has the longest half life
of 40hours.
•Dolasetronmay prolong QT interval.
•They also decrease dopamine synthesis and decreases dopamine release.
•They are also effective in hyperemesis in pregnancy and post operative
nausea.
•Ramosetron can be used in irritable bowel syndrome.
•Transdermal patches of granisetron are also available for the prevention
of cancer chemotherapy induced vomiting.

18. 6. NEUROKININ 1 (NK1 ) RECEPTOR
ANTAGONIST
The agonistfor NK-1 receptoris substance P which is a
neuropeptide whose concentration increases during emesis.
So these drugs block the NK 1 receptors and thereby block
the actions of substance P in the CTZ and NTS.
They ae higly effective in the treatment of delayed emesis
following moderately to highly ematogenic chemotherapy.
It increases the efficacy of standard antiemetic regimens
( eg. Dexamethosone+5 HT3 antagonist)
Aprepitantis a highly selective antagonist , orally active and
enter the brain. It is metabolized byCYP3A4enzymes.
Fasoprepitantis the intravenous prodrug of Aprepitant.
It is well tolerated by patients.

Flattulence may occur.

19. 7. ADJUVANT ANTIEMETICS
Dronabinol and Nabilone
These are the derivatives of cannabinoids.
They produce antiemetic effect by blocking the CB1
receptorspresent in and around the CTZ.
Their antiemetic effect is inhibited by Naloxone.
Dronabinol is also a appetite stimulant used in AIDS with
anorexia.
ADR-Hallucinations, insomnia, drowsiness, thinking
abnormalities. They also produce some cental
sympathomimetic side effects like tachycardia ,palpitation
and hypotension
They are used as prophylactivc agent in chemotherapy
induced vomiting.

20. Glucocorticoids like dexamethasone ,
methylprednisolone, betamethasone etc. are
commonly used in combination with ondansetron or
metoclopramide in the treatment of anticancer drug
induced acute and delayed vomiting.
The beneficial effect of steroids is due to their anti -
inflammatory effect.
Benzodiazepines like diazepam, lorazepam and
alprazolamare used in the treatment of psychogenic
and anticipatory vomiting.
The beneficial effects of benzodiazepines is due to
their sedative, amnesic and antianxiety effects.

21. Drugs Uses Important side effects
Anticholnergics
(Scopolamine) Motion sickness
Sedation, dryness of
mouth, blurred vision and
urinary retention
5-HT 3-receptor
antagonists
Cancer chemotherapy-induced
vomiting, radiation sickness and post-
operative vomiting
Headache, dizziness and
diarrhoea
Neuroleptics Drug-induced, disease­induced, post-
operative, cancer chemotherapy and
radiation-induced vomiting
Extrapyramidal
symptoms, sedation,
dystonic reactions and
orthostatic hypotension
Neurokinin
(NK1) receptor
antagonist
Cancer chemotherapy­ induced
vomiting
Dizziness, diarrhoea and
fatigue
Benzodiazepines
(Adjuvant
antiemetics)
Psychogenic and anticipatory vomiting Sedation and drowsiness

22. Drugs Uses Important side effects
Dronabinol Vomiting due to cytotoxic drugs and
radiation sickness
Sedation, dysphoria,
hallucinations and drug
dependence
Glucocorticoids
(Adjuvant
antiemetics)
Adjuvant antiemetlc along with
ondansetron or metoclo­pramide in
cancer chemotherapy-induced
vomiting
MetabolicDisturbances
Prokinetic drugs-
•
Metoclopramide
•Domperidone
•Drug-induced, disease­induced,
post-operative, cancer
chemotherapyinduced vomiting and
radiation sickness,
•Preferred antiemetic in children and
levodopa-lnduced vomiting
•Drowsiness, dizziness,
diarrhoea, acute dystonias and other extrapyramidal symptoms (EPS)
•Dryness of mouth,
diarrhoea and headache
Antihistamines Motion sickness, morning sickness, post operative, Meniere's disease,
drug induced, radiation sickness, cancer chemotherapy-induced vomiting
Drowsiness and dryness of mouth

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