This document discusses nausea, vomiting, and antiemetics. It defines nausea, retching, and vomiting and describes the symptoms and causes of nausea and vomiting. It discusses the anatomy of emesis, including the chemoreceptor trigger zone and vomiting center in the brainstem. It outlines the mechanisms of vomiting and describes various types of drug-induced vomiting. It also discusses the therapeutic use of emetic agents and the management of nausea and vomiting, including lifestyle changes, pharmacotherapy using various classes of antiemetics, and prokinetic drugs.

1. Emesis and Antiemetics
GMC Jagdalpur

2. Nausea
Nausea is an unpleasant sensation
of wanting to vomit, and is often
associated with
cold sweat,
pallor,
salivation,
loss of gastric tone,
duodenal contraction, and
the reflux of intestinal contents into the
stomach.
 Nausea generally precedes vomiting, but can
occur by itself.

3. Retching
 Retching is a
strong involuntary
effort to vomit, and
follows nausea.
 During retching, the
abdominal muscles,
chest wall and
diaphragm all contract
without any expulsion of
gastric contents.

4. Vomiting
Vomiting is the forceful expulsion of
the contents of the gastrointestinal
system out through the mouth.
From an evolutionary perspective, it is
thought to have evolved as a defence
mechanism of the body, serving a
function to rid the body of noxious
substances that have been ingested,
rather than allowing them to be retained
and absorbed by the intestine.

5. Stomach itself does not actively expel its
contents during vomiting.
The stomach, oesophagus, 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.

6. Symptoms of emesis
Profuse salivation;
Sweating;
Elevated heart rate;
Pallor;
Nausea; and
Retching movements.

7. Causes of nausea and vomiting
Conditions Reasons
Irritation of the stomach
and duodenum
Indigestion; Allergies; Bowel obstructions;
obstructions; Gallstones; Liver problems;
problems; Pancreatitis.
Infectious causes Viral labyrinthitis; Viral gastroenteritis;
Influenza; Whooping cough; Food
poisoning.
Endocrine Pregnancy.
Labyrinth causes Motion sickness; Meniere’s disease.
Increased intracranial
pressure
Haemorrhage. Meningitis;
Lesions in parts of the brain.
Drug/treatment induced Cancer chemotherapy; Opiates;
Digoxin; Immunotherapy; Nicotine,
Antibiotics; Radiotherapy; Alcohol excess.
Central nervous system Anticipation; Migraine; Bulimia nervosa;

8. Area Postrema
 surrounds 4th ventricle
 outside blood brain barrier & monitors blood

9. Anatomy of Emesis
 Chemoreceptor trigger zone (CTZ) in the area
postrema (AP) at the bottom of the fourth
ventricle has high concentration of:
• 5-HT3
• D2
• M1
• NK1
• opioid
 The CTZ has connections to the Nucleus of the
Tractus Solitarius (NTS) & Reticular
Formation (aka vomiting center) which
contains:
• 5-HT3
• M1
• NK1

10. Mechanisms of emesis
Afferent inputs go to the central nervous
system (CNS), relaying the signals of
emetic stimuli;
These signals are received, recognised,
and centrally processed. They then form
integrated emetic efferent signals coming
from the CNS;
These motor and chemical efferent
pathways relay signals that lead to the
coordinated respiratory, gastrointestinal
and abdominal muscle expulsive actions
of vomiting.

12. Chemoreceptor trigger zone
(CTZ)
 The CTZ is located in the medulla of the brain.
 It has a defensive blood-brain barrier for
detecting circulating toxins in the blood
and cerebrospinal fluid (CSF), and is sensitive
to a number of circulating emetic agents,
including morphine, intravenous copper
sulphate, and certain circulating metabolic
emetic agents associated with uraemia,
infections and radiation.
 When activated, the CTZ does not initiate
vomiting itself, but relays stimuli to
the integrative vomiting centre which produces
the actual act of emesis.

13. Integrative vomiting centre
The integrative vomiting centre coordinates
activities of the nearby neural structures to
produce a complex patterned response,
resulting in the processing and action of the
vomiting reflex.
The centre is located in the medulla.
The motor component of the vomiting centre
is controlled by both somatic
and autonomic systems, meaning that both
voluntary and involuntary systems are
involved in the process.
Their inputs are coordinated by the vomiting

14. Somatic efferent pathways control
respiratory and abdominal
musculature.
Visceral efferent components
mediating changes in gastric tone and
motility, while salivation, pallor and
sweating are autonomic
epiphenomena.
The autonomic nervous system is not
essential for the mechanical act of
vomiting.

15. Afferent pathways
The vomiting centre is predominantly
activated by three different mechanisms:
By nervous impulses from the
stomach, intestinal tract, and other
portions of the body, resulting in a
reflexive activation;
By stimulation from the higher brain
centres;
By the chemoreceptor trigger zone
(CTZ) sending impulses.

16.  Afferent impulses may also arise from other sites,
such as unpleasant sights and odours, as well as
severe parietal pain.
 The most common afferent pathways are in the
viscera, or abdominal organs.
 Vomiting can be provoked by occlusion of the
coronary vessels, distension of the intestine, and
irritation of the gastrointestinal mucosa.
 In the gastrointestinal tract, mechanoreceptors in
the intestinal wall are activated by abnormal
contractions, distension or physical damage.
 Potentially harmful chemical stimuli can also
activates chemoreceptors located in the intestinal
wall.
 These receptors then release information to the

17. Efferent pathways
 The vomiting reflex is mediated by both the
autonomic and somatic systems, and
consists of two phases:
 Prodomal phase (pre-ejection):
gastric muscles followed by small intestinal
retrograde peristalsis;
 Ejection phase: Comprises of retching and
vomiting including expulsion of gastric
contents.

23. Consequences of vomiting

24. Types of emesis (Drug induced)
 Acute emesis: symptoms occurring within the
first 24 hours after drug therapy;
 Delayed emesis: symptoms occurring after 24-
48 hours after last dose of drug therapy;
 Anticipatory emesis: a conditioned response in
patients who have developed significant drug-
drug-induced nausea and vomiting during
previous cycle of therapy.

25. Post-operative nausea and
vomiting (PONV)
 Age: M/C in Younger & elderly patients
 Gender: Women tend to suffer more than men do.
 Nutrition: overweight or obese pts
 Past history: H/o motion sickness or previously h/o
nausea and vomiting after a surgical procedure
 Cancer therapy: Patients undergoing chemotherapy
and radiotherapy are more likely to suffer as well;
 Anaesthetic and surgical factors: inhalational agents
and medications (such as morphine
 Some surgical factors: such as operations around the
ear and inner ear, eyes, mouth and some abdominal
abdominal surgery.

26. Consequences of vomiting
Severe and prolonged vomiting can cause the
following harmful consequences:
 Dehydration, which can be lethal, especially in
children;
 Protracted vomiting may result in starvation,
malnutrition and vitamin deficiency;
 Severe post-operative vomiting can increase
bleeding, aspiration pneumonia, and induce
the re-opening of surgical wounds as a result
of involuntary muscle contractions associated
with vomiting;
 Metabolic alkalosis.

27. Therapeutic use of Emetic agents

28. Common examples of emetics are:
Powdered mustard suspension, strong
common salt solution, IPECAC and
apomorphine.
Mustard and common salt are
commonly used household emetics
because they are easily available.
They are indicated in case of
poisonings.
They act reflexly by irritating the
stomach.

29. Apomorphine
 It is a semisynthetic derivative of morphine.
 Acts on CTZ.
 It is given in a dose of 6 mg i.m./s.c. route.
 It takes minimum 5 minutes for its action.
 It should not be given in the patients who are
having respiratory distress as it also acts as a
respiratory depressant.
 Its action is unpredictable when given by oral
route.
 For induction of vomiting, very high dose is
required, which is not safe.

30. Ipecacuanha
It is obtained from dried root of Cephaelis
ipecacuanha which contains an alkaloid
called Emetine.
It causes vomiting by irritating the gastric
mucosa reflexly as well as by acting on
CTZ.
To induce vomiting, it is given orally in a
dose of 15–30 ml in adults, 10–15 ml in
children and 5 ml in infants.
It takes minimum 15 minutes for its
action.
The syrup of IPECAC is safer than

31. Contraindications of emetics use
Kerosene poisoning (aspiration may cause
chemical pneumonia).
CNS stimulant drug poisoning (emetics
precipitate convulsions).
Morphine poisoning (emetics do not works
properly).
Corrosive poisoning (it may lead to G.I.
perforation/esophageal erosion).
Unconscious patients (increases chances of
aspiration).
Paediatric patients. (increases chances of

32. Management of Emesis
Lifestyle
Pharmacotherapy

33. Dietary management of nausea
Avoid foods that:
are fatty/greasy/fried;
are spicy or hot;
have strong odours.
Eat small amounts more frequently and eat
slowly;
Eat before you get hungry, because hunger
can make feelings of nausea stronger;

34. Avoid eating in a room that is too warm,
or has cooking odors that might
disagree with you;
Sip cold clear fluids
Have foods and drinks at room
temperature or cooler; hot foods may
add to nausea;
Rest after meals, because activity may
slow digestion.
It’s best to rest sitting up for about an
hour after meals;

35. CLASSIFICATION OF ANTIEMETICS
Anticholinergics Hyoscine, Dicyclomine
H1 antihistaminics Promethazine, Diphenhydramine,
Dimenhydrinate, Doxylamine, Meclozine
(Meclizine), Cinnarizine.
Neuroleptics(D2
blockers)
Chlorpromazine, Triflupromazine,
Prochlorperazine, Haloperidol, etc.
Prokinetic drugs Metoclopramide, Domperidone, Cisapride,
Mosapride, Itopride, levosulpride.
5-HT3 antagonists Ondansetron, Granisetron, Palonosetron,
Ramosetron
NK1 receptor
antagonists
Aprepitant, Fosaprepitant
Adjuvant antiemetic Dexamethasone, Benzodiazepines,

37. Anticholinergics
 Antiemetic action is exerted by blocking
conduction of nerve impulses from the
vestibular apparatus to the vomiting centre
(which involves cholinergic link).
 These drugs have poor efficacy in vomiting of
other etiologies.
 Hyoscine and Dicyclomine are the most
commonly used anticholinergic drugs in G.I.
system.

38. Hyoscine
It has shorter duration of action.
It is given in a dose of 0.2–0.4 mg oral or
i.m.
It is very effective for motion
The most common adverse effects are dry
mouth and sedation.
Transdermal hyoscine patch is applied
behind the pinna.
It contains 1.5 mg of Hyoscine and
delivers the drug for consecutive three
days.

39. Dicyclomine
It is also used for motion sickness as a
prophylaxis.
It is given in a dose of 10–20 mg
orally.
It is used as an antispasmodic agent.
Don’t give in lactating mother?
The most common adverse effects are
dry mouth and sedation.

40. H1 Antihistaminics
H1 antihistaminic drugs have weak antiemetic
property.
The antiemetic action is due to antihistaminic,
anticholinergic and weak antidopaminergic
action.
These drugs are useful to prevent motion
sickness, morning sickness and postoperative
vomiting.
The main side effects are dry mouth, sedation,
confusion, dizziness, and urinary retention.

41. Drug Dose and Route Main uses
Promethazine 25 mg, tablet & i.v. Motion sickness,
chemotherapy induce
vomiting
Diphenhydramine 25–50 mg oral
Dimenhydrinate 25–50 mg oral
Doxylamine 10-20mg oral Morning sickness
Meclozine
(Meclizine)
25–50 mg oral Sea sickness
Cinnarizine 25–50 mg oral Vertigo, labyrinthitis

42. NEUROLEPTICS (D2-BLOCKERS)
 Phenothiazines, haloperidol are potent
antiemetics.
 They block D2 receptors in the CTZ;
antagonize apomorphine induced vomiting
and have additional antimuscarinic as well as
H1 antihistaminic property.
 but less effective in motion sickness?

43. They have broad spectrum antiemetic
action effective in:
Drug induced and postoperative nausea
and vomiting (PONV).
Disease induced vomiting: gastroenteritis,
uraemia, liver disease, migraine, etc.
Malignancy associated and cancer
chemotherapy (mildly emetogenic)
induced vomiting.
Radiation sickness vomiting (less
effective).
Morning sickness: should not be used

44. S/E
M/C sedation.
Acute muscle dystonia may seen in
children and girls.
Not given in undiagnosed cause of
vomiting; because its delayed the
symptom of intestinal obstruction,
appendicitis.

45. Prochlorperazine
An D2 antagonist, given in a dose of 5–
10 mg BD/TDS oral, &/or 12.5–25 mg
by deep i.m. injection.
It is indicated in vertigo and some
case of chemotherapy induced
vomiting.
These drugs are least preferred as
antiemetics due to availability of better
safer antiemetics.

46. MIDAZOLAM
Short-acting benzodiazepine with a
rapid onset of action which has been
demonstrated efficacious as
antiemetic in postoperative emesis
resistant to the usual treatments
Midazolam decreases dopamine imput
at the CTZ or dopaminergic neuronal
activity and 5-HT release by binding
to the GABA benzodiazepine complex

47. OLANZAPINE
Antipsychotic drug that blocks multiple
neurotransmitters:
dopamine at D1, D2, D3 and D4 brain
receptors,
serotonin at 5-HT2a, 5-HT2c, 5-HT3 and 5-
HT6 receptors,
catecholamines at alpha 1 adrenergic
receptors
histamine at H1 receptors
Used for CINV

48. Gabapentin
A g-aminobutyric acid analogue
approved in 1994 as an anticonvulsant
In an anedoctal report, complete
resolution of chemotherapy-induced
nausea was seen in a patient with breast
cancer, after she was placed on
gabapentin for the treatment of hot
flushes
The mitigation of tachykinin
neurotransmitter activity useful to
control both hot flushes and emesis has
been suggested as possible mechanism of
action

49. Ghrelin
 Stimulates gastric motility
 Protects gastric mucosa
 Increases appetite

50. PROKINETIC DRUGS
Metoclopramide, domperidone, cisapride,
mosapride, itopride, levosulpride

52. Metoclopramide
It is also called gastric hurrying agent.
It has both peripheral and central actions.
Peripherally: Metoclopramide has more
prominent effect on upper GIT;
increases gastric peristalsis while relaxing the
pyloric sphincter and the first part of
duodenum.
It also increases the tone of lower esophageal
sphincter (LES).
Centrally: Metoclopramide blocks the D2
receptors in CTZ.

53. D2 antagonism
It blocks D2 receptors — hastening
gastric emptying and enhancing LES
tone by augmenting ACh release.
The central antidopaminergic (D2)
action of metoclopramide on CTZ is
clearly responsible for its antiemetic
property.
It also antagonised apomorphine
induced vomiting, CPZ like
extrapyramidal effects and
hyperprolactinaemia.

54. 5-HT4 agonism
Metoclopramide acts in the g.i.t. to
enhance ACh release from myenteric
motor neurones.
This results from 5-HT4 receptor
activation on primary afferent neurones
(PAN) of the ENS via excitatory
interneurones.
The gastric hurrying and LES tonic
effects are mainly due to this action
which is synergised by bethanechol and
attenuated by atropine.

55. 5-HT3 antagonism
At high concentrations
metoclopramide can block 5-HT3
receptors present on inhibitory
myenteric interneurones and in NTS/
CTZ.
The central anti 5-HT3 action appears
to be significant only when large doses
are used to control CINV.

56. Pharmacokinetics
It is rapidly absorbed orally.
It acts in ½–1 hr when given orally,
within 10 min after i.m. and 2 min
after i.v. injection.
Action lasts for 4–6 hours.
It crosses the BBB and placental
barrier.
It is metabolized in liver and excreted
by urine.

57. Indications
 Vomiting due to different reasons such as drug
induced, disease associated, postoperative and
radiation sickness, etc.
 It is not preferred in motion sickness due to poor
effectiveness.
 It can be used for morning sickness only when
other drugs fail.
 It is used as Gastrokinetic agent to accelerate
gastric emptying in conditions such as:
 diabetic gastroparesis associated gastric stasis and
 when emergency general anaesthesia has to be given and the patient
has taken food less than 4 hours before.
 To facilitate duodenal intubation
 Dyspepsia and persistent hiccups.
 GERD

58. Adverse effects
The most common side effects are loose
stools, sedation , dizziness and muscle
dystonias (due to extrapyramidal side
effects in children).
Long-term use can cause galactorrhoea,
gynaecomastia and parkinsonism.
Doses
Adults: 10 mg TDS oral or i.m.
Children: 0.2–0.5 mg/kg TDS oral or i.m.

59. Domperidone
Domperidone is a D2 receptor inhibitor.
It acts as metoclopramide but has chemical
chemical structure like haloperidol.
Pharmacokinetics
It is well absorbed orally, but due to first pass
pass metabolism, it has poor bioavailability
(15%).
It is metabolized in liver and excreted in urine.

60.  Dose
 Adult: 10–40 mg TDS.
 Children: 0.3–0.6 mg/kg in three divided doses.
 Indications
 These are same as metoclopramide but less effective as
gastrokinetic agent.
 It is not useful in chemotherapy induce emesis.
 Adverse effects
 The side effects are less as compared to metoclopramide.

61. Cisapride
It is 5-HT4 receptors agonist and promotes
Ach release in the gut wall causing
prokinetic activity.
It is not an antiemetic as it does not act on
D2 receptors.
Therefore, no extrapyramidal side effects
are seen. The t½ is 10 hours.
It was commonly indicated as prokinetic
agent, particularly for gastroesophageal
reflux disease and gastroparesis.
Its clinical use has been banned in India
since 2011 due to cardiac side effects like Q-
T prolongation etc..

62. Mosapride
It is a congener of Cisapride.
It is also a 5-HT4 receptors agonist and
poor 5-HT3 antagonistic action on
myenteric plexus.
Like cisapride, it does not act on D2
receptors hence, hyperprolactinemia and
extrapyramidal side effects are not seen.
The common side effects are abdominal
pain, diarrhoea, headache, dizziness, and
insomnia.

63. It may also cause Q-T prolongation when
co-prescribed with macrolides and azoles.
So, it should be given carefully in cardiac
patients.
It is given in a dose of 5 mg (elderly 2.5
mg) TDS.
It is indicated in
diabetic gastroparesis,
non-ulcer dyspepsia,
GERD (as adjuvant to H2blockers/PPIs),
and
some cases of chronic constipation.

64. Itopride
 It is a safer prokinetic drug.
 It has D2 antidopaminergic and anti-cholinesterase
activity. Thus, it potentiates the Ach action on GIT
causing prokinetic activity.
 No drug interactions are seen with macrolides and
azoles.
 It can be given safely to cardiac patients as no Q-T
prolongation has been recorded yet.
 The side effects are diarrhoea, abdominal pain,
headache.
 Galactorrhoea and gynaecomastia occur rarely.
 No extrapyramidal side effects are seen.
 It is given in a dose of 50 mg TDS before meals.

65. Levosulpride
It is a selective antagonist of dopamine
D2 receptor activity on both central and
peripheral levels.
It is typical neuroleptic and a prokinetic
agent.
It is used in a treatment of anxiety
disorders, dyspepsia, irritable bowel
syndrome (IBS), etc.
It is metabolized in liver and
urine with a t ½ of 9.7 hr. when
and 4.3 hr by i.v. route.

66.  It is usually given in combination with PPI
(rabeprazole) (rabeprazole 20mg+ levosupride
75mg).
 It can be given safely to cardiac patients as no Q-T
prolongation has been recorded yet.
 The common side effects are diarrhoea and
constipation. (dose dependent)
 It should not be used to stimulate the GI motility
in presence of GI haemorrage, obstruction and
perforation.
 The patients should be advised to avoid driving or
work on machinery as it causes dizziness and
somnolence in some patients.
 The newer prokinetic drugs are sultopride

67. 5-HT3 ANTAGONISTS
Ondansetron, Granisetron, Palonosetron,
Ramosetron

68. 5-HT3 ANTAGONISTS
These antiemetic drugs were
developed to control cancer
chemotherapy or radiotherapy
induced vomiting and proved their
worth.
They block the depolarizing action of
5-HT exerted through 5-HT3
receptors on vagal afferents in the GIT
as well as in nucleus tractus solitarius
(NTS) and CTZ.

69. Cytotoxic drugs/radiation produce
nausea and vomiting by causing
cellular damage
release of mediators including 5-HT
from intestinal mucosa
activation of vagal afferents in the
gut
emetogenic impulses to the NTS and
CTZ
vomiting

70. They are highly effective in postoperative
nausea and vomiting (PONV) and disease
or drug induced vomiting.
They are not effective in apomorphine or
motion sickness induced vomiting.
Nowadays, these drugs are the most
commonly used antiemetics.

71. Ondansetron
It is given by both oral and i.v. route.
It is metabolized in liver and excreted
in urine and faeces.
The t ½ 3–5 hrs and duration of
action is 8-12 hrs, which may be
longer at higher doses.

72. Indications & Dose
 Cancer chemotherapy (highly emetogenic drugs) induced
vomiting;
 8 mg i.v. by slow injection over 15 min ½ hr before
chemotherapeutic infusion, followed by 2 similar doses at 4
at 4 hours interval.
 Alternatively, single 24 mg i.v. dose on first day can also be
be used.
 To prevent delayed emesis:
 8 mg oral is given twice a day for 3–5 days.
 To prevent postoperative nausea and vomiting (PONV):
 4–8 mg i.v. given before induction of anesthesia and given 8
given 8 hourly postoperatively if required.
 For radiotherapy and less emetogenic drugs:
 8 mg orally given 1–2 hr prior to the procedure and then at
at eight hrly interval till required.

73. Granisetron
It is ten times more potent than
ondansetron.
It is more effective during the repeat
cycle of chemotherapy.
Its t ½ is 8-12 hrs therefore, given in BD
doses.
The side effects are similar to
ondansetron.

74. Indication and Dose
 Cancer chemotherapy (highly emetogenic drugs)
induced vomiting;
1–3 mg diluted in 20–50 ml saline and infused i.v.

75. Palonosetron
It is the longest acting 5-HT3 antagonist
and given in a single dose only .
It is more effective in suppressing delayed
vomiting occurring between 2-5 days after
chemotherapy.
It is given by both oral and i.v. routes.
It is metabolized in liver and excreted in
urine.
It has t½ of 40 hrs.

76. In addition to the common side effects of 5-
HT3 antagonist, it also causes Q-T
prolongation, when co-administered with
erythromycin, moxifloxacin, anti-psychotics,
antidepressants, etc.
It should always be given by slow i.v.
infusion as rapid i.v. injection may cause
blurring of vision.
Indications & Dose
Cancer chemotherapy (highly emetogenic
induced vomiting:
250 µg by slow i.v. injection 30 min before
chemotherapy. Do not repeat before 7 days.
To prevent post operative nausea and
(PONV):
75 μg i.v. as a single injection just before induction.

77. Ramosetron
 It is similar to ondansetron in general properties.
 It is also indicated for diarrhoea predominant
it has shown potential to normalize disturbed
function.
 Indications & Dose
 Cancer chemotherapy (highly emetogenic
vomiting : 0.3 mg injected i.v. before chemotherapy,
repeated once daily.
 For low emetogenic chemotherapy:
0.1 mg once daily.
 To prevent post operative nausea and vomiting
Ramosetron 0.3 mg i.v. equally effective as
ondansetron 8 mg i.v.

78. NK1 RECEPTOR ANTAGONISTS
Aprepitant, fosaprepitant
The substance-P released due to emetogenic
emetogenic chemotherapy activates
neurokinin (NK1) receptors in CTZ and NTS
NTS and plays a role in the causation of
vomiting.
Aprepitant and Fosaprepitant antagonists
antagonists block the NK1 receptors and act
act as antiemetics in chemotherapy induced
induced vomiting.

79. Aprepitant
 Aprepitant has high affinity to NK1 receptors.
 It is well absorbed orally.
 It penetrates BBB and is metabolized in liver
and excreted in faeces and urine.
 t½ is 9–13 hours.
 It should not be given to the patients who have
been already prescribed Q-T interval prolonging
drugs.
 The main side effects are weakness, fatigue,
flatulence and rarely rise in liver enzymes.

80. Indications & Dose
 Cancer chemotherapy (highly emetogenic drugs)
induced vomiting:
Oral aprepitant (125 mg + 80 mg + 80 mg over 3
over 3 days) combined with standard i.v.
ondansetron/ palonosetron + dexamethasone
regimen significantly enhances the antiemetic
efficacy against highly emetogenic cisplatin based
based chemotherapy.
It is highly useful in patients undergoing multiple
multiple cycles of chemotherapy.
 To prevent post operative nausea and vomiting
PONV:
A single (40 mg) oral dose of aprepitant is well
effective in PONV.

81. Fosaprepitant
 It is a parenterally administered prodrug of
aprepitant.
 It is given as 150 mg running i.v. infusion
administered over 20-30 minutes.
 In Cancer, chemotherapy (highly
emetogenic drugs) induced vomiting:
 It is given in a dose of 150 mg in conjuction with
standard i.v. ondansetron/ palonosetron +
dexamethasone regimen.

82. CASOPITANT
Potent and selective oral NK1 receptor
antagonist which has shown activity in
preventing chemotherapy-induced
nausea and vomiting in preclinical
studies

83. ADJUVANT ANTIEMETICS
(Corticosteroids, benzodiazepines,
cannabinoids)

84. Cannabinoids
 They are obtained from Cannabis indica, and
possesses good antiemetic activity.
 Tetrahydrocannabinol (THC) is the active principle.
 They act by agonistic action on cannabinoid receptors
(CB-1), which are located in vomiting centre and CTZ.
 They are also good appetite stimulants.
 They are metabolized in liver and metabolites are
excreted slowly over days to weeks in the feces and
urine.
 They are not commonly used due to availability of
better drugs.
 They are used only in those patients, who do not
respond to other antiemetics.
 The common side effects are euphoria, dysphoria,
sedation, hallucinations, and dry mouth.

85. Dronabinol is the purest form of THC and is usually
given in a dose of 5 mg/m2 just prior to chemotherapy
chemotherapy and every 2–4 hours as needed.
Nabilone
It is a man made cannbinoid, having antiemetic property.
It has been approved by US-FDA for its clinical use.
It is used only in those patients, who do not respond to other
other antiemetics.
It is given in a dose of 1-2 mg before 1-3 hour of
chemotherapy; then every 8-12 hours during the course of
chemotherapy and for 2 days following cessation of
chemotherapy.

86. Benzodiazepines (BZDs)
 BZDs have sedative action and relieve the
psychogenic component of vomiting; thereby
used as adjuvant to antiemetics.
 They also suppress dystonic side effects of
metoclopramide.
 The commonly used BZDs are diazepam,
lorazepam (oral/i.v.), and alprazolam (oral
only).

87. Corticosteroids
 Corticosteroids (dexamethasone,
methylprednisolone) have antiemetic
properties, but exact mechanism of action is
unknown.
 These agents enhance the efficacy of 5-HT 3
receptor antagonists.
 The commonly used corticosteroid is
dexamethasone, which is given in a dose of 8–
20 mg intravenously before chemotherapy,
followed by 8 mg/day orally for 2–4 days.

88. Therapeutic window
High Therapeutic
Index
Low Therapeutic
Index
– 5-HT3 antagonists
– NK1 antagonists
– corticosteroids
(combo)
– cannabinoids
– dopamine
antagonists
– benzodiazepines

90. DIGESTANTS
 These are substances intended to promote
digestion of food.
 Used as appetite stimulants or health tonics.
 They are occasionally beneficial, only when
elaboration of enzymes in g.i.t. is deficient.
 Their routine use in tonics and appetite
improving mixtures is irrational

91. Pancreatin
 It is a mixture of pancreatic enzymes obtained
from hog and pig pancreas.
 It contains amylase, trypsin and lipase/
 Indicated in chronic pancreatitis or other
exocrine pancreatic deficiency states.
 It reduces the Fat and nitrogen content of
stools and helps in diarrhoea/steatorrhoea.
 It has to be used as enteric coated tablets or
capsules.
 S/E: Nausea, diarrhoea and hyperuricaemia.

92.  Pepsin
 May be used along with HCl in gastric achylia due to
atrophic gastritis,
gastric carcinoma,
pernicious anaemia, etc.
 Papain
 It is a proteolytic enzyme obtained from raw papaya.
 Its efficacy after oral ingestion is doubtful.
 Diastase and Takadiastase
 These are amylolytic enzymes obtained from the fungus
fungus Aspergillus oryzae.
 They have been used in pancreatic insufficiency, but
efficacy is equivocal.

93. Methyl polysiloxane
Dimethyl polysiloxane, Simethicone, Dimethicone
 It is a silicone polymer, a viscous amphiphilic liquid—
liquid—reduces surface tension and collapses froth,
froth, ‘antifoaming agent’.
 It is not absorbed from g.i.t. and is pharmacologically
pharmacologically inert.
 It is added with antacid, digestant and antireflux
preparations.
 Mostly indicated for flatus.
 Also indicated for GERD and peptic ulcer
 Dose:
40–120 mg 3 to 4 times a day.

94. GALLSTONE DISSOLVING DRUGS