ANTIEMETICS

INTRODUCTION:
Drugs, which are used for the treatment and
prevention of vomiting, are known as antiemetic.
These drugs are also useful for the condition during
which the patient feels as if he is going to vomit but
the act of vomiting does not occur. This is known as
nausea.
CLASSIFICATION:
1-H1-ANTAGONISTS:
Diphenhydramine
Promethazine
Hydroxyzine
Cyclizine
2-ANTIMUSCARINICS:
Hyoscine
3-D2-ANTAGONISTS:
Phenothiazinesexcept for thioridazine and mesoridazine
Metoclopramide
domeperidone
4-5-HT3-RECEPTOR INHIBITORS:
Ondansetron
Granistron
Tropisetron
5-MISCELLANEOUS DRUGS:
a-MARIJUANA DERIVATIVES:
Tetrahydrocanabinol(THC)
Dronabinol
Nabilone
b-CORTICOSTEROIDS:
Dexamethasone
Methylprednisolone
C-BENZODIAZEPINES:

Two Brainstem sites:
1-chemoreceptor trigger zone:
Is located outside BBB. so it can directly respond to
chemical stimuli in the blood or CSF.
2-vomiting center:
Located in lateral reticular formation of the area
medulla.
Responds to input from periphery (pharynx,
GIT),higher brainstem, cortical structures. This
vestibular system functions mainly in motion
sickness.
 METOCLOPRAMIDE:
(D2antagonist)
It is an antiemetic as well as stimulant to the
motility of the upper GIT.
It produces its antiemetic effect by blocking the D2
receptors in the chemoreceptor trigger zone(it is
located outside BBB. so it can directly respond to
chemical stimuli in the blood or CSF).
It causes increased motility of the
upper gut by increasing the
effect of acetylcholine.
CLINICAL USES:
Itis used in nausea and vomiting caused by GIT
disorders, cytotoxic drugs, migraine, and
chemotherapy.
To stimulate emptying of stomach in patients
undergoing emergency surgery and during labour.
For reflux oesophagitis:
 it causes emptying of stomach and increases
the tone of lower esophageal sphincter, thus
preventing the passage of gastric contents into the
esophagus.
ADVERSE EFFECTS:
Blockers of dopaminergic receptors can cause extra
pyramidal effects such as dystonias (Torticollis
(abnormal asymmetrical head n neck
condition),occulogyric crisis(involuntary upper
deviation of eye), facial spasm ,trismus etc).They are
more likely to occur in children and young adults.
Its prolonged use can cause tardive
dyskinesia,especially in old women.
Diarrhea can occur.
Increased prolactin secretion with metoclopramide
can cause gynaecomastia males and galactorrhea.
 DOMPERIDONE:
(D2 antagonist)
Its antiemetic effect is produced by blockade of
dopaminergic receptors in the chemoreceptor trigger
zone.
It is relatively impermeable to blood brain barrier, but
the chemoreceptor trigger zone lies outside this
barrier, hence domperidone can act on it.
It causes closure or spasm of the lower oesophageal
sphinter, thus preventing the gastric contents to pass
into the esophagus.
It increases the motility of gastric antrum and
relaxation of pyloric sphincter thus causing emptying
CLINICAL USES:
Prevention and treatment of nausea and vomiting
due to gastrointestinal diseases, drugs(including
chemotherapeutic agents) and radiotherapy etc
For prevention of esophageal reflux and for
prevention and treatment of reflux oesophagitis.
ADVERSE EFFECTS:
1-Dystonia and other CNS effects are rare.
2-Can cause abdominal pain and diarrhea.
especially in larger doses.
3-Gynaecomastia and galactorrhea can occur.
ONDANSETRON (ZOFRAN):
It blocks 5-HT3 receptors in the CNS and in the gut.
CLINICAL USES:
It is used for the prevention and treatment of nausea
and vomiting due to cytotoxic drugs and radiotherapy.
ADVERSE EFFECTS:
Constipation, headache, dizziness and a sensation of
warmth and flushing of the head and epigastrium can
occur.
Transient abnormalities of liver enzymes and
hypersensitivity reactions are reported.
 NABILONE:
It is a synthetic canabinoid, resembling
tetrahydrocannabinol (THC).
It is effective for the treatment and prevention of
vomiting due to cytotoxic drugs.
ADVERSE EFFECTS:
Drowsiness, Dryness of mouth, decreased
appepite,dizziness,euphoria,postural hypotension,
mental confusion and psychosis.
WHAT HAPPENS:
Chemoreceptor agents:
Chemoreceptor agents can directly activate
vomiting center.
Some neuroreceptors also involved D2 and 5HT3
(serotonin)
Sometimes the colour or smell of agents can trigger.
Chemotherapeutic (cellular damage)drugs can also
act peripherally by irritating cell causing release of
serotonin which act on 5HT3 receptor sensory
signal to the medulla…leading to emesis.
VOMITING DURING PREGNANCY:
Occurs during initial weeks of pregnancy, becomes
maximum at 10-11 weeks and stops at 13 th to 14th
week. This can be treated by:
a-Reassurance to the patient that the disease is
temporary.
b-Taking something to eat before rising up from the
bed in the morning.
c-In severe cases, an H1-antagonist or a
phenothiazine, such as promethazine can be used.
MOTION SICKNESS:
It occurs due to stimulation of the vestibular system
during air, sea or land journey. This should be better
prevented than treated.
Following drugs can be used for
 the prevention of motion sickness:
1-Cyclizine
2-Dimenhydrinate
3-Hyoscine
4-Promethazine
5-Cinnarizine
Drug should be used one hour before the start of
journey, and its administration is repeated according
to the duration of its effect.
TREATMENT:
For the treatment of motion sickness, parenteral
injection or rectal administration of drug may be
required.
Hyoscine is also available in the form of a skin
patch, which is applied on the skin behind the ear.
It is effective for about 24 hours, but can cause dry
mouth, blurred vision and drowsiness.
DRUG INDUCED VOMITING:
Metoclopramide or a phenothiazine such as
chlorpromazine can be used for the treatment of
drug induced vomiting(such as vomiting due to
opioids). Cyclizine or other drugs can also be used
for motion sickness.
Vomiting induced by cytotoxic drugs can be severe,
especially with cisplatin. This can be prevented and
treated with 5-HT3 antagonists, such as
ondansetron.
Dexamethasone and lorazepam can also be used.
Dexamethasone decreases the vomiting by an
unknown mechanism while lorazepam by causing
amnesia, prevents anticipatory nausea and vomiting.
For less severe nausea and vomiting with cytotoxic
drugs,metaclopramide can be used in place of
ondansetron,especially in older people, because it
produces less extra pyramidal adverse effects in this
age group.