2. EMESIS
•Protective reflex - to get rid the stomach and
intestine of toxic substances and prevent their
further ingestion.
Pre-ejection phase: Gastric relaxation &
retroperistalsis
Retching: Rhythmic action of respiratory muscles
preceding vomiting and consisting of contraction of
abdominal and intercostal muscles and diaphragm
against a closed glottis
Ejection: intense contraction of the abdominal
muscles and relaxation of the upper
esophageal sphincter
6. EMETICS
According to site of action:
a.Centrally acting: Apomorphine &
Morphine
b.Peripherally acting: Mustard,
Potassium tartrate (tartar emetic)
and hypertonic sodium chloride
c.Both: Ipecacuanha
7. APOMORPHINE
D2 AGONIST
• Given SC/IM -6mg
Causes vomiting within 15 min
Vomiting is often accompanied by sedation
Should not be used if respiration is depressed
Large doses often produce restlessness, tremors, occasionally
convulsions
Sometimes may cause hypotension, syncope and coma
8. Emetics –Peripherally acting
Mustard:
Volatile oil
safe and easily available
Dose -1 tsp inwater
Sodium chloride:
Given orally
Withdraws fluid from the cells lining the stomach
causes irritation which causes reflex emesis
10. LIST OF DRUGS INDUCE
VOMITING
Anticancer drugs
Amiodarone
Apomorphine
Chloroquine, quinine
Diltiazem
Emetine
Ergot derivatives
Erythromycin, tetracyclines
Fluroquinolones
Metronidazole
11.
12. ANTICHOLINERGICS
HYOSCINE
Dosage: 0.2-0.4 mg oral, i.m.
Most effective drug for motion sickness
But action is brief; & sedation & other anticholinergic
side-effects
MOA – Block cholinergic NT in the vestibular-emetic
centre pathway not useful for vomiting other than
due to motion sickness
TTDS – 1.5 mg over 3 days; applied behind pinna,
good efficacy and minimal side effects
DICYCLOMINE – 10-20 mg P/O For prophylaxis of
motion sickness and morning sickness; no
teratogenicity seen now; blocks M receptors 12
13. H1 ANTIHISTAMINES
13
PROMETHAZINE,
DIPHENHYDRAMINE,
DIMENHYDRINATE –
• Motion sickness for 4-6 hrs
• ADE – sedation & mouth dryness
++
Combined with metoclopramide, it
abolishes its extra pyramidal side
effects combination is useful in
motion sickness (more efficacy,
less side effects)
DOXYLAMINE –
• A sedative H1-antihistamine + anti
cholinergic
Combined with pyridoxine for early
pregnancy morning sickness
Pk - Oral absorption – slow
ADE – dry mouth, drowsiness,
vertigo & Abd. Upset
Dose - 10-20 mg at bedtime is the
dose frequency can be
increased to thrice daily if needed
CYCLIZINE & MECLIZINE –
• Less sedative & less
anticholinergic side-effects
Meclizine = longer acting, protects
against sea sickness for ~ 24 hrs.
CINNARIZINE –
• Anti-vertigo drug in motion
sickness
Inhibits Ca++ influx from
endolymph into vestibular sensory
cells regain labyrinthine reflexes
no vertigo / emesis
14. GENERAL POINTS ABOUT H1
BLOCKERS IN EMESIS Rx -
First choice in motion sickness
Taken ½ - 1 hr before journey; like all
anti-motion sickness drugs
Once motion sickness starts, it is difficult
to control higher/parenteral doses
required
Due to some teratogenic potential, avoid
them if possible
Other modalities – reassure & diet
adjustment
17-05-2023 14
15. NEUROLEPTICS
Potent anti-emetics
Block D2 receptors in CTZ + antimuscarinic + antiH1
properties
Broad spectrum anti-emetic action
Drug-induced & post-GA nausea/vomiting
Gastroenteritis-, uraemia-, liver disease- & migraine-
induced vomiting
Malignancy- & chemotherapy-induced vomiting
Radiation sickness vomiting (less effective)
Hyper emesis gravid arum
Less effective in motion sickness as vestibular
pathway does not involve DA
17-05-2023 15
16. PROCHLORPERAZINE
D2 – blocker phenothiazine labyrinthine
suppressant
Antivertigo & antiemetic actions
Useful in vertigo-associated & chemotherapy-
induced nausea/vomiting
ADE: Extra pyramidal side-effects & muscle
dystonia
Antiemetic dose << anti-psychotic dose
Not given till cause of emesis is diagnosed
17-05-2023 16
17. PROKINETIC AGENTS -
Promote gastrointestinal transit and speed gastric
emptying by enhancing coordinated propulsive
motility.
Metoclopramide
Domperidone/Tegaserod
Cisapride/Mosapride
METOCLOPRAMIDE
GIT ACTIONS: Speeds gastric emptying
decreases transit time in stomach + LES tone is
increased
CNS: On CTZ, it anti-emesis
Pk – crosses placenta, actions last 4-6 hrs.
17-05-2023 17
18. Dopamine
5-HT4 agonism
5-HT3
antagonism
Inhibitory transmitter in GIT
• Delay gastric emptying when food is
present in stomach
• Cause gastric dilatation and LES
relaxation attending nausea and
vomiting.
• G.i.t. to enhance ACh release from
myenteric motor neurons
• Gastric hurrying and LES tonic
• 5-HT3 receptors present on inhibitory
myenteric interneurones and in NTS/
CTZ.
19. ADE
Sedation, muscle
dystonia in children,
loose stools, long term
use parkinsonism,
galactorrhoea,
gynecomastia
USES
1) Antiemetic: migraine,
radiation sickness,
postoperative & drug-
induced emesis;
2) gastro kinetic:
duodenal intubation,
emergency GA, Relieve
gastric stasis due to
vagotomy/DM;
3) Dyspepsia &
hiccoughs;
4) GERD: With PPIs &
H2-blockers
17-05-2023 19
20. • D 2 antagonist
• Chemically related to haloperidol but pharmacologically related
to metoclopramide
• Has lower ceiling antiemetic and prokinetic actions
• Poorly crosses BBB
• Rare extra pyramidal side effects
• Absorbed orally, but bioavailability is only 15% due to first pass
metabolism
• Completely metabolized and excreted in urine
• t ½ is 7.5hr
Domperidone
Cont…
21. Cisapride
5-HT4 agonistic (which promotes ACh release from
myenteric neurons) and 5-HT3 antagonistic (minor)
action in the myenteric plexus.
Little antiemetic property, because it lacks D2
receptor antagonism
G a s t r i c e m p t y i n g i s a c c e l e r a t e d
LES tone is improved, esophageal peristalsis
augmented
Enteric neuronal activation via 5-HT4 receptor also
promotes cAMP-dependent Cl– secretion in the
colon, increasing water content of stool
Devoid of action on CTZ and does not produce
extrapyramidal symptoms
Primary indication of cisapride has been GERD
22. Ventricular arrhythmias and death, mainly
among patients who took CYP3A4
inhibitors like azole antifungals,
macrolide antibiotics, antidepressants,
HIV protease inhibitors,.
At high concentrations, cisapride blocks
delayed rectifying K+ channels in heart—
prolongs Q-Tc interval and predisposes to
torsades de pointes/ventricular fibrillation
Itopride
23. A 55-year-old woman with type 1 diabetes of 40
years’ duration complains of severe bloating and
abdominal distress, especially after meals.
Evaluation is consistent with diabetic
gastroparesis. Which of the following is a
prokinetic drug that could be used in this
situation?
(A) Alosetron
(B) Cimetidine
(C) Loperamide
(D) Metoclopramide
(E) Sucralfate
25. 5HT3 ANTAGONISTS
Role of Serotonin in EMESIS
Vagal,spinal visceral afferents send
impulses to
NTS and CTZ.
Extrinsic primary
afferent neurones (PAN) of the
enteric nervous
system (ENS).
Release of 5-HT from
Enterochromaffin cells
5-HT spilled into
circulation
reach CTZ via
vascular route
Substance P
Bradykinin
Neurokinin
Cannabinoid
Opioid
27. PK
Absorbed well
Rapid onset of action
METABOLISM T1/2
Ondansetron CYP1A2, CYP2D6, and
CYP3A4
3-6 hours
Granisetron-
10times more
potent
CYP3A4 6-9 hours
Dolasetron Plasma carbonyl
reductase
to its active metabolite,
hydrodolasetron.CYP2
D6 and CYP3A4
7-9 hrs
Palonosetron CYP2D6, but also by
CYP3A4 and CYP1A2.
40 hrs
28. CLINICAL USES
Prevention and treatment of
Chemotherapy-induced nausea and
vomiting- Acute
Palanosetron even for delayed
Postoperative nausea and vomiting in
adults and children
Drug overdosage, g.i. disorders,
uraemia
Neurological injuries
29. ADVERSE EFFECTS
Well tolerated
Headache and dizziness.
Mild constipation and abdominal discomfort
occur in few patients.
Hypotension, bradycardia, chest pain and
allergic reactions are
PALANOSETRON – Additive Q-T
prolongation can occur when given
Cisapride, moxifloxacin, erythromycin, anti-
psychotics and antidepressants
30. NEUROKININ1 RECEPTOR
ANTAGONISTS
Substance P from
emetogenic stimuli
ActIvation of NK1 Receptor
at CTZ and NTS
1. Aprepitant
2. Rolapitant
3. Netupitant
DELAYED VOMITING
Always with SETRONS and
DEXAMETHASONE
31. APREPITANT
• Extensively
bound to plasma
proteins (>95%)
• Metabolized
primarily by
hepatic CYP3A4
• Excretion-
Stools
• t1/2 is 9–13hrs
ROLAPITANT
• t1/2 at about
180 h.
• CYP3A4 to form
an active
metabolite, M19
(C4-
pyrrolidinehydro
xylated
• rolapitant).
• Eliminated
mainly via the
hepatic/biliary
route.
• CYP2D6
INHIBITORS
NETUPITANT
• T1/2-~ 80 h;
• extensively
metabolized by
CYP3A4 (major)
and CYP2C9
and CYP2D6
• (minor) to active
metabolites.
• Urine and
faeces
32. THERAPEUTIC USES A/E
CINV,prior to highly
emetogenic drugs
Neutropenia,
Hiccups,
Decreased appetite
Dizziness
Rise in liver enzymes.
33. CANNABINOIDS
Dronabinol, Nabilone
Δ9 Tetrahydrocannabinol - Cannabis indica
Moderately emetogenic chemotherapy.
CB1 subtype of cannabinoid receptors
located on neurones in the CTZ and/ or the
vomiting centre itself.
Inhibits proemetic effects of endogenous
compounds such as dopamine and
serotonin
34. • Highly lipid soluble
• Onset – 2 hr
• Extensive first-pass
metabolism with limited
systemic bioavailability
after single doses (only
• 10%–20%).
• Faeces
• Large Vd
.
• CNS-central
sympathomimetic activity.
This can lead to
palpitations, tachycardia,
vasodilation, hypotension,
and conjunctival injection
(bloodshot eyes).
• Abstinence syndrome
(irritability, insomnia, and
restlessness)
• Marijuana-like “highs”
Prophylactic agent in patients
receiving cancer
chemotherapy when other
antiemetic medications are
not effective.
AIDS related cachexia
