Antiemetic Drugs
Dr. Ibrahim El-Shenbaby
MD, PhD Clinical pharmacology
Mansoura University
Horus University
Sultan Qaboos University
Whats:+2 01007418721
Tel: 93873136
Room: 0007 COMHS, SQU
Ext.: 1185
i.elshenbaby@squ.om
Objectives
1. Explain the neural pathways and pharmacologic receptors involved in
nausea and vomiting in order to understand the mechanisms by which
antiemetic drugs act.
2. List 3-4 classes of drugs used to control emesis.
3. Describe the mechanisms of action, clinical applications and main
adverse effects of some of the classes of antiemetic agents.
Pain,smell, sight
Fear &memory
Physiology of Emesis
Receptors involved in vomiting reflex

Muscarinic M1

Histaminergic H1

Dopaminergic D2

Serotoninergic 5HT3

NK1 receptor for substance P

Cannabinoids CB1 (agonists)
Several classes of antiemetic drugs are available that antagonize
these receptors.
The antiemetic drugs are classified according to their primary action; some
agents affect multiple receptors
Receptors involved
Antiemetic classes

Muscarinic M1
1) Muscarinic blockers

Histaminergic H1
2) H1-blockers

Dopaminergic D2
3) Dopamine blockers

Serotoninergic 5HT3
4) 5-HT3 blockers

NK1 receptor for substance P
5) NK1 blockers

Cannabinoids CB1
6) CBI partial agonists
7) Others (B6, BDZ, steroids)
1. Muscarinic blockers:

Atropine

Hyoscine
Antiemetic mechanism

They block M1 receptors in the vestibulocerebellar pathway, vomiting
center, and chemoreceptor trigger zone (CTZ).
Uses as antiemetic

Prevention and treatment of vomiting due to motion sickness.
Adverse effects

Blurred vision

Glaucoma

Dry mouth

Urine retention

Tachycardia
2. H1-blockers:

Diphenhydramine

Cyproheptadine

Cyclizine

Meclizine
Antiemetic mechanism

They block H1 (also M1) receptors in the vestibulocerebellar pathway,
vomiting center, and CTZ.

They have sedative action.
Uses as antiemetic

Vomiting due to motion sickness (diphenhydramine)

Vomiting of pregnancy (cyclizine and meclizine)

True vertigo: combined with VDs to improve labyrinthine blood
flow.
Adverse effects

Sedation (excitation may occur in children).

Atropine-like actions (dry mouth, blurred vision, urine retention).

Hypotension
3. 5-HT3 blockers:

Ondansetron

Granisetron

Tropisetron
Antiemetic mechanism

They block 5HT3 receptors in the GIT, vomiting center, and CTZ.
Uses as antiemetic

Vomiting due to cancer chemotherapy or radiotherapy.

Postoperative nausea and vomiting.
Adverse effects

Headache, dizziness, and constipation.
4. Dopamine blockers

Metoclopramide

Domperidone

Phenothiazines e.g. Chlorpromazine

Haloperidol
Antiemetic mechanism

They block D2 receptors in the CTZ
Uses as antiemetic

Vomiting due to cancer chemotherapy.

Postoperative nausea and vomiting.

Vomiting due to drugs or fevers.
Adverse effects

Extrapyramidal effects e.g. dystonia and dyskinesia.

Hyperprolactinemia

Sedation

Postural hypotension
5. Neurokinin-1 receptor blockers:

Aprepitant
Antiemetic mechanism

Substance-P induces vomiting through stimulation of NK-1 receptors.
Aprepitant blocks this receptor.
Uses as antiemetic

In combination with 5-HT3 blockers to treat vomiting due to cancer
chemotherapy
Adverse effects

Diarrhea and fatigue
6. Cannabinoid derivatives:

Nabilone and Dronabinol
Antiemetic mechanism

It is a partial agonist at central and peripheral cannabinoid receptors (CB1).

The exact mechanism is unclear.
Uses as antiemetic

Vomiting due to cancer chemotherapy

Patients refractory to other antiemetics.
Adverse effects

Hallucinations

Psychotropic effects

Drug abuse.

Sedation

Postural hypotension
7. Vitamin B6 (pyridoxin)
Antiemetic mechanism

May be related to the balance between GABA (CNS inhibitory
transmitter) and glutamate (CNS excitatory transmitter).
Uses as antiemetic

Vomiting in pregnancy (50 mg at bedtime).

Vomiting in children
8. Corticosteroids

Dexamethasone

Prednisolone
Antiemetic mechanism

The exact mechanism is unclear.
Uses as antiemetic

Combined with Vit B6 to treat vomiting in pregnancy.

Vomiting due to cancer chemotherapy.
Adverse effects

Most of these side effects occur after long duration of therapy:
a.
Iatrogenic Cushing syndrome: occurs if doses up to 100 mg
hydrocortisone are used daily for > 2 weeks. It is characterized by moon
face, buffalo hump, thin limbs, osteoporosis, hypertension, DM, edema, etc.
b.
Immune suppression → flaring of infections (especially viral &TB).
c.
Hypertension due to salt & water retention
d.
Hyperglycemia.
e.
Peptic ulcer: due to prolonged inhibition of gastroprotective PGs.
f. ↑ IOP (Glaucoma): due to ↓ Aqueous humor drainage.
g. Osteoporosis.
h. Growth retardation in children.
i. Skin atrophy & hypopigmentation after prolonged topical use.
j. Sudden withdrawal after prolonged administration causes acute
addisonian crisis
9. Benzodiazepines

Lorazepam

Diazepam
Antiemetic mechanism

Allosteric facilitation of central GABA inhibitory transmission
Uses as antiemetic


Stress-related vomiting
To controls symptoms in Ménière disease
Adverse effects
– Physical dependence (treated by gradual withdrawal)
– Paradoxical or rebound excitement.
– Apnea after rapid i.v. injection (flumazenil is the antidote)
– Tolerance.