Antiemetics. Vomiting :The act of vomiting and the sensation of nausea that accompanies it are protective reflexes that serve to rid the stomach and intestine of toxic substances and prevent their further ingestion. Pathophysiology of Emesis. Cerebral cortex. Cancer chemotherapy Opioids.
Vomiting :The act of vomiting and the sensation of nausea that accompanies it are protective reflexes that serve to rid the stomach and intestine of toxic substances and prevent their further ingestion
Chemoreceptor Trigger Zone (CTZ)
Vomiting Centre (medulla)
Muscarinic Histaminic H1
Muscarinic, 5 HT3 & Histaminic H1
5 HT3,,Opioid Receptors
Chemo & radio therapy Gastroenteritis
Pharynx & GIT
5 HT3 receptors
1- Chemotherapy-induced vomiting
2- Post irradiation vomiting
3- Postoperative vomiting
4- Vomiting of pregnancy
5- Motion sickness
Group of drugs used as antiemetics
Serotonin 5 HT3 Antagonists:
Dopamine D2 Antagonist:
Mechanism of action:
1- Peripheral 5-HT3 receptor blockade on intestinal vagal afferents.
2- Central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone
Antiemetic action is mainly against:
Emesis mediated by vagal stimulation (e.g. postoperative and chemotherapy)
High first pass metabolism
Excreted by liver & kidney
No dose reduction in renal insufficiency but needed in hepatic insufficiency
The most common adverse effects are:
1- Headache and dizziness
2- Constipation or diarrhoea
Chemotherapy induced nausea and vomiting
postradiation nausea & vomiting
Vomiting of pregnancy
Corticosteroids have antiemetic properties
Mechanism of action: possibly by suppressing peritumoral inflammation and prostaglandin production.
Use: to enhance efficacy of 5HT3 receptor antagonists in the treatment of chemotherapy-induced vomiting.
Mechanism of antiemetic action: Centraldopamine-receptor blockade
Side effects: (mainly extrapyramidal):
prevention or treatment of motion sickness.
Adverse effects: sedation, dizziness,confusion, dry mouth, cycloplegia, and urinary retention.
readily absorbed after oral administration
It undergoes extensive first-pass metabolism with limited systemic bioavailability after single doses Mmetabolites are excreted primarily via the biliary-fecal route
For the prevention of chemotherapy-induced nausea and vomiting
Neurogenic control of GIT moyility: the ENS
Neurons in both plexuses release acetylcholine at their terminals.
Parasympathetic : act by releasing acetylcholine at nerve terminals. It causes contraction of muscles in the wall of the intestine and relaxation of the sphincters and increases gland secretion
Sympathetic: act by releasing norepinephrine at nerve terminals. It causes relaxation of muscles in the wall of the intestine and contraction of the sphincters
Types of cholinergic receptors are M2 and M3 (present in the GIT in a 4:1 ratio). M3 receptor is more important in muscle contraction.
1- Cholinergic agents
Stimulate cholinergic receptors. Enhance contractions in an uncoordinated manner that produces no net propulsive activity. Not useful for treating motility disorders
enhance coordinated GIT propulsive motility. Prokinetic agents act at receptor sites on the motor neuron itself increasing the release of acetylcholine at the motor nerve terminal without interfering with the normal physiological pattern and rhythm of motility. Useful for treating motility disorders
1- ACh is not used pharmacologically because:
Acetylcholinesterase Inhibitors. These drugs inhibit the degradation of ACh , allowing ACh to accumulate at sites of release.
Decreased motility of the GIT results from suppression of ACh release from myenteric motor neurons mediated by stimulation of D2 dopaminergic receptors.
1- Antagonize the inhibitory effect of dopamine on myenteric motor neurons,
2- Relieve nausea and vomiting by antagonism of dopamine receptors in the chemoreceptor trigger zone
1- Enhance coordinated GIT propulsive motility of the upper digestive tract where it increases lower esophageal sphincter tone and stimulates antral and small intestinal contractions. Metoclopramide has no clinically significant effects on motility of the colon.
2- Antiemetic action:
1- Oral (rapid absorption)
2- I.m. in cases of nausea and vomiting
3- I.v. infusion in chemotherapy-induced vomiting
1- Extrapyramidal effects(more commonly in children and young adults and at higher doses).
2- Galactorrhea by blocking the inhibitory effect of dopamine on prolactin release (infrequent)
1-Enhance coordinated GIT propulsive motility of the upper digestive tract where it increases lower esophageal sphincter tone and stimulates antral and small intestinal contractions. It has no clinically significant effects on motility of the colon.
Mechanism of action:
dopamine D2 receptor antagonist
2- Antiemetic action
Mechanism of action:
dopamine D2 receptor antagonist (of D2 receptors in CTZ which is outside BBB)