Download Antiemetic drugs

Antiemetic drugs
1. Muscarinic blockers
• Atropine , Hyoscine
Antiemetic mechanism:
• They block M1 receptors in the vestibulocerebellar
pathway and CTZ.
Uses as antiemetic :
• Prevention (and less effectively to treat) vomiting
due to motion sickness
Adverse effects; antimuscarinic side effects
2. H1-blockers
• Diphenhydramine, Cyclizine, Meclizine
Antiemetic mechanism:
• They block H1 (also M1) receptors in the vestibulocerebellar
pathway and CTZ.
Uses as antiemetic
• Vomiting due to motion sickness
• Vomiting of pregnancy
• Vertigo
Adverse effects:
• Sedation (excitation may occur in children).
• Atropine-like actions
• Hypotension (block alpha1)
3. 5-HT3 blockers
• Ondansetron
Antiemetic mechanism:
• Competitively block 5HT3 receptors in the GIT and CTZ.
Uses as antiemetic:
• Vomiting due to cancer chemotherapy or radiotherapy.
• Postoperative nausea and vomiting.
• Not effective against motion sickness
Adverse effects:
• Generally are well tolerated
• Dizziness, headache, and constipation.
• Prolong QT interval, torsade de points is reported
especially if co-administered with another drug that
prolong the QT interval
4. Dopamine blockers
• Benzamides; (Metoclopramide, Domperidone)
• Phenothiazines (e.g. Prochlorperazine, chlorpromazine)
Antiemetic mechanism:
• Benzamide
– Metoclopramide causes central and peripheral dopamine
D2 antagonism
– Domperidone is a D2-blocker with selective peripheral
activity in the upper gastrointestinal tract.
• Phenothiazines
– Antagonizing D2-dopamine receptors in the area
postrema of the midbrain, also block M, H1
Uses:
• Vomiting due to drugs or febrile illness
• Vomiting due to cancer chemotherapy.
• Postoperative nausea and vomiting.
Adverse effects:
• Benzamides;
– Metoclopramide; (anxiety, restlessness, and
depression, hyperprolactinemia, irreversible tardive
dyskinesia and QT interval prolongation
– Domperidone; it does not cross the blood-brain
barrier and therefore lacks the neurologic side
effects of metoclopramide
• Phenothiazine
– Sedation, Hyperprolactinemia, Postural hypotension
– Extrapyramidal effects e.g. dystonia and dyskinesia
5. Cannabinoids
• Dronabinol
Antiemetic mechanism:
• It is a cannabinoid receptor agonist.
• the drug likely activates specific cannabinoid receptors
in the vomiting center, which results in decreased
excitability of target neurons
Uses as antiemetic:
• Vomiting due to cancer chemotherapy
• Patients refractory to other antiemetics.
Adverse effects:
• Sedation
• Paranoia
• Dysphoria
• Hypotension
• Drug abuse.
NB;
• The modest antiemetic activity of this and their
relatively unfavorable side effect profile, especially in
older patients, has limited their clinical use.
6. Vitamin B6
• Pyridoxine is a water-soluble vitamin
Antiemetic mechanism:
• Is unknown
Uses as antiemetic:
• Vomiting in pregnancy. Pyridoxine has a good safety
profile with minimal side effects
• Vomiting in children
7. Corticosteroids
• Dexamethasone the commonest steroid used
Antiemetic mechanism;
• The exact mechanism is unclear.
Uses as antiemetic:
• Effective and well-tolerated antiemetic for chemotherapy
induced emesis
8. Neurokinin-1 receptor blockers
• Aprepitant
Antiemetic mechanism
• Neurokinin 1 (NK1) receptor antagonist on nucleus of tractus
solitaries and Visceral afferent nerves
• So it prevent both peripheral and central stimulation of the
vomiting center
Uses as antiemetic:
• In combination with 5-HT3 blockers to treat vomiting due to
cancer chemotherapy
Adverse effects:
• Diarrhea and fatigue
• Inhibit CYP3A4 so increase the level of many drugs
Prokinetic Drugs
• A gastroprokinetic agent, gastrokinetic,
or prokinetic, is a type of drug which
enhances gastrointestinal motility by increasing
the frequency of contractions in the small
intestine or making them stronger, but without
disrupting their rhythm.
• They are used to treat irritable bowel
syndrome,
gastritis,
acid
reflux
disease, gastroparesis, and functional dyspepsia.
1. Cholinomimetic agents
• Not commonly used
A. Cholinomimetic agonists;
– Bethanechol stimulate muscarinic M3 receptors on
smooth muscle cells and at myenteric plexus
synapses. Due to multiple cholinergic effects and the
advent of less toxic agents, it is now seldom used.
B. The acetylcholinesterase inhibitor:
– Intravenous neostigmine can be used in the
treatment of acute large bowel distention .
– Cholinergic effects include excessive salivation,
nausea, vomiting, diarrhea, and bradycardia.
2. D2 receptor antagonists.
Mechanism of action
• Metoclopramide and domperidone are dopamine D2
receptor antagonists.
Pharmacological action
• Increase esophageal peristaltic amplitude
• Increase lower esophageal sphincter pressure
• Enhance gastric emptying
• Have no effect on small intestine or colonic motility.
• Antinausea and antiemetic action.
Therapeutic Uses
1. Impaired Gastric Emptying due to postsurgical disorders
(vagotomy, antrectomy) and diabetic gastroparesis.
2. Prevention and treatment of emesis.
3. Gastroesophageal
Reflux
Disease
(GERD):
Metoclopramide is used mainly in combination with acid
suppressors in patients with regurgitation or refractory
heartburn.
3. Macrolides
• Macrolide antibiotics such as erythromycin directly
stimulate motilin receptors on gastrointestinal
smooth muscle and promote gastric peristalsis,
however, tolerance rapidly develops.
• It may be used in patients with acute upper
gastrointestinal hemorrhage to promote gastric
emptying of blood prior to endoscopy.
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