Antiemetic and emetic drugs

Antiemetic and emetic drugs

Antiemetics and emetics are two groups of drugs with opposing actions. Antiemetic drugs decrease nausea, reducing the urge to vomit. Emetic drugs, which are derived from plants, produce vomiting.

Antiemetics

The major antiemetics are:

• antihistamines, including buclizine, cyclizine, dimenhydrinate, diphenhydramine, hydroxyzine hydrochloride, hydroxyzine pamoate, meclizine, and trimethobenzamide
• phenothiazines, including chlorpromazine, perphenazine, prochlorperazine maleate, promethazine, and thiethylperazine maleate
• serotonin 5-HT₃ receptor antagonists, including dolasetron, granisetron, and ondansetron.

Top of the charts

Ondansetron is currently the antiemetic of choice in the United States.

Pharmacokinetics

The pharmacokinetic properties of antiemetics may vary slightly.

Absorption, metabolism, and excretion

Oral antihistamine antiemetics are absorbed well from the GI tract and are metabolized primarily by the liver. Their inactive metabolites are excreted in urine.

Phenothiazine antiemetics and serotonin 5-HT₃ receptor antagonists are absorbed well, extensively metabolized by the liver, and excreted in urine and stool.

Pharmacodynamics

The action of antiemetics may vary.

What’s going on here?

The mechanism of action that produces the antiemetic effect of antihistamines is unclear.

Don’t pull the trigger!

Phenothiazines produce their antiemetic effect by blocking the dopaminergic receptors in the chemoreceptor trigger zone in the brain. (This area of the brain, near the medulla, stimulates the vomiting center in the medulla, causing vomiting.) These drugs may also directly depress the vomiting center.

Stopping serotonin stimulation

The serotonin 5-HT₃ receptor antagonists block serotonin stimulation centrally in the chemoreceptor trigger zone and peripherally in the vagal nerve terminals, both of which stimulate vomiting.

Pharmacotherapeutics

The uses of antiemetics may vary.

Lend me your ear

Antihistamines are specifically used for nausea and vomiting caused by inner ear stimulation. As a consequence, these drugs prevent or treat motion sickness. They usually prove most effective when given before activities that produce motion sickness and are much less effective when nausea or vomiting has already begun.

 

Other antiemetics

Here are other antiemetics currently in use.

Scopolamine

Scopolamine prevents motion sickness, but its use is limited because of its sedative and anticholinergic effects. One transdermal preparation, Transderm-Scō p, is highly effective without producing the usual adverse effects.

Metoclopramide

Metoclopramide is used primarily to treat GI motility disorders including gastroparesis in diabetic patients. It’s also used to prevent chemotherapy-induced nausea and vomiting.

Diphenidol

Diphenidol is used to prevent vertigo (whirling sensation) and to prevent or treat generalized nausea and vomiting. However, its use is limited because of the auditory and visual hallucinations, confusion, and disorientation that may occur.

Dronabinol

Dronabinol, a purified derivative of cannabis, is a Schedule II drug (meaning it has a high potential for abuse) used to treat chemotherapy-induced nausea and vomiting in the patient who doesn’t respond adequately to conventional antiemetics. It has also been used to stimulate appetite in the patient with acquired immunodeficiency syndrome. However, dronabinol can accumulate in the body, and the patient can develop tolerance or physical and psychological dependence.

Severe cases

Phenothiazine antiemetics and serotonin 5-HT₃ receptor antagonists control severe nausea and vomiting from various causes. They’re used when vomiting becomes severe and potentially hazardous, such as postsurgical or viral nausea and vomiting. Both types of drugs are also prescribed to control the nausea and vomiting resulting from chemotherapy and radiotherapy. 

 

Drug interactions

Antiemetics may have many significant interactions.

• Antihistamines and phenothiazines can produce additive CNS depression and sedation when taken with CNS depressants, such as barbiturates, tranquilizers, antidepressants, alcohol, and opioids.
• Antihistamines can cause additive anticholinergic effects, such as constipation, dry mouth, vision problems, and urine retention, when taken with anticholinergic drugs, including tricyclic antidepressants, phenothiazines, and antiparkinsonian drugs.
• Phenothiazine antiemetics taken with anticholinergic drugs increase the anticholinergic effect and decrease the antiemetic effects.
• Droperidol used with phenothiazine antiemetics increases the risk of extrapyramidal (abnormal involuntary movements) effects.

Warning!

Adverse reactions to antiemetics

Use of these antiemetic drugs may lead to adverse reactions:

• Antihistamine and phenothiazine antiemetics produce drowsiness and sometimes paradoxical central nervous system (CNS) stimulation.
• CNS effects associated with phenothiazine and serotonin 5-HT₃ receptor antagonist antiemetics include confusion, anxiety, euphoria, agitation, depression, headache, insomnia, restlessness, and weakness.
• The anticholinergic effect of antiemetics may cause constipation, dry mouth and throat, painful or difficult urination, urine retention, impotence, and visual and auditory disturbances.
• Phenothiazine antiemetics commonly cause hypotension and orthostatic hypotension with an increased heart rate, fainting, and dizziness.