Classification by blocked receptor type
Antiemetics are divided into several pharmacological groups depending on the specific receptors they bind to:
- $D_2$ dopamine receptor antagonists: metoclopramide, domperidone, thiethylperazine.
- $5-HT_3$ serotonin receptor antagonists: ondansetron, tropisetron, granisetron.
- $H_1$ histamine receptor antagonists: meclozine.
- Muscarinic acetylcholine receptor antagonists: scopolamine, Aeron.
Dopamine receptor antagonists
This group is widely used in clinical practice, but the drugs differ significantly in their ability to cross the blood-brain barrier (BBB).
Metoclopramide has a mixed mechanism of action. In the CNS, it blocks $D_2$ and $5-HT_3$ receptors in the trigger zone. In the periphery, it acts as a prokinetic: it stimulates gastric motility, increases lower esophageal sphincter tone, and relaxes the pylorus. The onset of action is rapid (5–15 minutes). The drug relieves hiccups and is effective against postoperative and radiation-induced vomiting, as well as vomiting caused by cardiac glycosides or cytostatics. Due to BBB penetration, it may cause extrapyramidal symptoms and endocrine disorders (hyperprolactinemia, amenorrhea, gynecomastia). It is contraindicated during lactation and in muscle dyskinesia.
Domperidone is a selective peripheral antagonist. It crosses the BBB poorly, making it virtually free of central adverse effects. This makes it the drug of choice for vomiting induced by dopaminergic agents (e.g., in Parkinson's disease treatment). It is used for dyspepsia and delayed gastric emptying. Contraindicated in children under 5 years of age.
Thiethylperazine is a phenothiazine derivative with potent central action. It directly suppresses the vomiting center and the trigger zone. It is prescribed in courses (2–4 weeks) for vestibular disorders and motion sickness. It has a wide range of adverse reactions, from dry mouth and tachycardia to drowsiness, speech disorders, and hypotension. Contraindicated in children under 15 years of age, pregnant women, and patients with depression, coma, or acute glaucoma.
Serotonin receptor antagonists
The main representative of this group is ondansetron. The drug blocks $5-HT_3$ receptors both peripherally and in the central nervous system.
Its specific clinical niche is the prevention and treatment of severe emesis induced by cytostatic therapy (chemotherapy) and radiation therapy in cancer patients. The drug is highly effective, but has strict limitations: it is contraindicated in the first trimester of pregnancy and during lactation. Common adverse effects include cephalgia, constipation, dizziness, and arterial hypotension.
Histamine and muscarinic receptor antagonists
Drugs from these groups are particularly relevant for kinetosis (motion sickness) and vestibular disorders.
Meclozine provides combined blockade of central $H_1$ histamine and $M_1$ muscarinic receptors. It is characterized by a rapid onset and a very long duration of action (about 24 hours). It is used for air and motion sickness, as well as for radiation-induced vomiting.
Aeron is a combination drug consisting of camphoric acid salts of alkaloids (scopolamine and hyoscyamine). It exerts central and peripheral anticholinergic effects. It is effective for the prevention of motion sickness and the relief of sudden vertigo attacks in Ménière's disease. However, it causes typical atropine-like effects (thirst, dry mouth) and is strictly contraindicated in glaucoma due to the risk of increased intraocular pressure.
Briefly: answers to topical questions
Which antiemetic drugs are phenothiazine derivatives?
Thiethylperazine is an antiemetic drug that belongs to phenothiazine derivatives.
- Thiethylperazine is an effective centrally acting antagonist that directly suppresses the activity of the vomiting center and the trigger zone.
Its mechanism of action is based on the blockade of central $\text{D}_2$ receptors. The drug is used for vomiting of any origin and vestibular disorders (dizziness, motion sickness).
What adverse effects are typical for ondansetron?
Ondansetron is associated with several adverse effects involving the nervous, cardiovascular, and digestive systems. These include:
- Cephalgia (headache);
- Dizziness;
- Arterial hypotension;
- Constipation — occurs because repeated use slows down bowel motility;
- Allergies — various allergic reactions.
At the same time, ondansetron does not affect the patient's motor coordination and performance.
What types of receptors are present in the chemoreceptor trigger zone of the vomiting center?
The chemoreceptor trigger zone of the vomiting center contains two main types of receptors. According to the receptor map, this trigger zone contains:
- Dopamine receptors ($D_2$ receptors);
- Serotonin receptors ($5-HT_3$ receptors).
These receptors respond to chemical agents in the blood and cerebrospinal fluid, and their blockade by specific drugs (e.g., metoclopramide) provides a central antiemetic effect.
Which antiemetics belong to the group of $NK_1$ receptor antagonists?
Neurokinin-1 ($NK_1$) receptor antagonists include the following antiemetic drugs:
- Aprepitant — a selective, high-affinity centrally acting antagonist that binds to brain receptors and is administered orally;
- Fosaprepitant — a prodrug designed for intravenous administration.
These agents inhibit both the acute and delayed phases of emesis and enhance the antiemetic activity of glucocorticoids and $5-HT_3$ receptor antagonists.
To memorize domperidone's safety profile: "Domperidone = PERIPHERY home." It works predominantly in the periphery (crosses the BBB poorly), making it safe for patients with Parkinson's disease because it does not block the central dopamine they need.
Class and exam questions
Why is metoclopramide contraindicated in suspected GI perforation?
Metoclopramide has a pronounced prokinetic effect — it actively stimulates propulsive gastric motility. In ulcers, bleeding, or perforations, enhanced peristalsis can lead to a sharp deterioration in the patient's condition.
Which drug should be chosen to manage chemotherapy-induced nausea and vomiting?
The drugs of choice in oncological practice are $5-HT_3$ receptor antagonists (e.g., ondansetron, tropisetron). They specifically and effectively suppress the emetic reflex induced by cytostatics.
What is the main difference between domperidone and metoclopramide?
Domperidone practically does not cross the blood-brain barrier. Due to this, it does not cause central extrapyramidal symptoms that are characteristic of metoclopramide and neuroleptics.
Can aeron be used in glaucoma?
No, Aeron is strictly contraindicated in glaucoma. As an anticholinergic agent, it can increase intraocular pressure, which may trigger an acute attack of the disease.
What else to study on this topic
- Mechanism of extrapyramidal symptoms development during the administration of central $D_2$ antagonists.
- Endocrine adverse effects of antiemetics: pathogenesis of hyperprolactinemia, amenorrhea, and gynecomastia.
- Specifics of antiemetic use in pregnant women (treatment of nausea and vomiting of pregnancy).
- Pharmacokinetics of ondansetron and its analogues (tropisetron, granisetron).
- The role of prokinetics in the management of dyspeptic syndrome and delayed gastric emptying.
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