Dolasetron
Encyclopedia
Dolasetron is a serotonin
5-HT3 receptor antagonist
used to treat nausea
and vomiting
following chemotherapy
. Its main effect is to reduce the activity of the vagus nerve
, which is a nerve that activates the vomiting center in the medulla oblongata
. It does not have much antiemetic
effect when symptoms are due to motion sickness. This drug does not have any effect on dopamine
receptors or muscarinic receptors.
Dolasetron breaks down slowly, staying in the body for a long time. One dose usually lasts 4 to 9 hours and is usually administered once or twice daily. This drug is removed from the body by the liver
and kidney
s.
. Headache, dizziness, and constipation are the most commonly reported side effects associated with its use. There is a potential for prolonging of the QT interval to occur as well. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver
's cytochrome P450
system and it has little effect on the metabolism of other drugs broken down by this system.
Intravenous dolasetron is contraindicated in Chemotherapy-induced nausea and vomiting (CINV). Doxorubicin and cyclophosphamide are as emetogenic as cisplatin, and preventive drugs should always be considered. The 5HT3 agonists are the mainstays of prevention and are frequently used in combination with other drugs such as corticosteroids and the NK1 receptor antagonist aprepitant. However, the FDA recently issued a drug communication stating that the injection form of dolasetron, a 5HT3 agonist, should no longer be used in adult or pediatric patients with CINV. Dolasetron injection can increase the risk of developing torsade de pointes, a potentially fatal abnormal heart rhythm. Patients with underlying heart conditions or existing heart rate or rhythm problems are at increased risk. Although the oral form of this agent can still be used, careful monitoring and correction of potassium and magnesium levels should be initiated prior to and during treatment. In addition, in older patients and in patients with heart failure, a slow heart rate, underlying cardiac disease, and those with renal impairment, monitoring with electrocardiography is indicated when this drug is used. Congenital long-QT syndrome and drugs that prolong the PR or QRS interval are contraindications to dolasetron therapy. Dolasetron injection may still be used for the prevention and treatment of postoperative nausea and vomiting. As per Food and Drug Administration.
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
5-HT3 receptor antagonist
5-HT3 antagonist
The 5-HT3 antagonists are a class of medications that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain....
used to treat nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
following chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. Its main effect is to reduce the activity of the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
, which is a nerve that activates the vomiting center in the medulla oblongata
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...
. It does not have much antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
effect when symptoms are due to motion sickness. This drug does not have any effect on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
receptors or muscarinic receptors.
Dolasetron breaks down slowly, staying in the body for a long time. One dose usually lasts 4 to 9 hours and is usually administered once or twice daily. This drug is removed from the body by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s.
Clinical uses
- ChemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
-induced nausea and vomiting- 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenousIntravenous therapyIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
ly about 30 minutes before beginning therapy.
- 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenous
- Post-operativePostoperative nausea and vomitingPostoperative nausea and vomiting is an unpleasant complication affecting about a third of the 10% of the population undergoing general anaesthesia each year. This equates to about two million people in the United Kingdom annually.-Impact:...
and post-radiation nausea and vomiting - Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritisGastroenteritisGastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...
- Unlike most other 5HT3 antagonists, data is lacking for use of dolasetron with aprepitant in chemotherapy-induced nausea and vomiting (CINV).
- It is also sometimes used as an antiemetic (anti-vomiting medication) in veterinary medicine for dogs and cats.
Adverse effects
Dolasetron is a well-tolerated drug with few side effectsAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
. Headache, dizziness, and constipation are the most commonly reported side effects associated with its use. There is a potential for prolonging of the QT interval to occur as well. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
's cytochrome P450
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
system and it has little effect on the metabolism of other drugs broken down by this system.
Intravenous dolasetron is contraindicated in Chemotherapy-induced nausea and vomiting (CINV). Doxorubicin and cyclophosphamide are as emetogenic as cisplatin, and preventive drugs should always be considered. The 5HT3 agonists are the mainstays of prevention and are frequently used in combination with other drugs such as corticosteroids and the NK1 receptor antagonist aprepitant. However, the FDA recently issued a drug communication stating that the injection form of dolasetron, a 5HT3 agonist, should no longer be used in adult or pediatric patients with CINV. Dolasetron injection can increase the risk of developing torsade de pointes, a potentially fatal abnormal heart rhythm. Patients with underlying heart conditions or existing heart rate or rhythm problems are at increased risk. Although the oral form of this agent can still be used, careful monitoring and correction of potassium and magnesium levels should be initiated prior to and during treatment. In addition, in older patients and in patients with heart failure, a slow heart rate, underlying cardiac disease, and those with renal impairment, monitoring with electrocardiography is indicated when this drug is used. Congenital long-QT syndrome and drugs that prolong the PR or QRS interval are contraindications to dolasetron therapy. Dolasetron injection may still be used for the prevention and treatment of postoperative nausea and vomiting. As per Food and Drug Administration.
See also
- 5-HT3 receptor antagonist: Drug discovery and development