Domperidone is a drug with antiemetic and prokinetic properties, that is, it prevents vomiting and improves intestinal transit. Here we will explain in more detail different aspects about this drug:
- Mechanism of action
- Pharmacological actions
- Adverse reactions
Mechanism of action
Domperidone is a drug with a structure similar to that of butyrophenones (known antipsychotics) that acts peripherally. By not crossing the , it binds to its receptors in the postrema area.
The postrema area is a medullar structure that is located in the brain stem and is responsible for controlling vomiting.
The receptors to which domperidone binds belong to the neurotransmitter dopamine, specifically the D2 dompaminergic receptors. This drug performs an antagonistic action by binding to these receptors, which means that it will prevent the binding of dopamine with its own receptor , thereby inhibiting the physiological actions characteristic of this neurotransmitter.
Domperidone is mainly administered orally , although it also accepts the rectal route. What is not possible is its administration parenterally because it produces serious adverse effects on the heart.
The oral administration is justified by its good fasting absorption reaching its maximum concentration in blood at 30/60 minutes. Although absorbed so well, the bioavailability of the drug will be reduced by the strong metabolism suffered at the liver , which is known as a first-pass effect.
This metabolism is carried out by enzymatic systems of the liver. Enzymatic complexes will trigger hydroxylation and N-dealkylation reactions on domperidone, giving rise to secondary molecules with no biological activity. Other interesting features about this drug are:
- It binds to plasma proteins between 91-93%, so you have to be careful about the interactions you may suffer.
- It is not able to cross the blood-brain barrier and hardly the placenta . This property decreases extrapyramidal effects and adverse reactions.
- The bioavailability of domperidone increases if it is administered with meals.
- It is eliminated mainly via urine and fecal. Patients with severe renal impairment may have increased drug concentrations so they should consult their doctor.
The antiemetic effects characteristic of domperidone are due to a combination of different actions. On the one hand, it has a peripheral gastrokinetic action in the wall of the digestive tract that will accelerate the transit , increasing the speed of gastric emptying and improving the function of the sphincters. On the other hand, its antagonism on the receptors of dopamine D2 in the posterma area, which manages to inhibit vomiting.
Another action that triggers this drug is the stimulation of prolactin secretion in the pituitary gland. Prolactin is the hormone responsible for the production of milk in the mammary gland. In short, domperidona presents actions:
- Antiemetics : inhibits the vomiting center.
- Prokinetic : helps prevent vomiting and improves intestinal transit in general. It is used in the treatment of diseases that occur with gastroesophageal reflux, associated with serotonin 5-HT2 receptor antagonists.
- It favors the production of milk in the breasts .
Domperidone presents quite important adverse reactions at the cardiac level. These reactions motivated his withdrawal from parenteral administration presentations a few years ago, which is why his main route of administration is oral. The adverse effects produced by this drug at the level of the myocardium are mainly ventricular arrhythmias that can have a fatal outcome. As well, the people who have the greatest risk of suffering these adverse effects are:
- In people older than 60 years.
- Patients who are taking high doses of domperidone will also be more likely to suffer these effects.
- People who are being medicated with other drugs that are also susceptible to trigger these reactions.
Apart from arrhythmias, which is the most serious undesirable effect, may cause, among others, diarrhea, drowsiness or pruritus. However, these adverse effects are very rare.
Visit this article: Cardiac arrhythmia: symptoms and consequences
Patients who are being medicated with domperidone and in turn with another drug should be cautious depending on the drug that is. This is because there are medications that can increase the concentration of domperidone in the blood, which would increase the possibility of suffering from these undesirable side effects. The main groups of drugs that can interact negatively with domperidone are:
- Inhibitors of hepatic metabolism : ketoconazole, for example, is an antifungal agent capable of inhibiting enzymatic complexes of the liver, which are responsible for metabolizing domperidone. Being inhibited the drug will remain in its active form longer, which will increase its effects increasing the likelihood of triggering adverse reactions.
- Drugs that prolong the QT interval : the prolongation of the QT interval can be the origin of a polymorphic ventricular tachycardia, known as Torsades de Pointes. These effects can be added to the cardiac problems presented by domperidone, which can cause sudden cardiac death in the patient.