Phenytoin

Benjamin Clanner-Engelshofen is a freelance writer in the medical department. He studied biochemistry and pharmacy in Munich and Cambridge / Boston (USA) and noticed early on that he particularly enjoyed the interface between medicine and science. That is why he went on to study human medicine.

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The active ingredient phenytoin is used to treat epilepsy, cardiac arrhythmias and nerve pain (neurogenic pain). Since it is essential for some clinical pictures, the World Health Organization has added phenytoin to the list of essential medicines. Here you can read everything you need to know about phenytoin: effect, use and side effects.

This is how phenytoin works

The disease epilepsy is intensively researched worldwide, but not all mechanisms by which the disease develops are known. However, the various manifestations of epilepsy are mostly due to a "malfunction" in the brain. Individual nerve cells (neurons) or entire associations of nerve cells in the brain suddenly send out high-frequency signals that reach other brain regions via the nerve cell extensions. This overexcitation of neurons can be limited to individual areas in the brain (focal seizure, focal seizure) or not limited (generalized seizure). The rapid transmission of signals along the neuronal processes is based on the influx of sodium ions. This process can be inhibited with active ingredients such as phenytoin: some of the sodium channels are blocked in the process. This prevents the overexcited areas of the brain from reaching further areas and reduces the risk of having a seizure.

Sodium ions are also used in the heart to transmit signals. By blocking the sodium channels, phenytoin can stop the cardiac arrhythmias triggered by too fast signals and thus normalize the heart rhythm.

Experts assume that the relief of nerve pain (neurogenic pain) with phenytoin is based on a blockage of the sodium channel: This inhibits the transmission of pain signals.

Ingestion, breakdown and excretion of phenytoin

After ingestion, the active ingredient is absorbed in the intestine. Since it is not readily soluble in water, it is transported in the blood with the help of transport proteins (albumin). Phenytoin is broken down in the liver and then largely excreted in the stool with the bile. The time until half of the absorbed dose is excreted depends on the blood level of the active ingredient, but is usually between 20 and 60 hours.

When is phenytoin used?

The active ingredient phenytoin is approved as an anti-epileptic for the treatment of certain types of seizures. These include focally initiated generalizing and generalized tonic-clonic seizures, simple and complex partial seizures, and combinations of these types of seizures. Phenytoin can also be used in acute seizures as well as in "status epilepticus", ie a particularly long seizure. It is also approved for the prevention and treatment of seizures during neurosurgical operations and for severe brain trauma.

As a second choice, phenytoin can be used to relieve nerve pain.

The treatment of cardiac arrhythmias with phenytoin is what is known as “off-label use”, i.e. an application outside the licensing area.

This is how phenytoin is used

To treat and prevent epileptic seizures, phenytoin is usually taken in one to three single doses per day, with a total daily dose of 300 milligrams of phenytoin. At the beginning of the treatment, the dosage is "creeping in", so a very low dosage is administered first, which is then slowly increased. Higher dosages may be necessary for more severe forms of the disease. The dose increase - especially if the dosage is increased quickly - may only be carried out under medical supervision. The tablets should be swallowed with a glass of water. In the case of long-term use, the total daily dose can be divided into one or two individual doses.

The duration of use depends on the reason for taking it; it can be short-term (for neurosurgical operations) or long-term (for symptom control in epilepsy).

What are the side effects of phenytoin?

Many adverse drug reactions are dose-dependent when treated with phenytoin. Therefore, the dosage is usually chosen by the doctor in such a way that, if possible, there are few or no side effects.

Skin changes such as excessive pigmentation and hair growth can occur in one in one hundred to one thousand patients. Gum growth is also possible.

Rare phenytoin side effects include changes in the blood count, severe cardiac arrhythmias, liver disorders and allergic reactions (rash, itching, swelling). If allergic reactions occur, phenytoin should be discontinued and a doctor should be contacted.

What should be considered when taking phenytoin?

Additionally taken active ingredients can interact with phenytoin. This is often the case when both active ingredients are transported or broken down in the body via the same routes. As a result, phenytoin can either be broken down more quickly or with a delay.

The combination with certain antibiotics (ciprofloxacin, rifampicin), anti-epileptic drugs (vigabatrin, primidon), HIV drugs (lopinavir, ritonavir) and other active ingredients (dexamethasone, theophylline) can lead to an increased breakdown of phenytoin and thus to a reduction in its effect. come. Alcohol abuse and folic acid (vitamin B9) can also reduce the effect of phenytoin.

Delayed breakdown of phenytoin can cause its blood levels to rise dangerously. This is possible, for example, when certain antibiotics (chloramphenicol, erythromycin, sulfonamides), anti-epilepsy drugs (valproate, topiramate, oxcarbazepine), pain relievers (acetylsalicylic acid, phenylbutazone, propyphenazone), antidepressants (fluoxetine, amipriptyline), and anti-pilzine drugs are taken at the same time (Ketoconazole, Fluconazole, Amphotericin B).

Phenytoin stimulates the production of the drug-degrading enzyme cytochrome P450 3A4. This means that active substances that are metabolized via this enzyme are broken down more quickly. This affects numerous different drugs, which is why the simultaneous use of phenytoin and other drugs should always be clarified with a doctor or pharmacist beforehand.

The anti-epileptic phenytoin must not be stopped suddenly, as this can lead to an accumulation of seizures and the occurrence of status epilepticus.

Depending on the dose, phenytoin can lead to malformations in the unborn child. In pregnant women with epilepsy, the dose should therefore be reduced to a maximum, depending on the severity of the disease, in order to achieve freedom from seizures as safely as possible. In addition, phenytoin should not be combined with other anti-epileptic drugs during pregnancy.

Only small amounts of phenytoin pass into breast milk, so weaning is not necessary. However, the infant should always be monitored to ensure that he is steadily gaining weight and that he is not overly tired.

Patients of Thai or Han Chinese descent may be at an increased risk of a severe allergic skin reaction (Stevens-Johnson syndrome) when treated with phenytoin.

Children and adolescents weighing less than 50 kilograms can be treated with an appropriately adapted dosage.

How to get phenytoin medication

The active ingredient phenytoin is available from pharmacies after a doctor's prescription. Because of the wide range of interactions, the doctor or pharmacist should be asked for advice at the start of treatment and any change in medication.

How long has phenytoin been known?

Phenytoin was first chemically produced in 1908 by the German chemist Heinrich Biltz, who sold his development to the Parke-Davis pharmaceutical company. It was not until 1938 that scientists discovered the good anticonvulsant effectiveness of phenytoin. In contrast to the anti-epileptic phenobarbital, however, the strong soporific side effect is absent. It was approved in the USA in 1953. Since the patent has long expired, there are now numerous generics with the active ingredient phenytoin on the German pharmaceutical market.

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