Medicines for the Treatment of Hyperammonaemia

Definition

Among the metabolic disorders, hyperammonemia is characterized by the exaggerated surplus of ammonia in the blood: we are talking about a very serious clinical condition that can lead the patient to encephalopathy and death in a short time.

Causes

There are two types of hyperammonemia:

  1. Primary hyperammonemia: expression of genetic metabolic mutations, in which the enzymes involved in the complex urea cycle are unable to perform their function correctly
  2. Secondary hyperammonaemia: also in this case, the metabolic mutation can be of genetic origin. The inborn error of the intermediate metabolism may be due to the reduced activity of enzymes that do not belong to the urea cycle, but are still involved in important metabolic reactions (eg defects in the oxidation of fatty acids). Secondary hyperammonemia it can also result in liver failure, cirrhosis, hepatitis, acute viral infections, ingestion of toxins, liver disease, severe reactions to drugs (e.g. for the treatment of tuberculosis)
  • Unproven hypotheses: Leukemia drugs may promote secondary hyperammonaemia status.

Symptoms

The symptomatological picture of hyperammonemia, evidently severe, is characterized by the presence of metabolic encephalopathy often associated with respiratory alkalosis, impaired liver function, agitation, confusion, disorientation, somnolence. Often times, the disease soon degenerates into coma and convulsions. .


Normally, ammonia levels in the blood are between 21 - 50 µmol / l (15 - 60 µg / 100ml).

Information on Hyperammonemia - Medicines to Treat Hyperammonemia is not intended to replace the direct relationship between health professional and patient. Always consult your doctor and / or specialist before taking Hyperammonemia - Medicines to Treat Hyperammonemia.

Medicines

"Hyperammonemia is a" clinical emergency in all respects: the patient must "be promptly rescued and hospitalized, since the symptoms associated with the disease can precipitate dramatically and create irreversible damage, up to death. The excess ammonia goes promptly removed to avoid irreparable damage to the nervous system.
The administration of glucose and lipids seems to be a rather useful therapeutic option for reducing ammonia synthesis through the metabolism of endogenous proteins; for the same reason, the administration of arginine is also sometimes recommended. In some patients suffering from hyperammonaemia, a Intravenous therapy with sodium benzoate and sodium phenylacetate seems to guarantee a better result.

A step back to understand ... let's briefly remember that ammonia, a substance containing nitrogen, is a product derived from the catabolism of proteins; before elimination through the urine, ammonia is generally converted by the kidneys into urea, a less toxic substance than the previous one.

In any case, dialysis is the most effective treatment option ever to eliminate the excess ammonia; alternatively, it is possible to subject the patient to haemofiltration, particularly indicated in newborns suffering from hyperammonemia.
Pharmacological cure goes always accompanied by an important dietary modulation, consisting in the complete suspension of the protein intake; it should be emphasized, however, that it is the organism itself that refuses food in the context of hyperammonemia (self-protection).


The following are the classes of drugs most used in the therapy against hyperammonaemia, and some examples of pharmacological specialties; it is up to the doctor to choose the active ingredient and the dosage most suitable for the patient, based on the severity of the disease, the state of health of the patient and his response to treatment:


Emergency therapy for the treatment of hyperammonaemia:

  1. Total abolition of protein intake
  2. Maintain an adequate caloric intake, capable of inhibiting endogenous catabolism
  3. Intravenous infusion of drugs, useful for activating alternative routes aimed at eliminating nitrogen
  • L-Arginine hydrochloride (eg Bioarginine): intravenously, administer the drug at a dose of 600 mg / kg in 1 hour, followed by 2-4 mmol / kg over 24 hours, dividing the load into 4 doses.
  • Sodium Benzoate (eg. Sodium benzoate TN): intravenously, administer the drug at an initial dose of 250 mg / kg; continue the therapy with 250mg / kg per day, equally divided into 4 doses.
  • Sodium phenylbutyrate (eg. Ammonaps): available in the form of tablets or granules, the drug is indicated for the treatment of patients suffering from hyperammonemia or with disorders of the urea cycle. The drug is not used alone: ​​it is recommended, in fact, to follow all the instructions of the doctor who, in all likelihood, will recommend taking this drug in combination with others, together with a personalized diet with very low protein content. The dosage must be established by the doctor according to the ammonia values ​​in the The granules are reserved for infants with hyperammonaemia who are unable to swallow tablets.
  1. Emergency dialysis (in case of failure of the drug therapy described above): indicated to speed up the elimination of accumulated ammonia.

Alternative drugs for the treatment of hyperammonaemia

  • Carglumic acid (eg Carbaglu): the daily load must be divided equally into two doses, and is around 100 mg total. Begin therapy with a drug dose of 100-250 mg / kg, to be taken orally, immediately before the two main meals. It is recommended to follow this therapeutic scheme in association with other therapies for the treatment of hyperammonemia. The precise dosage must be established based on the plasma concentration of ammonia. The maintenance dose is generally less than 100 mg per day, to be taken always divided into two doses within 24 hours, before meals. Consult your doctor.

Maintenance therapy (relapse prevention): maintenance therapy following episodes of hyperammonaemia is based on both dietary correction and preventive pharmacological treatment:

  1. The chances of hyperammonemia occurring following the first episode are very high; therefore, it is recommended to carefully follow all the doctor's instructions, including full compliance with personalized dietary rules. It is recommended to follow a low-protein diet; The specific daily protein content depends on the severity of the condition and the age of the patient. For example, newborns who have recovered from a first episode of hyperammonemia are recommended to limit their hypoprotein intake to the maximum. The proteins not taken must be replaced with dietetic products formulated with essential amino acids associated with a supplementation of trace elements and vitamins.
  2. Dietary correction to prevent hyperammonaemia relapses is not always sufficient; patients with a past history of hyperammonaemia must in fact take other drugs, such as sodium benzoate, arginine and phenylbutyrate orally (previously analyzed for emergency treatment). The dosage should be established by the doctor and customized specifically for each individual patient; however, most patients with a previous history of hyperammonaemia are treated with 250 mg / kg per day of sodium benzoate, phenylbutyrate and arginine, for preventive purposes.
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