Definition
Among the metabolic disorders, hyperammonemia is characterized by an 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:
- Primary hyperammonemia: expression of genetic metabolic mutations, in which the enzymes involved in the complex urea cycle are not able to properly fulfill their function
- Secondary hyperammonemia: also in this case, the metabolic mutation can be of genetic derivation. The congenital error affecting the intermediate metabolism may be due to the reduced activity of enzymes that do not belong to the urea cycle, but are nevertheless involved in important metabolic reactions (eg defects of fatty acid oxidation). Secondary hyperammonaemia can also result in hepatic insufficiency, cirrhosis, hepatitis, acute viral infections, ingestion of toxins, liver diseases, serious reactions to drugs (eg for the treatment of tuberculosis)
- Unspecified hypothesis: drugs for the treatment of leukemia can promote secondary hyperammonaemia status.
Symptoms
The symptomatology of hyperammonaemia, evidently severe, is characterized by the presence of metabolic encephalopathy often associated with respiratory alkalosis, alteration of liver function, agitation, confusion, disorientation, drowsiness. Often times, the disease soon degenerates towards coma and convulsions.
Normally, ammonia levels in the blood range between 21 - 50 µmol / l (15 - 60 µg / 100 ml).
Information on Hyperammonemia - Drugs for the Treatment of Hyperammonemia is not intended to replace the direct relationship between health professional and patient. Always consult your doctor and / or specialist before taking Hyperammonemia - Drugs for the treatment of Hyperammonemia.
drugs
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 precipitously and cause irreversible damage, until death. Excess ammonia should be promptly removed to avoid irreparable damage to the nervous system.
The administration of glucose and lipids appears to be a rather useful therapeutic option for reducing ammonia synthesis through the metabolism of endogenous proteins; for the same reason, also the administration of arginine is sometimes recommended. In some patients with hyperammonemia, intravenous therapy with sodium benzoate and sodium phenylacetate appears to guarantee a better result.
A step back to understand ... let's remember briefly that ammonia, a substance containing nitrogen, is a product derived from the catabolism of proteins; before elimination by urine, ammonia is generally converted by the kidneys into urea, a substance that is less toxic than the previous one.
However, dialysis is the most effective therapeutic option ever to eliminate the excess of ammonia; alternatively, it is possible to subject the patient to haemofiltration, particularly indicated in newborns suffering from hyperammonemia.
The pharmacological treatment is always accompanied by an important dietary modulation, consisting in the complete suspension of the protein intake; to underline, however, that it is the organism itself that refuses food in the context of hyperammonemia (self-protection).
Emergency therapy for the treatment of hyperammonemia:
- Total abolition of protein intake
- Maintain an adequate caloric intake capable of inhibiting endogenous catabolism
- Intravenous infusion of drugs, useful for activating alternative ways to eliminate 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, splitting the load into 4 doses.
- Sodium Benzoate (eg Sodium benzoate TN): intravenously, administer the drug at an initial dose of 250 mg / kg; continue 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 in any case with disorders of the urea cycle. The drug is not used in monotherapy: it is recommended, in fact, to follow all the indications of the doctor who, in all probability, will advise taking this drug in association with others, together with a personalized diet regimen with a very low protein content. The dosage should be determined by the doctor according to the ammonia values in the blood. The granules are reserved for newborns suffering from hyperammonemia, unable to swallow tablets.
- Emergency dialysis (in the case of failure of the drug therapy described above): indicated to accelerate the elimination of accumulated ammonia.
Alternative medications for the treatment of hyperammonemia
- Carglumic acid (eg Carbaglu): the daily load must be split equally in two doses, and is around 100 mg in total. Begin therapy with a 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 should be established based on the plasma ammonia concentration. The maintenance dose is generally less than 100 mg per day, to be taken always divided into two doses over 24 hours, before meals. Consult your doctor.
Maintenance therapy (relapse prevention) : maintenance therapy following episodes of hyperammonemia is based on both dietary correction and preventive drug treatment:
- The chances of hyperammonaemia appearing after the first episode are very high; therefore, it is recommended to follow all the doctor's instructions carefully, including full compliance with customized dietary rules. It is recommended to follow a low protein diet; the specific daily intake of proteins depends on the severity of the condition and the age of the patient. For example, newborns healed of a first episode of hyperammonemia are advised to limit hypoprotein intake as much as possible. The proteins not taken should be replaced with dietary products formulated with essential amino acids associated with supplementation with trace elements and vitamins.
- The dietary correction to prevent relapses of hyperammonemia is not always sufficient; patients with a past history of hyperammonemia should in fact take other medications, such as sodium benzoate, arginine and phenylbutyrate orally (previously analyzed for emergency treatment). The dosage must be established by the doctor and customized specifically for each individual patient; however, most sufferers with a history of hyperammonemia are treated with 250 mg / kg a day of sodium benzoate, phenylbutyrate and arginine, for preventive purposes.
