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content:valproate [2020/02/17 11:00] – [Disadvantages] icna | content:valproate [2022/04/30 11:54] (current) – changed pubmed syntax administrator@icnapedia.org | ||
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====== Valproate ====== | ====== Valproate ====== | ||
- | Valproic acid (2-propyl pentanoic acid, 2-propyl valeric acid) is a short-chain branched fatty acid. Prior to the serendipitous discovery of its anti-epileptic activity in 1963, valproic acid was used as an organic solvent. | + | Valproic acid (2-propyl pentanoic acid, 2-propyl valeric acid) is a short-chain branched fatty acid. Prior to the serendipitous discovery of its anti-epileptic activity in 1963, valproic acid was used as an organic solvent[(: |
===== Authorised indications ===== | ===== Authorised indications ===== | ||
UK-SmPC: In the treatment of generalized, | UK-SmPC: In the treatment of generalized, | ||
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**Systemic: | **Systemic: | ||
- | * the most serious are fatal hepatotoxicity and acute haemorrhagic pancreatitis. | + | * the most serious are **fatal hepatotoxicity** and **acute haemorrhagic pancreatitis**. |
- | * fatal hepatotoxicity | + | |
* primarily age-dependent and occurs mainly in children receiving polypharmacy and with organic brain disease | * primarily age-dependent and occurs mainly in children receiving polypharmacy and with organic brain disease | ||
* the risk is 1/600 before the age of 3 years. | * the risk is 1/600 before the age of 3 years. | ||
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* an abnormally low prothrombin level, particularly in association with other relevant abnormalities, | * an abnormally low prothrombin level, particularly in association with other relevant abnormalities, | ||
* any concomitant use of salicylates should be stopped, since they employ the same metabolic pathway. | * any concomitant use of salicylates should be stopped, since they employ the same metabolic pathway. | ||
- | * acute haemorrhagic pancreatitis with markedly increased amylase and lipase levels is another rare, but serious, adverse effect of valproate treatment. It develops within the first 3 months of treatment, is more prevalent in children and with polytherapy. | + | |
* hyperammonaemic encephalopathy, | * hyperammonaemic encephalopathy, | ||
* Thrombocytopenia and other haematological abnormalities: | * Thrombocytopenia and other haematological abnormalities: | ||
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* for focal epilepsis in young children since the doses of valproate required to be effective are much higher in focal than generalised epilepsies. Besides there are other, more effective and safer drugs for focal seizures | * for focal epilepsis in young children since the doses of valproate required to be effective are much higher in focal than generalised epilepsies. Besides there are other, more effective and safer drugs for focal seizures | ||
- | Source: Panayiotopoulos CP. (2005). The Epilepsies: Seizures, Syndromes and Management. Oxfordshire | + | ==== History ==== |
+ | Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton[(:cite: | ||
+ | |||
+ | Two colleagues, H. Meunier and Y. Meunier, working for a small company, Berthier Laboratories, | ||
+ | |||
+ | It was first released as antiepileptic drug in France in 1967 after the publication of preclinical studies by Carraz et al. in 1964[(: | ||
+ | ==== References ==== | ||
+ | ~~REFNOTES~~ |