Acute changes of blood ammonia may predict short‐term adverse effects of valproic acid

Abstract

Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically.

Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both?

“…Hypotheses that might explain such interindividual differences would include an individual threshold above which the ammonaemia level in the brain alters consciousness, especially when its blood level rises rapidly (Zaccara et al, 1987), or blood-brain barrier permeability changes, both phenomena known to be more important in some Figure 6. Effect of anticonvulsants on ammonaemia epileptic patients (Wang and Saab, 2003;Zaccara et al, 1984).…”

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…Some examples are VPA-induced encephalopathy [99,120] and PHT-induced dyskinesia. [121] Other systems or organs can also be involved.…”

Valproate hepatotoxicity syndrome: Hypotheses of pathogenesis

“…A dose-related hyperammonaemia is a documented effect of VPA therapy [31][32][33][34][35]. Co-treatmerit with other antiepileptic drugs appears to enhance this effect of VPA [36 37].…”