Divalproex Case Study

Clinical Question:
Should divalproex or gabapentin be used for female adolescents with partial focal seizures and decreased liver function?

Evidence Based Answer: Gabapentin and divalproex are both effective anticonvulsant medications for partial seizures in female adolescent patients1,2. However, divalproex has adverse effects that are detrimental to patients with preexisting liver impairment3. Gabapentin does not have these detrimental effects on the liver like divalproex does because it is eliminated from the body through the kidneys instead of the liver4. If divalproex is more effective for the patient than gabapentin it may be paired with diammonium glycyrrhizinate to combat the detrimental effects on the liver. This is combination

Since the drug is metabolized by the liver it can lead to VAP-induced hepatotoxicity. Divalproex leads to VAP-induced hepatotoxicity by various methods. Some of these methods include the overexpression of Keap1 which leads to an increased inhibition of Nrf2 a transcription factor that leads to the protection of hepatic cells from antioxidants. Another method is by inducing the overexpression of NF-kappa B which leads to the production and release of the proinflammatory cytokines IL-1 beta, IL-6 and TNF alpha3. Nrf2-ARE is the pathway that is limited by divalproex. This is an important pathway needed to protect the liver and prevent damage. Nrf2-ARE pathway prevents oxidative damage. Nrf2 translocate into the nucleus when the liver is in oxidative stress in order to active and transcribe different genes that produce phase II detoxifying enzymes as well as antioxidant enzymes. These enzymes will bind to ARE and become activated to protect hepatic cells from oxidative damage. Without Nrf2 cells have a greater probability of becoming damaged by

Diammonium glycyrrhizinate is the active chemical found in liquorice root. It has been used in Asian countries in order to combat liver diseases that have been induced by chemical and drug toxicity3. In a recent study it was tested for combating VAP-induced hepatotoxicity. The experiment was performed in mice and shows promising results for the use of diammonium glycyrrhizinate with divalproex in order to counter the effects of VAP-induced hepatotoxicity. In the study, mice that were treated with diammonium glycyrrhizinate and divalproex had liver enzyme counts closer to the control group than the group receiving just divalproex. It was also shown that diammonium glycyrrhizinate suppresses Keap1 therefore allowing Nrf2 to protect the hepatic cells from the increase in antioxidants. It also decreased the levels of NF-kappa B in order to decrease inflammation due to the proinflammatory