Pancreatitis Associated with Valproic Acid: A Review of the Literature

Chapman, Scott A; Wacksman, G. Paulina; Patterson, Betty D.

doi:10.1592/phco.21.20.1549.34480

Cited by 41 publications

(36 citation statements)

References 41 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The occurrence of pancreatitis associated with VPA was recently reviewed, and it is regarded as a rare condition (22,100). Its mechanism has not been established.…”

Section: Hepatotoxicitymentioning

confidence: 99%

Valproate: Past, Present, and Future

2003

View full text Add to dashboard Cite

Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonicclonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus.The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated.At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.

show abstract

“…The occurrence of pancreatitis associated with VPA was recently reviewed, and it is regarded as a rare condition (22,100). Its mechanism has not been established.…”

Section: Hepatotoxicitymentioning

confidence: 99%

Valproate: Past, Present, and Future

2003

View full text Add to dashboard Cite

show abstract

“…On average, patients with VPA pancreatitis were not taking supratherapeutic doses of the medication. The mean adult dose was 2.1 gm/day (with a standard deviation of 1.5 gm) and the mean pediatric dose was 47.6 mg/kg/day, well below the manufacturer recommended maximum dose of 60 mg/kg/day (3).…”

mentioning

confidence: 77%

“…The first case of VPA-associated pancreatitis occurred in 1979 in an 8-year-old boy (1). Since that time there have been over 40 documented cases of pancreatitis caused by VPA in both children and adults (1)(2)(3). The majority of these cases, 58%, involved patients under the age of 20 years (1,2).…”

mentioning

confidence: 99%

Epigastric pain

Phillips

Nadel

Brown

2006

The Journal of Emergency Medicine

View full text Add to dashboard Cite

Dr. Richard Phillips:Today's case is that of a 27-yearold woman with a history of bipolar disorder who presented to the Emergency Department (ED) complaining of a 3-week history of epigastric and right upper quadrant (RUQ) pain. She described the pain as sharp and constant with intermittent exacerbations that radiated to the back. There was no change in the quality of the pain with food intake. There was no recent history of trauma. The review of systems was notable for nausea, emesis, dark stools for a few days, lightheadedness for one week, and a fever of 38.3°C 2 days before presentation.Three weeks before presentation, the patient was seen in the ED complaining of multiple episodes of hematemesis. At that time it was believed that her symptoms were secondary to gastritis; she was started on antacids, which resolved her symptoms. The symptoms returned 4 days before presentation, at which time she saw her primary care physician, who reaffirmed the diagnosis of gastritis and sent her home with proton pump inhibitors.Dr. Eric Nadel: Are there any questions about the initial presentation?Dr. William Krauss: I would like to know more about her medical history, social history and medications before we proceed.Dr. Phillips: The patient's past medical history was notable only for bipolar disorder diagnosed 8 years ago for which she had been admitted to an inpatient psychiatric facility twice in the last 6 weeks before this presentation. The patient had no prior surgeries. The only medications included olanzapine 20 mg taken at night and valproic acid 1000 mg, also taken at night. The patient lived alone and was unemployed at the time. She denied alcohol and drug use but did admit to smoking in excess of two packs of cigarettes per day for the last 12 years. The family history was non-contributory; she was adopted and had not been in contact with her biological parents.In the ED, the patient's vital signs were: temperature 36.7°C, blood pressure (supine) 122 mm Hg/76 mm Hg, heart rate (supine) 80 beats per minute, blood pressure (sitting) 110 mm Hg/77 mm Hg and heart rate (sitting) 92 beats per minute, respirations 20 breaths per minute. The patient was in no acute distress. Mucous membranes were moist and clear of lesions. Cardiac examination demonstrated an audible S1 and S2 in regular rate and rhythm without evidence of any murmurs, rubs or gallops. The lungs were clear to auscultation bilaterally. The abdomen was soft with RUQ tenderness but no evidence of rebound or guarding. Rectal examination revealed no tenderness and the stool was negative for occult blood. The cranial nerves II-XII were intact and she was alert and oriented to person, place and time. The lower extremities were warm and well perfused without evidence of peripheral edema.Dr. Nadel: Are there any questions about the initial assessment and thoughts as to ED management?Dr. Danny Pallin: The differential diagnosis in this case is extensive and includes cholecystitis, cholelithiaCase Presentations of the Harvard Emergency Medicine Residency are coor...

show abstract

“…Treatment of epilepsy requires long-term or a life-long administration of the drugs, which increases the risk of toxic reactions [18]. Valproates used as AEDs enhanced the clearance Fig.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Modulates Superoxide Dismutase, Uric Acid-Independent FRAP and Zinc in Blood of Adult Epileptic Patients

Płonka-Półtorak¹,

Zagrodzki

Chłopicka

et al. 2011

Biol Trace Elem Res

View full text Add to dashboard Cite

We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7-14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.

show abstract

Pancreatitis Associated with Valproic Acid: A Review of the Literature

Cited by 41 publications

References 41 publications

Valproate: Past, Present, and Future

Valproate: Past, Present, and Future

Epigastric pain

Valproic Acid Modulates Superoxide Dismutase, Uric Acid-Independent FRAP and Zinc in Blood of Adult Epileptic Patients

Contact Info

Product

Resources

About