Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid represents a new class of anticonvulsants that are widely employed in the management of many types of seizure disorders. Compared with other anticonvulsants, it has been considered relatively free of adverse effects. Recently, acute hepatic failure has been ascribed to valproic acid. Now experience is accumulating that implicates this agent in causing pancreatitis. Contributing to this evidence, the patient described herein had well-documented, recurrent pancreatitis while he was taking valproic acid. Nonspecific vomiting and abdominal pain frequently occur with valproic acid; however, pancreatitis must be considered whenever these symptoms are severe or protracted.
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PMID:Recurrent pancreatitis induced by valproic acid. A case report and review of the literature. 616 6

Valproic acid, used alone or in combination with other anticonvulsants in 100 children with epilepsy, improved seizure control in all age groups. Mean improvement in seizure control was 82%. Petit mal seizures responded best, but other types of seizures, even with associated mental and physical handicaps, also responded well. A substantial improvement in alertness and behavior often occurred. Leukopenia (27%) and an elevated SGOT value (44%) were frequent but transient. Other side effects included alopecia (1), gastrointestinal distress with vomiting (7), pancreatitis (1), thrombocytopenia (1), edema (2), and coma (2). Three severely retarded children with frequent seizures died while receiving valproic acid, but it is not clear that death was caused by valproic acid. Children must be monitored carefully for potential toxic effects, and drug interactions with other anticonvulsants may cause problems in treatment.
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PMID:Valproic acid therapy in childhood epilepsy. 677 26

We describe a case of a 31-year-old woman with cerebral palsy who developed fatal acute hemorrhagic pancreatitis while being treated with valproic acid to control her seizure activity. Acute pancreatitis is usually due to alcohol ingestion or biliary tract disease, and unusual causes include trauma, metabolic diseases, or drugs. Valproic acid is considered a safe drug, although rare cases of severe toxicity such as hepatitis and acute pancreatitis, including two fatalities, have been reported. Our review of the literature revealed that most patients who developed acute pancreatitis had serum levels of the drug within the therapeutic range, and most of the cases occurred either secondary to a recent increase in the dose or to initiation of treatment. It also appeared that the fatalities occurred due to a delayed diagnosis of acute pancreatitis, either resulting from an unsuspected diagnosis or to the deteriorated mental status of the patients receiving the drug, which precluded their ability to elaborate symptomatology. We believe that early diagnosis and withdrawal of the drug are significant factors determining the course of valproic-acid-associated pancreatitis.
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PMID:Fatal acute pancreatitis caused by valproic acid. 777 87

Thirty-five years since its introduction into clinical use, valproate (valproic acid) has become the most widely prescribed antiepileptic drug (AED) worldwide. Its pharmacological effects involve a variety of mechanisms, including increased gamma-aminobutyric acid (GABA)-ergic transmission, reduced release and/or effects of excitatory amino acids, blockade of voltage-gated sodium channels and modulation of dopaminergic and serotoninergic transmission. Valproate is available in different dosage forms for parenteral and oral use. All available oral formulations are almost completely bioavailable, but they differ in dissolution characteristics and absorption rates. In particular, sustained-release formulations are available that minimise fluctuations in serum drug concentrations during a dosing interval and can therefore be given once or twice daily. Valproic acid is about 90% bound to plasma proteins, and the degree of binding decreases with increasing drug concentration within the clinically occurring range. Valproic acid is extensively metabolised by microsomal glucuronide conjugation, mitochondrial beta-oxidation and cytochrome P450-dependent omega-, (omega-1)- and (omega-2)-oxidation. The elimination half-life is in the order of 9 to 18 hours, but shorter values (5 to 12 hours) are observed in patients comedicated with enzyme-inducing agents such as phenytoin, carbamazepine and barbiturates. Valproate itself is devoid of enzyme-inducing properties, but it has the potential of inhibiting drug metabolism and can increase by this mechanism the plasma concentrations of certain coadministered drugs, including phenobarbital (phenobarbitone), lamotrigine and zidovudine. Valproate is a broad spectrum AED, being effective against all seizure types. In patients with newly diagnosed partial seizures (with or without secondary generalisation) and/or primarily generalised tonic-clonic seizures, the efficacy of valproate is comparable to that of phenytoin, carbamazepine and phenobarbital, although in most comparative trials the tolerability of phenobarbital was inferior to that of the other drugs. Valproate is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Many of these syndromes are associated with multiple seizure types, including tonic-clonic, myoclonic and absence seizures, and prescription of a broad-spectrum drug such as valproate has clear advantages in this situation. A number of reports have also suggested that intravenous valproate could be of value in the treatment of convulsive and nonconvulsive status epilepticus, but further studies are required to establish in more detail the role of the drug in this indication. The most commonly reported adverse effects of valproate include gastrointestinal disturbances, tremor and bodyweight gain. Other notable adverse effects include encephalopathy symptoms (at times associated with hyperammonaemia), platelet disorders, pancreatitis, liver toxicity (with an overall incidence of 1 in 20,000, but a frequency as high as 1 in 600 or 1 in 800 in high-risk groups such as infants below 2 years of age receiving anticonvulsant polytherapy) and teratogenicity, including a 1 to 3% risk of neural tube defects. Some studies have also suggested that menstrual disorders and certain clinical, ultrasound or endocrine manifestations of reproductive system disorders, including polycystic ovary syndrome, may be more common in women treated with valproate than in those treated with other AEDs. However, the precise relevance of the latter findings remains to be evaluated in large, prospective, randomised studies.
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PMID:Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. 1226 62

Valproic acid is a widely used drug in the treatment of epilepsy and, compared to other anticonvulsant drugs, is considered safe. The most common side effects of valproic acid ingestion or therapy are transient nausea, vomiting, abdominal cramps, and diarrhea. Most of these complaints are mild. However, more serious adverse reactions can occur such as hepatotoxicity and pancreatitis. It has been proposed that, whenever possible, valproic acid not be used in the younger child, the child with a severe seizure disorder or other neurological disorders, mental retardation, developmental delay, organic brain disease, congenital abnormalities, or the child who is taking multiple anticonvulsant drugs, as these factors may increase the likelihood of hepatotoxicity and/or pancreatitis. In the present report, we describe a fatal case of acute hemorrhagic pancreatitis in a four and a half-year-old Hispanic female child who was receiving valproic acid in combination with another anticonvulsant drug for control of focal seizures. The patient also received the macrolide antibiotic azithromycin. For pediatricians and forensic pathologists valproic acid-induced pancreatitis can be a challenging diagnosis which must not be mistaken for abdominal trauma. We discuss the workup of the patient and differential diagnosis.
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PMID:Pathological case of the month: sudden death in a child as a result of pancreatitis during valproic acid therapy. 1239 3

Valproic acid (VPA) is a commonly prescribed medication approved for use in the United States for epilepsy, migraine, and bipolar disorder. Although the common adverse effects associated with VPA are typically benign, less common but more serious adverse effects can occur. These include hepatotoxicity, teratogenicity, possible polycystic ovaries with the potential for sterility or carcinogenesis, and pancreatitis. A characteristic clinical profile has been determined for several of these adverse effects. We report four children with VPA-induced pancreatitis, one of which was fatal, and review the literature. Three of these children presented within a 4-year period (1995-1999) at the same institution. Because previous reviews have included either a small number of patients, or both pediatric and adult patients, we reviewed only pediatric cases to minimize any effect from adults with more serious co-existing medical illnesses. We attempted to determine the following: (1) if there are any characteristics that are predictive of pancreatitis and whether it will be fatal; (2) whether different clinical and laboratory characteristics exist for nonfatal vs fatal cases; and (3) if a specific pediatric patient profile, similar to that with VPA associated hepatotoxity or polycystic ovary-androgenism syndrome, could be identified.
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PMID:Acute pancreatitis in children from Valproic acid: case series and review. 1269 68

In the past 6 years, 11 children on valproic acid have developed pancreatitis in our children's hospital. Valproic acid has been used as one of the primary anticonvulsants for generalized seizures in children for the past 25 years. A literature review reveals mostly singular reports of pancreatitis over the past decade. The charts of the 11 patients with valproic acid-induced pancreatitis were reviewed. Dosage, valproic acid serum levels, duration of therapy, and concomitant medications were examined. Families were contacted by telephone to determine the formulation (brand name vs generic) of valproic acid at the time of diagnosis. Six girls and five boys were studied. The ages ranged from 4 to 16 years. Eight of 11 children presented with an acute abdomen. Unexpectedly, three children presented with a flulike illness. Serum lipase values ranged from 341 to 5576 U/L (normal range < 190 U/L). The dose of valproic acid ranged from 20 to 50 mg/kg. Serum levels ranged from 334 to 884 micromol/L (therapeutic range 350-800 micromol/L). Six of the patients were on monotherapy. Seven children were on brand-name drugs. Four of the children had an abnormal neurologic syndromic diagnosis (West syndrome, Rett syndrome, Lowe syndrome, and Angelman's syndrome). Six of the children had a history of drug allergies with a skin rash. Valproic acid was reintroduced in one child and resulted in a second episode of pancreatitis. Resolution of symptoms usually took several weeks following discontinuation of the drug. No association was found with valproic acid dosage, type of preparation, serum levels, duration of therapy, or presence of concomitant medications. Pancreatitis is a severe adverse effect of valproic acid use in children. Dose, duration of treatment, serum valproic acid levels, generic preparation, and the presence of concomitant antiepileptic drugs do not appear to be risk factors. Children with known drug sensitivity might be at risk. Lipase levels at the time of an acute abdomen or a flulike illness in epileptic children taking valproic acid can reveal early stages of pancreatitis and are recommended.
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PMID:Valproic acid-induced pancreatitis in childhood epilepsy: case series and review. 1552 53

A 12-year-old boy developed pancreatitis, complicated by a pancreatic pseudocyst, as an adverse reaction to valproic acid (VPA) treatment for epilepsy. Pancreatitis subsided within three weeks after discontinuation of VPA. The pancreatic pseudocyst was managed without surgery and resolved spontaneously in four weeks. Valproic acid was concluded to be the most probable cause, since no other explanation was found. According to the literature VPA is a rare but known cause of pancreatitis. A computer-assisted literature search revealed seven previously reported cases of VPA-induced pancreatitis complicated by a pancreatic pseudocyst. Six of these patients were under 20 years of age. Four patients were treated conservatively; three needed cystostomy or external drainage. All patients recovered. Patients using VPA, especially children, presenting with acute abdominal pain should be suspected of valproic acid-induced pancreatitis. If VPA induced pancreatitis is complicated by a pseudocyst, conservative treatment should be the first line of treatment.
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PMID:Pancreatitis, complicated by a pancreatic pseudocyst associated with the use of valproic acid. 1584 73

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted by carnitine deficiency. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose and its incidence is increasing, because of use of VPA in psychiatric disorders. Although it usually results in mild central nervous system depression, serious toxicity and even fatal cases have been reported. Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA. Carnitine supplementation during VPA therapy in high-risk patients is now recommended by some scientific committees and textbooks, especially paediatricians. L-carnitine therapy could also be valuable in those patients who develop VHT or VHE. A few isolated observations also suggest that L-carnitine may be useful in patients with coma or in preventing hepatic dysfunction after acute VPA overdose. However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions.
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PMID:Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? 1627 30

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.
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PMID:Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children. 1678 50


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