This report describes a patient who had significant postoperative bleeding 4 days after undergoing surgery while using a tranexamic acid (4.8%) mouth rinse protocol for local control of hemostatis. Patients undergoing dentoalveolar surgery who are receiving chronic oral anticoagulants are treated with a tranexamic acid mouth rinse at our hospital. ...

3-Hydroxymethylphenytoin valproic acid ester (VAL-PHT) was designed as a new prodrug combining valproic acid and phenytoin, two anticonvulsant drugs with different pharmacological profiles. The compound was hydrolyzed by rat plasma esterases in vitro but exhibited only activity in the maximal electroshock seizure test (MES test) after intraperitoneal administration to mice. ...

Phenobarbital (phenobarbitone) and phenytoin are the most useful anticonvulsants in neonates because adverse effects are most readily reversed when these drugs are used. Most anticonvulsants are very rarely associated with haematological adverse effects. Platelet function is particularly vulnerable to valproic acid (sodium valproate) therapy. Barbiturates and phenytoin can precipitate metabolic ...

Valproic acid is an anticonvulsant that is strongly bound to serum albumin. The nonsteroidal antiinflammatory drugs mefenamic acid and fenoprofen are also strongly bound to albumin. We observed significant displacement of valproic acid from protein binding by mefenamic acid and fenoprofen at both therapeutic and slightly above therapeutic concentrations. The ...

A 31-y-old epileptic man developed coma and shock after suicidally ingesting large amounts of valproic acid and gabapentin. His peak valproic acid, level was 1306.9 micrograms/mL (therapeutic range = 30-100 micrograms/mL). His peak gabapentin level was 60.0 micrograms/mL (therapeutic range = 2.0-8.0 micrograms/mL). His hypotension was refractory to crystalloid and ...

The anticonvulsive drug, valproic acid (VPA), inhibits the biosynthesis of carnitine, and may contribute in this way to carnitine deficiency associated with VPA therapy. The conversion of [3H]-butyrobetaine into [3H]-carnitine was determined 60 min following a single intraperitoneal (i.p.) dose of 1.2 mmol/kg VPA in rats. The fraction of radioactivity ...

GABA is a major inhibitory neurotransmitter in mammals, whose uptake in glial cells is inhibited by nipecotic acid. In addition to GABA, glycine is an important inhibitory neurotransmitter. Valproic acid (VPA) is one of the four established antiepileptics and (E)-2-ene valproic acid ((E)-2-ene VPA) is its major active metabolite. The ...

Because binding of valproic acid to plasma proteins affects the efficacy of the drug in the treatment of epilepsy (only the unbound fraction of the drug is effective) we have compared two methods which use different binding parameters to predict the in-vivo concentration of unbound valproic acid in serum. The ...

OBJECTIVE: To compare the efficacy and acceptability of ethamsylate, mefenamic acid, and tranexamic acid for treating menorrhagia. DESIGN: Randomised controlled trial. SETTING: A university department of obstetrics and gynaecology. SUBJECTS: 76 women with dysfunctional uterine bleeding. INTERVENTIONS: Treatment for five days from day 1 of menses during three consecutive menstrual ...

Aspirin, Neem oil, valproic, adipic, benzoic, isovaleric, 3-mercaptopropionic and 4-pentenoic acids are implicated in the pathogenesis of Reye's syndrome, Jamaican vomiting sickness, and related chemical toxicities. These disorders are characterized by hyperammonemia, hypoglycemia, microvesicular steatosis and encephalopathy. The goal of this study was to determine whether chemicals implicated in Reye's-related ...

Bipolar disorder is associated with increased levels and function of the G-protein, Gs alpha which may be normalized by treatment with mood stabilizing medications (i.e. lithium salts and the anticonvulsants, valproic acid and carbamazepine). In C6 glioma cells, endogenous ADP ribosylation was markedly increased by lithium chloride (+83%, P < ...

Cardiopulmonary bypass (CPB) increases risk of postoperative bleeding and need for transfusion. The aim of this study was to evaluate the effects of aprotinin, epsilon aminocaproic acid and tranexamic acid on coagulation patterns and need for banked blood transfusion. Ninety-six consecutive patients who underwent coronary artery bypass surgery were randomly ...

Tranexamic acid has the potential to be a pharmacologic adjunct for the prophylaxis of hemorrhagic complications occurring in the oncology population. The studies and cases reviewed here suggest that tranexamic acid administration may be a therapeutic option for bleeding prophylaxis in APL where enhanced fibrinolysis accompanies the disease state. Because ...

In the present study, compounds derived from the anticonvulsant drug valproic acid (VPA, 2-n-propylpentanoic acid) and analogues known to be teratogenic were synthesized with an additional carbon-branching in one of the side chains. The substances were tested for their ability to induce anticonvulsant activity and sedation in adult mice, and ...

Displacement of valproic acid (90-95% bound to albumin) and carbamazepine (80% bound to albumin) by salicylate, leading to higher concentrations of pharmacologically active free drugs, has been reported. We studied the possibility of displacement of valproic acid and carbamazepine by other strongly albumin-bound nonsteroidal antiinflammatory drugs tolmetin, ibuprofen, and naproxen. ...

This study evaluated whether valproic acid, a branched-chain fatty acid which has been used in the treatment of seizures, would influence the binding Of L-tryptophan to rat hepatic nuclei. Previous studies have indicated that binding of L-tryptophan to hepatic nuclear envelope protein was saturable, stereospecific, and of high affinity. In ...

The hepatotoxic metabolite of the anticonvulsant drug valproic acid (VPA), namely (E)-2-propyl-2,4-pentadienoic acid (E)-2,4-diene VPA), is known to react with glutathione (GSH) in vivo. Although glutathione-S-transferase (GST) was suspected of being the catalyst for this conjugation reaction, this was yet to be confirmed. In this study, GST activities were detected ...

The hepatotoxicity of the anticonvulsant drug valproic acid may be associated with the formation of potentially reactive metabolites, one of which is (E)-2-propyl-2,4-pentadienoic acid ((E)-2,4-diene VPA). This report describes the characterization of new GSH-related conjugates of this diene. Bile samples collected from male Sprague-Dawley rats dosed ip with (E)-2,4-diene VPA ...

Plasmin is a serine protease with trypsin-like specificity and is activated from plasminogen by several plasminogen activators. Since plasmin has lysine binding site in its heavy chain, lysine derivatives react with plasmin and then modify its activity. The effects of lysine derivatives such as epsilon-aminocaproic acid (EACA) and tranexamic acid ...

Spontaneous thalamocortical epileptiform activity was elicited in rodent thalamocortical slices by a medium containing no added Mg2+. Multiple varieties of activity were generated in these slices, including simple thalamocortical burst complex (sTBC) activity that resembled the spike-wave discharges of generalized absence epilepsy, and complex thalamocortical burst complex (cTBC) activity that ...

We previously reported higher free phenytoin concentration in predialysis serum compared to postdialysis serum. In our present study with valproic acid, we observed an opposite effect, where free valproic acid concentration was higher in postdialysis serum. The increased free valproic acid concentrations in postdialysis sera (15.4-77.4% higher in postdialysis sera) ...

Using a single-patient (n = 1) clinical trial, we studied a 7-year-old boy who presented with unsatisfactory progress in school and whose electroencephalogram had very active independent frontal spike discharges. He had not had clinical seizures. The patient was randomized to receive valproic acid, 125 mg twice daily, (four periods) ...

BACKGROUND: Increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. CASE REPORT: A 32-year-old female presented alert three hours postingestion of her own medication. ...

Sulphasalazine is cleaved into 5-aminosalicylic acid and sulphapyridine by colonic bacteria. The bulk of evidence favours sulphapyridine rather than 5-aminosalicylic acid as the active moiety (as well as the main producer of side-effects) though a therapeutic action from the 30% of sulphasalazine that is absorbed unaltered also cannot be excluded.

This article reviews critically the present status of lithium in the treatment and prophylaxis of manic-depressive illness compared to the two anticonvulsant drugs, carbamazepine and valproic acid. Lithium is used successfully in the prophylaxis and treatment of manic-depression. The mechanism by which it exerts its effects is still not very ...

Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage III) were diagnosed at our institution in the last 10 years. Five patients were treated with isoprinosine and the antiepileptic drug valproic acid. Three patients presented with myoclonic seizures refractory to valproic acid and the usual ...

The principal metabolite of valproic acid (VPA), 2-ene VPA, appears to share most of VPA's pharmacological and therapeutic properties while lacking its hepatotoxicity and teratogenicity, thus making it a useful lead compound for the development of safer antiepileptic drugs. Analogues of 2-ene VPA were evaluated for anticonvulsant activity in mice ...

The cytochrome P450-dependent terminal desaturation of valproic acid (VPA) is of both toxicological and mechanistic interest because the product, 4-ene-VPA, is a more potent hepatotoxin than the parent compound and its generation represents a rather novel metabolic reaction for the cytochrome P450 system. In the present study, lung microsomes from ...

The inhibitory effects of antifibrinolytic amino acids on clot lysis induced with recombinant staphylokinase (SakSTAR) or with streptokinase (SK) were evaluated in a human plasma milieu in vitro and in a hamster pulmonary embolism model in vivo. Addition of tranexamic acid to a system composed of 60 microliters 125I-fibrin-labeled plasma ...

An improved method for the quantitative determination of valproic acid (VPA) and sixteen of its metabolites has been developed using gas chromatography-mass spectrometry with selected-ion monitoring. The method is applicable to serum or urine and all metabolites are measured in a single chromatographic run of 29.5 min. Ions selected for ...

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the ...

OBJECTIVE: To examine the prescribing of mood stabilizers (lithium, carbamazepine, and valproic acid) in a 500-bed state-operated psychiatric hospital in New York. METHODS: All 129 inpatients receiving mood stabilizers were identified and their medical records reviewed using a standardized drug use evaluation form. Diagnosis, other indications, and prior experience with ...

Prolonged valproic acid treatment results in secondary carnitine deficiency. In thirteen children paired samples of plasma were drawn at the onset of, and after 9 months of continuous valproic acid treatment. At onset free plasma carnitine values were age dependent; they increased during childhood (r = 0.59, p = 0.016). ...

Serum carnitine was measured longitudinally before and after therapy in 15 patients receiving valproic acid, 14 patients receiving carbamazepine and 8 patients receiving phenobarbital. The patients who received valproic acid showed a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2) mumol/l without valproic acid, 29.1 (1.6) ...

The incidence of post-extraction bleeding and the amount of replacement therapy needed to control bleeding in 24 hemophilic children following the local use of tranexamic acid mouthwash have been investigated. The results of the study showed that 91.6% of patients who used tranexamic acid mouthwash as a supplement to systemic ...

Large conductance calcium-activated K+ (KCa) channels are rapidly activated by niflumic acid dose-dependently and reversibly. External niflumic acid was about 5 times more potent than internal niflumic acid, and its action was characterized by an increase in the channel affinity for [Ca2+], a parallel left shift of the voltage-activation curve, ...

Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting ...

We have studied four organic acids of similar structure to further understand the basis of their developmental toxicity. Valproic acid (2-propyl pentanoic acid), ethylhexanoic acid, and octanoic acid are isomeric C8 organic acids but their teratologic potency varied widely. Valproic acid induced a moderate to severe teratologic outcome after a ...

Much attention has focussed on the role of valproic acid induced secondary carnitine deficiency in predisposing children to life-threatening hepatotoxicity and a Reye-like syndrome. One mechanism by which valproic acid therapy induces serum and tissue depletion of carnitine is through inhibition of plasmalemmal carnitine uptake. In cultured control human skin ...

Ten patients with cystitis associated with tiaprofenic acid were reviewed. All patients displayed similar cystoscopic and histological features, and all failed a variety of initial therapies but achieved a dramatic improvement or resolution of symptoms with discontinuation of the tiaprofenic acid. Drug-induced cystitis may be more common than previously recognized.

The interaction between the amino acid glycine and valproate (VPA), an antiepileptic drug (AED) that occasionally causes hepatotoxicity, was studied in rat hepatocytes in monolayer culture. Valproate caused a dose-dependent increase in leakage of lactic acid dehydrogenase (LDH), and glycine prevented this toxic response. L-Carnitine, L-alanine, and L-cysteine did not ...

Zidovudine is metabolized to an inactive 5'-glucuronide and has a short plasma half-life requiring frequent dosing. The present study in six patients without symptoms who were infected with human immunodeficiency virus was undertaken to determine if coadministration of valproic acid which, like zidovudine, is metabolized by glucuronidation, would alter zidovudine ...

Both aprotinin and tranexamic acid are effective inhibitors of fibrinolysis in vitro and in vivo and both agents can act as plasmin inhibitors in purified systems, although there is some debate on their exact mechanism of action in vivo. The studies reported here using an in vitro clot lysis system ...

The joint action for malformations induced by 18 binary mixtures of four carboxylic acids was determined, using Xenopus embryos. The acids were selected to evaluate whether joint actions for mixtures changed when the data were analyzed by specific malformations or malformation syndromes as opposed to joint actions determined when any ...

A girl with intractable epilepsy who received high dose valproic acid showed bone marrow suppression, which improved after the end of valproic acid treatment and the administration of supportive treatments. Valproic acid markedly suppressed the in vitro colony growth in this patient. It is believed that high dose valproic acid ...

OBJECTIVE: To describe the association of choreiform movements with the use of valproic acid. DESIGN: Case series. PATIENTS: Three patients who developed chorea during long-term treatment with valproic acid. All patients had severe brain damage; one had a preexisting unilateral vascular lesion in the caudate nucleus. At the time chorea ...

Clearance of valproic acid from brain tissue is believed to occur via a carrier-mediated system(s). The present study was designed to determine whether clearance was capacity-limited (saturable) and whether it occurred primarily at the choroid plexus. Ten rabbits were anesthetized with halothane and surgically prepared for ventriculocisternal perfusion. In group ...

The authors describe the first case of an isolated bilateral radial ray reduction occurring in a fetus exposed in utero to valproic acid; the diagnosis was made by ultrasound during the second trimester. This case of an isolated radial ray reduction associated with valproic acid use in pregnancy is a ...

Valproic acid, an antiepileptic drug, is extensively metabolized in humans. Two putative metabolites, 2-n-propyl-3-aminopentanoic acid (3-aminovalproic acid, 3-amino-VPA; 2a) and 2-n-propyl-4-aminopentanoic acid (4-amino-valproic acid, 4-amino-VPA; 4a), which may result from the transamination of the respective keto acids 1a and 3a may explain the unusual extended seizure protection elicited by valproic ...

Limited studies indicate increased free fraction of valproic acid in uremia. One study also described displacement of valproic acid from protein binding by salicylate in children with epilepsy. The authors studied in vitro interaction of valproic acid and salicylate in uremic sera and compared their results with same interactions in ...