scholarly journals Valproic acid autoinduction: a case-based review

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sean Bennett ◽  
Mujeeb U. Shad
Keyword(s):  
Valproic Acid ◽  
Drug Interactions ◽  
Case Series ◽  
Free Fraction ◽  
Biologically Active ◽  
Diagnostic Challenge ◽  
Displacement Reactions ◽  
Underlying Mechanisms ◽  
Case Based ◽  
Protein Displacement

AbstractAlthough valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention that in addition to autoinduction increased elimination of VPA may be mediated by several pharmacokinetic (PK) factors, such as drug interactions, genetic polymorphisms of metabolic enzymes, and protein displacement reactions. As VPA is metabolized by multiple metabolic pathways, the risk for drug interactions is relatively high. There is also a growing evidence for high genetic inducibility of some enzymes involved in VPA metabolism. Protein displacement reactions with VPA increase the biologically active and readily metabolizable free fraction and pose a diagnostic challenge as they are usually not requested by most clinicians. Thus, monitoring of free fraction with total VPA levels may prevent clinically serious outcomes and optimize VPA treatment in clinically challenging patients. This case-based review compares the clinical data from three published cases and a new case of VPA autoinduction to enhance clinicians' awareness of this relatively rare but clinically relevant phenomenon along with a discussion of potential underlying mechanisms.

Antiretroviral concentrations in the presence and absence of valproic acid

2020 ◽  
Vol 75 (7) ◽  
pp. 1969-1971
Author(s):  
A Calcagno ◽  
J Cusato ◽  
M Ferrara ◽  
A De Nicolò ◽  
A Lazzaro ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Plasma Concentrations ◽  
Integrase Inhibitor ◽  
Major Effect ◽  
Therapeutic Drug ◽  
Hiv Integrase ◽  
Drug Drug Interaction ◽  
Underlying Mechanisms ◽  
Protein Displacement

Abstract Objectives An unexpected drug–drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. Methods We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. Results One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45–56) and 23.4 kg/m2 (20.8–26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62–227) in individuals on valproic acid versus 760 ng/mL (333–1407) in those not receiving valproic acid]. Conclusions Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug–drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction.

scholarly journals IgG4-related intracranial disease

2018 ◽  
Vol 32 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Shahine Goulam-Houssein ◽  
Jeffrey L Grenville ◽  
Katerina Mastrocostas ◽  
David G Munoz ◽  
Amy Lin ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Surgical Intervention ◽  
Case Series ◽  
Hypertrophic Pachymeningitis ◽  
Diagnostic Challenge ◽  
Perineural Spread ◽  
Related Disease ◽  
The Third ◽  
Igg4 Related Disease ◽  
Intracranial Involvement

IgG4-related disease (IgG4-RD) is a multi-organ chronic inflammatory process caused by infiltration of IgG4-positive plasma cells in one or more organs. Intracranial involvement has only recently become better recognized. Our case series adds to the growing literature on the varying presentations of intracranial IgG4 by describing the clinical and imaging findings of three patients who presented to our institution with intracranial involvement. Our first patient presented with a mass-forming IgG4 pachymeningitis mimicking a sphenoid wing meningioma, which is to our knowledge the largest mass-forming pachymeningitis published in the literature. Our second case depicts another presentation of extensive IgG4 pachymeningitis involving both cavernous sinuses and surrounding Meckel’s caves. The third case describes a patient with presumed lymphocytic hypophysitis, which was later determined to be IgG4-related hypophysitis with concomitant pachymeningitis and perineural spread along the optic nerves. The delayed diagnoses in our cases illustrates the diagnostic challenge that clinicians face in differentiating intracranial IgG4-RD from other infiltrative diseases such as sarcoidosis, granulomatous disease, tuberculosis and lymphoma. Earlier consideration of IgG4-related hypophysitis and hypertrophic pachymeningitis in the differential diagnosis can prevent significant morbidity including unnecessary surgical intervention and organ failure secondary to extensive fibrosis.

scholarly journals Acute Pancreatitis as a Complication of Antiepileptic Treatment: Case Series and Review of the Literature

2021 ◽  
Vol 13 (1) ◽  
pp. 98-103
Author(s):  
Agnieszka Pawłowska-Kamieniak ◽  
Paulina Krawiec ◽  
Elżbieta Pac-Kożuchowska
Keyword(s):  
Valproic Acid ◽  
Acute Pancreatitis ◽  
Metabolic Disorders ◽  
Genetic Factors ◽  
Clinical Symptoms ◽  
Gallstone Disease ◽  
Young Patients ◽  
Case Series ◽  
Review Of The Literature ◽  
Acid Therapy

Acute pancreatitis (AP) appears to be rare disease in childhood. In children, it has a different aetiology and course, and requires different management than in adult patients. The diagnosis of AP is based on at least two of the three criteria, which include typical clinical symptoms, abnormalities in laboratory tests and/or imaging studies of the pancreas. There are many known causes leading to AP in children including infections, blunt abdominal trauma, genetic factors, gallstone disease, metabolic disorders, anatomical defects of the pancreas, systemic diseases, as well as drugs, including antiepileptic drugs, and especially preparations of valproic acid. In our study, we present four cases of young patients diagnosed with acute pancreatitis as a complication of valproic acid therapy and we present a review of the literature. We believe that the activity of pancreatic enzymes should be monitored in children treated with valproate preparations in the case of clinical symptoms suggesting AP.

Improvement of restless legs syndrome by nabat: a case series and new hypotheses for research

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruohollah Seddigh ◽  
Amir-Abbas Keshavarz-Akhlaghi
Keyword(s):  
Restless Legs Syndrome ◽  
Case Series ◽  
Restless Legs ◽  
Underlying Mechanisms ◽  
Special Benefit

Abstract: Although many hypotheses have been suggested, the pathophysiology of restless legs syndrome (RLS) has not been fully understood. In this case series, we describe eleven cases with RLS whose symptoms subsided by the use of crystallized sucrose. This kind of sugar, known as: Case series.: All patients felt relief 30–60 min after taking 100 grams of dissolved: Sucrose seems to carry a special benefit for patients with RLS, and it provides evidence for growing literature demonstrating the different underlying mechanisms of RLS. Possible causes for this concurrence are also discussed.

Reversible cognitive impairment associated with a high free fraction but subtherapeutic total blood level of valproic acid due to hypoalbuminemia in a bipolar patient

2017 ◽  
Vol 41 (S1) ◽  
pp. S420-S420
Author(s):  
G. Dautzenberg ◽  
M. Nederlof ◽  
E. Heerdink ◽  
A. Beekman
Keyword(s):  
Valproic Acid ◽  
Cognitive Impairment ◽  
Binding Capacity ◽  
Free Fraction ◽  
Bipolar Patient ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Reference Ranges ◽  
Total Blood ◽  
Pharmacologically Active

Valproic acid (VPA) is widely used in the treatment of epilepsy and bipolar disorder. It is largely bound to serum proteins (80–95%) in particular albumin, with a saturable binding capacity. Under conditions of hypoalbuminemia, protein binding of VPA will decrease and its pharmacologically-active free fraction will rise, even to toxic levels while measuring subtherapeutic VPA total blood levels [1].We present an elderly bipolar patient with (sub)clinical total levels of VPA and a high free fraction of VPA due to hypoalbuminemia (14–24 g/L) leading to severe reversible cognitive impairment.VPA and the free fraction in particular, was the most likely cause of the cognitive impairment [2]. There was a time-correlation with increasing blood levels of total VPA (68 mg/L, reference 80–120 mg/L [3]), notably the free fraction (37.5 mg/L, reference 5–15 mg/L), and the intoxication.For therapeutic drug monitoring in laboratories, generally, total VPA concentrations (free + protein-bound) are measured instead of free fractions, due to technical difficulties, a lack of established reference ranges [4] and (inter)national guidelines [5,6] not requiring it. This presentation and literature points out that it is clinically relevant to measure the free fraction [7,8], especially in patients with hypoalbuminemia [9–11] to prevent unnecessary side effects and toxicity.We recommend measuring albumin during VPA use; particularly in patients with nephrotic syndrome, liver disease [12] or older adults [13–15]. Hypoalbuminemia demands a free fraction measurement.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Cardiac Outpouchings: Definitions, Differential Diagnosis, and Therapeutic Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Riccardo Scagliola ◽  
Gian Marco Rosa ◽  
Sara Seitun
Keyword(s):  
Differential Diagnosis ◽  
Clinical Practice ◽  
Therapeutic Approach ◽  
Tissue Characterization ◽  
Case Reports ◽  
Case Series ◽  
Diagnostic Challenge ◽  
Comprehensive Overview ◽  
Search Data ◽  
Data Location

Background and Aims. Cardiac outpouchings encounter a series of distinct congenital or acquired entities (i.e. aneurysms, pseudoaneurysms, diverticula, and herniations), whose knowledge is still poorly widespread in clinical practice. This review aims to provide a comprehensive overview focusing on definition, differential diagnosis, and prognostic outcomes of cardiac outpouchings, as well as further insights on therapeutic options, in order to assist physicians in the most appropriate decision-making. Methods. The material reviewed was obtained by the following search engines: MEDLINE (PubMed), EMBASE, Google Scholar, and Clinical Trials databases, from January 1966 until March 2021. We searched for the following keywords (in title and/or abstract): (“cardiac” OR “heart”) AND (“outpouching” OR “outpouch” OR “aneurysm” OR “pseudoaneurysm” OR “false aneurysm” OR “diverticulum” OR “herniation”). Review articles, original articles, case series, and case reports with literature review were included in our search. Data from patients with congenital or acquired cardiac outpouchings, from prenatal to geriatric age range, were investigated. Results. Out of the 378 papers initially retrieved, 165 duplicates and 84 records in languages other than English were removed. Among the 129 remaining articles, 76 were included in our research material, on the basis of the following inclusion criteria: (a) papers pertaining to the research topic; (b) peer-reviewed articles; (c) using standardized diagnostic criteria; and (d) reporting raw prevalence data. Location, morphologic features, wall motion abnormalities, and tissue characterization were found to have a significant impact in recognition and differential diagnosis of cardiac outpouchings as well as to play a significant role in defining their natural history and prognostic outcomes. Conclusions. Careful recognition of cardiac outpouchings remains a diagnostic challenge in clinical practice. Due to a broad cluster of distinctive and heterogeneous entities, their knowledge and timely recognition play a pivotal role in order to provide the most appropriate clinical management and therapeutic approach.

scholarly journals Clinical studies on serum concentration of free fraction of phenytoin, carbamazepine and valproic acid.

1990 ◽  
Vol 16 (5) ◽  
pp. 277-287 ◽  
Author(s):  
JUN HOSOYA ◽  
HIDEYO NAGAOKA ◽  
SYU ISHIKAWA ◽  
YOSHITO NAKAGAWA ◽  
YOSHIAKI HIGASHITANI ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Clinical Studies ◽  
Free Fraction

Isolated tricuspid valve endocarditis in immunocompetent juvenile patients: a series of three cases

2021 ◽  
Vol 14 (8) ◽  
pp. e244312
Author(s):  
Atanu Chandra ◽  
Shrestha Ghosh ◽  
Uddalak Chakraborty ◽  
Debojyoti Ray
Keyword(s):  
Risk Factors ◽  
Infective Endocarditis ◽  
Tricuspid Valve ◽  
Age Groups ◽  
Case Series ◽  
Venous Catheter ◽  
Diagnostic Challenge ◽  
Native Valve ◽  
Younger Age ◽  
High Index Of Suspicion

Right-sided native valve infective endocarditis is common in patients with congenital or valvular heart disease, intracardiac device, central venous catheter and intravenous drug abuse, usually manifesting in adulthood. However, in the absence of predisposing risk factors and in younger age groups, this disease may pose a diagnostic challenge. We report a case series of three juvenile patients with isolated tricuspid valve infective endocarditis without any risk factors and paucity of cardiovascular findings in two of them, in an attempt to highlight the importance of maintaining a high index of suspicion to arrive a timely diagnosis.

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