Adverse drug reactions induced by valproic acid
TL;DR: A systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity.
About: This article is published in Clinical Biochemistry.The article was published on 2013-10-01. It has received 234 citations till now. The article focuses on the topics: Adverse drug reaction & Adverse effect.
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TL;DR: Since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment.
Abstract: After more than a century from its discovery, valproic acid (VPA) still represents one of the most efficient antiepileptic drugs (AEDs). Pre and post-synaptic effects of VPA depend on a very broad spectrum of actions, including the regulation of ionic currents and the facilitation of GABAergic over glutamatergic transmission. As a result, VPA indirectly modulates neurotransmitter release and strengthens the threshold for seizure activity. However, even though participating to the anticonvulsant action, such mechanisms seem to have minor impact on epileptogenesis. Nonetheless, VPA has been reported to exert anti-epileptogenic effects. Epigenetic mechanisms, including histone deacetylases (HDACs), BDNF and GDNF modulation are pivotal to orientate neurons toward a neuroprotective status and promote dendritic spines organization. From such broad spectrum of actions comes constantly enlarging indications for VPA. It represents a drug of choice in child and adult with epilepsy, with either general or focal seizures, and is a consistent and safe IV option in generalized convulsive status epilepticus. Moreover, since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment. Furthermore, VPA-induced neuroprotection is under investigation for benefit in stroke and traumatic brain injury. Hence, VPA has still got its place in epilepsy, and yet deserves attention for its use far beyond neurological diseases. In this review, we aim to highlight, with a translational intent, the molecular basis and the clinical indications of VPA.
154 citations
TL;DR: The array of tools and models for the study of liver steatosis is discussed, and the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed.
134 citations
Cites background from "Adverse drug reactions induced by v..."
...This protonophoric effect can slightly uncouple mitochondrial respiration and may induce opening of the mitochondrial permeability transition pore, serving as another stimulus of VPA-induced cell death [54]....
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...ICR mice develop microvesicular steatosis after receiving tetracycline [71], and a time-dependent and dose-dependent increase in TGs is seen after treatment with VPA [47,176]....
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...Recently, a new mechanism of VPA-induced hepatic steatosis has been described, namely inhibition of carnitine palmitoyl transferase 1, which transfers FFA into the mitochondria, by VPA-CoA....
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...The induction of steatosis by VPA associated with microvesicular fat deposition in the liver was first shown in male Crl Swiss mice [173]....
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...Sprague Dawley rats repeatedly exposed to VPA produce liver steatosis correlating with lipid accumulation, preferably in the perivenous zone [174]....
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TL;DR: ‘Precision medicine’ focuses on the identification of an underlying genetic aetiology allowing personalised therapeutic choices, and certain human leukocyte antigen, HLA, alleles are associated with an increased risk of idiosyncratic adverse drug reactions.
115 citations
TL;DR: The evidence supporting the notion that environmental stressors linked to ASD can also adversely affect both mitochondria and GI function is reviewed, and enteric bacteria that are overrepresented in children with ASD produce short-chain fatty acid metabolites that are potentially toxic to the mitochondria.
Abstract: Autism spectrum disorder (ASD) affects a significant number of individuals worldwide with the prevalence continuing to grow. It is becoming clear that a large subgroup of individuals with ASD demonstrate abnormalities in mitochondrial function as well as gastrointestinal (GI) symptoms. Interestingly, GI disturbances are common in individuals with mitochondrial disorders and have been reported to be highly prevalent in individuals with co-occurring ASD and mitochondrial disease. The majority of individuals with ASD and mitochondrial disorders do not manifest a primary genetic mutation, raising the possibility that their mitochondrial disorder is acquired or, at least, results from a combination of genetic susceptibility interacting with a wide range of environmental triggers. Mitochondria are very sensitive to both endogenous and exogenous environmental stressors such as toxicants, iatrogenic medications, immune activation, and metabolic disturbances. Many of these same environmental stressors have been associated with ASD, suggesting that the mitochondria could be the biological link between environmental stressors and neurometabolic abnormalities associated with ASD. This paper reviews the possible links between GI abnormalities, mitochondria, and ASD. First, we review the link between GI symptoms and abnormalities in mitochondrial function. Second, we review the evidence supporting the notion that environmental stressors linked to ASD can also adversely affect both mitochondria and GI function. Third, we review the evidence that enteric bacteria that are overrepresented in children with ASD, particularly Clostridia spp., produce short-chain fatty acid metabolites that are potentially toxic to the mitochondria. We provide an example of this gut–brain connection by highlighting the propionic acid rodent model of ASD and the clinical evidence that supports this animal model. Lastly, we discuss the potential therapeutic approaches that could be helpful for GI symptoms in ASD and mitochondrial disorders. To this end, this review aims to help better understand the underlying pathophysiology associated with ASD that may be related to concurrent mitochondrial and GI dysfunction. Keywords: autism spectrum disorders ; Clostridia spp.; electron transport chain; enteric bacteria; fatty acid metabolism; gastrointestinal; mitochondrial dysfunction; oxidative stress; propionic acid; short-chain fatty acids (Published: 7 May 2015) Citation: Microbial Ecology in Health & Disease 2015, 26: 27458 - http://dx.doi.org/10.3402/mehd.v26.27458
109 citations
Cites background from "Adverse drug reactions induced by v..."
...This disorder is well known because valproic acid can trigger acute liver failure leading to death (74)....
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TL;DR: AHS iPSCs‐Hep are more sensitive to the VPA‐induced mitochondrial‐dependent apoptotic pathway, and this effect is mediated by mPTP opening, suggesting that targeting mP TP opening could be an effective method to prevent hepatotoxicity by VPA in AHS patients.
84 citations
Cites background from "Adverse drug reactions induced by v..."
...VPA, one of the most widely used antiepileptic drugs worldwide, has adverse drug reactions, such as hepatotoxicity, in patients with mitochondrial disorders.(10) Individuals with AHS are at extremely increased risk of developing fatal VPA-induced hepatotoxicity, which has been a defining feature of AHS....
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References
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TL;DR: Risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics, chlormezanone, quinolones, and aminopenicillins among drugs usually used for short periods.
Abstract: Background Toxic epidermal necrolysis and Stevens–Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case–control study to quantify the risks associated with the use of specific drugs. Methods Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens–Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Results Among drugs usually used for short periods, the risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate rel...
1,219 citations
Book•
01 Jan 1978
TL;DR: The hepatotoxic effects of oncotherapeutic and immunosuppressive agents miscellaneous drugs and diagnostic chemicals afterthoughts on hepatotoxicity appendices are described.
Abstract: Part 1 General considerations: the spectrum of hepatotoxicity hepatic metabolism of foreign compounds vulnerability of the liver to toxic injury expressions of hepatotoxicity classification of hepatotoxins and mechanisms of toxicity hepatotoxic effects of ethanol chemical hepatocarcinogenesis. Part 2 Experimental hepatotoxicity: experimental hepatotoxicity direct hepatotoxins - haloaliphatics, phosphorus, iron and copper indirect cytotoxic hepatotoxins toxic cholestasis. Part 3 Environmental hepatotoxicity: syndromes of environmental hepatotoxicity occupational toxicity hepatotoxicity in the household the hepatotoxic potential of a polluted environment. Part 4 Iatrogenic hepatic injury: drug-induced liver disease anaesthetic agents psychotropic and anticonvulsant agents drugs used to treat rheumatic and musculospastic disease hormonal derivatives and related drugs hepatic injury from the treatment of infectious and parasitic diseases drugs used in cardiovascular disease hepatotoxic effects of oncotherapeutic and immunosuppressive agents miscellaneous drugs and diagnostic chemicals afterthoughts on hepatotoxicity appendices.
849 citations
TL;DR: A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR, finding that many cases were still related to a few "old" drugs with a known high risk, and risk was restricted to the first few weeks of drug intake.
843 citations
TL;DR: Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment, and the outcome was death in 9 cases, but no predictive factors for serious cases were found.
834 citations
"Adverse drug reactions induced by v..." refers background in this paper
...A more severe and prolonged course of disease was shown in DRESS cases accompanied by HHV-6 reactivation compared to cases lacking reactivation of latent viral infections [141,160]....
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...Symptoms of drug reaction with eosinophilia and systemic symptoms (DRESS) include fever, rash, internal organ involvement (particularly the liver) and hematologic abnormalities (eosinophilia or atypical lymphocytes) [160]....
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...DRESS is often accompanied by reactivation of latent viral infections [141,160]....
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TL;DR: Only 4.2% of live births to women with epilepsy had an MCM, and polytherapy exposure was greater than for monotherapy exposure, and carbamazepine was associated with the lowest risk of MCM.
Abstract: Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). Methods: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. Results: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p Conclusions: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.
752 citations