Hematological Consequences of Valproic Acid in Pediatric Patients: A Systematic Review with a Mechanistic Approach

Author(s):  
Bamdad Riahi-Zanjani ◽  
Mohammad Delirrad ◽  
Rana Fazeli-Bakhtiyari ◽  
Mahood Sadeghi ◽  
Hadi Zare-Zardini ◽  
...  

Purpose: Although valproate (VPA) has several advantages in controlling seizures, it may cause serious hematological consequences. Hematotoxicity of VPA is particularly important in pediatrics because patients at this age are at a growing risk of leukemia. For a conclusive agreement about the toxicity of VPA, in this study, we systematically reviewed the literature in which the hematological consequences of VPA had been emphasized. Methods: A systematic literature search was performed in June 2021 on electronic databases to find original research on the association between VPA therapy and hematotoxicity in pediatric patients. For this purpose, the following search terms “hematotoxicity”, “valproic acid” and “pediatrics” with different spellings and similar terms, were searched in the title, keywords, and abstracts of articles. The data were collected and used for qualitative data description. Results: A total of 36 relevant articles with an overall 1381 study population were included. The results showed that VPA could cause severe hematotoxicity in children even at therapeutic doses. Neutropenia, thrombocytopenia, and bone marrow depression are the most common complications associated with VPA therapy. Also, findings showed that after discontinuation of VPA and starting other antiepileptic drugs or reducing the administered VPA dose, hematologic damages were entirely resolved, and all the hematological parameters improved during two weeks. Conclusions: This review showed that VPA therapy could cause hematotoxicity in children; hence, it is recommended to monitor hematological indices during VPA therapy. Also, according to the suggested mechanistic pathways of VPA side effects, a combination of VPA with antioxidants may reduce hematological side effects.

Author(s):  
J. Bruni ◽  
L.J. Willmore ◽  
B.J. Wilder

SummaryValproic acid in therapeutic doses was used in the treatment of postanoxic intention myoclonus. Disappearance of the myoclonus occurred with marked improvement in the electroencephalogram. No significant side effects were noted. Hepatic function tests were monitored. Determination of valproic acid plasma levels was used to guide therapy. Levels above 55 ßg were generally required. The patient remains free of myoclonus after four and one half months.


2019 ◽  
Author(s):  
Jungu Kim ◽  
Su Cheol Kim ◽  
Jaegwon Jeong ◽  
Myeong Gyu Kim

BACKGROUND Methylphenidate, a stimulant used to treat attention deficit hyperactivity disorder (ADHD), has the potential for nonmedical uses such as study and recreation. In the era of active use of social networking services (SNSs), experience with the nonmedical use or side effects of methylphenidate might be shared on Twitter. OBJECTIVE To analyze monthly tweets about methylphenidate, its nonmedical use and side effects, and user sentiments about methylphenidate. METHODS Tweets mentioning methylphenidate from August 2018 to July 2019 were collected using search terms for methylphenidate and its brand names. Only tweets written in English were included. The monthly number of tweets about methylphenidate and the number of tweets containing keywords related to the nonmedical use and side effects of methylphenidate were analyzed. Precision was calculated as the number of true nonmedical use or side effects divided by the number of tweets containing each keywords. Sentiment analysis was conducted using the text and emoji in tweets, and tweets were categorized as very negative (less than -3), negative (-3 to -1), neutral (0), positive (1 to 3), or very positive (more than 3), depending on the sentiment score. RESULTS A total of 4,169 tweets were ultimately selected for analysis. The number of tweets per month was lowest in August (n=264) and highest in May (n=435). There were 292 (7.0%) tweets about nonmedical uses of methylphenidate. Among those, 200 (4.8%) described use for studying, and 15 (0.4%) described use for recreation. In 91 (2.2%) tweets, snorting methylphenidate was mentioned. Side effects of methylphenidate, mainly poor appetite (n=74, 1.8%) and insomnia (n=54, 1.3%), were reported in 316 (7.6%) tweets. The average sentiment score was 0.027 ± 1.475, and neutral tweets were the most abundant (n=1,593, 38.2%). CONCLUSIONS Tweets about methylphenidate were most abundant in May, mentioned nonmedical use for study or recreation, and contained information about side effects. Analysis of Twitter has the advantage of saving the cost and time needed to conduct a survey, and could help identify nonmedical uses and side effects of drugs.


2020 ◽  
Vol 4 (s1) ◽  
pp. 110-110
Author(s):  
Brandon Joseph Sonn ◽  
Kennon Heard ◽  
Andrew Monte

OBJECTIVES/GOALS: Acetaminophen (Tylenol, APAP) toxicity has been well documented and well explored over the last 50 years. However, there has been no investigation into identification of specific metabolites that can predict which patients will have adverse reactions to therapeutic doses of APAP. METHODS/STUDY POPULATION: 205 subjects recruited from the Denver, CO community received the highest recommended daily dosing of APAP, 4 grams, for 16 days. Subjects were grouped by 1) alanine aminotransferase (ALT) at any monitored time point above 60units/L (n = 20) vs 2) no increase in ALT at any time point (n = 185). Blood was collected at days 0, 4, 7, 16, and 31. Samples were run on ultra-high performance liquid chromatography mass spectrometry with 27 heavy-labeled standards for metabolites documented to be associated with APAP metabolism. Data will be analyzed to look for significant changes in metabolite and demographic variable expressions using t-tests, chi square and logistic regression, as appropriate. RESULTS/ANTICIPATED RESULTS: It is expected that there will be greater elevations of conjugated non-toxic APAP metabolites (APAP-glucuronide, APAP-sulfate) in subjects whose ALT did not elevate because of successful hepatoprotection. Conjugated APAP metabolites are expected to only be present in samples taken after APAP therapy initiation confirming exposure as compared to being predictive of toxic response. Increases in lactate and cysteine in pre-exposure samples would allow for prediction of APAP toxicity as they are expected to have increased expression in subjects whose ALT became elevated which is indicative of increased hepatic damage due to oxidative damage. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of metabolites and/or demographic factors associated with toxic response to APAP prior to administration could advise APAP recommendations. Quantification of post-APAP administration metabolites would identify extent of successful hepatoprotective mechanisms.


Author(s):  
Azin Ayatollahi ◽  
Alireza Firooz ◽  
Ensieh Lotfali ◽  
Faraz Mojab ◽  
Azam Fattahi

Introduction: Dandruff and seborrheic dermatitis [SD] are similar skin conditions but have different severities. Because the current therapies are not able to completely remove dandruff, herbal extracts with better effectiveness and fewer side effects are being used in the pharmaceutical and cosmetic industries. Due to the adverse effects of chemical drugs, the use of natural products and traditional medicine has sharply increased over the past few decades. Therefore, in this review, we report herbs used as anti-dandruff agents in traditional medicine around the world. Methods: The review was conducted on the literature available on the medicinal utility of certain plants as antidandruff agents using PubMed and Google Scholar and the following search terms: Dandruff and Plants or Medicinal Plant and Dandruff treatment; and Essential oil and Dandruff. Results: Because the current therapies are not able to completely remove dandruff, herbal extracts with better effectiveness and fewer side effects are being used in the pharmaceutical and cosmetic industries. Nowadays, there are many different types of herbal antidandruff shampoo. They are effective and safe without the side effects of chemical agents. Recently, a large number of physicians have turned to herbal medicine. Clinical evidence of the therapeutic effects from herbal products has led to the study of many more herbs for their therapeutic roles. Conclusion: Herbal are now accepted to act a essential role in the development of favourable therapeutics, either alone or in combination with conventional antibiotics. However, the major challenges to this include finding compounds with satisfactorily lower MICs, low toxicity, and high bioavailability for effective and safe use in humans and animals.


2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Sébastien Chateauvieux ◽  
Franck Morceau ◽  
Mario Dicato ◽  
Marc Diederich

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.


2020 ◽  
Vol 4 (1) ◽  
pp. 46-51
Author(s):  
Leny Candra Kurniawan ◽  
Ikhwan Abdullah

Diabetic Peripheral Neuropathy is a type of nerve damagethat occurs due to diabetes. High blood sugar levels in thelong term can cause damage to nerve fibers throughout thebody, such as legs, feet, blood circulation, heart, digestivesystem, and urinary tract. Diabetic Peripheral Neuropathy isa serious complication of diabetes that often causes pain inthe limbs. Pain management Diabetic Peripheral Neuropathyis usually by administering pain medication for a long periodof time. These medicines will have side effects. The use ofacupuncture as an alternative to help reduce the intensity ofpain in peripheral diabetic neuropathy has proven to beeffective and relatively without side effects. The advantage ofacupuncture therapy is that it has relatively no side effects.The general aim of this study is to reduce the intensity of painin peripheral neuropathy. The research design usesquantitative methods. The study population was all patientswith peripheral neuropathy who visited the Harmoni HealthyClinic in March-May 2019. The sampling method used wasaccidental sampling. The benefits of this study provide analternative for DM sufferers to reduce the intensity ofneuropathic pain naturally with acupuncture without fear.side effects. From the results of this study it is known thatthere is an influence of Jin’s Three Needle acupuncture inreducing the intensity of pain in Peripheral Neuropathy.Calculations using statistical SPSS 21 with paired sample ttest obtained significant results (0.00) from the value of α(0.05), then H1 is accepted. So with a significance level of5%, it can be concluded that Jin's Three Needle acupuncturecan reduce the intensity of pain in diabetic peripheralneuropathy


2021 ◽  
Vol Volume 14 ◽  
pp. 417-430
Author(s):  
Xikun Wu ◽  
Weichong Dong ◽  
Haoran Li ◽  
Xiuling Yang ◽  
Yiran Jin ◽  
...  

1993 ◽  
Vol 7 (1_suppl) ◽  
pp. 19-23 ◽  
Author(s):  
Stuart A. Montgomery ◽  
P. Bebbington ◽  
P. Cowen ◽  
W. Deakin ◽  
P. Freeling ◽  
...  

Depression is a common illness which affects some 3% of the population per year. At least 25% of those with marked depression do not consult their general practitioner and in half of those who do the illness is not detected. Depression is easy to recognize when four or five of the core symptoms have been present for 2 weeks which often coincides with some occupational and social impairment. The core symptoms are depressed mood, loss of interest or pleasure, loss of energy or fatigue, concentration difficulties, appetite disturbance, sleep disturbance, agitation or retardation, worthlessness or self blame and suicidal thoughts. A diagnosis of depression is made when five of these core symptoms, one of which should be depressed mood or loss of interest or pleasure, have been present for 2 weeks. Four core symptoms are probably sufficient. Response to antidepressants is good in those with more than mild symptoms. When there are only few or very mild depressive symptoms evidence of response to antidepressants is more uncertain. Antidepressants are effective, they are not addictive and do not lose efficacy with prolonged use. The newer antidepressants have fewer side effects than the older tricyclics, they are better tolerated and lead to less withdrawals from treatment. They are less cardiotoxic and are safer in overdose. Antidepressants should be used at full therapeutic doses. Treatment failure is often due to too low a dose being used in general practice. It may be difficult to reach the right dose with the older tricyclics because of side effects. To consolidate response, treatment should be continued for at least 4 months after the patient is apparently well. Stopping the treatment before this is ill-advised as the partially treated depression frequently returns. Most depression is recurrent. Long-term antidepressant treatment is effective in reducing the risk of new episodes of depression and should be continued to keep the patient well.


PEDIATRICS ◽  
1974 ◽  
Vol 53 (4) ◽  
pp. 551-557
Author(s):  
H. Hooshmand

Any drug, regardless of how benign and well tolerated, is potentially toxic. The toxicity may be due to (1) dosage; (2) the size of the patient; (3) drug interaction; (4) drug specificity for the disease; (5) the nature of the disease for which the drug is used; and (6) the mode and frequency of medication. DOSE OF ANTICONVULSANT Dose of anficonvulsant is very important (Table I). Any anticonvulsant in higher than therapeutic doses has toxic potential. It is well known that anticonvulsants in large enough doses can act as convulsants. This is especially true for diphenylhydantoin, benzodiazepines, and lidocaine. THE SIZE OF THE PATIENT The size of the patient should be considered in dosage. It is safer and more accurate to adjust dosage to body surface than to weight (Table I). As the child grows, there may be a need to gradually increase the dose of anticonvulsants if seizure control is poor, or if the serum level of the anticonvulsant starts to decline. DRUG INTERACTION The relationship. of multiple drug therapy and its toxic effects on the brain is quite complicated, and many forms of toxicity can result. Toxicity may be the result of a combination of pharmacologically similar drugs. Such a combination may enhance the side effects of drowsiness and ataxia. The patient may suffer from these side effects without attaining therapeutic levels of individual anticonvulsants in the blood. In other words, a combination of drugs such as phenobarbital and primidone may result in severe ataxia and drowsiness.


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