Phenotypic interaction of simultaneously administered isoniazid and phenytoin in patients with tuberculous meningitis or tuberculoma having seizures

Adole, Prashant Shankarrao; Singh, Amandeep; Kharbanda, P; Sharma, Sadhna

doi:10.1016/j.ejphar.2013.05.032

Cited by 9 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various studies 14 15 16 have shown difference in frequencies and distribution of various alleles of NAT-2 gene among Indians. We have demonstrated a correlation between the INH levels and phenytoin toxicity in TBM or tuberculoma patients in our earlier study 17 . Therefore, the aim of this pilot study was to elucidate whether any allelic variant of NAT2 gene acted as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma taking INH and phenytoin simultaneously.…”

supporting

confidence: 50%

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

Adole¹,

Kharbanda²,

Sharma³

2016

Indian J Med Res

Self Cite

View full text Add to dashboard Cite

Background & objectives:Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously.Methods:Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR.Results:The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group.Interpretation & conclusions:Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

show abstract

supporting

confidence: 50%

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

Adole¹,

Kharbanda²,

Sharma³

2016

Indian J Med Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Children with TBM are more likely to experience seizures relative to adults; this may be attributed to the immaturity of CNS, blood-brain barrier, and the immune system of this vulnerable group [4,26]. The incidence of seizures in children with TBM has been estimated between 50 and 74% [4,[26][27][28][29]; with higher rates being reported in pediatric patients under the age of 4 years [30][31][32][33]. While the reported risk of late unprovoked seizures among CNS infection survivors in the developed countries is estimated at 6.8-8.3%, it is much higher in resource-poor countries [34].…”

Section: Epidemiologymentioning

confidence: 99%

“…In children, seizures are the presenting symptom in 10-20% of the affected cases, and over 50% of children with TBM develop seizures at the initial days of admission [42]. While in adults, seizures were reported as the initial presenting feature in 10-15% of TBM cases [28,43].…”

Section: Epidemiologymentioning

confidence: 99%

The prevalence, characteristics and outcome of seizure in tuberculous meningitis

Abdulaziz

Zhou

2020

Acta Epileptologica

View full text Add to dashboard Cite

Seizures are a common finding in patients with tuberculous meningitis (TBM), and associate with four times increased risk of death and neurological disability, especially in children. It has been reported that brain inflammation, diffuse neuronal injury, and reactive gliosis may all contribute to the pathogenesis of seizures in TBM. Early seizure onset may be associated with meningeal irritation and cerebral oedema; while, the late seizures are usually due to infarction, hydrocephalus, tuberculoma and paradoxical response. Moreover, recurrent uncontrolled seizures can evolve to status epileptics resulting in an increased risk of chronic epilepsy and poor prognosis. Therefore, this review aimed to assess the frequency of seizures in patients with TBM, and discuss the etiologies, mechanisms, and characteristics of seizures in TBM. Besides, we have searched the literature to identify the prognostic factors for chronic epilepsy after TBM.

show abstract

“…INH is reported to decrease the clearance of many drugs including phenytoin, carbamazepine, diazepam, vincristine, primidone and acetaminophen 13 . The risk of phenytoin toxicity is higher if INH is given along with it which is supported by several reports 14 ,15. However, Kay et al 16 showed that concomitant administration of INH and rifampicin increased the clearance of phenytoin.…”

mentioning

confidence: 54%

“…As a result, any small change in the dose leads to disproportionately higher plasma concentration of phenytoin 17 18 19 . INH induced phenytoin toxicity has been widely reported 14 15 20 . An in vitro study done in human liver microsomes found that INH was a potent and concentration dependent inhibitor of CYP2C19 and CYP3A enzymes, but it did not produce significant inhibition of CYP2C9 enzyme 13 .…”

mentioning

confidence: 99%

NAT2 gene polymorphism: covert drug interaction causing phenytoin toxicity

Adithan

Subathra

2016

Indian J Med Res

View full text Add to dashboard Cite

Phenotypic interaction of simultaneously administered isoniazid and phenytoin in patients with tuberculous meningitis or tuberculoma having seizures

Cited by 9 publications

References 25 publications

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

The prevalence, characteristics and outcome of seizure in tuberculous meningitis

NAT2 gene polymorphism: covert drug interaction causing phenytoin toxicity

Contact Info

Product

Resources

About