ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Fosphenytoin (FOS) administered intravenously offers several benefits over intravenously administered phenytoin, including a faster infusion rate, decreased pain and irritation at the infusion site, and fewer cardiovascular complications. However, some studies suggest that the intravenous administration of FOS in some patients may also induce adverse cardiovascular events. Here, we investigated the clinical characteristics of patients who experienced hypotension following an intravenous infusion of a FOS loading dose. METHODS: We reviewed the medical records of consecutive patients who received an intravenous (IV) dose of FOS between July 2013 and June 2015. Various clinical and demographic parameters were analysed, including comorbidities, drug history, seizure aetiology and type, incidence of hypotension/cardiac arrhythmia and the dosing data (ie the total dose, concentration and FOS IV infusion rate). Hypotension was defined as a ≥20 mm Hg decrease in systolic blood pressure or a ≥10 mm Hg decrease in diastolic blood pressure during or after FOS IV infusion. These parameters were compared between patients with and without hypotension. RESULTS AND DISCUSSION: Of the 28 included patients, 11 (39%) had hypotension associated with an IV infusion of FOS, two of whom also had an atrioventricular block. Most patients (22/28, 79%) who received an IV infusion of FOS had status epilepticus (SE). The presence of SE was significantly associated with the development of hypotension (P=.026); hypotension occurred in half of the patients with SE, but did not occur in six patients without SE. Hypotension was also associated with old age (≥60 years, P=.034) and the presence of a systemic infection (P=.04). WHAT IS NEW AND CONCLUSION: Our study shows that hypotension associated with an IV infusion of FOS is not a rare adverse event, especially in patients with SE. Moreover, we found that old age and the presence of a systemic infection increased the risk of hypotension. These findings suggest that FOS should be infused under careful cardiovascular monitoring, especially in patients who are at higher risk of developing hypotension.
Subject(s)
Anticonvulsants/adverse effects , Blood Pressure/drug effects , Hypotension/chemically induced , Phenytoin/analogs & derivatives , Adult , Age Factors , Aged , Aged, 80 and over , Anticonvulsants/administration & dosage , Female , Humans , Hypotension/epidemiology , Incidence , Infusions, Intravenous , Male , Middle Aged , Phenytoin/administration & dosage , Phenytoin/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND AND OBJECTIVE: Lymphocyte-oriented kinase deficiency encoded by the serine/threonine kinase 10 (STK10) gene correlates with the intracellular adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1) complex in aspirin hypersensitivity. This study investigated the association between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant asthma (AIA). METHODS: A total of 54 SNPs were genotyped in 163 AIA patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: Logistic regression revealed that a synonymous variant (rs2306961G>A) had the most significant association with AIA (P = .008 under the codominant model; P = .004 under the dominant model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT could play a role in regulating expression of STK10 in airway epithelium. Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is unique to rs2306961G>A, were significantly associated with aspirin hypersensitivity in asthmatics (P < .05). CONCLUSIONS: Although replications in independent cohorts and further functional evaluations are needed, our preliminary findings suggest that STK10 polymorphisms might be susceptible genetic markers of AIA and that gene expression could be mediated by tissue-specific codon usage.
Subject(s)
Asthma, Aspirin-Induced/genetics , Biomarkers/metabolism , Protein Serine-Threonine Kinases/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Asthma, Aspirin-Induced/epidemiology , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Haplotypes , Humans , Korea , Male , Middle Aged , Organ Specificity , Polymorphism, Single Nucleotide , Protein Serine-Threonine Kinases/genetics , RiskABSTRACT
At least 11 HLA-DRB1*12 alleles have been identified to date. We report a new HLA-DRB1*12 allele, DRB1*1210, that was identified in the Korean population. This new allele differs from HLA-DRB1*120101 by a single nucleotide at position 40 (G-->A) in exon 1 that falls within codon--16 (GTT-->ATT). This change results in a single valine to isoleucine amino acid alteration.
