Life-Threatening and Rare Adverse Effects of Phenytoin

Polat, İpek; Karaoğlu, Pakize; Ayanoğlu, Müge; Yış, Uluç; Hız, Semra

doi:10.1097/pec.0000000000000495

Cited by 6 publications

(3 citation statements)

References 1 publication

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“…Neurotoxic effects are concentration-dependent and range from occasional mild nystagmus, ataxia, lethargy, tremor, to coma and seizures at high concentrations [59]. Cardiovascular toxicity effects due to rapid infusion can lead to bradycardia, hypotension, and asystole [60,61]. Due to its formulation, it is possible for crystallization of phenytoin to occur within the blood [57].…”

Section: Phenytoinmentioning

confidence: 99%

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management

Kirmani¹,

Au²,

Ayari³

et al. 2021

Aging and disease

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Super-refractory status epilepticus (SRSE) is a life-threatening neurological emergency with high morbidity and mortality. It is defined as "status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawal of anesthesia." This condition is resistant to normal protocols used in the treatment of status epilepticus and exposes patients to increased risks of neuronal death, neuronal injury, and disruption of neuronal networks if not treated in a timely manner. It is mainly seen in patients with severe acute onset brain injury or presentation of new-onset refractory status epilepticus (NORSE). The mortality, neurological deficits, and functional impairments are significant depending on the duration of status epilepticus and the resultant brain damage. Research is underway to find the cure for this devastating neurological condition. In this review, we will discuss the wide range of therapies used in the management of SRSE, provide suggestions regarding its treatment, and comment on future directions. The therapies evaluated include traditional and alternative anesthetic agents with antiepileptic agents. The other emerging therapies include hypothermia, steroids, immunosuppressive agents, electrical and magnetic stimulation therapies, emergent respective epilepsy surgery, the ketogenic diet, pyridoxine infusion, cerebrospinal fluid drainage, and magnesium infusion. To date, there is a lack of robust published data regarding the safety and effectiveness of various therapies, and there continues to be a need for large randomized multicenter trials comparing newer therapies to treat this refractory condition.

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Section: Phenytoinmentioning

confidence: 99%

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management

Kirmani¹,

Au²,

Ayari³

et al. 2021

Aging and disease

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“…Phenytoin has a narrow therapeutic index with a large propensity to produce ADRs due to patient interindividual variability. Adverse side effects of phenytoin are common and often include rashes, headache, behavioral changes, Steven-Johnson syndrome, cardiovascular collapse, and arrhythmias, especially with rapid intravenous administration, in both children and adults (Bansal et al, 2013;Polat et al, 2015). Many pediatric patients with severe epilepsy are often treated with polytherapy, and interactions between phenytoin and other AEDs and the resulting adverse effects have been documented; for example, concurrent treatment with phenytoin and valproic acid produced phenytoin toxicity in an adolescent epileptic patient despite adhering to pediatric dosing guidelines for phenytoin (Carvalho et al, 2014).…”

mentioning

confidence: 99%

Consequences of Phenytoin Exposure on Hepatic Cytochrome P450 Expression during Postnatal Liver Maturation in Mice

et al. 2018

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The induction of cytochrome P450 (P450) enzymes in response to drug treatment is a significant contributing factor to drug-drug interactions, which may reduce therapeutic efficacy and/or cause toxicity. Since most studies on P450 induction are performed in adults, enzyme induction at neonatal, infant, and adolescent ages is not well understood. Previous work defined the postnatal ontogeny of drug-metabolizing P450s in human and mouse livers; however, there are limited data on the ontogeny of the induction potential of each enzyme in response to drug treatment. Induction of P450s at the neonatal age may also cause permanent alterations in P450 expression in adults. The goal of this study was to investigate the short- and long-term effects of phenytoin treatment on mRNA and protein expressions and enzyme activities of CYP2B10, 2C29, 3A11, and 3A16 at different ages during postnatal liver maturation in mice. Induction of mRNA immediately following phenytoin treatment appeared to depend on basal expression of the enzyme at a specific age. While neonatal mice showed the greatest fold changes in CYP2B10, 2C29, and 3A11 mRNA expression following treatment, the levels of induced protein expression and enzymatic activity were much lower than that of induced levels in adults. The expression of fetal CYP3A16 was repressed by phenytoin treatment. Neonatal treatment with phenytoin did not permanently induce enzyme expression in adulthood. Taken together, our data suggest that inducibility of drug-metabolizing P450s is much lower in neonatal mice than it is in adults and neonatal induction by phenytoin is not permanent.

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“…7 Immediate-type reactions such as urticaria, angioedema and anaphylaxis due to AEDs are very rare compared to delayed-type reactions. 1,[8][9][10][11] Standardised diagnosis of these reactions includes first skin prick and intrardermal tests, respectively, and if negative, DPT is recommended. 1,12 We performed prick-intradermal tests, respectively, with the same levetiracetam commercial drug (Keppra® 500mg/5ml) administered to our patient at the time of reaction, and all tests were negative.…”

Section: Discussionmentioning

confidence: 99%

Anaphylaxis to levetiracetam in an adolescent: a very rare occurence

et al. 2021

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Antiepileptic drug (AED)-induced hypersensitivity reactions(HSR) which are reported to be more common in children, present with a variety of clinical manifestations ranging from benign maculopapular exanthems to severe delayed reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms(DRESS) and also organ-specific disease such as agranulocytosis and drug-induced liver injury. 1 Immediate-type HSRs such as urticaria/ angioedema or anaphylaxis are very rare with AEDs. Delayed reactions are more commonly seen with aromatic AEDs like phenytoin and carbamazepine than the new generation or non-aromatic AEDs. 1 Levetiracetam is an increasingly used new non-aromatic AEDs and reported to have a safer tolerability profile in daily practice. 2 Here, we report an adolescent case of anaphylaxis due to levetiracetam, in order to point out that new AEDs can result in HSRs and also, severe immediate reactions should be expected Case ReportA 15-year-old girl with no previous diagnosis of epilepsy presented to the pediatric emergency department with a history of two seizures in the same day. Later in the emergency department, the patient experienced another seizure with jaw-locking, nystagmus, spasms in legs and arms

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Life-Threatening and Rare Adverse Effects of Phenytoin

Cited by 6 publications

References 1 publication

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management

Consequences of Phenytoin Exposure on Hepatic Cytochrome P450 Expression during Postnatal Liver Maturation in Mice

Anaphylaxis to levetiracetam in an adolescent: a very rare occurence

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