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Anticonvulsant Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
In addition, mothers receiving these anticonvulsants should be given 20 mg of vitamin K in the final month of pregnancy (Delblay et al., 1982). The newborn should receive 1 mg of vitamin K at birth and again in 12 hours. Umbilical cord prothrombin, partial thromboplastin values, and vitamin-K-dependent clotting factors should be evaluated shortly after delivery (Bleyer and Skinner, 1976; Srinivasan et al., 1982). Folic acid and vitamin D supplements should be considered for pregnant women on phenytoin and other similar anticonvulsants, in addition to vitamin K supplementation in the third trimester (Yerby, 2003).
Phenytoin
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
The main advantages of PHT in the treatment of status epilepticus are its effectiveness in controlling convulsions, relatively long half-life, and lack of significant central nervous system depression. Disadvantages are its cardiovascular toxicity if given too rapidly, the time required for giving the full loading dose, and its relative ineffectiveness in suppressing focal epileptic activity. Phenytoin is effective in suppressing experimental seizures as soon as adequate brain concentrations are attained, which, in rats, is only a few minutes. The parenteral form of PHT was developed in the 1950s originally for intramuscular (i.m.) use. Ironically, it is poorly absorbed by this route because it crystallizes in muscle and should not be given i.m. The currently available preparation contains propylene glycol and ethanol. Propylene glycol itself is cardiotoxic (44). The PHT preparation currently available in the United States may be diluted to 5 mg/ml or less in normal saline solution (45). This permits steady administration by infusion equipment. Injection of a bolus of undiluted PHT by hand can be dangerous. Blood pressure and EKG should be monitored during PHT infusion. To overcome these problems with the current preparation, a disodium phosphate ester of phenytoin has been developed. It is water soluble and has an excellent safety profile given i.v. or i.m. (46). If a person’s seizures do not respond to PHT infusion, there is a very high probability that a significant acute CNS insult has occurred. PHT infusion may thus aid in diagnosis.
Cardiovascular Drugs
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: The use of Phenytoin during pregnancy has been associated with teratogenic effects in the newborns. If its use was mandatory, it is recommended to give Folic Acid 5 mg/day at the beginning or even before the start of pregnancy.
Phenytoin and damage to the cerebellum – a systematic review of published cases
Published in Expert Opinion on Drug Safety, 2022
Robin Ferner, Rachael Day, Sally M Bradberry
Phenytoin (diphenylhydantoin, Dilantin®) was introduced into clinical practice as an antiseizure medication (anti-epileptic drug, anticonvulsant) by Merritt and Putnam in 1938 [1]. A review of 329 patients in 1939 supported ‘the strong anticonvulsant properties and marked toxic effects of this drug,’ for by that time, the adverse effects of ataxia, nystagmus, tremor, dizziness, and visual and psychological disturbance had been observed in treated patients [2]. By the 1960s, the adverse effects had been correlated with serum concentrations of phenytoin: ‘nystagmus appearing at approximately 20 [mg/L], ataxia at about 25–30 [mg/L], and disorientation and somnolence at greater than 35 [mg/L].’ [3] The ataxia, nystagmus, and tremor are characteristic of cerebellar dysfunction. Phenytoin has non-linear pharmacokinetics, and this makes dosage adjustment difficult. A small increase in dose can result in an unexpectedly large increase in plasma concentration, and consequent phenytoin toxicity. In most cases, cerebellar signs disappear when phenytoin treatment is stopped, or the dosage is reduced.
Clinical considerations for rapid administration of undiluted or minimally diluted levetiracetam bolus doses
Published in Expert Review of Neurotherapeutics, 2022
Justin P. Reinert, Loulwa Maktabi, Donald Branam, Mercedes Snyder
An open label, multicenter RCT was conducted by Dalziel et al. in 2019 to determine whether IV LEV or phenytoin was the superior second-line medication option in children for convulsive SE [11]. Patients between the ages of 3–16 years of age who had failed initial treatment with benzodiazepine were included in the trial. Two hundred and thirty-three patient encounters were described in the trial, with 119 being randomized to the LEV arm. Patients who received LEV were given a 40 mg/kg bolus dose over 5 minutes, whereas the phenytoin cohort received 20 mg/kg over 20 minutes. While not statistically significant, a greater number of patients in the phenytoin cohort had a cessation of seizure activity within 5 minutes of drug infusion than with LEV (60% vs. 50%, p = 0.16). Patients who received LEV were more likely to be intubated and had a longer intensive care unit and hospital admission, but no significant adverse drug effects or infusion reactions were noted to be exclusive to the LEV cohort [11].
Incidence of neurobehavioral side effects associated with levetiracetam compared to phenytoin in traumatic brain injury patients
Published in Brain Injury, 2021
Jerika V. Nguyen, Tian Yaw, Holly Gratton
Adverse effects of phenytoin may include ataxia, nystagmus, gingival hyperplasia, osteomalacia, bone marrow suppression, and rash(4). Common adverse effects of levetiracetam include behavioral problems, headaches, and dizziness(5). Behavioral adverse effects, such as agitation, hostility, and emotional lability associated with levetiracetam have been described in the literature. These affected 7.6% of adult and pediatric patients with epilepsy on levetiracetam in a systematic review of randomized controlled trials, a significantly higher rate compared to patients on placebo(6). A recent Cochrane review demonstrated no significant evidence to suggest that behavioral adverse effects are significantly associated with levetiracetam in adults, whether individually or grouped(7). However, children using levetiracetam may have a higher risk of developing behavioral side effects compared to those who do not (7,8).