Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures. Pharmacokinetics
Phenytoin elimination kinetics show mixed-order, non-linear elimination behaviour at therapeutic concentrations. Where phenytoin is at low concentration it is cleared by first order kinetics, and at high concentrations by zero order kinetics. A small increase in dose may lead to a large increase in drug concentration as elimination becomes saturated. The time to reach steady state is often longer than 2 weeks. History
Phenytoin (diphenylhydantoin) was first synthesized by German chemist Heinrich Biltz in 1908. Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, outside people including H. Houston Merritt and Tracy Putnam discovered phenytoins usefulness for controlling seizures, without the sedative effects associated with phenobarbital. According to Goodman and Gilmans Pharmacological Basis of Therapeutics:

In contrast to the earlier accidental discovery of the antiseizure properties of potassium bromide and phenobarbital, phenytoin was the product of a search among nonsedative structural relatives of phenobarbital for agents capable of suppressing electroshock convulsions in laboratory animals. It was approved by the FDA in 1953 for use in seizures. Jack Dreyfus, founder of the Dreyfus Fund, became a major proponent of phenytoin as a means to control nervousness and depression when he received a prescription for Dilantin in 1966. He has claimed to have supplied large amounts of the drug to Richard Nixon throughout the late 1960s and early 1970s, although this is disputed by former White House aides and Presidential historians.
For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present.The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from bone marrow storage pools, decreased margination of leukocytes onto vessel walls, decreased extravasation of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.Certain medications, including corticosteroids, lithium and beta agonists, may cause leukocytosis.Leukocytosis is an expected finding in healthy women during the post-partum period and is not a cause for alarm unless accompanied by clinical manifestations of infection. Diagnosis
Leukocyte counts
Below are blood reference ranges for various types of leukocytes/WBCs. The 97.5 percentile (right limits in intervals in image, showing 95% prediction intervals) is a common limit for defining leukocytosis. Treatment
While treatment is usually not necessary in the majority of cases, hyperleukocytosis (WBC count > 50 or 100 × 109/L), which can be seen in some leukemic patients, is treated to prevent leukostasis. See also
Bacterial infection
Complete blood count
Leukocytosis in head trauma
White blood cell

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