Primidone was recently shown to directly inhibit the TRPM3 ion channel; whether this effect contributes to its anticonvulsant effect is not known, but gain of function mutations in TRPM3 were recently shown to be associated with epilepsy and intellectual disability. Pharmacokinetics
Primidone converts  to phenobarbital and PEMA; it is still unknown which exact cytochrome P450 enzymes are responsible. The phenobarbital, in turn, is metabolized to p-hydroxyphenobarbital. The rate of primidone metabolism was greatly accelerated by phenobarbital pretreatment, moderately accelerated by primidone pretreatment, and reduced by PEMA pretreatment. In 1983, a new minor metabolite, p-hydroxyprimidone, was discovered.Primidone, carbamazepine, phenobarbital and phenytoin are among the most potent hepatic enzyme inducing drugs in existence. This enzyme induction occurs at therapeutic doses. In fact, people taking these drugs have displayed the highest degree of hepatic enzyme induction on record. In addition to being an inducer of CYP3A4, it is also an inducer of CYP1A2, which causes it to interact with substrates such as fluvoxamine, clozapine, olanzapine, and tricyclic antidepressants, as well as potentially increasing the toxicity of tobacco products. Its metabolite, phenobarbital, is a substrate of CYP2C9, CYP2B6, CYP2C8, CYP2C19, CYP2A6, CYP3A5, CYP1E1, and the CYP2E subfamily. The gene expression of these isoenzymes is regulated by human pregnane receptor X (PXR) and constitutive androstane receptor (CAR). Phenobarbital induction of CYP2B6 is mediated by both. Primidone does not activate PXR.The rate of metabolism of primidone into phenobarbital was inversely related to age; the highest rates were in the oldest patients (the maximum age being 55).
New world arena viruses are further broken down into three clades, A, B, and C. The Guanarito arena virus belongs to clade B and is the cause of VHF. On the biosafety level scale of one to four, with four causing the most risk, the viruses causing hemorrhagic fevers have been assigned a four by the CDC. Host
The short-tailed cane mouse, the main host of GTOV, is native to western Venezuela and resides in large numbers in tall grass, cultivated agricultural fields, human homes, and outbuildings. It is speculated that demographic and ecological changes in the rural areas increased the frequency of contact between humans and infected rodents such that VHF emerged. History
From September 1989 through December 2006, the State of Portuguesa recorded 618 cases of VHF. Nearly all of the cases were individuals who worked or lived in Guanarito during the time they became infected. The case fatality rate was 23.1%.Because the virus is contracted by aerosol dissemination, concern arose shortly after the first cases emerged in 1989 due to fear of biological warfare. Potential biological terrorism agents were identified and categorized in 1999 by the Centers for Disease Control and Prevention (CDC) as part of the Congressional initiative to further response capabilities to biological weapons. Arenaviruses causing hemorrhagic fevers, along with a genus of virus called filoviruses, were categorized in Category A; these are pathogens with the highest potential impact on public health safety.