Phenytoin as an anticonvulsant
Epilepsy is a group of neuronal disorders which exhibits episodic high frequency discharges of impulses by a group of neurons. Epilepsy is normally treated with drugs however surgery can be done in severe cases. The high frequency discharges can cause seizures which can be divided into partial seizures (the seizure starts and remains local) or generalized (the seizures starts locally but spread).Partial seizures can be divided into simple and complex where as generalized is divided into, tonic- clonic, absence, myoclonic, febrile and status epilepticus. (1)
Phenytoin (figure 1) is an anticonvulsant drug which is used to treat epilepsy as it helps in the management of complex partial seizures and tonic clonic seizures. It works by blocking high frequency action potentials which are firing repeatedly. This stabilizes the inactivated state of the voltage gated sodium channels which results in a lesser amount of channels available for opening. This leaves the affected cells in a less excitable state until the drug dissociates.(2) However this drug has been shown to cause fetal malformations in mothers who are using this drug as a form of treatment. Fetal malformations are increased 2 to 3 times more in babies of epileptic mothers.
Side Effects
Phenytoin is a known teratogen, which is implicated particularly with the clef lip/palate. Fetal hydration syndrome is caused when the developing fetus is exposed to phenytoin(3). The child who has this syndrome can suffer with cleft lip/palate (Figure 2),microcephaly (a smaller then average head), mental retardation, hypoplastic nails (absence or undeveloped nails shown in figure 3), Intrauterine growth restriction (poor growth of the baby in the womb) and developmental delay.(4)
Mechanism of action
The mechanism of action of how teratogenic substances cause their effects on a fetus is not yet understood. Most teratogenic substance (in this case phenytoin) causes its effect by indirectly reacting with DNA. It stops DNA synthesis by affecting the folate metabolism.(1) Folate is important in pregnancy as is reduces the chances of drug induced and spontaneous malformations.
Do the benefits out weigh the risks...?
The FDA (Food and Drug Administration) has a pregnancy category which gives the risk of fetal malformations due to a drug (pharmaceutical). The FDA has classed phenytoin as a class D drug(5). This means that there is evidence which links the drug to potential fetal risk, however the benefits of the drug outweighs the risk to the fetus.(6)
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Epilepsy is a group of neuronal disorders which exhibits episodic high frequency discharges of impulses by a group of neurons. Epilepsy is normally treated with drugs however surgery can be done in severe cases. The high frequency discharges can cause seizures which can be divided into partial seizures (the seizure starts and remains local) or generalized (the seizures starts locally but spread).Partial seizures can be divided into simple and complex where as generalized is divided into, tonic- clonic, absence, myoclonic, febrile and status epilepticus. (1)
Phenytoin (figure 1) is an anticonvulsant drug which is used to treat epilepsy as it helps in the management of complex partial seizures and tonic clonic seizures. It works by blocking high frequency action potentials which are firing repeatedly. This stabilizes the inactivated state of the voltage gated sodium channels which results in a lesser amount of channels available for opening. This leaves the affected cells in a less excitable state until the drug dissociates.(2) However this drug has been shown to cause fetal malformations in mothers who are using this drug as a form of treatment. Fetal malformations are increased 2 to 3 times more in babies of epileptic mothers.
Side Effects
Phenytoin is a known teratogen, which is implicated particularly with the clef lip/palate. Fetal hydration syndrome is caused when the developing fetus is exposed to phenytoin(3). The child who has this syndrome can suffer with cleft lip/palate (Figure 2),microcephaly (a smaller then average head), mental retardation, hypoplastic nails (absence or undeveloped nails shown in figure 3), Intrauterine growth restriction (poor growth of the baby in the womb) and developmental delay.(4)
Mechanism of action
The mechanism of action of how teratogenic substances cause their effects on a fetus is not yet understood. Most teratogenic substance (in this case phenytoin) causes its effect by indirectly reacting with DNA. It stops DNA synthesis by affecting the folate metabolism.(1) Folate is important in pregnancy as is reduces the chances of drug induced and spontaneous malformations.
Do the benefits out weigh the risks...?
The FDA (Food and Drug Administration) has a pregnancy category which gives the risk of fetal malformations due to a drug (pharmaceutical). The FDA has classed phenytoin as a class D drug(5). This means that there is evidence which links the drug to potential fetal risk, however the benefits of the drug outweighs the risk to the fetus.(6)
Visual impairments? click play for audio: