How Genes Influence The Breakdown Of Phenytoin?

What Is Phenytoin?

Phenytoin is an anticonvulsant or antiepileptic drug used to control certain types of seizures in epileptic patients.

It works by slowing down seizure-causing impulses in the brain.

Phenytoin is commonly available in three oral forms:

Extended-release capsule
Chewable tablet and
Liquid or oral suspension

Phenytoin is also available in the injectable form and should be administered only by a healthcare provider.

The injectable form of phenytoin is used in tonic-clonic epilepticus to prevent and treat seizures before or after neurosurgery.

The dosage of phenytoin prescribed to a patient depends upon their condition and type of seizures.

A majority of phenytoin consumed gets eliminated as an inactive substance via bile.

Is Phenytoin A Controlled Substance?

Phenytoin is not a controlled medication.

No studies show it may be addictive or prone to abuse.

When Is Phenytoin Used?

Phenytoin helps treat grand mal seizures, tonic-clonic seizures, and complex partial seizures.

In some cases, phenytoin is also used to treat irregular heartbeat associated with certain conditions.

How Does Phenytoin Work?

Like most anticonvulsants, phenytoin works by preventing nerve cells (neurons) in the brain from becoming too active and thereby blocking the spread of seizures in the brain.

The neurons in the brain work at a certain rate under normal conditions.

However, these neurons are forced to work quicker than normal during a seizure.

When many neurons begin working at a rapid rate together, it leads to an uncontrollable surge and gives rise to a seizure.

Taking anticonvulsants like phenytoin prevents this uncontrollable surge, preventing a seizure.

How Does Phenytoin Prevent Seizures?

Phenytoin prevents the neurons in the brain from firing uncontrollably together.

By preventing the overactivity of neurons in the brain, phenytoin helps block or prevent seizures.

Side Effects Of Phenytoin

Despite its widespread use in treating and managing epileptic conditions, phenytoin may cause side effects in some individuals.

Common side effects due to phenytoin include:

Drowsiness
Dizziness
Slurring of speech
Headache
Difficulty in sleeping
Skin rash
Constipation
Nausea
Vomiting
Irregular eye movements
Tremors or shaking in the hands

Since most epileptic patients need to take phenytoin lifelong, some long-term side effects of phenytoin include:

Gum overgrowth
Excessive growth of hair on the body
Acne

Serious side effects of phenytoin that require immediate medical attention include:

Slow heartbeat
Unusual eye movements
Confusion
Blurred vision
Increased thirst or urination
Depression
Bipolar disorder
Mood problems
Suicidal thoughts
Signs of liver failure (vomiting, nausea, stomach or abdominal pain, yellow skin or eyes, dark urine)

Does Phenytoin Cause Gingival Hyperplasia?

In some people, long-term use of phenytoin may cause gingival hyperplasia or overgrowth of gums.

The incidence of phenytoin-induced gum overgrowth lies between 3% to 93%.

In fact, around 50% of people on long-term phenytoin therapy are prone to develop gingival hyperplasia.

It may take around 2 to 3 months for the gingival overgrowth to become noticeable.

The front teeth are usually more prone to overgrowth, often leading to poor oral hygiene in people with the condition.

Phenytoin: Interactions With Other Drugs

Phenytoin interacts with other drugs, which may change how one or both drugs work.

Drug interactions also affect the clearance of the drugs, often increasing the risk of overdosage and related symptoms.

Some significant drug interactions of phenytoin include:

Phenytoin and Delavirdine

Delavirdine is used in HIV treatment.

Taking delavirdine with phenytoin may significantly reduce levels of delavirdine, making it less effective in treating HIV.

Phenytoin and Carbamazepine

Carbamazepine is an anticonvulsant.

Taking carbamazepine with phenytoin may increase the metabolism of phenytoin, often decreasing its level in blood.

Reduced phenytoin levels in the blood may result in loss of seizure control and symptoms like drowsiness, visual problems, behavioral changes, and poor muscle coordination.

Phenytoin and Warfarin

Warfarin is a blood thinner, and taking it with phenytoin may increase your risk of bleeding.

Taking this combination of drugs may also increase phenytoin levels in the blood, often resulting in adverse effects due to the drug.

Phenytoin and Cyclosporine

Cyclosporine is an immunosuppressant that prevents the rejection of donated organs.

Taking phenytoin with cyclosporine may increase the risk of organ rejection.

Phenytoin and Valproic acid

This drug is used to treat epilepsy and bipolar disorder.

Taking valproic acid with phenytoin may increase the risk of liver damage.

Phenytoin and Doxycycline

Doxycycline is a broad-spectrum antibiotic used to treat bacterial infections.

Taking phenytoin with doxycycline reduces the effectiveness of doxycycline and may cause your infection to worsen.

Phenytoin: Gene-Drug Interactions

The CFHR4 Gene

Complement Factor H Related 4 or CFHR4 gene gives instructions for an enzyme that plays a role in lipid transport.

rs78239784 is a single nucleotide polymorphism or SNP in the CFHR4 gene.

Patients with the GG genotype may be at a greater risk of developing phenytoin-induced maculopapular exanthema than people with GT and TT genotypes.

The CYP2C9 Gene

Cytochrome P450 family 2 subfamily C member 9 or CYP2C9 gene plays an important role in the metabolism (breaking down) of steroid hormones, fatty acids, and drugs like warfarin and phenytoin.

Some genotypes of the CYP2C9 gene reduce phenytoin clearance and increase one’s risk of developing adverse central nervous system and skin effects.

Recommendations To Use Phenytoin

Medical history

Inform your doctor if you have any of the following medical conditions:

Some blood disorders
Diabetes
Liver diseases
Lupus (a skin condition)
Folate or vitamin B-1 deficiency
Current medications

Tell your doctor about all the medications you are currently taking to avoid adverse drug interactions and subsequent negative effects.

Nutritional and herbal supplements and vitamins may interact with phenytoin.

So, inform your doctor if you are taking any of these.

Pregnancy and breastfeeding

Phenytoin may harm your unborn child - so, it should be taken during pregnancy only when required.

Though studies are limited, existing research states that phenytoin passes into breast milk.

Inform your doctor if you are breastfeeding before taking phenytoin.

Genetic testing

Genetic testing helps your doctor understand how phenytoin will affect you.

It will also help your doctor determine the right dosage of phenytoin for you.

Analyze Your Genetic Response to Phenytoin

Summary

Phenytoin is an anticonvulsant drug used to treat epilepsies like tonic-clonic, grand-mal, and complex partial seizures.
Phenytoin works by preventing the overactivity of nerve cells in the brain.
Though phenytoin is safe, it may cause side effects in some people.
Gingival hyperplasia is one of the most common side effects of taking phenytoin long-term.
Before taking phenytoin, inform your doctor about medications you are currently taking to avoid adverse drug interactions.
The CFHR2 and CYP2C9 are two genes studies studied with phenytoin.
Inform your doctor about your medical history, allergies, pregnancy, and breastfeeding status before taking phenytoin.
Genetic testing may help your doctor prescribe the right dose of phenytoin.

References

A Sneak Peek Into The Personalized Medicine Report

Know Your Response To Drug Therapies Using Your 23andMe, AncestryDNA Raw Data!