8.10 Anticonvulsants

Medications used for seizures are called anticonvulsants or antiseizure drugs. Antiseizure drugs stabilize cell membranes and suppress the abnormal electric impulses in the cerebral cortex. These drugs prevent seizures but do not provide a cure. Antiseizure drugs are classified as CNS depressants. There are many types of medications used to treat seizures such as phenytoin, phenobarbital, benzodiazepines, carbamazepine, valproate, and levetiracetam.^[1]

There are three main pharmacological effects of antiseizure medications. First, they increase the threshold of activity in the motor cortex, thus making it more difficult for a nerve to become excited. Second, they limit the spread of a seizure discharge from its origin by suppressing the transmission of impulses from one nerve to the next. Third, they decrease the speed of the nerve impulse conduction within a given neuron.

Some drugs work by enhancing the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which plays a role in regulating neuron excitability in the brain.^[2] Gabapentin, although structurally similar to GABA and classified as an anticonvulsant, is commonly used to control chronic neuropathic pain. Neuropathic pain is defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory nervous system.”^[3] An example of neuropathic pain is tingling or burning in the lower extremities that often occurs in patients with diabetes.

Phenytoin

Phenytoin, which was discovered in 1938, was the first anti-seizure medication and is still being used to control seizures.^[4]

Mechanism of Action

Phenytoin improves evidence of seizures by interfering with sodium channels in the brain, resulting in a reduction of sustained high-frequency neuronal discharges.

Indications for Use

Phenytoin is indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and for the prevention and treatment of seizures occurring during or following neurosurgery.

Nursing Considerations Across the Lifespan

Phenytoin should not be administered to pregnant women because it will cause harm to the fetus. When given intravenously, there is a Black Box Warning that the rate of administration should not exceed 50 mg per minute in adults and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous phenytoin.

Phenytoin has a narrow therapeutic drug level, usually between 10-20 mcg/ml, so serum drug monitoring is required. Serum levels of phenytoin sustained above the therapeutic range may produce confusional states referred to as delirium, psychosis, or encephalopathy. Accordingly, at the first sign of acute toxicity, serum levels should be immediately checked.

Abrupt discontinuation can cause status epilepticus, so in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary.

Use with caution in patients with renal or hepatic impairment. Elderly patients may require dosage adjustment.

There are many potential drug interactions with phenytoin. Read drug label information before administering. Phenytoin is extensively bound to plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes, so it is susceptible to inhibitory drug interactions, which may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity.

Adverse/Side Effects

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with phenytoin treatment. The onset of symptoms is usually within 28 days, but can occur later. Phenytoin should be discontinued at the first sign of a rash.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking antiepileptic drugs, including phenytoin. Some of these events have been fatal or life threatening. DRESS typically presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement. These findings should be immediately reported to the provider. Acute hepatotoxicity has been reported with phenytoin. These events may be part of the spectrum of DRESS or may occur in isolation.

Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression.

The most common adverse reactions encountered with phenytoin therapy are nervous system reactions and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion.^[5]

Patient Teaching & Education

Patients should be advised to take medications as directed and that doses should be evenly spaced throughout the day.  It may take several weeks to obtain the desired medication effect.  Abrupt withdrawal of medication may cause status epilepticus.  Patients should avoid alcohol and other CNS depressants while taking anticonvulsant drug therapy.  Additionally, diabetic patients should monitor their blood glucose levels carefully.

Now let’s take a closer look at the medication grid for phenytoin in Table 8.10a.^[6]

Table 8.10a Phenytoin Medication Grid

Class/Subclass	Prototype/Generic	Administration Considerations	Therapeutic Effects	Adverse/Side Effects
Anticonvulsant	phenytoin	Careful cardiac monitoring is needed during and after administering intravenous phenytoin For IV infusions, an in-line filter (0.22 to 0.55 microns) should be used. Cannot be given with D5W due to preciptiation and no faster than 50 mg/minute in adults Monitor serum drug levels Contraindicated with patient with heart block Use cautiously in patients with hepatic or renal impairment Taper dose; do not stop abruptly	Decrease or prevent seizure activity	Cardiovascular risk associated with rapid IV infusion Discontinue and notify the provider if a rash occurs Notify the provider immediately if fever, rash, lymphadenopathy, and/or facial swelling occur Cardiovascular: arrhythmia and hypotension CNS: Nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion GI: Constipation, gingival hyperplasia, and hepatotoxicity Hematology: Thrombocytopenia, pancytopenia, and agranulocytosis

Levetiracetam

Levetiracetam is indicated as adjunctive therapy in the treatment of partial onset seizures in patients 12 years of age and older with epilepsy. It is generally well tolerated.

Mechanism of Action

The exact mechanism of action is unknown. This medication may interfere with sodium, calcium, potassium, or GABA transmission.^[7]

Indications for Use

Levetiracetam is used for partial onset seizures in patients with epilepsy.

Nursing Considerations Across the Lifespan

Plasma levels can gradually decrease during pregnancy and should be monitored closely. Safety and effectiveness in pediatric patients 12 years of age and older have been established.

Levetiracetam immediate release and solution can be used in patients as young as 1 month.

Levetiracetam should not be stopped abruptly or withdrawal seizures may occur. Use with caution in patients with renal impairment.

Adverse/Side Effects

Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed; monitor patients for psychiatric signs and symptoms.

The most common adverse reactions are somnolence and irritability. Advise patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam.

This drug can cause anaphylaxis or angioedema after the first dose or at any time during treatment. Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported, as well as coordination difficulties and hematologic abnormalities.

Patient Teaching & Education

Medications should be taken as directed and may cause increased dizziness and somnolence.  Patients, family, and caregivers should also monitor carefully for suicidality during medication therapy.

Now let’s take a closer look at the medication grid for levetiracetam in Table 8.10b.^[8]

Table 8.10b Levetiracetam Medication Grid

Class/Subclass	Prototype/Generic	Administration Considerations	Therapeutic Effects	Adverse/Side Effects
Anticonvulsant	levetiracetam	Taper dose; do not stop abruptly or seizures may occur Monitor plasma levels for pregnant women Use cautiously if renal impairment	Decrease seizure activity	Behavioral/mood changes (psychotic symptoms, suicidal ideation, irritability, and aggressive behavior) Anaphylaxis or angioedema Somnolence, fatigue, and irritability Serious skin conditions Coordination difficulties Hematopoietic abnormalities

 

Gabapentin

Gabapentin is indicated as an adjunct treatment for partial seizures, but is most commonly used to treat neuropathic pain.^[9]

Mechanism of Action

The exact mechanism of action is unknown. It is structurally similar to GABA, but does not act on GABA receptors or influence GABA.

Indications for Use

Gabapentin is used for partial seizures and neuropathic pain.

Nursing Considerations Across the Lifespan

This drug can cause harm to the fetus of pregnant women.

Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence of central nervous system related adverse events. The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems); 2) hostility, including aggressive behaviors; 3) thought disorder, including concentration problems and change in school performance; and 4) hyperkinesia (primarily restlessness and hyperactivity).

In elderly patients, peripheral edema and ataxia tended to increase in incidence with age. Fall precautions should be considered.

Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency.

Adverse/Side Effects

Antiepileptic drugs, including gabapentin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including gabapentin. Some of these events have been fatal or life threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. If these symptoms occur, they should be immediately reported to the provider.

Gabapentin may cause dizziness, somnolence, and other symptoms and signs of CNS depression. Patients should be advised neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely.^[10]

Patient Teaching & Education

Patients receiving gabapentin therapy should take medication as directed and be careful to not exceed dosage recommendations.  Patients should not take gabapentin within 2 hours of antacid medications.  Additionally, gabapentin may cause increased drowsiness and dizziness.  Patients, family, and caregivers should also monitor for suicidality.

Now let’s take a closer look at the medication grid for gabapentin in Table 8.10c.^[11]

Table 8.10c Gabapentin Medication Grid

Class/Subclass	Prototype/Generic	Administration Considerations	Therapeutic Effects	Adverse/Side Effects
Anticonvulsant	gabapentin	Administer first dose at bedtime to decrease dizziness and drowsiness Monitor for worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior Taper dose; do not stop abruptly	Decreased neuropathic pain or seizures	Increased suicidal ideation Immediately report fever, rash, and/or lymphadenopathy CNS depression: dizziness, somnolence, and ataxia