Chapter 14 Antiepileptic Drugs
Phenobarbital and Primidone (Mysoline)
Class: Barbiturates Primidone is metabolized in the liver to phenobarbital. Use of primidone can provide anticonvulsant activity with a lower serum level of phenobarbital than that attained with phenobarbital itself. This can reduce the likelihood of sedation and fatigue associated with phenobarbital. In third-world countries, oral phenobarbital is often the drug of choice for routine seizure prophylaxis because of its low cost. The most common adverse effect of phenobarbital is sedation, although tolerance to this effect usually develops with continued therapy. Therapeutic effects are generally seen at serum drug levels of 10 to 40 mcg/mL. A major advantage of this drug is its long half-life, which allows once-a-day dosing. This can be a substantial advantage for patients who have a difficult time remembering to take their medication or for those who have erratic schedules. Even if a patient takes his or her dose 12 or even 24 hours late, therapeutic blood levels may still be maintained. Contraindications include known drug allergy, porphyria (a disorder of the synthesis of heme, a component of hemoglobin), liver or kidney impairment, and respiratory illness. Adverse effects: dizziness, drowsiness, lethargy cardiovascular, CNS, gastrointestinal (GI), and dermatologic reactions. Phenobarbital interacts with many drugs because it is a major inducer of hepatic microsomal enzymes, including the cytochrome P-450 system enzymes, which causes more rapid clearance of some drugs. Phenobarbital is available in oral and injectable forms, whereas primidone is available only for oral use. **Do not abruptly stop taking!
Clonazepam (Klonopin)
Class: Benzodiazepine Indications: strong anticonvulsant activity, treats absence, myoclonic, akinetic seizures, infantile spasms. Mechanism of Action: suppresses spike and wave discharge in absence seizures (petit mal) and decreases the spread and discharge in minor motor seizures. Adverse Effects: palpitations, increased salivation, anemia, leukopenia, thrombocytopenia, sedation, respiratory depression. Nursing Implications: periodic liver function tests, anticonvulsant activity is often lost after 3 months of treatment: dosage may need to be adjusted. Monitor for overdose: somnolence, confusion, irritability, abdominal cramps, coma.
Phenytoin (Dilantin) and Fosphenytoin (Cerebyx)
Class: Hydantoins Phenytoin: indicated for the management of tonic-clonic and partial seizures. Contraindications include known drug allergy and heart conditions that involve bradycardia. Adverse effects: The most common adverse effects are lethargy, abnormal movements, mental confusion, and cognitive changes. Gingival hyperplasia is a well-known adverse effect of long-term oral phenytoin therapy. Scrupulous dental care can help prevent this. Other adverse effects associated with long-term phenytoin therapy can cause acne, hirsutism, and hypertrophy of subcutaneous facial tissue resulting in an appearance known as Dilantin facies and osteoporosis. Also: nystagmus, ataxia, drowsiness, rash, thrombocytopenia, hepatitis. Therapeutic drug levels are usually 10 to 20 mcg/mL. At toxic levels, phenytoin can cause nystagmus, ataxia, dysarthria, and encephalopathy. It increases the metabolism of other drugs and reduces their blood levels. Because phenytoin is highly protein bound, exaggerated phenytoin levels can be seen in patients with very low serum albumin concentrations. With lower levels of albumin, more of the free, unbound, pharmacologically active phenytoin molecules will be present in the blood. This most commonly occurs in patients who are malnourished or have chronic renal failure. It is generally necessary to maintain phenytoin levels well below 20 mcg/mL in such patients. The long half-life of the drug allows for twice- or even once-daily dosing. It is very irritating to veins when injected and must be given by slow intravenous (IV) push (not exceeding 50 mg/min in adults) directly into a large vein through a large-gauge (20-gauge or larger) venous catheter. Phenytoin is only to be diluted in normal saline (NS) for IV infusion, and a filter must be used. Follow each dose by an injection of a saline flush to avoid local venous irritation. Avoid subcutaneous or perivascular injection. Fosphenytoin (Cerebyx) is an injectable prodrug of phenytoin. It can be given intramuscularly or intravenously—by IV push or continuous infusion—without causing burning on injection associated with phenytoin. Fosphenytoin is given at a rate of 150 mg PE/min or less to avoid hypotension or cardiorespiratory depression. **Implement fall-prevention measures after infusion of either phenytoin or fosphenytoin because of possible ataxia and dizziness. Assess: check skin for measles like rash. assess gums and teeth. assess liver function. **If dysrhythmias or hypotension occur, discontinue the infusion immediately, monitor patient vital signs, and contact the prescriber immediately.
Carbamazepine (Tegretol)
Class: Iminostilbenes Carbamazepine (Tegretol) is the second most commonly prescribed antiepileptic drug in the United States, after phenytoin. It was originally marketed in the late 1960s for the treatment of trigeminal neuralgia (a painful facial nerve condition). It is considered a first-line treatment for partial seizures and generalized tonic-clonic seizures. It may actually worsen myoclonic or absence seizures. Therefore its use is contraindicated in both of these conditions as well as in cases of known drug allergy and bone marrow depression. Carbamazepine is associated with autoinduction of hepatic enzymes. Autoinduction is a process in which, over time, a drug stimulates the production of enzymes that enhance its own metabolism, and leads to lower than expected drug concentrations. With carbamazepine, this process usually occurs within the first 2 months after starting the drug. Adverse effects: Nausea, headache, dizziness, unusual eye movements, visual changes, behavioral changes, rash, abdominal pain, abnormal gait, GI upset. Assess: check for drug related anemia, or bone marrow suppression. **Do not give with grapefruit juice.
Oxcarbazepine (Trileptal)
Class: Iminostilbenes Oxcarbazepine (Trileptal) is a chemical analogue of carbamazepine. Its precise mechanism of action has not been identified, although it is known to block voltage-sensitive sodium channels, which aids in stabilizing excited neuronal membranes. It is indicated for partial seizures and secondarily generalized seizures. Contraindications include known drug allergy. Common adverse reactions include headache, dizziness, and nausea. Unlike carbamazepine, this drug is not a hepatic enzyme inducer. As a result, it is associated with far fewer common drug interactions than is carbamazepine. Oxcarbazepine is available for oral use only.
Ethosuximide (Zarontin)
Class: Succinimide Ethosuximide (Zarontin) is used in the treatment of uncomplicated absence seizures. It is not effective for secondary generalized tonic-clonic seizures. The only listed contraindication for either use is known drug allergy. Adverse effects: nausea, abdominal pain, dizziness, drowsiness.
Gabapentin (Neurontin)
Gabapentin (Neurontin) is a chemical analogue of GABA, a neurotransmitter that inhibits brain activity. The exact mechanism of action is unknown, but is believed to work by increasing the synthesis and synaptic accumulation of GABA between neurons. It is indicated as an adjunct drug for the treatment of partial seizures and for prophylaxis of partial seizures. Evidence also shows gabapentin to be effective as single-drug therapy for new-onset epilepsy. It is most commonly used to treat neuropathic pain. Contraindications include known drug allergy. Adverse effects: dizziness, drowsiness, nausea, visual and speech changes, edema. Gabapentin is available for oral use only.
Lamotrigine (Lamictal)
Lamotrigine (Lamictal) is indicated for simple or complex partial seizures, for generalized seizures related to Lennox-Gastaut syndrome (an atypical form of absence epilepsy that may persist into adulthood), and, most recently, for primary generalized tonic-clonic seizures. It is also used for the treatment of bipolar disorder. The only contraindication is known drug allergy. Adverse effects: drowsiness, ataxia, headache, nausea, blurred or double vision. One potentially serious adverse effect is a rash that can progress to the major dermatologic reaction known as Stevens-Johnson syndrome. This condition involves inflammation and sloughing of skin, potentially over the entire body, in a manner that resembles a third-degree burn. It is often reversible but can also be fatal. To avoid this condition, doses are very slowly titrated over several weeks. Drug interactions chiefly involve other antiepileptic drugs as well as other CNS depressants and oral contraceptives. Lamotrigine is available for oral use only. Assess: energy level, visual acuity, headaches.
Levetiracetam (Keppra)
Levetiracetam (Keppra) is indicated as adjunct therapy for partial seizures with and without secondary generalization. It is contraindicated in cases of known drug allergy. Its mechanism of action is unknown. It is generally well tolerated, Adverse effects: dizziness, drowsiness, hyperactivity, behavior changes such as anxiety, hostility, agitation or suicidal ideation. No drug interactions are currently listed; however, like all antiepileptic drugs, the potential for excessive CNS depression exists when it is used in combination with other sedating drugs. Levetiracetam is available in both oral and injectable forms.
Pregabalin (Lyrica)
Pregabalin (Lyrica), like gabapentin, is structurally related to GABA. However, it does not bind to GABA receptors but rather to the alpha2-delta receptor sites, which affect calcium channels in CNS tissues. Its mechanism of action is still not fully understood. Pregabalin is a Schedule V controlled substance. The drug is indicated as adjunct therapy for partial seizures, although it is most commonly used for neuropathic pain, and postherpetic neuralgia and fibromyalgia. Contraindications include known drug allergy. Adverse effects: dizziness, drowsiness, peripheral edema, blurred vision. No clinically significant drug interactions are listed to date; however, as with all antiepileptic drugs, the potential for additive CNS depression exists when other sedating drugs are used. Pregabalin is available for oral use only.
Tiagabine (Gabitril)
Tiagabine (Gabitril) is indicated as adjunct therapy for partial seizures. Contraindications include known drug allergy. Its exact mechanism of action has not been identified, but is known to have beneficial effects by inhibiting the reuptake of GABA from the neuronal synapses (spaces between neurons) in the brain. Although tiagabine is effective in controlling epileptic seizures, there have been several case reports of paradoxical seizures (opposite of what would intuitively be expected) in nonepileptic patients who are treated with the drug for other indications. Most of these cases involved patients being treated for bipolar disorder. Of even greater concern is that in some of these cases the seizure episodes progressed to status epilepticus. For these reasons, prescribers are currently advised to avoid off-label use of tiagabine. Adverse effects: dizziness, drowsiness, agitation, asthenia (weakness), GI upset, abdominal pain, rash, tremor Drug interactions chiefly involve other CNS depressant drugs. Tiagabine is available for oral use only. **Take with food.
Topiramate (Topamax)
Topiramate (Topamax) is a structurally unique drug chemically related to fructose. It is indicated as adjunct therapy for partial and secondarily generalized seizures, for generalized tonic-clonic seizures, and for drop attacks in Lennox-Gastaut syndrome. Contraindications include known drug allergy. Its exact mechanism of action is unknown. Common adverse effects: dizziness, drowsiness, GI upset ataxia. Angle-closure glaucoma can also occur, and the patient must immediately report any visual changes. Common drug interactions involve chiefly other antiepileptic drugs and oral contraceptives. Topiramate is available for oral use only. In 2011, the FDA notified health care professionals about an increased risk for cleft palate in children born to mothers who were taking topiramate during pregnancy.
Valproic Acid (Depakote)
Valproic acid is used primarily in the treatment of generalized seizures (absence, myoclonic, and tonic-clonic). It is also used for bipolar disorder and has been shown to be effective in controlling partial seizures. Also used for migraine headaches. Contraindications include known drug allergy, liver impairment, and urea cycle disorders (genetic disorders of urea metabolism). Common adverse effects include drowsiness; nausea, vomiting, and other GI disturbances; tremor; weight gain; and transient hair loss. The most serious adverse effects are hepatotoxicity and pancreatitis. Valproic acid can interact with many medications. Valproic acid is highly protein bound and competes with other highly protein-bound medications for binding sites. It also is metabolized by hepatic microsomal enzymes and competes for metabolism with other drugs. In contrast to phenobarbital and phenytoin, it is not a hepatic enzyme inducer. It is available in both oral and injectable forms. Valproic acid itself is chemically the simplest dosage form and is available as an oral liquid. Long-acting oral dosage forms are also available as divalproex sodium (Depakote), which comes in delayed- and extended-release tablets as well as capsules with long-acting granules (Depakote Sprinkles) that can be opened and sprinkled onto food. The injectable form is the salt valproate sodium (Depacon). **Take with 4-6 oz of water or food.
