12.1: Epilepsy and Anticonvulsant Drugs
By the end of this section, you should be able to:
- 12.1.1 Describe the pathophysiology of epilepsy.
- 12.1.2 Identify the clinical manifestations related to epilepsy.
- 12.1.3 Identify the etiology and diagnostic studies related to epilepsy.
- 12.1.4 Identify the characteristics of drugs used to treat epilepsy.
- 12.1.5 Explain the indications, action, adverse reactions, and interactions of drugs used to treat epilepsy.
- 12.1.6 Describe nursing implications of drugs used to treat epilepsy.
- 12.1.7 Explain the client education related to drugs used to treat epilepsy.
Overview of Epilepsy and Seizures
Seizures are a sudden and temporary disturbance in the electrical activity of the brain that can cause changes in behavior, movement, or consciousness. Epilepsy , on the other hand, is a neurological disorder characterized by recurrent seizures. In epilepsy, the seizures are typically unprovoked and can occur spontaneously without any apparent trigger. Epilepsy is a condition that affects approximately 3.4 million people in the United States, and it can have a significant impact on an individual’s quality of life (Centers for Disease Control and Prevention, 2020a, 2020c).
Etiology
Seizures can have various causes such as fever, head injury, brain infection, drug or alcohol withdrawal or overdose, electrolyte imbalances, and metabolic disorders. Seizures may also result from brain tumors or masses, stroke, or other neurological conditions. Sometimes the cause of a seizure cannot be identified—a condition called an idiopathic seizure (Centers for Disease Control and Prevention, 2020b, 2020c).
Epilepsy, on the other hand, is a long-term neurological condition thought to be linked to abnormalities in the structure and function of the brain, which can be present at birth or develop later in life due to various factors such as brain injury, tumor, or stroke. Genetic factors may also play a role in the development of epilepsy. Understanding the underlying cause of epilepsy is important for effective diagnosis and treatment of the condition (Centers for Disease Control and Prevention, 2020a, 2020c).
Pathophysiology
A seizure occurs when there is a sudden and abnormal burst of electrical activity in the brain. This activity can disrupt normal brain function and lead to a variety of symptoms, such as convulsions , loss of consciousness, and sensory or motor disturbances (Centers for Disease Control and Prevention, 2020a, 2020c).
Epilepsy is a chronic neurological disorder in which recurrent, unprovoked seizures occur. The underlying pathophysiology of epilepsy involves a disruption in the normal balance of excitatory and inhibitory activity in the brain. This imbalance can be due to structural or functional abnormalities in the brain, genetics, or changes in neurotransmitter activity. The abnormal electrical activity in the brain that occurs during an epileptic seizure is thought to be caused by a sudden release of excitatory neurotransmitters or a sudden decrease in inhibitory neurotransmitters (Centers for Disease Control and Prevention, 2020a, 2020c).
Diagnostic Testing
Diagnosis of seizures or epilepsy is multifaceted. The health care provider will obtain a thorough history and perform a neurological examination. The health care provider may order one or more of the following diagnostic tests to identify seizures or rule out other causes or structural abnormalities that could be contributing to the seizure diagnosis:
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Electroencephalogram (EEG)
- An EEG is a test that measures changes in the brain’s electrical patterns that relate to seizures or other neurological conditions. Small metal electrodes are attached to the scalp, and the electrical impulses of the brain appear as wavy lines on the EEG recording.
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Computed tomography (CT) scan
- A CT scan is a noninvasive imaging procedure that uses x-rays to produce horizontal and axial images of the brain.
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Magnetic resonance imaging (MRI)
- An MRI of the brain is a painless imaging procedure that uses large magnetic radio waves to produce clear images of the structures inside the skull.
-
Positron emission tomography (PET) scan
- A PET scan is an imaging procedure that uses a radioactive tracer substance to detect disease or injury in the brain.
Clinical Manifestations
Clinical manifestations of seizures can vary depending on the type of seizure a person is experiencing. There are several types of seizures, but they are generally classified into two groups: generalized seizures and focal seizures .
Generalized seizures involve abnormal activity in both sides of the brain from the beginning of the seizure. The two types of generalized seizures are absence seizures and tonic-clonic seizures (Centers for Disease Control and Prevention, 2020a, 2020c).
- Absence seizures, also known as petit mal seizures , cause rapid blinking or a few seconds of staring into space.
- Tonic-clonic seizures involve both tonic (muscle stiffness) and clonic (muscle jerking) phases and are commonly known as grand mal seizures .
Focal seizures, also known as partial seizures , begin in a specific area of the brain and can cause a wide range of symptoms depending on the area of the brain that is affected. There are three types of focal seizures: simple focal seizures , complex focal seizures , and secondary generalized seizures (Centers for Disease Control and Prevention, 2020a, 2020c).
- Simple focal seizures affect a small part of the brain and cause twitching movements or a change in sensation, such as an odd taste or smell.
- Complex focal seizures make a person confused or dazed. The person will be unresponsive to questions or directions for up to a few minutes.
- Secondary generalized seizures begin in one part of the brain but then spread to the other side. The person first has a focal seizure, followed by a generalized seizure.
Link to Learning
Alila Medical Media presents an educational video on epilepsy and seizures.
Drugs Used to Treat Epilepsy
Drugs that are used to treat epilepsy and seizures are generally termed anticonvulsant drugs . Anticonvulsant drugs are used to either control acute seizures or as maintenance to prevent seizures from occurring. Other drug classifications, such as some central nervous system depressants and mood stabilizers, have also been shown to be effective in the treatment of seizures and epilepsy. This section of the chapter will cover commonly prescribed classes of drugs used to treat seizures and epilepsy: hydantoins, barbiturates, succinates, benzodiazipines, iminostilbenes, valproates, pyrrolidine derivatives, and other anticonvulsants.
Importantly, numerous medications utilized for epilepsy treatment may interact with other drugs. Therefore, the nurse should thoroughly evaluate all the medications a client is currently taking, including over-the-counter products and herbal supplements. If any questions or concerns arise, the nurse should consult with a more knowledgeable health care provider or pharmacist to ensure the client’s safety and prevent the occurrence of potential drug interactions.
Hydantoins
Hydantoins are a class of anticonvulsant drugs that are used to prevent or control seizures. Hydantoins can reduce the occurrence and severity of seizures by stabilizing the neuronal membrane in the brain. Some commonly prescribed hydantoins include phenytoin and fosphenytoin. Although hydantoins can be effective in controlling seizures, they can have significant adverse effects, including dizziness, drowsiness, and coordination problems. Long-term use can lead to complications such as osteoporosis and gingival hyperplasia (gum overgrowth). Contraindications of hydantoins include hypersensitivity to hydantoins or substances they contain, sinus bradycardia or heart block, and liver disease. They should be used cautiously in people who are pregnant or breastfeeding as they can be harmful to the fetus or infant (Gupta & Tripp, 2022).
Therapeutic drug monitoring, which may be necessary for optimal treatment outcomes, is an essential task for nurses. Careful review of serum blood levels—trough levels and peak levels—is crucial to make appropriate dosing adjustments. Trough levels indicate the lowest concentration of the drug in the blood and are typically measured just before the client’s next scheduled dose. As a valuable indicator of the clinically effective range of serum levels, trough levels help confirm client compliance.
On the other hand, peak levels are indicative of an individual’s threshold for potential dose-related adverse effects and are measured at the peak concentration time. The goal is to achieve a therapeutic effect without clinical signs of toxicity, which is more likely to occur when serum total concentrations range between 10 and 20 mcg/mL. Therefore, close monitoring of serum blood levels, including both trough and peak levels, enables health care providers to optimize dosing, maximize therapeutic benefits, and minimize the risk of adverse effects.
Phenytoin ( Dilantin ) is the most prescribed hydantoin. Table 12.1 is a drug prototype table for hydantoins featuring phenytoin. It lists drug class, mechanism of action, adult and pediatric dosage s, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Anticonvulsant Mechanism of Action Decreases abnormal electrical activity in the brain through a voltage-dependent blockade of membrane sodium channels that are responsible for action potential |
Drug Dosage
Individualized based on disease process. Adults: Initial dose: 100 mg extended-release capsule orally 3 times daily. Upward titration with a maximum of 2 capsules 3 times daily. Serum blood level determinations may be necessary for optimal dosing adjustments. Children: Initial dose: 5 mg/kg/day in 2 or 3 equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. Recommended daily maintenance dosage: 4–8 mg/kg. Children >6 years old and adolescents may require the minimum adult dose (300 mg/day). |
|
Indications
To treat tonic-clonic and psychomotor seizures To prevent and treat seizures that occur during neurosurgery Therapeutic Effects Reduces seizure activity |
Drug Interactions
Azoles Antineoplastic agents Delavirdine Neuromuscular blocking agents Warfarin Calcium channel blockers Antilipemic agents Antacids Food Interactions No significant interactions |
|
Adverse Effects
Nystagmus Ataxia Slurred speech Decreased coordination Somnolence Mental confusion |
Contraindications
Hypersensitivity Prior history of acute hepatotoxicity attributed to phenytoin Bradycardia or heart block Caution: Monitor closely clients who have depression because this drug can increase suicidal thoughts or behavior Caution also advised for using this drug during pregnancy because it may cause potential harm to the fetus |
Barbiturates
Barbiturates are a class of drugs that act as central nervous system depressants, leading to sedation and relaxation. Barbiturates work by enhancing the actions of Gamma-aminobutyric acid (GABA) , the neurotransmitter that slows down brain activity. GABA is boosted by barbiturates, making them useful as sedatives, hypnotics, and anticonvulsants. Notably, barbiturates have a high risk of addiction, tolerance, and overdose, so their use has declined in favor of safer alternatives. Common adverse effects of barbiturates include dyspnea, confusion, bradycardia, dizziness, drowsiness, nausea, and vomiting. This class of drugs is contraindicated in people with hypersensitivity to barbiturates or their components, in those with hepatic insufficiency, and in those with respiratory disorders (Skibiski & Abdijadid, 2022).
Phenobarbital is the most used barbiturate for the treatment of seizures. Therapeutic drug monitoring is required. Phenobarbital is also a strong CYP inducer and will decrease the concentration of many other drugs. Table 12.2 is a drug prototype table for barbiturates featuring phenobarbital. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Barbiturate Mechanism of Action Inhibits the central nervous system by enhancing GABA, which slows activity in the brain |
Drug Dosage
Individualized based on disease process. Tablet: Adults: 50–100 mg orally 2 to 3 times daily. Titrate based on response and therapeutic drug monitoring. Children: Loading dose of 15–20 mg/kg produces blood levels of about 20 mcg/mL shortly after administration. Elixir: Adults : 60–200 mg daily. Children: 3–6 mg/kg/day. Intramuscular or intravenous (IV) Adults: 20–320 mg repeated every 6 hours as necessary. Children: 4–6 mg/kg/day for 7–10 days to blood level of 10–15 mcg/mL or 10–15 mg/kg/day. |
|
Indications
To treat seizures As a sedative Therapeutic Effects Reduces seizures Enhances sleep |
Drug Interactions
Anticoagulants Corticosteroids Griseofulvin Doxycycline Phenytoin, sodium valproate, valproic acid Monoamine oxidase inhibitors (MAOIs) Estradiol, estrone, progesterone, and other steroidal hormones Other central nervous system depressants Food Interactions No significant interactions |
|
Adverse Effects
Central nervous system depression (drowsiness, lethargy, vertigo, drowsiness) Respiratory depression Nausea Vomiting Headache |
Contraindications
Hypersensitivity Hepatic failure Respiratory disease Caution: Monitor closely for drug addiction and dependence Caution also advised during pregnancy because drug may cause fetal malformations |
Succinates
Succinates are a class of drugs that are used to treat seizures, including petit mal seizures. Succinates reduce the amount of calcium available for nerve activity by blocking calcium channels in the brain; abnormal electrical activity in the brain is then reduced, which helps to decrease the occurrence of seizures. Adverse effects include gastrointestinal upset, drowsiness, lethargy, hiccups, and headaches. They are contraindicated in persons with hypersensitivity to succinates or their properties and should be used cautiously in clients with renal or hepatic insufficiency (Hanrahan & Carson, 2022).
Ethosuximide (Zarontin) is the most used succinate. Table 12.3 is a drug prototype table for succinates featuring ethosuximide. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Anticonvulsant Mechanism of Action Blocks calcium channels in the brain, reducing the amount of calcium available for neuronal activity |
Drug Dosage
Individualized based on disease process. Adults: 500 mg orally daily (typically in 2 divided doses). Upward titration by 250 mg every 4–7 days to keep plasma ranges of 40–100 mcg/mL. Children: The initial oral dose for clients 3–6 years of age is 1 capsule (250 mg) daily; for clients ≥6 years of age, 2 capsules (500 mg) daily. |
|
Indications
To treat seizures Therapeutic Effects Reduces seizures |
Drug Interactions
Phenytoin Valproic acid Food Interactions No significant interactions |
|
Adverse Effects
Gastrointestinal upset (anorexia, nausea/vomiting, diarrhea, abdominal pain) Leukopenia Drowsiness Headache Dizziness Hiccups Pruritus/rash |
Contraindications
Hypersensitivity Caution: Use cautiously in people who are taking other anticonvulsant drugs as it may increase their serum levels Caution also advised during pregnancy as this drug may cause fetal malformations |
Benzodiazepines
Benzodiazepines are a class of drug that act on the benzodiazepine receptors (BZ-Rs) in the central nervous system. They work by enhancing the activity of the neurotransmitter GABA, which is inhibitory and slows brain activity. Dosing is individualized and depends on the drug being used. Benzodiazepines such as clonazepam, clorazepate, and diazepam are commonly prescribed to treat seizures.
Nurses should note that these drugs can result in sedation and use of these drugs in late pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns.
Table 12.4 lists common benzodiazepines and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|
Clonazepam
( Klonopin ) |
Adults:
Initial dose: 1.5 mg/day orally divided into 3 doses.
Increase dose by 0.5–1 mg every 3 days until seizures are adequately controlled. Children (up to 10 years of age or 30 kg of body weight) : Initial dose: 0.01–0.03 mg/kg/day; do not exceed 0.05 mg/kg/day given in 2 or 3 divided doses. Dosage should be increased by no more than 0.25–0.5 mg every third day until a daily maintenance dose of 0.1–0.2 mg/kg of body weight has been reached and seizures are controlled. Whenever possible, the daily dose should be divided into 3 equal doses. If this is not feasible, give the largest dose before bedtime. |
| Clorazepate |
Adults:
The maximum recommended initial dose in clients over 12 years old is 7.5 mg 3 times daily. Increase dose by no more than 7.5 mg every week to a maximum of 90 mg/day.
Children (9 –12 years): The maximum recommended initial dose is 7.5 mg 2 times a daily. Increase dose by no more than 7.5 mg every week not to exceed 60 mg/day. |
|
Diazepam
( Valium , Diastat , Valtoco ) |
Adults:
5–10 mg IV slowly; if seizure continues or recurs, may repeat if necessary at 10- to 15-minute intervals up to a maximum dose of 30 mg.
Children (3 months to 17 years of age with status epilepticus): First dose: 0.2 mg/kg (maximum 8 mg) by slow intravenous push (1 minute in duration). Second dose: (If necessary; 5 minutes after the first dose): 0.1 mg/kg (maximum 4 mg) by slow intravenous push (1 minute in duration). Adults: 2–10 mg orally 2–4 times daily. Children: 1–2.5 mg, 3 or 4 times daily orally initially; increase gradually as needed and tolerated. Because of varied responses to central nervous system–acting drugs, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months. |
|
Lorazepam
( Ativan ) |
Individualized based on disease process.
Adults: Oral dosing of 2–6 mg/day given in divided doses 2 to 3 times daily. IV dosing of 4 mg given slowly. If seizure continues or recurs after 10- to 15-minute observation period, an additional 4 mg IV may be slowly administered. Children: Not recommended in children less than 18 years of age. |
Adverse Effects and Contraindications
Common adverse effects of benzodiazepines include respiratory depression, drowsiness, confusion, headache, dizziness, tremor, and gastrointestinal upset. Benzodiazepines are contraindicated in hypersensitivity to the drug and its properties, in angle closure glaucoma, and with concomitant use with opioids. An increased risk of congenital malformations and other developmental abnormalities associated with benzodiazepine use during pregnancy has been identified.
Seizure rescue with benzodiazepines is a commonly used approach to manage seizures quickly and effectively. Benzodiazepines suppress excessive electrical activity in the brain. When a seizure occurs, administering a benzodiazepine promptly can help terminate the seizure and prevent its progression These medications can be administered orally, intravenously, intramuscularly, and via other routes depending on the situation and available resources.
The goal of seizure rescue with benzodiazepines is to provide rapid and effective control of seizures while ensuring the safety and well-being of the client. Benzodiazepines are a short-term solution for seizure management. Long-term treatment plans and adjustments should be made in collaboration with a health care provider to address the underlying cause of the seizure and prevent future occurrences.
Another widely used benzodiazepine for treating seizures is lorazepam. Table 12.5 is a drug prototype table for benzodiazepines featuring lorazepam. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Benzodiazepine Mechanism of Action Binds to the benzodiazepine receptors on the postsynaptic GABA-A ligand-gated chloride channel neuron in the central nervous system, thereby enhancing the inhibitory effects of GABA |
Drug Dosage
Individualized based on disease process. Adults: Oral dosing of 2–6 mg/day given in divided doses 2 to 3 times daily. IV dosing of 4 mg given slowly. If seizure continues or recurs after 10- to 15-minute observation period, an additional 4 mg IV may be slowly administered. Children: Not recommended in children less than 18 years of age. |
|
Indications
To treat seizures Preanesthetic Therapeutic Effects Reduces seizures Sedation |
Drug Interactions
Opioids Scopolamine Probenecid Food Interactions No significant interactions |
|
Adverse Effects
Hypotension Confusion Somnolence Headache Leukocytosis Respiratory suppression |
Contraindications
Hypersensitivity Acute narrow angle glaucoma Respiratory insufficiency Pregnancy/breastfeeding Caution: Use cautiously with other drugs that suppress the central nervous system due to respiratory suppression |
FDA Black Box Warning
Benzodiazepines
Benzodiazepines—when used in combination with opioid drugs—may depress the central nervous system, causing serious adverse effects including respiratory depression and death.
Clinical Tip
Lorazepam Intravenous Administration
Intravenous administration of lorazepam should be via slow intravenous push (2 mg/minute) for active seizures. If respiratory depression develops, flumazenil should be used as a competitive antagonist to reverse the effects of the lorazepam (Ghiasi et al., 2023).
Special Considerations
Substance Misuse and Dependence
Barbiturates and benzodiazepines are highly addictive and can result in dependence, tolerance, and even overdose. It is important for the health care provider to consider the client’s situation and perform a thorough medical and social history, including substance misuse or problematic use, which may also be referred to as substance abuse.
- Drug tolerance occurs when someone uses, misuses, or overuses a substance over a long period of time.
- Dependence occurs when someone uses high doses of a substance and they cannot function normally without the use of the substance.
- Substance use disorder occurs when someone is unable to control the use of the substance and they cannot stop using the substance.
- Overdose occurs when someone takes in a toxic amount of a substance. Overdose can lead to coma or even death.
(Source: Jahan & Burgess, 2022)
The National Institute on Drug Abuse (NIDA) is the leading federal agency supporting scientific research on substance use disorders. The NIDA provides research, education, and training resources and plays a role in the National Institute of Health HEAL (Helping to End Addiction Long-Term) Program , which looks at substance use disorders as a public health emergency in the United States.
The Substance Abuse and Mental Health Services Administration (SAMHSA) is a national helpline and confidential treatment referral service that provides clients and their families with needed resources regarding substance use disorders and mental health issues.
Iminostilbenes
Iminostilbenes are a class of anticonvulsant drug in which the compounds are structurally related to cyclic antidepressants. This class of drug shows efficacy in the first-line treatment for seizures. Iminostilbenes inhibit neuronal excitability by enhancing GABA; this drug requires therapeutic monitoring. Adverse reactions include urticaria, photosensitivity, congestive heart failure, edema, dyspnea, acute urinary retention, drowsiness, dizziness, coordination disturbances, headache, fatigue, abdominal pain, agranulocytosis, hyponatremia/SIADH, and leukopenia. Iminostilbenes are contraindicated in individuals with previous bone marrow depression and with hypersensitivity to the drug or its constituents; they should not be administered with tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, nefazodone, and delavirdine (Magheru et al., 2022).
The most common iminostilbene used in the treatment of seizures is carbamazepine ( Tegretol ). Table 12.6 is a drug prototype table for iminostilbenes featuring carbamazepine. It lists drug class, mechanism of action, adult and pediatric dosages, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Anticonvulsant Mechanism of Action Inhibits neuronal excitability by enhancing GABA, which decreases brain activity |
Drug Dosage
Individualized based on disease process and serum blood levels. Adults and children over 12 years of age: Initial dose of 200 mg orally twice daily. Increase at weekly intervals by adding up to 200 mg/day until the optimal response is obtained. Maintenance dosage to the minimum effective level, usually 800–1200 mg daily. Extended release: Initial dose of 200 mg orally twice daily. Increase weekly by adding 200 mg/day using a twice daily regimen until optimal response is reached. Maximum dose: 800–1200 mg daily. Children 6–12 years of age: Initial dose of 100 mg twice daily for tablets (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a 3–4 times daily regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily. Maintenance : Adjust dosage to the minimum effective level, usually 400–800 mg daily. Children <6 years of age: Initial dose of 10–20 mg/kg twice daily or 3 times daily as tablets. Increase weekly to achieve optimal clinical response administered 3 or 4 times daily. Maintenance : Typically, optimal clinical response is achieved at daily doses below 35 mg/kg. If satisfactory clinical response not achieved, measure plasma levels to determine if they are in the therapeutic range. No recommendation regarding safety of carbamazepine for use at doses above 35 mg/kg/24 hours. |
|
Indications
To treat seizures Therapeutic Effects Reduces seizure activity Sedation |
Drug Interactions
No significant drug interactions, other than contraindications listed below Food Interactions No significant interactions |
|
Adverse Effects
Photosensitivity Edema Dyspnea Urinary retention Drowsiness Coordination disturbances Headache Fatigue Agranulocytosis Leukopenia Bone marrow depression |
Contraindications
Hypersensitivity Bone marrow suppression Tricyclic antidepressants MAO inhibitors Nefazodone Delavirdine Caution: Monitor closely for serious dermatologic reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome Monitor closely for hyponatremia and SIADH |
FDA Black Box Warning
Carbamazepine
Carbamazepine may cause serious adverse effects including aplastic anemia and agranulocytosis.
Carbamazepine may cause serious dermatologic reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome.
Valproates
Valproates are anticonvulsants and mood stabilizers used in the treatment of seizures and bipolar disorder. Valproates act on GABA levels in the central nervous system, blocking voltage-gated sodium, potassium, and calcium ion channels causing decreasing brain activity. Adverse reactions include headache, somnolence, dizziness, drowsiness, thrombocytopenia, tremor, alopecia, emotional lability, petechiae, rash, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, tinnitus, and photosensitivity. Valproates are contraindicated in individuals with hepatic disorders and in those who have hypersensitivity to components of the drug.
Therapeutic drug monitoring measures the concentration of a valproic acid in the client’s blood and ensures that the drug is within the therapeutic range by adjusting the dosage, if necessary. Therapeutic range for valproic acid varies depending on the indication being treated. Generally, the total serum concentration of valproic acid is maintained between 50 and 100 µg/mL for epilepsy. However, individualized target ranges may be established based on factors such as age, comorbidities, concomitant medications, and treatment responses.
The most common valproate is valproic acid (Rahman & Nguyen, 2022). Table 12.7 is a drug prototype table for valproates featuring valproic acid. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Anticonvulsant and mood stabilizer Mechanism of Action Acts on the GABA levels in the central nervous system: blocking voltage-gated sodium, potassium, and calcium ion channels and decreasing brain activity |
Drug Dosage
Individualized based on disease process. Adults and children ≥10 years: 15 mg/kg/day. Increase at 1-week intervals by 5–10 mg/kg/day until seizures are controlled or side effects preclude further increases. Maximum recommended dosage: 60 mg/kg/day. If total daily dose exceeds 250 mg, it should be given in divided doses. Therapeutic drug monitoring range between 50–100 µg/mL. |
|
Indications
To treat seizures To treat bipolar disorder Therapeutic Effects Reduces seizure activity Reduces bipolar symptoms of mania |
Drug Interactions
Amitriptyline/nortriptyline Carbamazepine Clonazepam Diazepam Ethosuximide Lamotrigine Phenobarbital Phenytoin Propofol Rufinamide Tolbutamide Warfarin Zidovudine Food Interactions No significant interactions |
|
Adverse Effects
Headache Somnolence Dizziness Drowsiness Thrombocytopenia Emotional lability Rash Elevated liver enzymes Tinnitus |
Contraindications
Hypersensitivity Hepatic insufficiency Bone marrow depression Pregnancy Caution: Monitor closely for suicidal behavior and ideation Should be stopped if client develops acute pancreatitis |
FDA Black Box Warning
Valproates
Valproates may cause serious adverse effects including pancreatitis, abnormal bleeding, and clotting times. Valproates are known to cause abnormalities in the development of the fetus.
Pyrrolidine Derivatives
Pyrrolidine derivatives are novel anticonvulsant drugs used to treat seizures that were FDA approved in 2000. Pyrrolidine derivatives come in IV and oral formularies. Adverse effects include abdominal pain, nausea, anorexia, leukopenia, headache, mood swings, fatigue, somnolence, confusion, and increased risk for suicide. They are contraindicated with hypersensitivity to any of the drug’s components and in individuals with renal impairment.
Levetiracetam ( Keppra ) is the most used pyrrolidine derivative. Table 12.8 is a drug prototype table for pyrrolidine derivatives featuring levetiracetam. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Pyrrolidines Mechanism of Action Binds to a unique synaptic vesicle protein 2A (SV2A)—SV2A protein is a part of secretory vesicle membranes that mediates calcium-dependent vesicular neurotransmitter release; the binding of levetiracetam to SV2A appears to decrease the rate of vesicle release |
Drug Dosage
Individualized based on disease process. Adults and adolescents ≥16 years of age: Initiate treatment with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Children <16 years of age: 1 month to <6 months: Initiate treatment with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. 6 months to <4 years: Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a client cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group. 4 years to <16 years: Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a client cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 44 mg/kg. Maximum dose: 3000 mg/day. |
|
Indications
To treat seizures Therapeutic Effects Reduces seizures Sedation |
Drug Interactions
Baclofen Melatonin Opioids Trazodone Food Interactions No significant interactions |
|
Adverse Effects
Somnolence Fatigue Rash Coordination difficulties Emotional lability Headache |
Contraindications
Hypersensitivity Caution: Monitor closely for behavioral abnormalities such as increase in aggression, agitation, or anger and for psychotic symptoms such as hallucinations and delirium |
FDA Black Box Warning
Levetiracetam
Levetiracetam may cause serious or life-threatening behavioral manifestations and psychotic symptoms, including aggression, hostility, and homicidal ideation.
Other Anticonvulsants
There are many other anticonvulsants on the market; novel drugs continue to appear as treatment options improve. Table 12.9 lists common anticonvulsant drugs and typical routes and dosing for adult and pediatric clients .
| Drug | Class and Indication | Mechanism of Action | Adverse Effects and Contraindications | Dosage and Routes of Administration |
|---|---|---|---|---|
|
Gabapentin
( Neurontin ) |
Anticonvulsant
Indication: Adjunctive therapy for partial onset seizures, with or without secondary generalization, in adults and children 3 years and older with epilepsy |
Increases the concentration and probably the rate of synthesis of GABA in brain, which may enhance non-vesicular GABA release during seizures |
Adverse Effects:
in clients >12 years of age: Somnolence, dizziness, ataxia, fatigue, and nystagmus In clients 3–12 years: Viral infection, fever, nausea and/or vomiting, somnolence, and hostility Contraindications: Hypersensitivity to the drug or its ingredients |
In clients ≥12 years of age:
Starting dose: 300 mg orally 3 times daily. Recommended maintenance is 300–600 mg 3 times daily. In clients 3–11 years: Starting dose range is 10–15 mg/kg/day orally given in 3 divided doses and the recommended maintenance dose reached by upward titration over a period of 3 days. Recommended maintenance dose for 3–4 years of age: 40 mg/kg/day orally in 3 divided doses. Recommended maintenance dose for 5–11 years of age: 25–35 mg/kg/day orally in 3 divided doses. |
|
Lamotrigine
( Lamictal ) |
Anticonvulsant
Indication: Adjunctive therapy for partial seizures |
Blocks voltage-gated sodium ion channels and inhibits presynaptic glutamate and aspartate release |
Adverse Effects:
GI upset, dizziness, drowsiness, blurred vision, fatigue, and rash related to Stevens-Johnson syndrome
Contraindications: Hypersensitivity to the drug or its ingredients |
Oral dosing (in clients taking Valproate concurrently):
Weeks 1 and 2: 25 mg every other day. Weeks 3 and 4: 25 mg daily. Week 5 onward : Increase by 25–50 mg/day every 1–2 weeks. Maintenance dose: 200–250 mg daily. Extended-release oral dosing (in clients taking Valproate concurrently): Weeks 1 and 2: 25 mg every other day. Weeks 3 and 4: 25 mg daily. Week 5: 50 mg daily. Week 6: 100 mg daily. Week 7: 150 mg daily. Maintenance dose: 200–250 mg daily. Maximum dose: 400 mg/day |
|
Topiramate
( Topamax , Qudexy , Trokendi ) |
Anticonvulsant, Other
Indication: Treatment of partial or generalized seizures |
Stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity |
Adverse Effects:
Drowsiness, somnolence, fatigue, coordination difficulties
Contraindications: Hypersensitivity to the drug or its ingredients |
Adults and children ≥10 years of age:
400 mg/day orally in 2 divided doses.
The dose should be achieved by titrating as follows: Week 1: 25 mg in morning and evening. Week 2: 50 mg in morning and evening. Week 3: 75 mg in morning and evening. Week 4: 100 mg in morning and evening. Week 5: 150 mg in morning and evening. Week 6: 200 mg in morning and evening. Maximum dose: 400 mg/day. Children 2 – 9 years of age: Dosing in clients 2–9 years of age based on weight. Initial dose: 25 mg/day nightly for the first week. The dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. During subsequent weeks, the dosage can be increased by 25–50 mg/day as tolerated. Titration to the minimum maintenance dose should be attempted over 5–7 weeks of the total titration period. Additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25–50 mg/day weekly increments. |
|
Lacosamide
( Vimpat , Motpoly XR ) |
Anticonvulsant, Other
Indication: Treatment of partial seizures |
Blocks voltage-gated sodium ion channels and decreases brain activity |
Adverse Effects:
Dizziness, nausea, headache, fatigue, drowsiness
Contraindications: Hypersensitivity, second- and third-degree atrioventricular (AV) block, which may cause severe bradycardia |
Adults and adolescents ≥17 years of age or older:
Initial dose: 100 mg orally twice daily or 200 mg single loading dose, followed 12 hours later by 100 mg twice daily.
Increase by 50 mg twice daily every week to reach maintenance dose of 150–200 mg twice daily. Children weighing >50 kg: Initial dose 50 mg orally twice daily or 100 mg daily. Increase by 50 mg twice daily or 100 mg daily every week. Maintenance dose: 150–200 mg twice daily or 300–400 mg daily. Children weighing 30–50 kg: Initial dose: 1 mg/kg orally twice daily or 2 mg/kg daily. Increase by 1 mg/kg twice daily or 2 mg/kg daily every week. Maintenance: 2 mg/kg twice daily or 4–8 mg/kg/day. Children weighing 11–<30 kg: Initial dose: 1 mg/kg orally twice daily or 2 mg/kg daily. Increase by 1 mg/kg twice daily or 2 mg/kg daily every week. Maintenance: 3–6 mg/kg twice daily or 6–12 mg/kg/day. |
|
Zonisamide
( Zonegran , Zonisade ) |
Sulfonamide anticonvulsant
Indication: Adjunctive therapy for partial seizures |
Blocks voltage-gated sodium ion channels and inhibits presynaptic glutamate and aspartate release |
Adverse Effects:
Headache, fatigue, coordination difficulties, visual disturbances, drowsiness
Contraindications: Hypersensitivity to the drug or its ingredients |
Adults and adolescents ≥16 years of age:
Initial dose: 100 mg orally daily.
After 2 weeks the dose may be increased to 200 mg/day for at least 2 weeks. It can be increased to 300 mg/day and 400 mg/day with at least 2 weeks at each dose to achieve steady state at each level. |
Nursing Implications
The nurse should do the following for clients who are taking anticonvulsant drugs:
- Assess the client’s medical history, current drug list, and allergies.
- Assess client’s baseline weight and vital signs.
- Ensure the drug is prepared appropriately using aseptic technique and verify dosage before administration.
- Monitor the client’s response to the drug, including any changes in seizure patterns, neurological condition, and mental status.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an anticonvulsant drug should:
- Take the drug as prescribed and do not skip doses or stop therapy.
- Do not use alcohol or smoke—alcohol can depress the central nervous system, and smoking may cause vasoconstriction, resulting in reduced elimination of the drug.
- Keep a journal of symptoms and note improved or worsening symptoms.
- Take drug with food if gastrointestinal upset occurs.
- Have laboratory testing as scheduled by health care provider. Many anticonvulsants require titration and monitoring of blood levels to ensure safety and efficacy.
- Report symptoms of dyspnea, confusion, skin rash, abnormal bleeding, and/or infections to health care provider as these may represent an adverse reaction to anticonvulsant drugs.
- Speak to their health care provider if they are pregnant or plan to become pregnant before starting these drugs because they can impact the fetus.
- Store out of reach children and away from heat, moisture, and light.
The client taking anticonvulsant drugs should not :
- Drive or operate machinery with central nervous system depressants.
- Stop taking the drug unless directed by their health care provider, as this drug class reduces the risk of seizures.
FDA Black Box Warning
Lamotrigine
Lamotrigine may cause serious dermatologic reactions such as Stevens-Johnson syndrome or toxic epidermal necrosis.