12.1 Epilepsy and Anticonvulsant Drugs
3 min read•june 18, 2024
Epilepsy is a neurological disorder characterized by recurrent seizures. These seizures result from abnormal electrical activity in the brain, caused by an imbalance between excitatory and inhibitory .
Anticonvulsant drugs are the primary treatment for epilepsy. They work by reducing and raising the . Different classes of target various mechanisms in the brain to control seizures and improve quality of life for people with epilepsy.
Pathophysiology and Diagnosis of Epilepsy
Mechanisms and manifestations of epilepsy
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- Abnormal neuronal activity in the brain results from excessive and synchronous firing of neurons due to an imbalance between excitatory neurotransmitters like and inhibitory neurotransmitters like
- Clinical manifestations include seizures which can be generalized involving both hemispheres (, absence, , ) or focal and localized to one area of the brain ( without loss of consciousness, with altered consciousness)
- Non-seizure symptoms may include (sensory, motor, or psychological symptoms before a seizure) and (confusion, fatigue, or headache after a seizure)
Causes and diagnosis of epilepsy
- Common causes include genetic factors, structural brain abnormalities (traumatic brain injury, stroke, brain tumors, congenital malformations), metabolic disorders, and infections (meningitis, encephalitis)
- Diagnostic methods involve a neurological examination, (EEG) to record electrical activity in the brain and identify abnormal patterns associated with seizures, neuroimaging like MRI or CT scan, and blood tests to rule out metabolic causes
Neuronal excitability and seizure threshold
- Neuronal excitability refers to the ease with which neurons generate action potentials
- Seizure threshold is the level of stimulation required to trigger a seizure, influenced by factors such as genetics, brain injury, and medication
- Anticonvulsant drugs aim to reduce neuronal excitability and raise the seizure threshold
Anticonvulsant Drugs and Treatment Strategies
Classes of anticonvulsant drugs
- Sodium channel blockers like phenytoin, , and lamotrigine stabilize neuronal membranes and reduce excitability
- GABA enhancers such as (diazepam, lorazepam), barbiturates, and increase inhibitory GABA activity
- Calcium channel blockers including and gabapentin reduce calcium influx and neurotransmitter release
- Glutamate antagonists like topiramate and block excitatory glutamate receptors
- Other mechanisms involve levetiracetam binding to synaptic vesicle protein SV2A and zonisamide having multiple mechanisms (sodium and calcium channel blockade, GABA enhancement)
Effects and interactions of anticonvulsants
- Therapeutic effects aim for seizure control and reduction in frequency and severity
- Common side effects include drowsiness, dizziness, , cognitive impairment (memory, concentration), gastrointestinal upset (nausea, vomiting), weight changes, and potentially serious skin rash ()
- Drug interactions can occur with enzyme inducers (phenytoin, carbamazepine) decreasing levels of other drugs, enzyme inhibitors (valproic acid) increasing levels of other drugs, and oral contraceptives being less effective with enzyme-inducing anticonvulsants
Nursing considerations for anticonvulsants
- Assess for allergies and contraindications before administering anticonvulsants
- Monitor (phenytoin, carbamazepine, valproic acid) and assess for side effects, adverse reactions, and signs of toxicity (, ataxia, slurred speech)
- Educate patients on the importance of adherence, not stopping medications abruptly, and having regular follow-up with their healthcare provider
- Administer with food if gastrointestinal upset occurs
- Perform to ensure therapeutic levels and adjust dosages as needed
Patient education for epilepsy medications
- Emphasize the importance of taking medications as prescribed and discuss potential side effects and when to seek medical attention
- Advise on maintaining a consistent sleep schedule, keeping a seizure diary to track triggers and medication effectiveness, and the impact of epilepsy on daily activities (driving, swimming, working)
- Provide information on support groups and resources and emphasize the need for regular follow-up with healthcare providers
Treatment approaches for seizure types
- Generalized tonic-clonic seizures use first-line treatments like valproic acid, lamotrigine, levetiracetam and second-line options such as phenytoin, carbamazepine, topiramate
- are treated with first-line ethosuximide, valproic acid, lamotrigine while avoiding carbamazepine and gabapentin which may worsen absence seizures
- Focal seizures use first-line carbamazepine, lamotrigine, levetiracetam and second-line phenytoin, zonisamide, topiramate
- (prolonged or repetitive seizures) requires emergency treatment with benzodiazepines (diazepam, lorazepam), phenytoin, phenobarbital and refractory cases may need anesthesia (propofol, midazolam)
- Non-pharmacological treatments include (high-fat, low-carbohydrate) for refractory epilepsy in children, (VNS) for refractory focal seizures, and surgical resection of seizure focus in selected cases
- For , combination therapy or alternative treatment options may be considered
Key Terms to Review (31)
Absence Seizures: Absence seizures, also known as petit mal seizures, are a type of generalized seizure disorder characterized by brief episodes of impaired consciousness, staring spells, and lack of physical movement. These seizures typically last for a few seconds to a minute and are caused by abnormal electrical activity in the brain.
Anticonvulsants: Anticonvulsants are a class of medications primarily used to prevent and control seizures associated with epilepsy. They work by stabilizing the electrical activity in the brain, reducing the likelihood of abnormal neuronal firing that can lead to seizures. These drugs have applications beyond just epilepsy, as they are also used to treat other neurological and psychiatric conditions.
Antiepileptic Drug Monitoring: Antiepileptic drug monitoring is the process of measuring the concentration of anticonvulsant medications in a patient's blood to ensure optimal therapeutic levels and minimize the risk of adverse effects. This is a crucial aspect in the management of epilepsy, as it helps guide dosing and individualize treatment for each patient.
Ataxia: Ataxia is a neurological condition characterized by a lack of muscle coordination, which can affect an individual's balance, gait, and fine motor skills. It is often associated with damage or dysfunction in the parts of the brain responsible for coordinating movement, such as the cerebellum or the spinal cord.
Atonic: Atonic refers to a lack of muscle tone or tension, often associated with certain types of seizures in the context of epilepsy. It describes a state of flaccidity or loss of muscle control, which can lead to the individual falling to the ground during an epileptic episode.
Aura: An aura is a transient sensory phenomenon that often precedes or accompanies certain neurological and medical conditions, particularly epilepsy and migraine headaches. It is a subjective experience that can manifest as visual, auditory, or other sensory disturbances, signaling the onset of a seizure or a migraine attack.
Benzodiazepines: Benzodiazepines are a class of psychoactive drugs that have a calming and sedative effect on the central nervous system. They are commonly used as anxiolytics, sedative-hypnotics, and anticonvulsants, and are known for their ability to induce relaxation, reduce anxiety, and promote sleep.
Carbamazepine: Carbamazepine is an anticonvulsant and mood stabilizing medication primarily used in the treatment of epilepsy and bipolar disorder. It works by modulating the activity of sodium channels in the brain, which helps to prevent the abnormal electrical activity that leads to seizures and mood episodes.
Complex Focal: Complex focal, also known as focal impaired awareness seizures, are a type of partial or focal seizure that originates in a specific area of the brain and is accompanied by an alteration in consciousness or awareness. These seizures are characterized by a complex combination of sensory, motor, and cognitive symptoms that reflect the specific brain region involved.
Drug-Resistant Epilepsy: Drug-resistant epilepsy, also known as refractory or intractable epilepsy, is a condition where a person's seizures do not respond adequately to antiepileptic drug (AED) therapy. This form of epilepsy presents a significant challenge in clinical management and can have a profound impact on a patient's quality of life.
Electroencephalogram: An electroencephalogram (EEG) is a non-invasive diagnostic test that measures and records the electrical activity of the brain. It is a crucial tool in the evaluation and management of epilepsy and other neurological disorders that affect brain function.
Enzyme Induction: Enzyme induction is a process by which the expression and activity of enzymes are increased, often in response to the presence of a specific substrate or inducer. This mechanism is particularly relevant in the context of pharmacology, where it can influence the metabolism and clearance of drugs.
Ethosuximide: Ethosuximide is an anticonvulsant medication primarily used to treat absence seizures, a type of generalized seizure disorder characterized by a brief loss of consciousness or awareness. It works by reducing the excitability of neurons in the brain, thereby preventing the abnormal electrical activity that leads to seizures.
GABA: GABA (Gamma-Aminobutyric Acid) is the primary inhibitory neurotransmitter in the central nervous system. It plays a crucial role in regulating neuronal excitability and has been associated with various neurological and psychiatric disorders, including Parkinson's disease, epilepsy, mood disorders, and alcohol use disorder.
GABA structural analogs: GABA structural analogs are compounds that mimic the structure of gamma-aminobutyric acid (GABA), a neurotransmitter. These analogs are used to modulate neural activity and are often employed in the treatment of neurological conditions such as multiple sclerosis.
Glutamate: Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system, playing a crucial role in various neurological processes and disorders affecting the brain and nervous system.
Ketogenic Diet: The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate dietary regimen that induces a metabolic state called ketosis. This state shifts the body's primary fuel source from glucose to ketone bodies derived from fat, which can have therapeutic benefits for certain medical conditions, particularly epilepsy.
Myoclonic: Myoclonic refers to a sudden, brief, involuntary muscle jerk or twitch. This type of movement disorder is often associated with certain neurological conditions, particularly epilepsy, and can significantly impact a person's quality of life and daily functioning.
Neuronal Excitability: Neuronal excitability refers to the ability of a neuron to generate and propagate electrical signals, known as action potentials, in response to various stimuli. This fundamental property of neurons is crucial for the proper functioning of the nervous system, as it allows for the transmission of information between different parts of the body.
Neurotransmitters: Neurotransmitters are chemical messengers that transmit signals between neurons and target cells in the nervous system. They are responsible for the communication and coordination of various physiological and psychological processes in the body, and their imbalance or dysfunction can contribute to the development of various neurological and psychiatric disorders.
Nystagmus: Nystagmus is an involuntary, rhythmic, oscillatory eye movement that can occur in both horizontal and vertical directions. It is a neurological condition that affects the control of eye movements and can have implications in the context of epilepsy and anticonvulsant drug therapy.
Perampanel: Perampanel is an anticonvulsant drug used to treat partial-onset seizures and primary generalized tonic-clonic seizures in patients with epilepsy. It works by selectively blocking the AMPA receptor, a type of glutamate receptor, which helps to reduce neuronal excitability and prevent the spread of seizure activity in the brain.
Postictal State: The postictal state refers to the period immediately following a seizure, during which the brain and body are recovering from the intense neurological activity that occurred during the seizure. This transitional phase is a crucial aspect of understanding epilepsy and the mechanisms of anticonvulsant drugs.
Seizure Threshold: Seizure threshold refers to the level of neuronal excitability or stimulation required to trigger an epileptic seizure. It is a critical concept in understanding the pathophysiology of epilepsy and the mechanisms of action of anticonvulsant drugs.
Simple Focal: Simple focal, also known as partial seizures, are a type of epileptic seizure that originates from a specific, localized area of the brain. These seizures are characterized by symptoms that are limited to a particular part of the body or a specific function, reflecting the location of the abnormal electrical activity in the brain.
Status Epilepticus: Status epilepticus is a medical emergency characterized by a prolonged, uninterrupted seizure or a series of seizures without regaining consciousness in between. It is a life-threatening condition that requires immediate treatment to prevent brain damage, cardiovascular complications, and even death.
Stevens-Johnson Syndrome: Stevens-Johnson syndrome (SJS) is a rare, serious, and potentially life-threatening skin condition that typically begins with flu-like symptoms followed by a painful rash that spreads and blisters, eventually causing the top layer of the skin to die and shed. This condition is often triggered by certain medications and can affect the eyes, mouth, and genitals as well.
Therapeutic Drug Levels: Therapeutic drug levels refer to the range of drug concentrations in the body that produce the desired therapeutic effect without causing significant adverse effects. These levels are crucial in the management of various medical conditions, particularly in the context of epilepsy and the use of anticonvulsant drugs.
Tonic-Clonic: Tonic-clonic seizures, formerly known as grand mal seizures, are the most dramatic and severe type of epileptic seizure. They are characterized by a sudden loss of consciousness, muscle rigidity (the tonic phase), followed by rhythmic muscle contractions and jerking movements (the clonic phase).
Vagus Nerve Stimulation: Vagus nerve stimulation is a therapeutic technique that involves electrical stimulation of the vagus nerve, a cranial nerve that plays a crucial role in regulating various bodily functions, including epilepsy and seizure control. This approach is often utilized as an adjunctive treatment for certain types of epilepsy and other neurological disorders.
Valproic Acid: Valproic acid is a medication primarily used to treat epilepsy, migraine headaches, and mood disorders. It is an anticonvulsant drug that works by stabilizing electrical activity in the brain, reducing the frequency and severity of seizures, and modulating neurotransmitter levels to alleviate symptoms associated with various neurological and psychiatric conditions.