| epilepsy presence | Epilepsy affects approximately 3 percent of individuals by the time they are 80 years old. About 10 percent of the population will have at least one seizure in their lifetime. Globally, epilepsy is the third most common neurologic disorder after cerebrovascular and Alzheimer disease. Epilepsy is not a single entity. |
| epilepsy characteristics | Instead it is, an assortment of different seizure types and syndromes originating from several mechanisms that have in common the sudden, excessive, and synchronous discharge of cerebral neurons. This abnormal electrical activity may result in a variety of events, including loss of consciousness, abnormal movements, atypical or odd behavior, and distorted perceptions that are of limited duration but recur if untreated. The site of origin of the abnormal neuronal firing determines the symptoms that are produced. For example, if the motor cortex is involved, the patient may experience abnormal movements or a generalized convulsion. Seizures originating in the parietal or occipital lobe may include visual, auditory, and olfactory hallucinations. |
| epilepsy control | It is expected that seizures can be controlled completely in approximately 70 to 80 percent percent of patients with one medication. It is estimated that approximately 10 to 15 percent of patients will require more than one drug, and perhaps about 10 percent may not achieve complete seizure control. |
| II. IDIOPATHIC AND SYMPTOMATIC SEIZURES | In most cases, epilepsy has no identifiable cause. Focal areas that are functionally abnormal may be triggered into activity by changes in physiologic factors, such as an alteration in blood gases, pH, electrolytes, and blood glucose level and changes in environmental factors, such as sleep deprivation, alcohol intake, and stress. |
| epilepsy mechanism | The neuronal discharge in epilepsy results from the firing of a small population of neurons in some specific area of the brain that is referred to as the “primary focus.” Anatomically, this focal area may appear to be normal. However, advances in technology have improved the ability to detect abnormalities. Neuroimaging techniques, such as magnetic resonance imaging (MRI), positron-emission tomography (PET) scans, and single-photon-emission coherence tomography (SPECT) may identify areas of concern. Epilepsy can be labeled idiopathic if the etiology is unknown or symptomatic if it is secondary to an identifiable condition. |
| idiopathic epilepsy | When no specific anatomic cause for the seizure, such as trauma or neoplasm, is evident, a patient may be diagnosed with idiopathic or cryptogenic (primary) epilepsy. These seizures may result from an inherited abnormality in the central nervous system (CNS). Patients are treated chronically with antiseizure drugs or vagal nerve stimulation. Most cases of epilepsy are idiopathic. |
| symptomatic epilepsy | A number of causes, such as illicit drug use, tumor, head injury, hypoglycemia, meningeal infection, and the rapid withdrawal of alcohol from an alcoholic, can precipitate seizures. When two or more seizures occur, the patient may be diagnosed with symptomatic (secondary) epilepsy. a seizure that is caused by transient hypotension or is due to a drug reaction is not epilepsy and does not require chronic therapy. In other situations, antiseizure drugs may be given until the primary cause of the seizures can be corrected. |
| III. CLASSIFICATION OF SEIZURES | Seizures have been categorized by site of origin, etiology, electrophysiologic correlation, and clinical presentation. The International League Against Epilepsy (ILAE) developed a nomenclature for describing seizures. Seizures have been classified into two broad groups: partial (or focal), and generalized. A diagnosis may include classifying the seizure as partial or generalized epilepsy depending on the onset. |
| partial siezures | Partial seizures involve only a portion of the brain, typically part of one lobe of one hemisphere. The symptoms of each seizure type depend on the site of neuronal discharge and on the extent to which the electrical activity spreads to other neurons in the brain. Consciousness is usually preserved. Partial seizures may progress to become generalized tonic-clonic seizures. |
| simple partial ziezures | These seizures are caused by a group of hyperactive neurons exhibiting abnormal electrical activity, which are confined to a single locus in the brain. The electrical discharge does not spread, and the patient does not lose consciousness. The patient often exhibits abnormal activity of a single limb or muscle group that is controlled by the region of the brain experiencing the disturbance. The patient may also show sensory distortions. This activity may spread. Simple partial seizures may occur at any age. |
| 2. Complex partial: | These seizures exhibit complex sensory hallucinations and mental distortion. Motor dysfunction may involve chewing movements, diarrhea, and/or urination. Consciousness is altered. Simple partial seizure activity may spread to become complex and then spread to a secondary generalized convulsion. Complex partial seizures may occur at any age |
| B. Generalized seizures | Generalized seizures may begin locally and then progress to include abnormal electrical discharges throughout both hemispheres of the brain. Primary generalized seizures may be convulsive or nonconvulsive, and the patient usually has an immediate loss of consciousness. |
| 1. Tonic-clonic seizures | These seizures result in loss of consciousness, followed by tonic (continuous contraction) and clonic (rapid contraction and relaxation) phases. The seizure may be followed by a period of confusion and exhaustion due to the depletion of glucose and energy stores. |
| 2. Absence seizures | These seizures involve a brief, abrupt, and self-limiting loss of consciousness. The onset generally occurs in patients at 3 to 5 years of age and lasts until puberty or beyond. The patient stares and exhibits rapid eye-blinking, which lasts for 3 to 5 seconds. An absence seizure has a very distinct three-per-second spike and wave discharge seen on electroencephalogram. |
| 3. Myoclonic seizures | These seizures consist of short episodes of muscle contractions that may recur for several minutes. They generally occur after wakening and exhibit as brief jerks of the limbs. Myoclonic seizures occur at any age but usually begin around puberty or early adulthood. |
| 4. Febrile seizures | 4. Febrile seizures: Young children may develop seizures with illness accompanied by high fever. This tendency may run in siblings. Febrile seizures consist of generalized tonic-clonic convulsions of short duration and do not necessarily lead to a diagnosis of epilepsy. |
| 5. Status epilepticus: | 5. Status epilepticus: In status epilepticus, two or more seizures occur without recovery of full consciousness between them. These may be partial or primary generalized, convulsive or nonconvulsive. Status epilepticus is life-threatening and requires emergency treatment. |
| C. Mechanism of action of antiepileptic drugs | Drugs reduce seizures through such mechanisms as blocking voltagegated channels (Na+ or Ca2+), enhancing inhibitory γ-aminobutyric acid (GABA)-ergic impulses, and interfering with excitatory glutamate transmission. Some antiepileptic drugs appear to have multiple targets within the CNS, whereas the mechanism of action for some agents is poorly defined. Antiepilepsy drugs suppress seizures but do not “cure” or “prevent” epilepsy. |
| IV. DRUG CHOICE | Choice of drug treatment is based on the classification of the seizures, patient-specific variables (for example, age, comorbid medical conditions, lifestyle, and personal preference), and characteristics of the drug (such as cost and interactions with other medications). In newly diagnosed patients, monotherapy is instituted with a single agent until seizures are controlled or toxicity occurs. Compared to those receiving combination therapy, patients receiving monotherapy exhibit better adherence and fewer side effects. If seizures are not controlled with the first drug, monotherapy with an alternate antiepileptic drug or drugs should be considered. Failing that, consider vagal nerve stimulation. |
| V. PRIMARY ANTIEPILEPTIC DRUGS | The list of drugs approved includes felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, and zonisamide. These are labeled “second generation” older antiepileptics, such as carbamazepine, divalproex, ethosuximide, phenobarbital, phenytoin, and valproic acid.
However, several studies have failed to provide sufficient evidence that the second-generation drugs are significantly better than the older agents in terms of efficacy and lack of adverse effects. |
| A. Benzodiazepines | Benzodiazepines bind to GABA inhibitory receptors to reduce firing rate. Diazepam and lorazepam are most often used as an adjunctive therapy for myoclonic as well as for partial and generalized tonic-clonic seizures. Lorazepam has a shorter pharmacokinetic half-life but stays in the brain longer than diazepam. Diazepam is available for rectal administration to avoid or interrupt prolonged generalized tonicclonic seizures or clusters. Other benzodiazepines may be used in the treatment of various epilepsies but should be considered for use only after trials with monotherapy or combinations of most other medications for treatment of seizures fail. |
| B. Carbamazepinemechanism and use | Carbamazepine reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potentials in the epileptic focus and preventing their spread. Carbamazepine is effective for treatment of partial seizures and, secondarily, generalized tonic-clonic seizures. It is also used to treat trigeminal neuralgia and bipolar disorder. |
| carbamazepine pharmacokinetics | Carbamazepine is absorbed slowly and erratically following oral administration and may vary from generic to generic, resulting in large variations in serum concentrations of the drug. It induces its own drug metabolism and has an active metabolite. It is a substrate for CYP3A4 with minor metabolism by CYP1A2 and CYC2C8. The epoxide metabolite accounts for 25 percent of the dose, is active, and can be inhibited by drugs that inhibit UDP glucuronosyltransferase (UGT), leading to toxicity. Carbamazepine is an inducer of the isozyme families CYP1A2, CYP2C, and CYP3A and UGT enzymes, which may increase the clearance and reduce the efficacy of drugs that they metabolize. It is not as well tolerated by the elderly as are other available antiseizure medications. Carbamazepine induces formation of liver drug-metabolizing enzymes that increase metabolism of the drug itself and may increase the clearance of many other anticonvulsant drugs including clonazepam, lamotrigine, and valproic acid. Carbamazepine metabolism can be inhibited by other drugs (eg, propoxyphene, valproic acid). A related drug, oxcarbazepine, is less likely to be involved in drug interactions. |
| carbamazipines toxicity | Hyponatremia especially in the elderly, characteristic rash may develop early in therapy but may not require a change in treatment. Carbamazepine should not be prescribed for patients with absence seizures because it may cause an increase in seizures |
| C. Ethosuximide | Ethosuximide reduces propagation of abnormal electrical activity in the brain, most likely by inhibiting T-type calcium channels. It is effective in treating only primary generalized absence seizures. Use of ethosuximide is limited because of this very narrow spectrum of activity. |
| D. Felbamate | Felbamate has a broad spectrum of anticonvulsant action. The drug has multiple proposed mechanisms including 1) blocking voltage-dependent sodium channels, 2) competing with the glycine-coagonist binding site on the N-methyl-D-aspartate (NMDA) glutamate receptor, 3) blocking calcium channels, and 4) potentiating the action of GABA. It is an inhibitor of drugs metabolized by CYP2C19 and β-oxidation, and induces drugs metabolized by CYP3A4. It is reserved for use in refractory epilepsies (particularly Lennox-Gastaut syndrome) because of the risk of aplastic anemia (about 1:4000) and hepatic failure. |
| E. Gabapentin | Gabapentin is an analog of GABA. However, it does not act at GABA receptors, and it neither enhances GABA actions nor is converted to GABA. Its precise mechanism of action is not known. It is approved as adjunct therapy for partial seizures and for treatment of postherpetic neuralgia.Gabapentin has been shown to be well tolerated by the elderly population with partial seizures due to its relatively mild adverse effects. It may also be a good choice for the older patient because there are limited or no reported associated pharmacokinetic drug interactions. |
| gabapentin pharmacokinetics | Gabapentin exhibits nonlinear pharmacokinetics due to its uptake by a saturable transport system from the gut. Gabapentin does not bind to plasma proteins and is excreted unchanged through the kidneys. Reduced dosing is required in renal disease. |
| lacosamide | Lacosamide in vitro affects voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. Lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein mainly expressed in the nervous system and involved in neuronal differentiation and control of axonal outgrowth. The role of CRMP-2 binding in seizure control is unknown. Lacosamide is approved for adjunctive treatment of partial seizures. In clinical trials, the drug caused euphoria similar to that produced by alprazolam and is labeled as a controlled substance (Schedule V). |
| lacosamide adverse effects pharmacokinetics | It is available in an injectable formulation. The most common adverse events that limit treatment include dizziness, headache, and fatigue. |
| G. Lamotrigine | Lamotrigine blocks sodium channels as well as high voltage–dependent calcium channels. Lamotrigine is effective in a wide variety of seizure types, including partial seizures, generalized seizures, and typical absence seizures and in the Lennox-Gastaut syndrome. It is approved for use in bipolar disorder as well. Lamotrigine has also been shown to be well tolerated by the elderly population with partial seizures due to its relatively minor adverse effects. |
| lamotrigine pharmacokinetics adverse effects | Lamotrigine is metabolized primarily to the N-2 glucuronide through the UGT pathway. The half-life of lamotrigine (24–35 hours) is decreased by enzyme-inducing drugs (for example, carbamazepine and phenytoin) and increased by greater than 50 percent with the addition of valproate. Lamotrigine dosages should be reduced when adding valproate to therapy unless the valproate is being added in a small dose to provide a boost to the lamotrigine serum concentration. Rapid titration to high serum concentrations of lamotrigine have been reported to cause a rash, which in some patients may progress to a serious, life-threatening reaction. |
| H. Levetiracetam | Levetiracetam is approved for adjunct therapy of partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in adults and children. The exact mechanism of anticonvulsant action is unknown. It demonstrates high affinity for a synaptic vesicle protein (SV2A). The drug is well absorbed orally and excreted in urine mostly (66 percent) unchanged. The drug does not interact with CYP or UGT metabolism systems. Side effects most often reported include dizziness, sleep disturbances, headache, and weakness. |
| Other Clinical Uses | Several antiseizure drugs are effective in the management of bipolar affective disorders, especially valproic acid, which is now often used as a first-line drug in the treatment of mania. Carbamazepine and lamotrigine have also been used successfully in bipolar disorder. Carbamazepine is the drug of choice for trigeminal neuralgia, and its congener oxcarbazepine may provide similar analgesia with fewer adverse effects. Gabapentin has efficacy in pain of
neuropathic origin, including postherpetic neuralgia, and, like phenytoin, may have some value in migraine. Topiramate is also used in the treatment of migraine. Pregabalin is also approved for neuropathic pain. |
| I. Oxcarbazepine | Oxcarbazepine is a prodrug that is rapidly reduced to the 10-monohydroxy (MHD) metabolite responsible for its anticonvulsant activity. MHD blocks sodium channels, preventing the spread of the abnormal discharge. It is also thought to modulate calcium channels. It is approved for use in adults and children with partial onset seizures. Oxcarbazepine is a less potent inducer of CYP3A4 and UGT than carbamazepine. |
| I. Oxcarbazepine adverse effects | The adverse effects profile is similar to that of other antiepileptic drugs. It can cause nausea, vomiting, headache, and visual disturbances. |
| Status Epilepticus | Intravenous diazepam or lorazepam is usually effective in terminating attacks and providing short-term control. For prolonged therapy, intravenous phenytoin has often been used because it is highly effective and less sedating than benzodiazepines or barbiturates. However, phenytoin may cause cardiotoxicity (perhaps because of its solvent, propylene glycol), and fosphenytoin (watersoluble) is a safer parenteral agent. Phenobarbital has also been used in status epilepticus, especially in children. In very severe status epilepticus that does not respond to these measures, general anesthesia may be used. |
| J. Phenobarbital | Its primary mechanism of action is enhancing the inhibitory effects of GABA-mediated neurons. Phenobarbital in epilepsy should be used primarily in the treatment of status epilepticus. |
| Myoclonic and Atypical Absence Syndromes | Myoclonic seizure syndromes are usually treated with valproic acid; lamotrigine is approved for adjunctive use, but is commonly used as monotherapy. Clonazepam can be effective, but the high doses required cause drowsiness. Levetiracetam, topiramate, and zonisamide are also used as backup drugs in myoclonic syndromes.
Felbamate has been used adjunctively with the primary drugs but has both hematotoxic and hepatotoxic potential. |
| Absence Seizures | Ethosuximide or valproic acid are the preferred drugs because they cause minimal sedation. Ethosuximide is often used in uncomplicated absence seizures if patients can tolerate its gastrointestinal side effects. Valproic acid is particularly useful in patients who have concomitant generalized tonic-clonic or myoclonic seizures. Clonazepam is effective as an alternative drug but has the disadvantages of causing sedation and tolerance. Lamotrigine, levetiracetam, and zonisamide are also effective in absence seizures. |
| phenytoin | Phenytoin blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery. At very high concentrations, phenytoin can also block voltage dependent calcium channels and interfere with the release of monoaminergic neurotransmitters. Phenytoin is effective for treatment of partial seizures and generalized tonic-clonic seizures and in the treatment of status epilepticus. |
| zonisamide | Zonisamide is a sulfonamide derivative that has a broad spectrum of action. The compound has multiple effects on neuronal systems thought to be involved in seizure generation. These include blockade of both voltage-gated sodium channels and T-type calcium currents. It has a limited amount of carbonic anhydrase activity. |
| Zonisamide pharmacokinetics and adverse effects | Cross reactivity with other sulfonamides should be reviewed. Its use should be monitored in patients with reported allergies. Zonisamide is approved for use in patients with partial epilepsy. It is metabolized by the CYP3A4 isozyme and may, to a lesser extent, be affected by CYP3A5 and CYP2C19. In addition to typical CNS adverse effects, zonisamide may cause kidney stones. Oligohidrosis has been reported, and patients should be monitored for increased body temperature and decreased sweating. |
| phenytoin pharmacokinetics | nonlinear; elimination kinetics shift from first-order to zeroorder at moderate to high dose levels. The drug binds extensively to plasma The drug is 90 percent bound to plasma albumin.The oral bioavailability of phenytoin is variable because of individual differences in first-pass metabolism. Rapid-onset and extended-release forms are available. Phenytoin metabolism is proteins (97–98%), and free (unbound) phenytoin levels in plasma are increased transiently by drugs that compete for binding (eg, carbamazepine, sulfonamides, valproic acid). The metabolism of phenytoin is enhanced in the presence of Phenytoin induces drugs metabolized by the CYP2C and CYP3A families and the UGT enzyme system. Phenytoin itself induces hepatic drug metabolism, decreasing the effects of other antiepileptic drugs including carbamazepine, clonazepam, and lamotrigine. |
| partial siezures drug use | The drugs of first choice are carbamazepine (or oxcarbazepine) or lamotrigine or phenytoin. Alternatives include felbamate, phenolbarbital, topiramate, and valproic acid. Many of the newer anticonvulsants can be used adjunctively, including gabapentin and pregabalin, a structural congener. |
| phenytoin pharmacokinetics | Phenytoin exhibits saturable enzyme metabolism at a low serum concentration. Therefore, knowledge of zero-order pharmacokinetics and population parameters is important for dosing adjustment. Small increases in a daily dose can produce large increases in the plasma concentration, resulting in druginduced toxicity. |
| phenytoin adverse effects | Depression of the CNS occurs particularly in the cerebellum and vestibular system, causing nystagmus and ataxia. The elderly are highly susceptible to this effect. Gingival hyperplasia may cause the gums to grow over the teeth. Long-term use may lead to development of peripheral neuropathies and osteoporosis. Although phenytoin is the drug used most commonly worldwide for epilepsy due to its low cost per tablet, the cost of therapy may be much higher when the potential for serious toxicity and adverse eff ects is weighed. |
| fosphenytoin | Fosphenytoin is a prodrug and is rapidly converted to phenytoin in the blood, reaching high levels within minutes. Fosphenytoin may also be administered intramuscularly (IM). However, phenytoin sodium should never be given IM because it can cause tissue damage and necrosis. Fosphenytoin is the drug of choice and standard of care for IV and IM administration. Because of sound-alike and lookalike trade names, there is a risk for prescribing errors. |
| A. Generalized Tonic-Clonic Seizures drug use | Valproic acid, carbamazepine, and phenytoin are the drugs of choice for generalized tonic-clonic (grand mal) seizures. Phenobarbital (or primidone) is now considered to be an alternative agent in adults but continues to be a primary drug in infants. Lamotrigine and topiramate are also approved drugs for this indication, and several others may be used adjunctively in refractory cases. |
| L. Pregabalin | Pregabalin binds to the α2-δ site, an auxiliary subunit of voltage-gated calcium channels in the CNS, inhibiting excitatory neurotransmitter release. The exact role this plays in treatment is not known, but the drug has proven effects on partial onset seizures, neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. |
| life threatening toxicities | Lamotrigine has caused skin rashes and lifethreatening Stevens-Johnson syndrome or toxic epidermal necrolysis. Children are at higher risk (1–2% incidence), especially if they are also taking valproic acid. Zonisamide may also cause severe skin reactions. Reports of aplastic anemia and acute hepatic failure
have limited the use of felbamate to severe, refractory seizure states. Neural tube defects (eg, spina bifida) are associated with the use of valproic acid; carbamazepine has been implicated as a cause of craniofacial anomalies and spina bifida; and a fetal hydantoin syndrome has been described after phenytoin use by pregnant women. |
| L. Pregabalin adverse effects pharmacokinetics | More than 90 percent of pregabalin is eliminated renally, with no indication of CYP involvement. Drowsiness, blurred vision, weight gain, and peripheral edema have been reported. |
| resistance anti siezure drugs | Resistance to antiseizure drugs may involve increased expression of drug transporters at the level of the blood-brain barrier. |
| M. Rufinamide | Rufinamide in vitro acts at the sodium channels. It is approved for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children over age 4 years and in adults. Food increases absorption and peak serum concentrations. |
| rufinamide pharmacokinetics adverse effects | Serum concentrations of rufinamide are affected by other antiseizure medications. It is induced by carbamazepine and phenytoin and inhibited when given with valproate. Women taking birth control tablets should be counseled that they may not be effective when used concurrently with rufinamide. Adverse effects include the potential for shortened QT intervals. Patients with familial short QT syndrome should not be treated with rufinamide.it is a weak inhibitor of CYP2E1 and a weak inducer of CYP3A4 enzymes. |
| epilepsy drugs in pregnancy | Divalproex and barbiturates should be avoided. Those women already on divalproex and barbiturates should be switched to other drugs before pregnancy when possible. When seizures are controlled, maintenance medication may be reduced, if possible, to the lowest dose that provides control. If seizures are not controlled, medications and dosages will need to be adjusted prior to pregnancy, if possible. The frequency and severity of seizures may change during pregnancy.
Regular monitoring by both an obstetrician and a neurologist is important. All women with epilepsy should be encouraged to register with the AED (Antiepileptic Drug) Pregnancy Registry. |
| N. Tiagabine | Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding, and therefore, to enhanced inhibitory activity. Tiagabine is effective in decreasing the number of seizures in patients with partial onset epilepsy. Binding to albumin and α1-acid glycoprotein is greater than 95 percent. Metabolism is mainly completed by the CYP3A family of enzymes. |
| dbs | Deep brain stimulation (DBS) therapy uses a pacemaker-like device to deliver targeted electrical stimulation to the anterior nucleus of the thalamus.
The therapy is FDA approved with conditions for adjunctive treatment for
partial-onset seizures in adults with medically refractory epilepsy. DBS is
also FDA approved for treatment of advanced Parkinson disease and essential tremor. |
| Adverse effects tigabine | Adverse effects include fatigue, dizziness, and gastrointestinal upset. There is some indication in postmarketing surveillance that seizures have occurred in patients using tiagabine who did not have epilepsy. Tiagabine has not been approved for and should not be used for any other indication. |
| Vagal nerve stimulation (VNS) | Vagal nerve stimulation (VNS) requires surgical implant of a small pulse generator with a battery and a lead wire for stimulus. The device is implanted and its lead wires wrapped around the patient’s vagal nerve. The device is also approved for treatment of depression. The mechanism of action is unknown. Because it has diffuse involvement with neuronal circuits, there are a variety of mechanisms by which it may exert its effect on seizure control. VNS has been effective in treatment of partial onset seizures and has enabled reduction of drug therapy in some cases. It is an alternative for patients whose conditions have been refractory to multiple drugs and in those who are sensitive to the many adverse effects of antiseizure drugs and those who have difficulty adhering to medication schedules. However, VNS is a costly and invasive procedure. |
| O. Topiramate | Topiramate has several actions that are believed to contribute to its broad spectrum of antiseizure activity. Topiramate blocks voltage-dependent sodium channels, and it has been shown to increase the frequency of chloride channel opening by binding to the GABAA receptor. High-voltage calcium currents (L type) are reduced by topiramate. It is a carbonic anhydrase inhibitor and may act at glutamate (NMDA) sites. Topiramate is effective and approved for use in partial and primary generalized epilepsy. It is also approved for treatment of migraine. Topiramate is eliminated renally, but it also has inactive metabolites. It inhibits CYP2C19 and is induced by phenytoin and carbamazepine. Lamotrigine is reported to cause an increase in topiramate concentration. Coadministration of topiramate reduces ethinyl estradiol. Therefore, women taking the drug should be counseled to use additional methods of birth control. Adverse effects include somnolence, weight loss, and paresthesias. Renal stones are reported to occur at a higher incidence than in a nontreated population. Glaucoma, oligohidrosis, and hyperthermia have also been reported. The latter are specifically related to the carbonic anhydrase activity. |
| vigabatrin | Vigabatrin acts as an irreversible inhibitor of (GABA-T). GABA-T is the enzyme
responsible for metabolism of GABA. Vigabatrin is associated with adverse effects resulting in visual field loss ranging from mild to severe in 30 percent or more of patients. Physicians must be registered with SHARE to prescribe vigabatrin. |
| valproic acid divalroic acid | Valproic acid is available as a free acid. Divalproex sodium is a combination of sodium valproate and valproic acid that is converted to valproate when it reaches the gastrointestinal tract. It was developed to improve gastrointestinal tolerance of valproic acid. All of the available salt forms are equivalent in efficacy (valproic acid and valproate sodium). Commercial products are available in multiple-salt dosage forms and extended-release formulations. Therefore, the risk for medication errors is high, and it is essential to be familiar with all preparations. |
| valproic acid mechanism | Possible mechanisms of action include sodium channel blockade, blockade of GABA transaminase, and action at the T-type calcium channels. These varied mechanisms provide a broad spectrum of activity against seizures. is the drugs are effective for the treatment of partial and primary generalized epilepsies. |
