Presentation on theme: "EPILEPSY Seizures - Transient alteration of sensation, awareness or behavior due to disordered, abnormal firing of brain neurons. Epilepsy is a chronic."— Presentation transcript:
1EPILEPSYSeizures - Transient alteration of sensation, awareness or behavior due to disordered, abnormal firing of brain neurons.Epilepsy is a chronic disorder characterized by recurrent seizures.Epilepsy is from the Greek word "epilambabein," meaning to seize or to attack. Symptoms caused by a seizure may vary depending on where the seizure starts. For instance, if a seizure begins in the "sight" area, a person may see flashing lights at the onset of the seizure.EPILEPSY IS A NEUROLOGICAL CONDITION THAT MAKES PEOPLE SUSCEPTIBLE TO SEIZURES. A SEIZURE IS A CHANGE IN SENSATION, AWARENESS, OR BEHAVIOR BROUGHT ABOUT BY A BRIEF ELECTRICAL DISTURBANCE IN THE BRAIN.Epilepsy is a neurological condition that makes people susceptible to seizures. A seizure is a change in sensation, awareness, or behavior brought about by a brief electrical disturbance in the brain.
2EPILEPSY FOCAL SEIZURES (PARTIAL) : Focal Seizures Without Dyscognitive Features (Simple Partial Seizures)Eg., It include sensory, motor and psychic symptoms without impairment of cognition.Focal Seizures With Dyscognitive Features (Complex Partial Seizures)Focal seizures may also be accompanied by a transient impairment of the patient's ability to maintain normal contact with the environment.The patient is unable to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase.Eg., Psychomotor epilepsy – focus in temporal lobe.Focal Seizures Without Dyscognitive Features Focal seizures can cause motor, sensory, autonomic, or psychic symptoms without impairment of cognition. Example., Jacksonian march Focal seizures may also manifest as changes in somatic sensation (e.g., paresthesias), vision (flashing lights or formed hallucinations), equilibrium (sensation of falling or vertigo), or autonomic function (flushing, sweating, piloerection). Focal seizures arising from the temporal or frontal cortex may also cause alterations in hearing, olfaction, or higher cortical function (psychic symptoms) Focal Seizures with Dyscognitive FeaturesFocal seizures may also be accompanied by a transient impairment of the patient's ability to maintain normal contact with the environment. The patient is unable to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase. The seizures frequently begin with an aura (i.e., a focal seizure without cognitive disturbance) that is stereotypic for the patient. The start of the ictal phase is often a sudden behavioral arrest or motionless stare, which marks the onset of the period of impaired awareness. The behavioral arrest is usually accompanied by automatisms, which are involuntary, automatic behaviors that have a wide range of manifestations. Automatisms may consist of very basic behaviors such as chewing, lip smacking, swallowing, or "picking" movements of the hands, or more elaborate behaviors such as a display of emotion or running. The patient is typically confused following the seizure, and the transition to full recovery of consciousness may range from seconds up to an hour. Examination immediately following the seizure may show an anterograde amnesia or, in cases involving the dominant hemisphere, a postictalaphasia.A complex focal seizure typically begins with behavioral arrest and is followed by staring, automatisms, and postictal confusion. Automatisms frequently consist of chewing, lip smacking, mumbling, and fumbling with the handsFocal (previously ‘‘partial’’): the ﬁrst clinical and electroencephalographic changes indicate initial activation of a system of neurons limited to a part of one cerebral hemisphereMenstrually related hormonal fluctuations in estrogen and progesterone underlie the patterns of catamenial seizure exacerbation. Estrogens facilitate seizures, whereas progesterone protects against seizures. During the menstrual cycle, serum levels of estradiol and progesterone fluctuate.Estrogens (in particular estradiol, the most important of the different estrogen forms) have potent proconvulsant properties. They exert an excitatory effect on neurons by stimulating the N-methyl-D-aspartate (NMDA)- type glutamate receptor.5 In women with epilepsy, intravenous administration of conjugated estrogens activates epileptiform discharges and may result in seizures.6Progesterone hyperpolarizes neurons, acting via one of its natural endogenous metabolites, allopregnanolone, as an agonist at the γ- aminobutyric acid (GABA)-a receptor with a potency almost a thousandfold greater than that of pentobarbital and greater than the most potent benzodiazepine, nitroflurazepam.7,8 In women with partial seizures, intravenous infusion of progesterone, resulting in luteal phase plasma levels, suppresses interictal epileptiform discharges.9In a normally menstruating woman, the surge of serum estrogen levels at the time of ovulation may be associated with increased seizure tendency; as may the fall in serum progesterone levels just before and during menstruation.In a woman with an anovulatory cycle, estrogen levels rise at the end of the follicular phase and stay elevated throughout the luteal phase until premenstrually, as in normally menstruating women. Little or no progesterone is secreted, however, creating an estrogen:progesterone (E/P) imbalance with a relative excess of estrogen (or deficiency of progesterone) throughout the whole second (luteal) half of the menstrual cycle. Seizure exacerbation results.10A number of studies have suggested that both progesterone deficiency and estrogen excess relative to progesterone contribute to the catamenial pattern of seizure exacerbation in both normal women and in women with menstrual irregularities.1,2,10 The E/P ratio appears to determine the overall reproductive hormonal effect upon seizure frequency.10
3EPILEPSY GENERALIZED SEIZURES: Involve both the hemisphere from outset.Generalized, Tonic-Clonic Seizures:Absence Seizures: Typical absence seizures are characterized by sudden, brief lapses of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion.3. Myoclonic Seizures: Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body.Generalized SeizuresGeneralized seizures are thought to arise at some point in the brain but immediately and rapidly engage neuronal networks in both cerebral hemispheres. Several types of generalized seizures have features that place them in distinctive categories and facilitate clinical diagnosis.Typical Absence SeizuresTypical absence seizures are characterized by sudden, brief lapses of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion. Although the brief loss of consciousness may be clinically inapparent or the sole manifestation of the seizure discharge, absence seizures are usually accompanied by subtle, bilateral motor signs such as rapid blinking of the eyelids, chewing movements, or small-amplitude, clonic movements of the hands.Typical absence seizures are associated with a group of genetically determined epilepsies with onset usually in childhood (ages 4–8 years) or early adolescence and are the main seizure type in 15–20% of children with epilepsy. The seizures can occur hundreds of times per day, but the child may be unaware of or unable to convey their existence. Since the clinical signs of the seizures are subtle, especially to parents who may not have had previous experience with seizures, it is not surprising that the first clue to absence epilepsy is often unexplained "daydreaming" and a decline in school performance recognized by a teacher.The electrophysiologic hallmark of typical absence seizures is a generalized, symmetric, 3-Hz spike-and-wave discharge that begins and ends suddenly, superimposed on a normal EEG background. Periods of spike-and-wave discharges lasting more than a few seconds usually correlate with clinical signs, but the EEG often shows many more brief bursts of abnormal cortical activity than were suspected clinically. Hyperventilation tends to provoke these electrographic discharges and even the seizures themselves and is routinely used when recording the EEG.Atypical Absence SeizuresAtypical absence seizures have features that deviate both clinically and electrophysiologically from typical absence seizures. For example, the lapse of consciousness is usually of longer duration and less abrupt in onset and cessation, and the seizure is accompanied by more obvious motor signs that may include focal or lateralizing features. The EEG shows a generalized, slow spike-and-wave pattern with a frequency of 2.5 per second, as well as other abnormal activity. Atypical absence seizures are usually associated with diffuse or multifocal structural abnormalities of the brain and therefore may accompany other signs of neurologic dysfunction such as mental retardation. Furthermore, the seizures are less responsive to anticonvulsants compared to typical absence seizures.Generalized, Tonic-Clonic SeizuresGeneralized-onset tonic-clonic seizures are the main seizure type in ~;10% of all persons with epilepsy. They are also the most common seizure type resulting from metabolic derangements and are therefore frequently encountered in many different clinical settings. The seizure usually begins abruptly without warning, although some patients describe vague premonitory symptoms in the hours leading up to the seizure. This prodrome is distinct from the stereotypic auras associated with focal seizures that generalize. The initial phase of the seizure is usually tonic contraction of muscles throughout the body, accounting for a number of the classic features of the event. Tonic contraction of the muscles of expiration and the larynx at the onset will produce a loud moan or "ictal cry." Respirations are impaired, secretions pool in the oropharynx, and cyanosis develops. Contraction of the jaw muscles may cause biting of the tongue. A marked enhancement of sympathetic tone leads to increases in heart rate, blood pressure, and pupillary size. After 10–20 seconds, the tonic phase of the seizure typically evolves into the clonic phase, produced by the superimposition of periods of muscle relaxation on the tonic muscle contraction. The periods of relaxation progressively increase until the end of the ictal phase, which usually lasts no more than 1 minute. The postictal phase is characterized by unresponsiveness, muscular flaccidity, and excessive salivation that can cause stridorous breathing and partial airway obstruction. Bladder or bowel incontinence may occur at this point. Patients gradually regain consciousness over minutes to hours, and during this transition there is typically a period of postictal confusion. Patients subsequently complain of headache, fatigue, and muscle ache that can last for many hours. The duration of impaired consciousness in the postictal phase can be extremely long (i.e., many hours) in patients with prolonged seizures or underlying central nervous system (CNS) diseases such as alcoholic cerebral atrophy.The EEG during the tonic phase of the seizure shows a progressive increase in generalized low-voltage fast activity, followed by generalized high-amplitude, polyspike discharges. In the clonic phase, the high-amplitude activity is typically interrupted by slow waves to create a spike-and-wave pattern. The postictal EEG shows diffuse slowing that gradually recovers as the patient awakens.There are a number of variants of the generalized tonic-clonic seizure, including pure tonic and pure clonic seizures. Brief tonic seizures lasting only a few seconds are especially noteworthy since they are usually associated with specific epileptic syndromes having mixed seizure phenotypes, such as the Lennox-Gastaut syndrome (discussed below).Myoclonic SeizuresMyoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body. A normal, common physiologic form of myoclonus is the sudden jerking movement observed while falling asleep. Pathologic myoclonus is most commonly seen in association with metabolic disorders, degenerative CNS diseases, or anoxic brain injury (Chap. 275). Although the distinction from other forms of myoclonus is imprecise, myoclonic seizures are considered to be true epileptic events since they are caused by cortical (versus subcortical or spinal) dysfunction. The EEG may show bilaterally synchronous spike-and-wave discharges synchronized with the myoclonus, although these can be obscured by movement artifact. Myoclonic seizures usually coexist with other forms of generalized seizures but are the predominant feature of juvenile myoclonic epilepsy (discussed below).Generalized: the ﬁrst clinical changes indicate initial involvement ofboth hemispheresGeneralized seizures are conceptualized as originating at somepoint within and rapidly engaging bilaterally distributed networkTonic clonic seizures : Some people experience a forewarning or ‘aura’ before a tonic-clonic seizure; most, however, lose consciousness without warning. During the initial tonic phase, the muscles suddenly contract, causing the patient to fall and lie rigidly for 10–30 s. If the throat or larynx is affected, a high-pitched sound called stridor may be emitted when the patient inhales. Spasms caused by alternate relaxation and contraction of muscles occur for 30–60 s as the seizure enters the clonic phase. The patient may lose bowel or bladder control. The full seizure usually lasts a total of 2–3 minutes, and the patient may remain unconscious for some minutes afterwards. On regaining consciousness, the patient is usually confused and extremely tired. A severe throbbing headache similar to migraine often follows a tonic-clonic seizure.Age: In 90% of cases, West syndrome (infantile spasms, IS) occurs in the first year of life, primarily in children aged 3–6 months. West syndrome usually disappears by age 5, but is often replaced by other seizure typesWest syndrome( infantile spasm) Type of seizure: This is a generalised syndrome, characterised by spasms, hypsarrhythmia, and mental retardation. In affected infants, spasms typically begin soon after awakening and are manifest as a sudden bending forward and stiffening of the body, arms, and legs; arching of the torso may also occur. Individual spasms typically last for 1–5 seconds and occur in clusters of up to 100 spasms. Patients may experience many clusters per day.
4ANTIEPILEPTIC DRUGS Seizures: Defective synaptic function. Inhibition of inhibitory synapse.Excitation of excitatory synapse.Antiepileptic drugs act by restoration of normal synaptic activity.Activation of inhibitory synapse.Inhibition of excitatory synapse.The proconvulsant effects of estrogen have been demonstrated in both animals and humans, whereas progesterone has been found to have anticonvulsant properties. Catamenial epilepsy affects approximately one-third of women with epilepsy. This type of epilepsy has generally been defined as an increase in seizure frequency beginning immediately before or during menses
5ANTIEPILEPTICS DRUGSDrugs acting by prolonging the inactivation of Na channels: Carbamazepine, Phenytoin, Valproate, Topiramate, Lamotrigine, ZonisamideDrugs enhancing GABA-A induced inhibition: Benzodiazepines, Barbiturates, Valproate, Topiramate, Gabapentin, Tiagabine, VigabatrinDrugs affecting the ‘T’ Ca Current: Ethosuximide, ValproateDrugs inhibit glutamate synaptic function: Topiramate, Lamotrigine, FelbamatePartial seizures evolving to secondarily generalized seizures (this may be generalized tonic-clonic, tonic, or clonic)
6ANTI EPILEPTICS Topiramate Topiramate After the sodium channel lets enough sodium into the cell so that it reaches a maximum voltage, the channel temporarily becomes inactivated. An inactivated channel means that not only can no more sodium get through to relay the current message, but also the channel cannot be immediately reset, and thus will let no new messages be relayed. This intermediate stage between open and closed is called the refractory period. The sodium channel returns to the closed position only after the membrane voltage returns to a normal level (restoring the normal voltage involves the exit and entry of different ions). Once the channel is back in the closed position it can be opened again when the voltage rises enough.TopiramateTopiramate
7ANTIEPILEPTIC DRUGS Phenytoin (Dilantin®) Zero order kinetics. Plasma monitoring.Enzyme inducer.Uses of Phenytoin:Generalized Tonic-Clonic Seizures.Partial seizures and Status epilepticusFosphenytoin (Cerebyx®) is a prodrug used i.v as a substitute for phenytoin.Not a global CNS depressant, Oral absorption is variablePhenytoin, in both its acidic and sodium salt forms, is erratically bioavailable whether it is injected or taken orally due to its high melting point, weak acidity, and its being only sparingly soluble in water. Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants available was much more limited. One solution was to develop a prodrug that did not have these drawbacks.Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996 for use in epilepsy.Fosphenytoin is approved in the United States for the short term (five days or less) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised, such as endotracheal intubation, status epilepticus or some other type of repeated seizures; vomiting, and/or the patient is unalert or not awake or both. Side effects are similar to phenytoin, except that fosphenytoin causes less hypotension and more paresthesia.
8ANTIEPILEPTIC DRUGSPhenytoin, Carbamazepine and Valproate act by prolonging the inactivation of Na channels
9ANTIEPILEPTIC DRUGS Phenytoin toxicity: Ataxia, vertigo and nystagmus. Gum hypertrophy, Hirsutism.Megaloblastic anemia / Osteomalacia.In pregnancy – fetal hydantoin syndrome – cleft lip and palate.Should not be used in absence seizures.Phenytoin also commonly causes gingival hyperplasia due to folate deficiency. Phenytoin has been associated with drug-induced gingival enlargement (overgrowth of the gums), probably due to above-mentioned folate deficiency; indeed, evidence from a randomized controlled trial suggests that folic acid supplementation can prevent gingival enlargement in children who take phenytoinPhenytoin induces the metabolism of steroids and Vit - D
10Phenytoin induced gum hyperplasia and coarsening of facial features
11ANTIEPILEPTIC DRUGS BARBITURATES : Phenobarbital (Luminal®), Primidone (Mysoline®)It has specific anticonvulsant action.It is an enzyme inducer.It is contraindicated in acute intermittent or variegate porphyria.Long term administration cause behavioral abnormalities, impaired learning and memory.
12ANTIEPILEPTIC DRUGSCarbamazepine (Tegretol®) Oxcarbazepine (Trileptal®)Prolong the inactivated Na channel.Antidiuretic effect by ↑ ADH action.Metabolized to toxic epoxide derivative.Enzyme inducer and auto-induction may need dose adjustments.Not to be used in absence seizures.Oral absorption is slowcarbamazepine induces its own metabolism (CYP3A4) requiring dose adjustment after about 2-3 weeks
13ANTIEPILEPTIC DRUGS Carbamazepine toxicity: Sedation, ataxia, vertigo and diplopia.SIADH – ADH action (Hyponatremia)Fetal malformations – craniofacial abnormality and spina-bifida.Fatal skin reactions (Stevens–Johnson syndrome) in HLA-B*1502.Agranulocytosis and aplastic anemia
14ANTIEPILEPTIC DRUGS Uses of Carbamazepine (CBZ): Partial / Generalized tonic-clonic epilepsy.Trigeminal neuralgia.Bipolar disorder.Oxcarbazepine is an analog of CBZ.Less potent inducer of cytochrome P450 than CBZ.
15ANTIEPILEPTIC DRUGS Valproate (Depakene) It is a broad spectrum antiepileptic drug.Mechanism of action:Prolong inactivated state of Na channel.Attenuation of calcium T Current.Inhibition of degradation of GABA by transaminase.Attenuates excitatory action of glutamate at NMDA receptors.Oral absorption is good
16ANTIEPILEPTIC DRUGS VALPROATE TOXICITY: Acute pancreatitis Hepatotoxicity – in children < 2 years.Antagonist of folic acid – neural tube defects – spina bifida.It is an enzyme inhibitor.GI: nausea, vomiting, anorexia, abdominal pain, bowel disturbancesTo diminish theseTitrate dose slowlyTake with foodTransient hair lossIt is a known folate antagonist, which can cause neural tube defects.
18ANTIEPILEPTIC DRUGS ZONISAMIDE (Zonegran) Prolong the inactivated Na channel.Inhibits Ca ‘T’ currents.Add on therapy for Focal (Partial) seizuresAtaxia and anorexia are the adverse effects.It has also been studied for obesity with significant positive effects on body weight and there are three ongoing clinical trials for this indicationZonisamide has been studied for and used as a migraine preventative medication, and has also been shown to be effective in some cases of neuropathic pain. It has also been used by psychiatrists as a mood stabilizer
19ANTIEPILEPTIC DRUGS ETHOSUXIMIDE (Zarontin) Thalamus plays a role in 3-Hz spike-wave rhythms typical of absence seizuresPrimary action is on thalamocortical system involved in absence seizures.Acts by suppression of the ‘T’ Ca current.Used in absence seizures.Skin rash (SJS) and agranulocytosis.
20ANTIEPILEPTIC DRUGS LAMOTRIGINE (Lamictal) Prolongs the inactivation Na channels.Inhibits Calcium channels.Block of glutamate receptors.Used in Partial epilepsy, GTC seizures, Myoclonic seizures, Absence seizures, Lennox Gastaut Syndrome and Bipolar disorder.Ataxia and SJS are adverse effects.SERIOUS RASHES REQUIRING HOSPITALIZATION AND DISCONTINUATION OF TREATMENT HAVE BEEN REPORTED IN ASSOCIATION WITH THE Lamotrigine also acts as a mood stabilizer . USE OF LAMICTAL. THE INCIDENCE OF THESE RASHES, WHICH HAVE INCLUDED STEVENS-JOHNSON SYNDROME, IS APPROXIMATELY 0.8% (8 PER 1,000) IN PEDIATRIC PATIENTS (AGE <16 YEARS) RECEIVING LAMICTAL AS ADJUNCTIVE THERAPY FOR EPILEPSY AND 0.3% (3 PER 1,000) IN ADULTS ON ADJUNCTIVE THERAPY FOR EPILEPSY. In women using oral contraceptives, Lamotigrine should be considered for the initial therapy because it has no effect on cytochrome P 450 and does not interfere with the effectiveness of oral contraceptives.
21LAMOTRIGINE Lamotrigine (LTG) induced Stevens-Johnson Syndrome. Valproate added to lamotrigine increases LTG concentrations approximately two-fold.Lamotrigine induced stevens-johnson syndrome is common in childrenTitrate dose slowly to reduce risk of skin rashEnzyme inducing AEDs such as carbamazepine and phenobarbital added to lamotrigine (LTG) reduce LTG concentrations by 40%valproate added to lamotrigine increases LTG concentrations approximately two-fold
22ANTIEPILEPTIC DRUGS TOPIRAMATE (Topamax) Prolong the Na inactivated channels.Enhance GABA current.Blocks the AMPA (glutamate) receptor.Carbonic anhydrase inhibitor.Used in the treatment of Partial seizures, Generalized tonic-clonic seizures, Lennox-Gastaut syndrome and migraine prophylaxis.Weight loss and renal stonesTopiramate (brand name Topamax) is an anticonvulsant drug. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose and such use is somewhat controversial. This drug has been investigated for use in treatment of obesity, especially to aid in the reduction of binge eating, and also as a possible treatment for alcoholism. However, these uses are not actively promoted by the manufacturer, and like its use for bipolar disorder, are off-label uses. The drug is also used in clinical trials to treat Post Traumatic Stress Disorder. A pilot study suggests that Topiramate is possibly effective against infantile spasm. In May 2006 the U.S. National Institutes of Health web site clinical trials. gov listed several studies sponsored by Ortho-McNeil which propose to examine the use of topiramate on migraine, cluster, and severe headaches within various demographics. Other off-label and investigational uses of Topiramate include: treatment of bulimia nervosa, obsessive-compulsive disorder, smoking cessation, treatment of neuropathic pain. Topiramate adverse effects : Cognitive impairment, confusion, dizziness, ataxia, headacheAgitation, emotional liabilityNausea, anorexia, weight lossAcute angle-closure glaucoma The Food and Drug Administration (FDA) has issued a notification alerting physicians who prescribe topiramate, and their patients, to the risk of vision loss (blindness). Acute myopia and secondary angle closure glaucoma, in a small subset of patients who take topiramate regularly, may cause transient (reversible), or permanent, loss of vision. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain.
23ANTIEPILEPTIC DRUGS BENZODIAZEPINES Lorazepam, Midazolam, Diazepam, Clonazepam.Clonazepam – Absence and Myoclonic seizures.Lorazepam, Midazolam, Diazepam – Status epilepticus.Sedation and tolerance are the disadvantages on long term use.Shortly after it was introduced in 1963, diazepam became the first choice for SE. Even though other benzodiazepines such as clonazepam were useful, diazepam was relied upon almost exclusively. This began to change in 1975 with a preliminary study on lorazepam conducted by Waltregny and Dargent, who found that its pharmacological effects were longer lasting than those of an equal dose of diazepam. This meant it did not have to be repeatedly injected like diazepam, the effects of which would wear off 5–15 minutes later in spite of its 30-hour half-life (due to extensive redistribution of diazepam outside the vascular compartment as diazepam is highly lipid soluble). It has also been found that patients who were first tried on diazepam were much more likely to require endotracheal tubing than patients who were first tried on phenobarbital, phenytoin, or lorazepam.Today, the benzodiazepine of choice is lorazepam for initial treatment due to its long (2–8 hour) duration of action and rapid onset of action, thought to be due to its high affinity for GABA receptors and to its low lipid solubility which causes it to remain in the vascular compartment. If lorazepam is not available, then diazepam should be given. Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as refractory.
24ANTIEPILEPTIC DRUGS GABAPENTIN (Neurontin) and PREGABALIN (Lyrica) Increased release of GABAInhibition of L-type Ca2+ channelsGabapentin used for Neuropathic pain (Post-herpetic neuralgia) and Partial seizures.Pregabalin is approved for treatment of chronic pain disorders.GABAPENTIN ALSO SEEMS TO BLOCK HIGH VOLATGE CALCIUM.Pregabalin is a 3-substituted analogue of gamma-amino butyric acid (GABA) and a compound related to Pfizer's hugely successful antiepileptic drug gabapentin. In July 2004, Pfizer secured Europe-wide approval for Lyrica (pregabalin) for use in the management of peripheral neuropathic pain as well as an adjunctive therapy in the treatment of partial epileptic seizures. Subsequently in December 2004 the company gained FDA approval for use of Lyrica (pregabalin) in neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia; making it the first FDA-approved treatment for both of these neuropathic pain states. Lyrica (pregabalin) is also being reviewed by the FDA as an adjunctive treatment for partial epileptic seizures in adults. Although not "indicated" (i.e., not FDA-approved), gabapentin has been found to be effective in prevention of frequent migraine headaches, neuropathic pain and nystagmus.Gabapentin has also been used in the treatment of bipolar disorder.Sedation and peripheral edema are the side effects.
25ANTIEPILEPTIC DRUGS VIGABATRIN (Sabril) A gamma vinyl analogue of GABA.Inhibitor of GABA transaminase.Used in refractory partial epilepsyAdverse effects includes – visual field defects (monitoring Q 6 months recommended) and psychosis.
26ANTIEPILEPTIC DRUGS TIAGABINE (Gabitril) It ↑ GABA by blocking the GABA reuptake transporter.It is used in Partial seizures.Somnolence, Depression and impaired concentration are adverse effects.
27increase GABA by blocking its reuptake. TIAGABINE (Gabitril)increase GABA by blocking its reuptake.
28ANTIEPILEPTIC DRUGS LEVETIRACETAM (Keppra) It modulates the release of glutamate and GABA.Approved in Partial seizures, Generalized tonic-clonic seizures and myoclonic seizures.Somnolence and ataxia are the adverse effects.Levetiracetam binds to a synaptic vesicle protein, SV2A. This is believed to impede nerve conduction across synapses.
29ANTIEPILEPTIC DRUGS Felbamate (Felbatol) It blocks NMDA receptors and potentiates GABA-A receptor response.Use of felbamate is restricted to patients with Lennox-Gastaut syndrome.Adverse effects includes aplastic anemia and hepatic failure.
30Blocks AMPA Block Na Channel ↑ GABA Partial seizures GTC seizures DrugMech actionIndicationsToxicityTopiramateBlocks AMPA Block Na Channel ↑ GABAPartial seizures GTC seizuresWeight loss Renal stonesLamotrigineBlock glutamate Block Na channelPartial seizures GTC seizuresSedation, SJSFelbamateBlock NMDA Potentiate GABAPartial seizures Lennox Gastaut syndromeAplastic anemia HepatotoxicityVigabatrinInhibit GABA transaminase ↑ GABAPartial seizuresVisual defectTiagabineBlock reuptake GABA transporter ↑ GABASedationGabapentinPromote GABA releaseChronic painClobazam: Notably used on a short-term basis around menstruation in women with catamenial epilepsyACETAZOLAMIDECarbonic anhydrase inhibitorUsed for treatment of seizures during menses and absence seizuresTolerance is the drawback
31Focal seizures (Partial) Carbamazepine Lamotrigine EpilepsyPreferred choiceOthersFocal seizures (Partial)Carbamazepine LamotrigineTopiramate ValproatePrimary GTCValproate LamotrigineTopiramate CarbamazepineAbsenceEthosuximideValproateMyoclonicLevetiracetam TopiramateStatus epilepticusLorazepam Midazolam DiazepamPhenytoinPhenobarbitalStatus epilepticus : Midazolam (N/A). Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa.Status epilepticus (SE) refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5-10 minutes, or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes.
33Status epilepticus Benzodiazepine Levetiracetam Newer AEDs Lamotrigine TopiramatePartial SeizuresSimpleComplexGeneralized SeizuresAbsenceMyoclonicTonic-ClonicStatus epilepticusHARRISON PRINCIPLE OF MEDICINEAntiepileptic Drug Selection for Generalized SeizuresValproic acid and lamotrigine are currently considered the best initial choice for the treatment of primary generalized, tonic-clonic seizures. Topiramate, zonisamide, phenytoin, and carbamazepine are suitable alternatives.Antiepileptic Drug Selection for Focal SeizuresCarbamazepine (or a related drug, oxcarbazepine), lamotrigine and phenytoin are currently the drugs of choice approved for the initial treatment of focal seizures, including those that evolve into generalized seizures. .Valproic acid is an effective alternative for some patients with focal seizures, especially when the seizures generalize. Gastrointestinal side effects are fewer when using the valproate semisodium formulation (Depakote). Valproic acid also rarely causes reversible bone marrow suppression and hepatotoxicity, and laboratory testing is required to monitor toxicity