Lamotrigine seizure activity

The anticonvulsant action of valproate may prevent ECT treatment from being effective by preventing seizure activity. This is also a theoretical/practical concern with carbamazepine, gabapentin, lamotrigine, and topiramate. As a rule of thumb, the co-administration of an anticonvulsant and ECT should be considered very cautiously ... 

After each depolarization, voltage-dependent sodium channels adopt an inactive state and remain refractory to reopening for a period of time. While those channels are unable to open, rapid repetitive firing is diminished, and spread of electrical seizure activity to adjacent brain regions is suppressed (14). Stabilization and prolongation of this inactive state appears to be the primary mechanism of action of phenytoin, carbamazepine, and lamotrigine and may be instrumental in the antiseizure actions of phenobarbital, oxcarbazepine, valproate, topiramate, and zonisamide (Fig. 20.2). 

Observational studies Lamotrigine has been evaluated in a study that included an open, 1-week screening phase, a 20-week escalation phase, and a 12-week maintenance phase in 54 children aged under 13 years who had newly diagnosed absence epilepsy and had not previously been treated with antiepileptic drugs [138 ]. Rash was reported in six patients (11%), urticaria in one patient (2%), and pruritus in two patients (4%). None of these events was serious or resulted in premature withdrawal. Three patients had adverse events that led to premature withdrawal increased seizure activity in one, tremor in one, and vomiting and dizziness in one patient. 

One unwanted side-effect of phenytoin is its anti-folate activity. A programme of synthetic chemistry to manipulate the structure of the anti-folate compound pyri-methium to try to replace that property with anticonvulsant activity resulted in the synthesis of lamotrigine. It proved to be an effective AED in partial and generalised epilepsy but experience has found it also to be of value in absence seizures. 

Epilepsy is a clinical disorder characterized by spontaneous, recurrent seizures arising from excessive electrical activity in certain parts of the brain [51]. Currently available drugs, such as phenytoin, carbamazepine, valproic acid, lamotrigine, and topiramate (for molecular structures see Fig. 6), provide symptomatic seizure suppression in only 60-70% of those receiving treatment [52-54]. These drugs are also associated with unwanted side... 

Lamotrigine has a broad spectrum of action and is effective in generalized and partial epilepsies. Its primary mechanism of action appears to be blockage of voltage-dependent sodium channels, although its effectiveness against absence seizures indicates that additional mechanisms may be active. Lamotrigine is almost completely... 

Lamotrigine was developed when some investigators thought that the antifolate effects of certain antiseizure drugs (eg, phenytoin) may contribute to their effectiveness. Several phenyltriazines were developed, and although their antifolate properties were weak, some were active in seizure... 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

Epileptic seizures are characterized by high-frequency bursts of action potentials that occur synchronized throughout neuronal networks. This type of epileptiform repetitive firing can be induced by the removal of extracellular magnesium. Use-dependent sodium channel blockers such as lamotrigine block the epileptiform activity at concentrations well below those required to block normal conduction [51]. Since the firing associated with epileptic seizures occurs with high frequency, the use-dependent properties of anticon-... 

Several authors have provided insight into the putative MBS receptor based on their structure-activity data. As noted by Unverferth et al. (281), there have been several attempts to postulate a general pharmacophore for the different anticonvulsant classes, all of which are anti-MES in animal studies and are, or have the potential to be, effective in generalized tonic-clonic seizures. These include benzodiazepines (282) barbiturates (283) triazolines (284) semicarbazones (248-261) and enami-nones (286-288), respectively and for different compounds with similar anticonvulsant profiles (289-292). The Unverferth model (Fig. 6.11) provides an excellent representation of the current anticonvulsants phenytoin (1), carbamazepine (2), lamotrigine (11), zonisamide (13), and rufinamide (60). Remace-mide (58) is also included as a possible candidate (Fig. 6.12). 

Absence seizure Abrupt onset of impaired consciousness associated with staring and cessation of ongoing activities typically lasting <30 seconds. Ethosuximide, valproate Lamotrigine... 

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