Newer anti-convulsants

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Antiepileptics-2 :

Antiepileptics-2 Newer Antiepileptic drugs Status epilepticus

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Hospitalize the patient ( ABCD ) Maintain airway and establish a proper iv line Collect blood for estimation of glucose, calcium and electrolytes . Maintain fluid and electrolyte balance. Status Epilepticus

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Molecular targets for antiseizure drugs at the excitatory, glutamatergic synapse. Presynaptic targets diminishing glutamate release include 1, voltage-gated (VG) Na + channels (phenytoin, carbamazepine , lamotrigine, and lacosamide ); 2, VG-Ca 2+ channels (ethosuximide, lamotrigine, gabapentin, and pregabalin , Valproate ) 3, K + channels ( retigabine ) 4.synaptic vesicle proteins, SV 2 A ( levetiracetam )

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5, CRMP-2, collapsin-response mediator protein-2 ( lacosamide) 6, AMPA receptors (blocked by phenobarbital, topiramate and lamotrigine ) 7, NMDA receptors (blocked by felbamate).

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Molecular targets for antiseizure drugs at the inhibitory, GABAergic synapse. These include "specific" targets: 1, GABA transporters (especially GAT-1, tiagabine); 2, GABA-transaminase (GABA-T, vigabatrin); 3, GABA A receptors (benzodiazepines);

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blocks voltage sensitive Na+ channels and thus stabilises the presynaptic membrance and prevents the release of excitatory neurotransmitters namely glutamate and aspartate. partial, generalised tonic-clonic, secondary generalised, absence and atonic seizure , myoclonic seizures Side effects include dizziness, ataxia, diplopia and skin rash Lamotrigine

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Zonisamide blockade of use dependent Na+ channels and inhibition of T type Ca2+ channels. partial, generalised tonic-clonic and myoclonic seizures. Side effects include drowsiness, amnesia, skin rash and kidney stones (due to carbonic anhydrase inhibition).

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Topiramate blockade of use-dependent Na+ channels, potentiation of GABA activity inhibition of kainate receptors for glutamate. generalised tonic-clonic, partial and absence seizures CNS depression, somnolence, amnesia

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Tiagabine inhibits GABA uptake by neurons and glia and thus increases the GABA content of brain. partial complex seizures Side effects include dizziness, fatigue, sleepiness, nausea, tremors and confusion.

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Vigabatrin irreversible inhibitor of GABA transaminase and thus elevates GABA levels simple and complex partial seizures but it can also be used for generalised seizures. adjunct drug for treating drug-refractory epilepsy and infantile spasm.

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Felbamate blocks voltage-dependent Na+ channels , blockade of NMDA receptors by antagonism atonic seizures, atypical absence seizures, partial seizures and generalised tonic-clonic seizures insomnia, nausea, dizziness and ataxia ,

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Levetiracetam SV 2 A allosteric modulations of not only GABA receptors but of high voltage activated Ca2+ channel and K+ channels. partial seizures

Lacosamide :

Lacosamide Lacosamide also binds collapsin response mediator protein 2 (crmp-2 ), a phosphoprotein involved in neuronal differentiation and axon outgrowth. Its anti-seizure mechanism of action is more likely mediated by its enhancing slow inactivation of Na + channels. Therapeutic Use refractory partial seizures demonstrated that addition of lacosamide

Rufinamide :

Rufinamide Rufinamide enhances slow inactivation of voltage gated Na + channels and limits sustained repetitive firing, the firing pattern characteristic of partial seizures. Therapeutic Use children with Lennox-Gastaut syndrome

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