pharma fouda 3_p109-110.pdf

Part 5 5: Antiiepileptiic Drugs s █ Basiic inform mation  Epilepsy, a chronic disease, occurs in appproximatelyy 1% of the popu lation. The cauuse of most cases of epilepsy iss unknown n, alth hough som me people de...

Part 5 5: Antiiepileptiic Drugs s █ Basiic inform mation  Epilepsy, a chronic disease, occurs in appproximatelyy 1% of the popu lation. The cauuse of most cases of epilepsy iss unknown n, alth hough som me people develop e epilepsy as a the result of brain b injury y, stroke, b brain tumor, andd drug toxicity. Ge enetic muttations arre linke ed to a sm mall proportion of the e disease.  Epilleptic seizu ures resultt from exc cessive and d abn normal cortiical nerve cell c activity in the brain n.  Thee diagnosiss typicallyy involves ruling outt other conditions thhat cause similar neuurological symptoms. This m may be confirmed d by braain imagin ng and elec ctroencephhalogram (EEG) ( but a normal te est does not excludee the condition.  Antiepileptic drugs d (AED Ds) are effe ective for about a 80% % of these patients. Lifelong L trea atment mayy be neces ssary.  It m may take we eeks to es stablish ade equate dru ug plasma levels and d to determ mine the ade equacy of therapeutiic improve ement. Lac mpliance iis respons ck of com sible for manny treatme ent failures.  AED Ds are mo ost effectiive and ha ave the le east adverse effectts when they are use ed as mono otherapy.  Add dition or withdrawal w of any drrug should d be gradual, becauuse seizurres may occ cur on withdrawal.  Som me AEDs are a terato ogenic; thiis may ca all for the reduction or termina ation of therrapy during g pregnanc cy. Classiification of o epileps sies: Epilepssies are characteriz c zed by eitther focall or generalized ab bnormal neuronal n discharrges. Drugg selection n, based o on seizure classifica ation, is lissted below w in the order o of general choice. c Simple Loc calized disc charge; co onsciousne ess is 1. Carbama azepine partial not altered. 2. Lamotriggine seizures Partial 3. Valproic acid Complex x Loc calized disc charge tha at becomes s partial widespread; aaccompanied by loss s of con nsciousnesss. 345  Tonic–clo onic Draamatic convvulsions with w either jerking 1. Valproic acid (grand ma al) of the extremiities or rigidity of the entire 2. Lamotriggine boddy; accomppanied by loss of 3. Carbama azepine connsciousnesss. Generalized Absence Suddden onsett of altered d consciouusness 1. Ethosuximide seizures (petit mal)) thatt lasts 10–4 45 secondds, with up to 2. Valproic acid hun ndreds of sseizures peer day; beg gins in 3. Clonazeppam chilldhood or adolescen nce. Myoclonic Lighhtning-like e jerks of one or more e 1. Valproic acid syndromes extrremities occcurring sin ngly or in bursts b 2. Lamotriggine of up u to a hun ndred; accompanied by alte eration of c consciousn ness. Status epilep pticus: Pro olonged se eizure (>20 0 min) of a any of the types prev viously desscribed; th he most com mmon is liffe-threaten ning generaalized tonic–clonic sttatus epileepticus. 1. Dip phenylhyd dantoin (P Phenytoin n) Mechaanism: it blocks Na a+, K+ andd Ca2+ channeels in the brain (and d heart) le eading to deccrease prropagation n of abn normal impulse es. It prooduces so ome degrree of drowsin ness. Therap peutic use es  Parttial and geeneralized seizures s  Stattus epileptticus: it sho ould be givven i.v. in the t form of fosphenyytoin (prod drug).  Ven ntricular arrrhythmia. Advers se effects – CNS S: Nystagmus, diplo opia, ataxia a. – Heppatotoxicityy. – Miccrosomal enzyme ind duction. – Bonne marrow depressio on & Mega loblastic anemia a e to ↓ folicc acid). (due – Teraatogenicityy: craniofacial abnorm malities. – Gingival hype erplasia: 2ry 2 to incrreased ex xpression of platelett derived growth facttor (PDGF)). – Lym mphadenop pathy. 346