GABA Barbiturates Benzodiazepines Gabapentin Levetiracetam Tiagabine Topiramate Valproate

GABA МЕХАНИЗЪМ НА ДЕЙСТВИЕ Barbiturates Benzodiazepines Gabapentin Levetiracetam Tiagabine Topiramate Valproate Vigabatrin Na+ Carbamazepine Lamotrigine Oxcarbazepine Phenytoin Topiramate Valproate Ca 2+ Ethosuximide Levetiracetam Pregabalin Valproate

INDIVIDUAL ANTIEPILEPTICS ▼CARBAMAZEPINE blocks voltage-dependent sodium ion reducing membrane excitability. The t 1/2 of drug falls from 35 20 h over the first few weeks of therapy due to the induction enzymes that metabolize it as well as other drugs (including corticosteroids, hormonal contraceptives, theophylline and w Standard tablets are taken twice a day. Carbamazepine is a first choice for focal and secondary generalized epileps aggravates myoclonic and absence seizure. It is useful for t of trigeminal neuralgia, postherepetic pains etc. Adverse reactions (ARs): reversible blurring of vision, diplo dizziness, ataxia, depression of AV conduction, skin rashes kidney dysfunction.

▼VALPROIC ACID (Sodium valproate) acts by inhibitin transaminase and increases the concentration of inhibitor transmitter GABA at its receptors. Valproic acid has t 1/2 1 90% bound to plasma albumin. It is a nonspecific inhibito bolism, and inhibits own metabolism, and that of lamot phenobarbital, phenytoin and carbamazepine. Valproic ac effective for treatment of generalized and partial epilepsy convulsion and post-traumatic epilepsy. ARs can be troublesome: weight gain, teratogenicity, pol ovary syndrome, and loss of hair which grows back cu Nausea can be a problem, rarely, liver failure (risk maxim 2– 12 weeks). Ketone metabolites may cause confusion in testing in diabetes mellitus.

▼PHENYTOIN (t 1/2 6– 24 h) is a potent inducer of hepatic met lizing enzymes affecting itself and other drugs (carbamazepin farin, adrenal and gonadal steroids, thyroxine, tricyclic antidep doxycycline, vitamin D, folate). Drugs that inhibit phenytoin me include: valproic acid, cimetidine, co-trimoxazole, isoniazid, ch phenicol, some NSAIDs, disulfiram. Phenytoin is 90% bound t albumin and small changes in binding will result in a higher co tion of free active drug. It is used to prevent all types of partial generalized seizure and st. epilepticus. It is not used for abse ARs: impairment of cognitive function (which has led many ph prefer carbamazepine and valproate), sedation, hirsutism, ski gum hyperplasia (due to the inhibition of collagen metabolism glycemia, anaemia, osteomalacia.

Saturation kinetics. Phenytoin is extensively hydroxylated in the liver and this process becomes saturated at about the doses needed for therapeutic effect. Thus phenytoin at low doses exhibits firstorder kinetics but saturation or zero-order kinetics develop as therapeutic plasma concentration range (10– 20 mg/L) is approached, i. e. the dose increments of equal size produce disproportional rise in steady-state plasma concentration.

▼BENZODIAZEPINES (in status epilepticus) • Diazepam given intravenously or rectally is highly effect stopping continuous seizure activity, especially generaliz clonic status epilepticus. The drug is occasionally given o a long-term basis, although it is not considered very effec this application, probably because of the rapid developm tolerance. A rectal gel is available for refractory patients acute control of bouts of seizure activity. • Lorazepam appears in some studies to be more effectiv longer-acting than diazepam in the treatment of status ep and is preferred by some experts. • Clonazepam (t 1/2 25 h) is a benzodiazepine used as a second line drug for treatment of primary generalized epi and status epilepticus.

Clonazepam, Clorazepate, Diazepam, Lorazepam, Nitrazepam GABAAbenzodiazepine receptor complex By Bennett and Brown (2003) s Z BD te si + GABAAsite + Cl+ Barbitu- rate sate Barbiturates

▼BARBITURATES (enzyme inducers) Antiepilepsy members include phenobarbital (phenoba ( t 1/2 100 h), methylphenobarbital and primidone (whic largely metabolized to phenobarbital, i. e. it is a prodrug). still used for generalized seizures; sedation is usual. Primidone and its active metabolites Basic & Clinical Pharmacology – 10 th Ed. (2007)

▼LAMOTRIGINE (t 1/2 6– 24 h) inhibits excitory neurotra glutamate. Lamotrigine is effective for treatment of partia secondarily generalized tonic-clonic seizure. It is genera tolerated but may cause serious ARs of the skin, includ Stevens–Johnson syndrome and toxic epidermal necrol ▼TOPIRAMATE (t 1/2 21 h) is used as adjunctive treatm partial seizure, with or without secondary generalization sedation, weight loss, acute myopia, raised intraocular p ▼ETHOSUXIMIDE (t 1/2 55 h) blocks T-type calcium ion channels. It is active in absence seizures (petit mal). ARs: gastric upset, CNS effects and allergic reactions.

Stevens–Johnson syndrome

MAIN INDICATIONS OF ANTIEPILEPTIC DRUGS

ИЗБОР НА АНТИЕПИЛЕПТИЧНО ЛЕКАР Grand mal: I избор – валпроати или Lamotrigine. Алтернатива – Carbamazepine, Topiramate или Phen Petit mal: I избор – Ehosuximide или валпроати. Алтернатива – Clonazepam или Lamotrigine Парциални гърчове: I избор – Carbamazepine ил валпроати. Алтернатива – Phenytoin, Lamotrigine, Vigabatrin, Top Status epilepticus: I избор – Diazepam или Loraze Алтернатива – Phenobarbital (i. m. /i/v. )

Treatment of status epilepticus in a Patient in opisthotonus (grand mal)