Ethosuximide Carbamazepine

Anxiolytics clonazepam, diazepam, temazepam, triazolam, alprazolam, midazolam, buspirone Anticonvulsants ethosuximide, carbamazepine Calcium channel blockers diltiazem, felodipine, nifedipine, verapamil... 

Ethosuximide Carbamazepine Reduced plasma concentration of ethosuximide. 

Detection and result The chromatogram was freed from mobile phase (first dried for 5 min in a stream of cold air, then heated for 10 min at 110°C and allowed to cool), immersed for 5 s in the reagent solution and finally heated for 2 min at 110°C. Grey to grey-blue zones were formed on a light background. The following hRf values were obtained primidone QiR( 10-15) carbamazepine hRf 40 — 45) phenytoin hR( 50 — 55) phenobarbital hRf 60) ethosuximide hRf 75) hexobarbital hRf 90 — 95). 

Fig. 1 Reflectance scan of a blank (A) and of a mixture of antiepileptics with 500 ng substance per chromatogram zone (B). Start (1), primidone (2), carbamazepine (3), phenytoin (4), phenobarbital (5), ethosuximide (6), hexobarbital (7) and solvent front (8).

Phenobarbitone was the first AED and was introduced in 1912. It was largely replaced in 1932 by phenytoin for the management of tonic-xilonic seizures and partial and secondary epilepsy. Carbamazepine followed, then ethosuximide for absence seizures and valproic acid. These remained, apart from the introduction of the benzodiazepines, the mainstay of therapy until the last decade. They were introduced solely on their ability to control experimentally induced seizures. Their mechanisms of action were unknown and no thought was given to the possibility of NT modification and in fact subsequent research has shown that with the exception of the benzodiazepines none of them work primarily through NT manipulation. They act directly on neuronal excitability. 

Atenolol, hydralazine, procainamide, quinidine, carbamazepine, chlorpromazine, ethosuximide, isoniazid, methyldopa, minocycline, penicillamine, phenylbutazone, phenytoin, thiazides, and valproic acid... 

Outside of the evidence-based guidelines, other pharmacologic treatments are commonly used or avoided. For initial treatment of absence seizures, ethosuximide and valproate are commonly used, not only in the United Kingdom, but also in the United States. Zonisamide may be also used for initial treatment of absence and myoclonic seizures. In absence and myoclonic seizures, carbamazepine, oxcarbazepine, gabapentin, tiagabine, and pregabalin should be avoided, as they have been associated with an exacerbation of these types of seizures. 

Antiepileptics Phenytoin Carbamazepine Valproic acid Gabapentin Vigabatrin Ethosuximide Benzodiazepines... 

From the clinical point of view, antiepileptic drugs are primarily divided into two categories those effective in treating major attacks (phenytoin, carbamazepine, mephobarbi-tal, and also primidone), and those effective in treating minor attacks (ethosuximide, acetazolamide, clonazepam, trimethadione, and valproic acid). 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Drugs that may affect valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

Anticonvulsant Carbamazepine, ethosuximide, lamotrigine, mesantoin, phenytoin, trimefhadione, valproic acid... 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Ethosuximide Reduces low threshold Ca2+ currents (T-type) Well absorbed orally, with peak levels in 3-7 h not protein-bound completely metabolized to inactive compounds tjy2 typically 40 h Absence seizures Toxicity Nausea, headache, dizziness, hyperactivity Interactions Valproate, phenobarbital, phenytoin, carbamazepine, rifampicin... 

Regarding the usefulness in measuring the serum concentrations of antiepileptic drugs, it is often of value to do so with those drugs that are liable to cause toxic side effects such as carbamazepine, ethosuximide, phenobarbitone and phenytoin. In general, there seems to be little advantage in determining the serum concentrations of the newer, and better tolerated, antiepileptics. 

For simple and complex partial seizures and secondary generalized tonic-clonic seizures, the first line drugs are - carbamazepine, valproate and phenytoin. Second line drugs include - acetazolamide, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxacarbamazepine, primidone, tiagabine, topiramate and vigabactin. 

For atypical absence, tonic and clonic seizures, first line treatment is with valproate and second line with acetazolamide, carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxacarbamazepine, phenobarbitone, phenytoin, primidone or topiramate. 

Valproate, phenobarbitone, carbamazepine, diphenylhydantoin Valproate, ethosuximide, primidone... 

Carbamazepine is a hepatic microsomal enzyme inducer and therefore will lower the serum concentration of a wide variety of drugs given concurrently. These include the antiepileptic drugs phenytoin, primidone, valproate, ethosuximide and clonazepam. In addition, carbamazepine can compromise the therapeutic effects of oral contraceptives, oral anticoagulants, beta-blockers, haloperidol and theophylline. 

Mode of action. The specific site of action of felbamate is unknown. There is experimental evidence that felbamate blocks NMDA receptors, but less potently than carbamazepine, ethosuximide, phenytoin or valproate. It also modulates sodium channel conductance but does not enhance GABAergic function. In addition to its protective action against chemically induced seizures felbamate has also been shown to have a neuroprotective action in models of hypoxic ischaemia as induced by bilateral carotid ligation. 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

Ethosuximide Ethosuximide interacts with isoniazid, phenytoin, phenobarbi-tone, carbamazepine, valproic acid, antipsychotics, and antidepressants.193... 

Carbamazepine can decrease piasma ieveis of acetaminophen, ciozapine, benzodiazepines, dicumaroi, doxycyciine, theophyiiine, warfarin, and haioperidoi as weii as other anticonvuisants such as phensuximide, methsuximide, ethosuximide, phenytoin, tiagabine, topiramate, iamotrigine, and vaiproate... 

Plasma levels of valproate may be lowered by carbamazepine, phenytoln, ethosuximide, phenobarbital, rifampin... 

Isoniazid inhibits the metabolism of phenytoin, carbamazepine and ethosuximide, increasing their effect. 

---