Valproic acid

Phenytoin, trimethadione, valproic acid Antithyroid drugs Methimazole Chelators... 

M. Ki ogh, K. Johansen, F. Tonnesen and K. E. Rasmusen, Solid-phase microexti action for the detemination of the free concentration of valproic acid in human plasma by cap-illai y gas chi omatography , J. Chromatogr. B 673 299-305 (1997). 

When the hydantoins are administered with the suc-cinimides there may be an increase in the hydantoin blood levels. Concurrent administration of valproic acid and the succinimides may result in either a decrease or an increase in succinimide blood levels. When primidone in administered with the succinimides, lower primidone levels may occur. 

The miscellaneous anticonvulsants are contraindicated in patients with known hypersensitivity to any of the dru. Carbamazepine is contraindicated in patients with bone marrow depression or hepatic or renal impairment and during pregnancy (Category D). Valproic acid is not administered to patients with renal impairment or during pregnancy (Category D). Oxcarbazepine (Trileptal), a miscellaneous anticonvulsant, may exacerbate dementia... 

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

MISSELLANEOUS ANTICONVULSANTS. Valproic acid (Depakene) is unrelated chemically to the other anticonvulsants. This drug is absorbed rapidly when taken orally Tablets should not be chewed but swallowed whole to avoid irritation to the mouth and throat. The capsules may be opened and the drug sprinkled on a small amount of food, such as pudding or applesauce This mixture must be swallowed whole immediately and not chewed. Zonisamide is administered orally once a day or in divided doses. The dose may be increased by 100 mg day every 1 to 2 weeks until control of the seizures is obtained or the patient reaches the maximum dosage of 600 mg/d. 

The following drugp have a decreased pharmacologic effect when administered with an antacid corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. 

C5H7NO2 105-56-6) see Allopurinol Amlexanox Bemegride Ethosuximide Etozolin Folic acid Gabapentin Paroxetine Phensuximide Sulfadimethoxine Theophylline Tinoridinc Trimethoprim Valdetamide Valproic acid ethyl 2-(2 -cyanobiphenyl-4-ylmethylamino)-3-nitroben-zoate... 

C2H7Br 106-94-5) see Prajmalium bitartrate Promestriene Ropivacaine hydrochloride Valproic acid propylene... 

Anticonvulsants Carbamazepine, valproic acid, gabapentin, topiramate... 

Temporal Relationships of Adverse Events. The temporal relationship between duration of product exposure and development of an adverse event is important in assessing causality. But how can data on temporal relationships be systematically summarized in a database containing thousands or even hundreds of thousands of subjects Temporal relationships cannot be clearly elicited if only frequencies of adverse events between treatment and control groups are compared. There can be many disparities in the subjects time of exposure or time at risk. Toxic manifestations of drugs may not occur until several months or even years after the initial exposure to the drug. How do we systematically assess delayed toxicity of a previously prescribed drug from the effect of a newly prescribed drug Such a scenario occurred with reported cases of pancreatitis associated with valproic acid therapy, in which some cases appeared several years after therapy [2]. 

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. 

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... 

Anticonvulsant drugs such as carbamazepine, diazepam, valproic acid, and phenobarbital also slightly increased the duration of the initial AD. However, the effects of these drugs on the other associated seizure events were quite different from PCP and ketamine. The effects of carbamazepine and diazepam, typical of the four compounds, are illustrated in figure 4. These compounds either suppressed the rebound spiking (diazepam, valproic acid, and phenobarbital) or lengthened the total seizure duration with no rebound suppression (carbamazepine). 

PCP, 15 mg/kg, and ketamine, 40 mg/kg, elevated the threshold for eliciting hippocampal afterdischarge (prekindling) by 61 percent and 267 percent, respectively (table 2). Valproic acid and carba-mazepine also elevated the threshold. In contrast, phenobarbita 1 and diazepam had no effect on the prekindling afterdischarge threshold, even at doses capable of altering the AD. 

Allopurinol, barbiturates, carbamazepine, cephalosporins, cyclophosphamide, ethambutol, fluconazole, ibuprofen, lamotrigine, macrolides, nitrofurantoin, penicillins, phenytoin, propranolol, quinolones, sulfonamide antimicrobials, sulindac, tetracyclines, thiazides, valproic acid, and vancomycin... 

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

Acetaminophen, bosentan, diclofenac, isoniazid, lovastatin, methyldopa, niacin, nefazodone, phenytoin, propylthiouracil, rifampin, trazodone, valproic acid, and venlafaxine... 

Alcohol, amiodarone, didanosine, 1-asparaginase, piroxicam, stavudine, tamoxifen, tetracycline derivatives, valproic acid, and zidovudine... 

Didanosine, 1-asparaginase, lamivudine, metformin, pentamidine, statins, stavudine, sulindac, valproic acid, and zalcitabine... 

Valproic acid/salts Losartan Meglumine antimoniate Piroxicam Procainamide Salicylates Sodium stibogluconate Zalcitabine... 

Valproic acid/ Modulate sodium Loading dose Half-life 50-100 mcg/mL Drowsiness, nausea, Hepatotoxicity,... 

Assess the AED serum concentration and adjust therapy as needed for agents with a defined therapeutic range (e.g., phenytoin, carbamazepine, valproic acid, and phenobarbital). Drug levels can also be used to determine adherence to medication regimens for agents that do not have defined ranges. 

Limdi NA, Shimpi AV, Faught E, et al. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 2005 64 353-355. 

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