Antiepileptic drugs gabapentin

The use of antiepileptic drugs (gabapentin, lamotrigine, and topiramate) as mood stabilizers has been... 

Figure 16.7 The structure of some established antiepileptic drugs (AEDs) and some newer ones. Note that while the structures of phenytoin and ethosuximide are similar and also close to that of phenobarbitone, they are effective in different forms of epilepsy. Vigabatrin, progabide and gabapentin are clearly related to GABA. Muscimol is a GABAa agonist but is not an effective antiepileptic drug...

Gabepentin is an antiepileptic drug that has analgesic activity in neuropathic pain states from varying origins. Two recent randomised controlled trials of gabapentin in... 

Drug/Lab test interactions Because false-positive readings were reported with the Ames N-Muitistix SG dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein. 

Topiramate, another antiepileptic drug, may also be helpful in a dose of 400 mg daily, built up gradually. Small quantities of alcohol may suppress essential tremor but only for a short time. Alprazolam (in doses up to 3 mg daily) or gabapentin (100-2400 mg/d) is helpful in some patients. Others are helped by intramuscular injections of botulinum toxin. Thalamic stimulation by an implanted electrode and stimulator is often worthwhile in advanced cases refractory to pharmacotherapy. Diazepam, chlordiazepoxide, mephenesin, and antiparkinsonism agents have been advocated in the past but are generally worthless. Anecdotal reports of benefit from mirtazapine were not confirmed in a double-blind study, which found no effect on the tremor in most patients. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Ratnaraj and Patsalos [37] described an HPLC method for simultaneous determination of vigabatrin and gabapentin in human serum after precolumn derivatization with o-phthaldialdehyde in the presence of mercaptoethanol and fluorimetric detection at 440 nm with excitation at 340 nm. Separation was achieved on a Hypersil BDS C18 (3 /tm) column (12.5 cm x 3 mm) with a mixture of 250 mM phosphate buffer, acetonitrile, water, and methanol as a gradient mobile phase (flow rate 0.45 ml/min). The method was linear over the concentration range of 25-400 yg/ml for vigabatrin. The lower limit of detection was 1 /(M for both analytes. Within- and between-batch RSD were 2-i% and 3-4%, respectively. No interference from other commonly prescribed antiepileptic drugs was observed. 

Gabapentin has been associated with hostility, especially in children. Two cases of aggression in adults taking gabapentin for bipolar disorder have been reported (285). Neither patient had a history of aggression. In one the symptoms appeared after 3 days of treatment (1200 mg/ day), and in the other after 48 hours (600 mg/day). In the second case, aggression was associated with auditory hallucinations. It is hard to associate new antiepileptic drugs... 

Clearance of tiagabine may be reduced and thus plasma levels increased if taken with a non-enzyme inducing antiepileptic drug (e.g., valproate, gabapentin, lamotrigine), so tiagabine dose may need to be reduced... 

Other antiepileptic drugs can also alter visual evoked potentials and brainstem evoked potentials. Visual field defects associated with various antiepileptic drugs (carba-mazepine, diazepam, gabapentin, phenytoin, tiagabine, and vigabatrin) have been reviewed (37). 

Devinsky O, Vasquez B, Luciano D. New antiepileptic drugs for children Felbamate, gabapentin, lamotri-gine, and vigabatrine. J Child Neurol 1994 9(Suppl) S33-45. 

Importantly, Loscher et al. found that carbamazepine, felbamate, gabapentin, lamotrigine, phenobarbital, and topiramate are substrates of ABCBl (P-gp) [38]. Crowe et al. also studied the transport of a variety of antiepileptic drugs including vigabatrin, gabapentin, phenobarbitone, lamotrigine, phenytoin, carbamazepine, and acetazolamide in colorectal tumor-derived Caco-2 cell monolayers. They found that only one antiepileptic, acetazolamide, is a weak ABCBl substrate [39]. 

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