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Developed for the treatment of partial and generalized seizure disorders, these second-generation anticonvulsants are finding wider use in the treatment of chronic and neuropathic pain syndromes; mood disorders, including bipolar disease; and migraine headache prophylaxis. Serious adverse effects with the therapeutic use of felbamate (aplastic anemia, hepatic failure) and vigabatrin (permanent visual field deficits) have led to restrictions in their use.

Characteristics of several of these drugs are listed in Table II–6.

Table II-6 Anticonvulsant Drugs (Newer)

  1. Mechanism of toxicity. Anticonvulsants suppress neuronal excitation by one of four major mechanisms.

    1. Blockade of voltage-gated sodium channels by lamotrigine, topiramate, zonisamide, and felbamate.

    2. Blockade of voltage-gated calcium channels by gabapentin, levetiracetam, and zonisamide.

    3. Inhibition of excitatory amines. Lamotrigine inhibits glutamate release via sodium channel effects on presynaptic membranes. Felbamate is a competitive glutamate antagonist at the N-methyl-d-aspartate (NMDA) receptor.

    4. Gamma-aminobutyric acid (GABA) enhancement. Tiagabine inhibits GABA transporter GAT-1, preventing reuptake into presynaptic neurons. Vigabatrin inhibits GABA transaminase, blocking GABA metabolism. Gabapentin is a GABA analog that has no known activity at GABA receptors.

    5. Pharmacokinetics (see Tables II–6 and II–61)

  2. Toxic dose varies with each medication. A 4-year-old boy had a 10-minute tonic-clonic seizure after the ingestion of 52 mg (3 mg/kg) of tiagabine. Ingestion of 91 g of gabapentin by an adult resulted in dizziness, slurred speech, and nystagmus that resolved after 11 hours. A 26-year-old man ingested 1350 mg of lamotrigine and presented with nystagmus, ataxia, tachycardia, and a QRS interval of 112 milliseconds, but never developed seizures; his 3-hour lamotrigine level was 17.4 mg/L (therapeutic range, 2.1–15 mg/L).

  3. Clinical presentation. See Table II–6.

  4. Diagnosis usually is based on the history of ingestion or is suspected in any patient on these medications who presents with altered mental status, ataxia, or seizures.

    1. Specific levels. Serum levels can be requested from reference laboratories but are not usually available in time to make them useful for emergency management decisions.

    2. Other useful laboratory studies include electrolytes, glucose, serum creatinine (gabapentin, topiramate), CBC (felbamate), liver aminotransferases, bilirubin (felbamate), and ECG ...

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