ANTICONVULSANTS
- Many anticonvulsants are metabolized by P450. Drug interaction, especially with warfarin, INH, cimetidine, erythromycin are common. One must see about dose adjustment when prescribing these medications together.
- Most commonly used are Phenytoin, Carbamezapine, Valproic ac, Phenobarbital, Gabapentin.
- They act by Na channel blockade and/or GABA stimulation.
PHENYTOIN
- toxicity can occur from PO or IV administration. This manifests with CNS ( when given PO or IV) and CV symptoms (IV only).
- There is correlation between the serum level and signs of toxicity. Nystagmus corresponds to serum level of 20, ataxia - 30, lethargy and seizure - 40.
- When given IV (15-20mg/kg up to 1000 mg in NS solution @ max 50 mg/min), it can cause hemodinamyc instability ( ¯ BP, AV node suppression, > PR/QRS) but this is not from Phenytoin but rather from its vectors, Propylene and Ethanol. For this reason pt is put on monitor during Phenytoin infusion.
- In ER pt is commonly treated with IV Phenytoin for seizure. PO administration will not increase serum level to therapeutic range for 6-8 hr., while IV reaches therapeutic level in 10-15 min.
- Treatment of toxicity is supportive in addition to AC. HD is not helpful. If ¯ BP occurs IVF challenge and turning off the infusion usually suffice. If bradycardia occurs Atropine is employed. When CNS symptoms occur with IV, they resolve in about ½-1 hr.
- During IV infusion extravasation can occur. This causes necrosis and Plastic surgery or Burn specialists must be consulted. Thus a good running IV is necessary.
CARBAMEZAPINE
- taken PO and achieves therapeutic level in 5 hrs.
- Pt that comes to ER and is only on Carbamezapine (Tegratol®), and states he/she had a seizure, can be given an extra pill without waiting for serum level, since the range for this is very wide (4-12
when only on Carbamezapine and 4-8 when on other antisz meds), and thus it is tailored to pt's need. T1/2 is 12 hr.
- Toxicity of Carbamezapine (Tegratol) is CNS and CV - (nystagmus, ataxia, N/V, arrhytmias , >QRS).
- Treatment is supportive e.g. AC and, if >QRS is noticed, NaHCO3 1-2mEq/kg is administered.
VALPROIC AC
- toxicity manifests with N/V, CNS, respiratory and hepatic failure.
- When OD is suspected LFTs must be obtained.
- Treatment is supportive, AC and HD maybe helpful. T1/2 = 12 hr.
GABAPENTINE
- probably least side effects as compared to other anticonvulsants.
- Ataxia and sedation are described
- treatment is with AC and supportive. T1/2 = 6 hr.