Diazepam drug resistance

The result of this anatomical characteristic of endothelial cells in the CNS is an increased resistance to water-soluble and ionized drugs entering the brain, and cerebrospinal fluid (CSF), from capillary blood. However, in a few areas of the brain the barrier is absent. These areas include the lateral nuclei of the hypothalamus, the area postrema of the fourth ventricle, the pineal body, and the posterior lobe of the hypophysis. Highly lipophilic compounds can cross the barrier. Tranquilizers such as diazepam and its analogs are known to gain access rapidly to the CSF with a half-life (tm) entry time of less than 1 minute. 

Treatment of palatal myoclonus is often unsuccessful, but phenytoin, carbamazepine, clonazepam, trihexyphenidyl, and baclofen have been effective in some patients. Clonazepam is effective in over half of patients with propriospinal myoclonus, but other anticonvulsants are usually not helpful. Segmental spinal myoclonus is often resistant to drug treatment, but diazepam, carbamazepine, tetrabenazine and, particularly, clonazepam are sometimes effective. 

B. Specific drugs and antidotes. Pyridoxine (vitamin Bg) is a specific antidote and usually terminates diazepam-resistant seizures and results in improved mental status. Administer at least 5 g IV (see p 499) if the amount of INH ingested is not known If the amount is known, give an equivalent amount in grams of pyridoxine to grams of ingested INH. Concomitant treatment with diazepam may improve outcome. If no pyridoxine is available, high-dose diazepam (0.3-0.4 mg/kg) may be effective for status epilepticus. Pyridoxine treatment may also hasten the resolution of metabolic acidosis. 

---