Phenobarbital Diazepam

Acute management of toxaphene-induced seizures in humans with anticonvulsants, especially diazepam, phenobarbital, and phenytoin (USPHS 1994). 

Felbamate Clonazepam Diazepam Phenobarbital Phenytoin Valproate High risk of toxicity with phenytoin, phenobarbital, and valproate Inhibition of metabolism of the affected drug... 

Administration of 2-PAM chloride (protopam and pralidoxime) is generally not recommended in carbamate poisoning since it has been shown to interfere with the efficacy of atropine. It was reported that the condition of patients suffering carbaryl-related poisoning deteriorated rapidly following the administration of 2-PAM. Seizure control with diazepam, phenobarbital, or phenytoin may be required. Cardiovascular support and intensive supportive care may be required in serious cases. 

Conventional anticonvulsants (e.g., diazepam, phenobarbital, and phenytoin) may be administered to treat pyriminil-induced seizures. Niacinamide has been demonstrated to be an effective antidote in pyriminil poisoning in rats but little information is available regarding its antidotal efficacy in humans. Insulin therapy could be instituted as a preventive measure for possible diabetes mellitus. Orthostatic hypotension due to pyriminil exposure may be treated with conventional mineralocorticoids. 

Noninterfering acetaminophen, clonazepam, diazepam, phenobarbital, phen doin, primidone, salicylic acid, theophylline... 

Occasionally, status epilepticus (an emergency situation characterized by continual seizure activity with no interruptions) can occur. Diazepam (Valium) is most often the initial drug prescribed for this condition. However, because the effects of diazepam last less than 1 hour, a longer-lasting anticonvulsant, such as phenytoin or phenobarbital, also must be given to control the seizure activity. 

Valerian Valeriana officinalis Restlessness, sleep disorders Rare if used as directed. May interact with the barbiturates (eg, phenobarbital), the benzodiazepines (eg, diazepam) and the opiates, (eg, morphine). 

A variety of drugs have been developed that act as sedatives, antidepressants, or stimulants some of these are effective in treating psychiatric disorders. Many of these drugs are weak bases. Examples are barbiturates such as phenobarbital, tranquilizers like diazepam (Valium), and amphetamines derived from phenylethylamine. 

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). 

In cases of lead encephalopathy with cerebral edema, edema can be treated with mannitol, corticosteroids, and hypothermia. Convulsions can be treated with diazepam, phenytoin, and/or phenobarbital (Garrettson 1990). 

Gammon, D.W., L.J. Lawrence, and J.E. Casida. 1982. Pyrethroid toxicology protective effects of diazepam and phenobarbital in the mouse and the cockroach. Toxicol. Appl. Pharmacol. 66 290-296. 

Diazepam is extremely lipophilic and quickly distributed into the brain, but redistributes rapidly into body fat, causing a very short duration of effect (0.25 to 0.5 hours). Therefore, a longer-acting anticonvulsant (e.g., phenytoin, phenobarbital) should be given immediately after the diazepam. The initial dose of diazepam can be repeated if the patient does not respond within 5 minutes. 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Drugs that may affect valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

Seizures. Simple isolated seizures may require only observation and supportive care. Repetitive seizures or status epilepticus require therapy. Give IV diazepam or lorazepam followed by fosphenytoin and/or phenobarbital. Pancuronium may also be considered. 

Exposed individuals with evidence of central nervous system depression or seizures should be evaluated for the presence of some other underlying disorder. Diazepam or phenobarbital may be administered to alleviate seizures. Supplemental oxygen can also be administered. If pulmonary edema occurs, conventional therapy should be considered. Additional information regarding the treatment of individuals exposed to cresols may be obtained from Bronstein and Currance (1988), Haddad and Winchester (1990), and Stutz and Janusz (1988). 

The anticonvulsant activity of diazepam, assessed by its protection against pentylenetetrazole-induced tonic convulsions, was strongly reduced in ai-(HIOIR) mice compared to wild-type animals (Rudolph et al. 1999). Sodium phenobarbital remained fully effective as anticonvulsant in ai(HlOlR) mice. Thus, the anticonvulsant activity of benzodiazepines is partially but not fuUy mediated by ai receptors. The anticonvulsant action of zolpidem is exclusively mediated by ai receptors, since its anticonvulsant action is completely absent in ai(HlOlR) mice (Crestani et al. 2000). 

Convulsions associated with fever often occur in children 3 months to 5 years of age. Epilepsy later develops in approximately 2 to 3% of children who exhibit one or more such febrile seizures. Most authorities now recommend prophylactic treatment with anticonvulsant drugs only to patients at highest risk for development of epilepsy and for those who have multiple recurrent febrile seizures. Phenobarbital is the usual drug, although diazepam is also effective. Phenytoin and carba-mazepine are ineffective, and valproic acid may cause hepatotoxicity in very young patients. 

Different sites on the same receptor (e.g., diazepam and phenobarbital both bind to the GABA-A receptor, but at different sites benzodiazepine site versus barbiturate site). 

Figure 4.12 The GABA-A channel functions as a receptor for many multiple different drug classes, including benzodiazepines (e.g., diazepam) and barbiturates (e.g., phenobarbital). There is also a steroid-binding site on the GABA-A channel which may be useful in the future design of general anesthetics.

VPA is also a nonspecific but weak inhibitor of the CYP-450 enzyme system, causing serum levels of other hepatically metabolized drugs to be increased. For example, concomitant use of VPA with diazepam, ethosuximide, or phenobarbital can increase the levels of these latter drugs. VPA may also cause an elevation in serum levels of CBZ s epoxide metabolite, possibly inducing toxicity. Usually, however, these changes are not clinically significant ( 367). 

Long-acting drugs such as chlordiazepoxide and diazepam and, to a lesser extent, phenobarbital are administered in progressively decreasing doses to patients during withdrawal from physiologic dependence on ethanol or other sedative-hypnotics. Parenteral lorazepam is used to suppress the symptoms of delirium tremens. 

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