Phenobarbital dosing

After consulting the physician, phenobarbital dose is reduced to 0.025 g. 1800 mg powder of simethicone from 12 tablets, 300 mg of phenobarbital powder, 1200 mg of magnesium carbonate powder from two tablets and 600 mg of lactose are needed for the 12 capsules. Size of the capsules is 1. 

When used for detoxification, phenobarbital is given in equal doses four times a day. The maximum daily dose of phenobarbital is 600 mg, but much lower doses are usually sufficient. The phenobarbital dose is lowered (i.e., tapered) by about 20% per day. If the patient is too drowsy, then a dose should be skipped. If breakthrough withdrawal symptoms continue to occur, then the pace of the detoxification should be slowed. Before using phenobarbital, liver function tests should be obtained. All barbiturates depend greatly on the liver to be metabolized. Alcoholics with cirrhosis or other forms of liver impairment may have difficulty clearing phenobarbital. Phenobarbital should not be used in patients with poor liver function. In addition, the barbiturates can worsen a medical condition known as porphyria and should be avoided in those with this disorder. Phenobarbital, as noted, is seldom used today for alcohol detoxification. 

B. Hepatic enzyme induction with chronic use, although this Is not encountered with acute phenobarbital dosing. 

A 6-month study in 11 epileptic patients taking phenobarbital 90 to 400 mg daily found that when they were also given valproic acid 11.2 to 42.7 mg/kg daily sedation developed. On average the dosage of phenobarbital was reduced to 54% of the original dose with continued good seizure control. Another 2 patients who did not have their phenobarbital dose reduced had an increase in their phenobarbital levels of 12% and 48%, respectively, when valproic acid was added. ... 

The potential for normal brain tissue injury is one of the limiting factors in the use of XRT for brain tumors. Pentobarbital is a cerebral radioprotectant in rodent and primate models after single doses, but is associated with significant risks. Of alternative barbiturates, thiopental given to tats receiving 70-Gy (7000-rad) whole-brain irradiation in a single fraction enhances the 30-day survival similarly to pentobarbital, whereas ethohexital and phenobarbital show no radioprotective activity (250). 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Table 3-5. Sedative-hypnotic dose equivalency (equal to 30 mg of phenobarbital) ...

The third protocol is to determine the level of drug use and calculate equivalent doses of phenobarbital (Table 3-5). The patient is stabilized on this dose (divided into administration every 8 hours) for a few days, and then the dose is tapered by 10% daily. Although this method has its proponents, the determination of equivalency is an approximation, drug histories are unreliable, and mixed sedative-hypnotic dependence will complicate the procedure. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

This rare inherited disorder also results from mutations in the gene encoding bilirubin-UGT, but some activity of the enzyme is retained and the condition has a more benign course than type I. Serum bilirubin concentrations usually do not exceed 20 mg/dL. Patients with this condition can respond to treatment with large doses of phenobarbital. 

Crowley, T.J. Dose-dependent facilitation or suppression of rat fighting by methamphetamine, phenobarbital, or imipramine. Psychopharmacologia 27 213-222, 1972. 

The interaction of ketamine with each of the three anticonvulsant compounds was also tested. Ketamine, 15 mg/kg, a dose showing no anti-PTZ effect and causing no overt behavioral changes, potentiated the effect of phenobarbital (20 mg/kg) in delaying the clonic and tonic convulsive responses and lethality (figure 3). Ketamine also potentiated the ability of phenytoin (20 mg/kg) to delay... 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

Must evaluate volume of medication administered to determine total propylene glycol exposure. High-dose lorazepam (i.e., >8-10 mg/h), phenytoin loading doses, and phenobarbital are the most likely offenders. 

Many experts would mechanically intubate the patient if a loading dose of phenobarbital is required... 

Phenytoin Similar to phenobarbital may need to increase methadone dose when phenytoin is added to a methadone maintenance drug regimen to avoid withdrawal symptoms. 

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

Phenobarbital can usually be dosed once daily, and bedtime dosing may minimize daytime sedation. 

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. 

When adequate doses of a BZ, phenytoin, and phenobarbital have failed, the condition is termed refractory. Failure to aggressively treat early increases the likelihood of nonresponse. Doses of agents used to treat refractory GCSE are given in Table 56-3. 

Factors that may enhance theophylline clearance and result in the need for higher doses include tobacco and marijuana smoking, hyperthyroidism, and use of drugs such as phenytoin, phenobarbital, and rifampin. 

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