PHENOBARBITAL- phenobarbital_tablet

Barbiturates are capable of producing all levels of CNS mood alteration, from excitation to mild sedation, hypnosis, and deep coma. Overdosage can produce death. In high enough therapeutic doses, barbiturates induce anesthesia. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. Barbiturate-induced sleep differs from physiologic sleep. Sleep laboratory studies have demonstrated that barbiturates reduce the amount of time spent in the rapid eye movement (REM) phase of sleep or the dreaming stage. Also, Stages III and IV sleep are decreased. Following abrupt cessation of barbiturates used regularly, patients may experience markedly increased dreaming, nightmares, and/or insomnia. Therefore, withdrawal of a single therapeutic dose over 5 or 6 days has been recommended to lessen the REM rebound and disturbed sleep that contribute to the drug withdrawal syndrome (for example, decrease the dose from 3 to 2 doses a day for 1 week). In studies, secobarbital sodium and pentobarbital sodium have been found to lose most of their effectiveness for both inducing and maintaining sleep by the end of 2 weeks of continued drug administration even with the use of multiple doses. As with secobarbital sodium and pentobarbital sodium, other barbiturates (including amobarbital) might be expected to lose their effectiveness for inducing and maintaining sleep after about 2 weeks. The short-, intermediate-, and, to a lesser degree, long-acting barbiturates have been widely prescribed for treating insomnia. Although the clinical literature abounds with claims that the short-acting barbiturates are superior for producing sleep whereas the intermediate-acting compounds are more effective in maintaining sleep, controlled studies have failed to demonstrate these differential effects. Therefore, as sleep medications, the barbiturates are of limited value beyond short-term use. Barbiturates have little analgesic action at subanesthetic doses. Rather, in subanesthetic doses, these drugs may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses; however, of the drugs in this class, only phenobarbital, mephobarbital, and metharbital are effective as oral anticonvulsants in subhypnotic doses. Barbiturates are respiratory depressants, and the degree of respiratory depression is dependent upon the dose. With hypnotic doses, respiratory depression produced by barbiturates is similar to that which occurs during physiologic sleep and is accompanied by a slight decrease in blood pressure and heart rate. Studies in laboratory animals have shown that barbiturates cause reduction in the tone and contractility of the uterus, ureters, and urinary bladder. However, concentrations of the drugs required to produce this effect in humans are not reached with sedative-hypnotic doses. Barbiturates do not impair normal hepatic function but have been shown to induce liver microsomal enzymes, thus increasing and/or altering the metabolism of barbiturates and other drugs (see PRECAUTIONS - Drug Interactions Barbiturates are absorbed in varying degrees following oral or parenteral administration. The salts are more rapidly absorbed than are the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach. Duration of action, which is related to the rate at which the barbiturates are redistributed throughout the body, varies among persons and in the same person from time to time. Phenobarbital is classified as a long-acting barbiturate when taken orally. Its onset of action is 1 hour or longer, and its duration of action ranges from 10 to 12 hours. Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver, and kidneys. Lipid solubility of the barbiturates is the dominant factor in their distribution within the body. The more lipid soluble the barbiturate, the more rapidly it penetrates all tissues of the body. Barbiturates are bound to plasma and tissue proteins to a varying degree with the degree of binding, increasing directly as a function of lipid solubility. Phenobarbital has the lowest lipid solubility, lowest plasma binding, lowest brain protein binding, the longest delay in onset activity, and the longest duration of action. The plasma half-life for phenobarbital in adults ranges between 53 and 118 hours with a mean of 79 hours. The plasma half-life for phenobarbital in children and newborns (less than 48 hours old) ranges between 60 to 180 hours with a mean of 110 hours. Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine and, less commonly, in the feces. Approximately 25% to 50% of a dose of phenobarbital is eliminated unchanged in the urine. The excretion of unmetabolized barbiturate is one feature that distinguishes the long-acting category from those belonging to other categories, which are almost entirely metabolized. The inactive metabolites of the barbiturates are excreted as conjugates of glucuronic acid.

Sedative Anticonvulsant en dash For the treatment of generalized and partial seizures.

The dose of phenobarbital must be individualized with full knowledge of its particular characteristics. Factors of consideration are the patient’s age, weight, and condition. Sedation: Adults: Anticonvulsant Use Phenobarbital has been used in the treatment and prophylaxis of febrile seizures. However, it has not been established that prevention of febrile seizures influences the subsequent development of epilepsy. Adults: 60 to 200 mg/day. Pediatric Patients: 3 to 6 mg/kg/day. Special Patient Population

The following adverse reactions have been reported: CNS Depression Respiratory/Circulatory Allergic Other The following adverse reactions and their incidence were compiled from surveillance of thousands of hospitalized patients who received barbiturates. Because such patients may be less aware of the milder adverse effects of barbiturates, the incidence of these reactions may be somewhat higher in fully ambulatory patients. More than 1 in 100 Patients: Nervous System: Less than 1 in 100 Patients: Nervous System: Respiratory System: Cardiovascular System: Digestive System: Other Reported Reactions:

Phenobarbital is contraindicated in patients who are hypersensitive to barbiturates, in patients with a history of manifest or latent porphyria, and in patients with marked impairment of liver function or respiratory disease in which dyspnea or obstruction is evident.

Usage in Pregnancy
Teratogenic Effects. Usage in Pregnancy WARNINGS Nonteratogenic Effects. in utero DRUG ABUSE AND DEPENDENCE
Nursing Mothers
Caution should be exercised when phenobarbital is administered to a nursing woman, because small amounts of barbiturates are excreted in the milk.

Most reports of clinically significant drug interactions occurring with the barbiturates have involved phenobarbital. However, the application of these data to other barbiturates appears valid and warrants serial blood level determinations of the relevant drugs when there are multiple therapies. Anticoagulants. Corticosteroids. Griseofulvin. Doxycycline. Phenytoin, Sodium Valproate, Valproic Acid. CNS Depressants. Monoamine Oxidase Inhibitors (MAOIs). Estradiol, Estrone, Progesterone, and other Steroidal Hormones.

WARNINGS
Habit Forming. DRUG ABUSE AND DEPENDENCE Pharmacokinetics CLINICAL PHARMACOLOGY DRUG ABUSE AND DEPENDENCE Acute or Chronic Pain. Usage in Pregnancy. DRUG ABUSE AND DEPENDENCE Usage in Pediatric Patients. Synergistic Effects.
Carcinogenesis
Animal Data. Human Data. A retrospective study of 84 children with brain tumors matched to 73 normal controls and 78 cancer controls (malignant disease other than brain tumors) suggested an association between exposure to barbiturates prenatally and an increased incidence of brain tumors.
Labor and Delivery
Hypnotic doses of barbiturates do not appear to impair uterine activity significantly during labor. Full anesthetic doses of barbiturates decrease the force and frequency of uterine contractions. Administration of sedative-hypnotic barbiturates to the mother during labor may result in respiratory depression in the newborn. Premature infants are particularly susceptible to the depressant effects of barbiturates. If barbiturates are used during labor and delivery, resuscitation equipment should be available. Data are not available to evaluate the effect of barbiturates when forceps delivery or other intervention is necessary or to determine the effect of barbiturates on the later growth, development, and functional maturation of the child.
OVERDOSAGE
Signs and Symptoms The manifestations of a long-acting barbiturate in overdose include nystagmus, ataxia, CNS depression, respiratory depression, hypothermia, and hypotension. Other findings may include absent or depressed reflexes and erythematous or hemorrhagic blisters (primarily at pressure points). Following massive exposure to phenobarbital, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, cardiac arrest, and death may occur. In extreme overdose, all electrical activity in the brain may cease, in which case a “flat” EEG normally equated with clinical death should not be accepted. This effect is fully reversible unless hypoxic damage occurs. Consideration should be given to the possibility of barbiturate intoxication even in situations that appear to involve trauma. Complications such as pneumonia, pulmonary edema, cardiac arrhythmias, congestive heart failure, and renal failure may occur. Uremia may increase CNS sensitivity to barbiturates if renal function is impaired. Differential diagnosis should include hypoglycemia, head trauma, cerebrovascular accidents, convulsive states, and diabetic coma. Treatment Physicians’ Desk Reference (PDR) Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal. Alkalinization of urine hastens phenobarbital excretion, but dialysis and hemoperfusion are more effective and cause less troublesome alterations in electrolyte equilibrium. If the patient has chronically abused sedatives, withdrawal reactions may be manifest following acute overdose.

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PHENOBARBITAL- phenobarbital_tablet Product manual source documgent