PHENOBARBITONE
DESCRIPTION:
WARNING: MAY BE HABIT-FORMING
The barbiturates are nonselective central nervous system (CNS) depressants that
are primarily used as sedative hypnotics. In subhypnotic doses, they are also
used as anticonvulsants. The barbiturates and their sodium salts are subject to
control under the Federal Controlled Substances Act.
Phenobarbital is a barbituric acid derivative and occurs as white, odorless,
small crystals or crystalline powder that is very slightly soluble in water;
soluble in alcohol, in ether, and in solutions of fixed alkali hydroxides and
carbonates; sparingly soluble in chloroform. Phenobarbital is 5-ethyl-5-
phenylbarbituric acid and has the empirical formula C12H12N2O3. Its molecular
weight is 232.24.
Phenobarbital is a substituted pyrimidine derivative in which the basic
structure is barbituric acid, a substance that has no CNS activity. CNS activity
is obtained by substituting alkyl, alkenyl, or aryl groups on the pyrimidine
ring.
ACTIONS/CLINICAL PHARMACOLOGY:
Barbiturates are capable of producing all levels of CNS mood alteration, from
excitation to mild sedation to 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, the dose should be
decreased from 3 to 2 doses/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 Drug Interactions Under Precautions).
Pharmacokinetics--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.
INDICATIONS AND USAGE:
A. Sedative
B. Anticonvulsant--For the treatment of generalized and partial seizures.
CONTRAINDICATIONS:
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.
WARNINGS:
1. Habit Forming--Phenobarbital may be habit forming. Tolerance and
psychological and physical dependence may occur with continued use (See Drug
Abuse and Dependence And Pharmacokinetics Under Actions/Clinical Pharmacology).
Patients who have psychologic dependence on barbiturates may increase the dosage
or decrease the dosage interval without consulting a physician and may
subsequently develop a physical dependence on barbiturates. In order to minimize
the possibility of overdosage or the development of dependence, the prescribing
and dispensing of sedative-hypnotic barbiturates should be limited to the amount
required for the interval until the next appointment. Abrupt cessation after
prolonged use in a person who is dependent on the drug may result in withdrawal
symptoms, including delirium, convulsions, and possibly death. Barbiturates
should be withdrawn gradually from any patient known to be taking excessive
doses over long periods of time (See Drug Abuse and Dependence).
2. Acute Or Chronic Pain--Caution should be exercised when barbiturates are
administered to patients with acute or chronic pain, because paradoxical
excitement could be induced or important symptoms could be masked. However, the
use of barbiturates as sedatives in the postoperative surgical period and as
adjuncts to cancer chemotherapy is well established.
3. Usage In Pregnancy--Barbiturates can cause fetal damage when administered to
a pregnant woman. Retrospective, case-controlled studies have suggested a
connection between the maternal consumption of barbiturates and a higher than
expected incidence of fetal abnormalities. Barbiturates readily cross the
placental barrier and are distributed throughout fetal tissues; the highest
concentrations are found in the placenta, fetal liver, and brain. Fetal blood
levels approach maternal blood levels following parenteral administration.
Withdrawal symptoms occur in infants born to women who receive barbiturates
throughout the last trimester of pregnancy (See Drug Abuse and Dependence).
If phenobarbital is used during pregnancy or if the patient becomes pregnant
while taking this drug, the patient should be apprised of the potential hazard
to the fetus.
4. Usage In Children--Phenobarbital has been reported to be associated with
cognitive deficits in children taking it for complicated febrile seizures.
5. Synergistic Effects--The concomitant use of alcohol or other CNS depressants
may produce additive CNS depressant effects.
PRECAUTIONS:
General--Barbiturates may be habit forming. Tolerance and psychological and
physical dependence may occur with continued use (See Drug Abuse and
Dependence).
Barbiturates should be administered with caution, if at all, to patients who are
mentally depressed, have suicidal tendencies, or have a history of drug abuse.
Elderly or debilitated patients may react to barbiturates with marked
excitement, depression, or confusion. In some persons, especially children,
barbiturates repeatedly produce excitement rather than depression.
In patients with hepatic damage, barbiturates should be administered with
caution and initially in reduced doses. Barbiturates should not be administered
to patients showing the premonitory signs of hepatic coma.
The systemic effects of exogenous and endogenous corticosteroids may be
diminished by phenobarbital. Thus, this product should be administered with
caution to patients with borderline hypoadrenal function, regardless of whether
it is of pituitary or of primary adrenal origin.
Information For Patients--The following information and instructions should be
given to patients receiving barbiturates.
1. The use of barbiturates carries with it an associated risk of psychological
and/or physical dependence. The patient should be warned against increasing the
dose of the drug without consulting a physician.
2. Barbiturates may impair the mental and/or physical abilities required for the
performance of potentially hazardous tasks, such as driving a car or operating
machinery. The patient should be cautioned accordingly.
3. Alcohol should not be consumed while taking barbiturates. The concurrent use
of the barbiturates with other CNS depressants (eg, alcohol, narcotics,
tranquilizers, and antihistamines) may result in additional CNS- depressant
effects.
Laboratory Tests--Prolonged therapy with barbiturates should be accompanied by
periodic laboratory evaluation of organ systems, including hematopoietic, renal,
and hepatic systems (See General Under Precautions And Adverse Reactions).
Drug Interactions--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.
1. Anticoagulants--Phenobarbital lowers the plasma levels of dicumarol and
causes a decrease in anticoagulant activity as measured by the prothrombin time.
Barbiturates can induce hepatic microsomal enzymes resulting in increased
metabolism and decreased anticoagulant response of oral anticoagulants (eg,
warfarin, acenocoumarol, dicumarol, and phenprocoumon). Patients stabilized on
anticoagulant therapy may require dosage adjustments if barbiturates are added
to or withdrawn from their dosage regimen.
2. Corticosteroids--Barbiturates appear to enhance the metabolism of exogenous
corticosteroids, probably through the induction of hepatic microsomal enzymes.
Patients stabilized on corticosteroid therapy may require dosage adjustments if
barbiturates are added to or withdrawn from their dosage regimen.
3. Griseofulvin--Phenobarbital appears to interfere with the absorption of
orally administered griseofulvin, thus decreasing its blood level. The effect of
the resultant decreased blood levels of griseofulvin on therapeutic response has
not been established. However, it would be preferable to avoid concomitant
administration of these drugs.
4. Doxycycline--Phenobarbital has been shown to shorten the half-life of
doxycycline for as long as 2 weeks after barbiturate therapy is discontinued.
This mechanism is probably through the induction of hepatic microsomal enzymes
that metabolize the antibiotic. If phenobarbital and doxycycline are
administered concurrently, the clinical response to doxycycline should be
monitored closely.
5. Phenytoin, Sodium Valproate, Valproic Acid- -The effect of barbiturates on
the metabolism of phenytoin appears to be variable. Some investigators report an
accelerating effect, whereas others report no effect. Because the effect of
barbiturates on the metabolism of phenytoin is not predictable, phenytoin and
barbiturate blood levels should be monitored more frequently if these drugs are
given concurrently. Sodium valproate and valproic acid increase the
phenobarbital serum levels; therefore, phenobarbital blood levels should be
closely monitored and appropriate dosage adjustments made as clinically
indicated.
6. CNS Depressants--The concomitant use of other CNS depressants, including
other sedatives or hypnotics, antihistamines, tranquilizers, or alcohol, may
produce additive depressant effects.
7. Monoamine Oxidase Inhibitors (MAOIs)--MAOIs prolong the effects of
barbiturates, probably because metabolism of the barbiturate is inhibited.
8. Estradiol, Estrone, Progesterone, And Other Steroidal Hormones--Pretreatment
with or concurrent administration of phenobarbital may decrease the effect of
estradiol by increasing its metabolism. There have been reports of patients
treated with antiepileptic drugs (eg, phenobarbital) who become pregnant while
taking oral contraceptives. An alternate contraceptive method might be suggested
to women taking phenobarbital.
Carcinogenesis--1. Animal Data. Phenobarbital sodium is carcinogenic in mice and
rats after lifetime administration. In mice, it produced benign and malignant
liver cell tumors. In rats, benign liver cell tumors were observed very late in
life.
2. Human Data--In a 29-year epidemiologic study of 9,136 patients who were
treated on an anticonvulsant protocol that included phenobarbital, results
indicated a higher than normal incidence of hepatic carcinoma. Previously, some
of these patients had been treated with thorotrast, a drug which is known to
produce hepatic carcinomas. Thus, this study did not provide sufficient evidence
that phenobarbital sodium is carcinogenic in humans.
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.
Usage In Pregnancy--1. Teratogenic Effects. Pregnancy Category D--See Usage in
Pregnancy Under Warnings.
2. Nonteratogenic Effects--Reports of infants suffering from long-term
barbiturate exposure in utero included the acute withdrawal syndrome of seizures
and hyperirritability from birth to a delayed onset of up to 14 days (See Drug
Abuse and Dependence).
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.
Nursing Mothers--Caution should be exercised when phenobarbital is administered
to a nursing woman, because small amounts of barbiturates are excreted in the
milk.
DRUG INTERACTIONS:
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.
1. Anticoagulants--Phenobarbital lowers the plasma levels of dicumarol and
causes a decrease in anticoagulant activity as measured by the prothrombin time.
Barbiturates can induce hepatic microsomal enzymes resulting in increased
metabolism and decreased anticoagulant response of oral anticoagulants (eg,
warfarin, acenocoumarol, dicumarol, and phenprocoumon). Patients stabilized on
anticoagulant therapy may require dosage adjustments if barbiturates are added
to or withdrawn from their dosage regimen.
2. Corticosteroids--Barbiturates appear to enhance the metabolism of exogenous
corticosteroids, probably through the induction of hepatic microsomal enzymes.
Patients stabilized on corticosteroid therapy may require dosage adjustments if
barbiturates are added to or withdrawn from their dosage regimen.
3. Griseofulvin--Phenobarbital appears to interfere with the absorption of
orally administered griseofulvin, thus decreasing its blood level. The effect of
the resultant decreased blood levels of griseofulvin on therapeutic response has
not been established. However, it would be preferable to avoid concomitant
administration of these drugs.
4. Doxycycline--Phenobarbital has been shown to shorten the half-life of
doxycycline for as long as 2 weeks after barbiturate therapy is discontinued.
This mechanism is probably through the induction of hepatic microsomal enzymes
that metabolize the antibiotic. If phenobarbital and doxycycline are
administered concurrently, the clinical response to doxycycline should be
monitored closely.
5. Phenytoin, Sodium Valproate, Valproic Acid- -The effect of barbiturates on
the metabolism of phenytoin appears to be variable. Some investigators report an
accelerating effect, whereas others report no effect. Because the effect of
barbiturates on the metabolism of phenytoin is not predictable, phenytoin and
barbiturate blood levels should be monitored more frequently if these drugs are
given concurrently. Sodium valproate and valproic acid increase the
phenobarbital serum levels; therefore, phenobarbital blood levels should be
closely monitored and appropriate dosage adjustments made as clinically
indicated.
6. CNS Depressants--The concomitant use of other CNS depressants, including
other sedatives or hypnotics, antihistamines, tranquilizers, or alcohol, may
produce additive depressant effects.
7. Monoamine Oxidase Inhibitors (MAOIs)--MAOIs prolong the effects of
barbiturates, probably because metabolism of the barbiturate is inhibited.
8. Estradiol, Estrone, Progesterone, And Other Steroidal Hormones--Pretreatment
with or concurrent administration of phenobarbital may decrease the effect of
estradiol by increasing its metabolism. There have been reports of patients
treated with antiepileptic drugs (eg, phenobarbital) who become pregnant while
taking oral contraceptives. An alternate contraceptive method might be suggested
to women taking phenobarbital.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
The following adverse reactions have been reported:
CNS Depression--Residual sedation or "hangover," drowsiness, lethargy, and
vertigo. Emotional disturbances and phobias may be accentuated. In some persons,
barbiturates such as phenobarbital repeatedly produce excitement rather than
depression, and the patient may appear to be inebriated. Irritability and
hyperactivity can occur in children. Like other nonanalgesic hypnotic drugs,
barbiturates such as phenobarbital, when given in the presence of pain, may
cause restlessness, excitement, and even delirium. Rarely, the use of
barbiturates results in localized or diffuse myalgic, neuralgic, or arthritic
pain, especially in psychoneurotic patients with insomnia. The pain may appear
in paroxysms, is most intense in the early morning hours, and is most frequently
located in the region of the neck, shoulder girdle, and upper limbs. Symptoms
may last for days after the drug is discontinued.
Respiratory/Circulatory--Respiratory depression, apnea, circulatory collapse.
Allergic--Acquired hypersensitivity to barbiturates consists chiefly in allergic
reactions that occur especially in persons who tend to have asthma, urticaria,
angioedema, and similar conditions. Hypersensitivity reactions in this category
include localized swelling, particularly of the eyelids, cheeks, or lips, and
erythematous dermatitis. Rarely, exfoliative dermatitis (eg, Stevens-Johnson
syndrome and toxic epidermal necrolysis) may be caused by phenobarbital and can
prove fatal. The skin eruption may be associated with fever, delirium, and
marked degenerative changes in the liver and other parenchymatous organs. In a
few cases, megaloblastic anemia has been associated with the chronic use of
phenobarbital.
Other--Nausea and vomiting; headache, osteomalacia.
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
The most common adverse reaction, estimated to occur at a rate of 1 to 3
patients per 100, is:
Nervous System: Somnolence
LESS THAN 1 IN 100 PATIENTS
Adverse reactions estimated to occur at a rate of less than 1 in 100 patients
are listed below, grouped by organ system and by decreasing order of occurrence:
Nervous System: Agitation, confusion, hyperkinesia, ataxia, CNS depression,
nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia,
anxiety, dizziness, abnormality in thinking
Respiratory System: Hypoventilation, apnea
Cardiovascular System: Bradycardia, hypotension, syncope
Digestive System: Nausea, vomiting, constipation
Other Reported Reactions: Headache, injection site reactions, hypersensitivity
reactions (angioedema, skin rashes, exfoliative dermatitis), fever, liver
damage, megaloblastic anemia following chronic phenobarbital use
DRUG ABUSE AND DEPENDENCE:
Controlled Substance--Phenobarbital is a Schedule IV drug.
Dependence--Barbiturates may be habit forming. Tolerance, psychological
dependence, and physical dependence may occur, especially following prolonged
use of high doses of barbiturates. Daily administration in excess of 400 mg of
pentobarbital or secobarbital for approximately 90 days is likely to produce
some degree of physical dependence. A dosage of 600 to 800 mg taken for at least
35 days is sufficient to produce withdrawal seizures. The average daily dose for
the barbiturate addict is usually about 1.5 g. As tolerance to barbiturates
develops, the amount needed to maintain the same level of intoxication
increases; tolerance to a fatal dosage, however, does not increase more than
twofold. As this occurs, the margin between intoxicating dosage and fatal dosage
becomes smaller.
Symptoms of acute intoxication with barbiturates include unsteady gait, slurred
speech, and sustained nystagmus. Mental signs of chronic intoxication include
confusion, poor judgment, irritability, insomnia, and somatic complaints.
Symptoms of barbiturate dependence are similar to those of chronic alcoholism.
If an individual appears to be intoxicated with alcohol to a degree that is
radically disproportionate to the amount of alcohol in his or her blood, the use
of barbiturates should be suspected. The lethal dose of a barbiturate is far
less if alcohol is also ingested.
The symptoms of barbiturate withdrawal can be severe and may cause death. Minor
withdrawal symptoms may appear 8 to 12 hours after the last dose of a
barbiturate. These symptoms usually appear in the following order: anxiety,
muscle twitching, tremor of hands and fingers, progressive weakness, dizziness,
distortion in visual perception, nausea, vomiting, insomnia, and orthostatic
hypotension. Major withdrawal symptoms (convulsions and delirium) may occur
within 16 hours and last up to 5 days after abrupt cessation of barbiturates.
The intensity of withdrawal symptoms gradually declines over a period of
approximately 15 days. Individuals susceptible to barbiturate abuse and
dependence include alcoholics and opiate abusers as well as other sedative-
hypnotic and amphetamine abusers.
Drug dependence on barbiturates arises from repeated administration of a
barbiturate or agent with barbiturate-like effect on a continuous basis,
generally in amounts exceeding therapeutic dose levels. The characteristics of
drug dependence on barbiturates include: (a) a strong desire or need to continue
taking the drug; (b) a tendency to increase the dose; (c) a psychic dependence
on the effects of the drug related to subjective and individual appreciation of
those effects; and (d) a physical dependence on the effects of the drug,
requiring its presence for maintenance of homeostasis and resulting in a
definite, characteristic, and self-limited abstinence syndrome when the drug is
withdrawn.
Treatment of barbiturate dependence consists of cautious and gradual withdrawal
of the drug. Barbiturate-dependent patients can be withdrawn by using a number
of different withdrawal regimens. In all cases, withdrawal requires an extended
period of time. One method involves substituting a 30-mg dose of phenobarbital
for each 100- to 200-mg dose of barbiturate that the patient has been taking.
The total daily amount of phenobarbital is then administered in 3 or 4 divided
doses, not to exceed 600 mg daily. If signs of withdrawal occur on the first day
of treatment, a loading dose of 100 to 200 mg of phenobarbital may be
administered IM in addition to the oral dose. After stabilization on
phenobarbital, the total daily dose is decreased by 30 mg/day as long as
withdrawal is proceeding smoothly. A modification of this regimen involves
initiating treatment at the patient's regular dosage level and decreasing the
daily dosage by 10% if tolerated by the patient.
Infants who are physically dependent on barbiturates may be given phenobarbital,
3 to 10 mg/kg/day. After withdrawal symptoms (hyperactivity, disturbed sleep,
tremors, and hyperreflexia) are relieved, the dosage of phenobarbital should be
gradually decreased and completely withdrawn over a 2-week period.
OVERDOSAGE:
Signs And Symptoms--The onset of symptoms following a toxic oral exposure to
phenobarbital may not occur until several hours following ingestion. The toxic
dose of barbiturates varies considerably. In general, an oral dose of 1 g of
most barbiturates produces serious poisoning in an adult. Death commonly occurs
after 2 to 10 g of ingested barbiturate. The sedated, therapeutic blood levels
of phenobarbital range between 5 to 40 mcgm/mL; the usual lethal blood level
ranges from 100 to 200 mcgm/mL. Barbiturate intoxication may be confused with
alcoholism, bromide intoxication, and various neurologic disorders. Potential
tolerance must be considered when evaluating significance of dose and plasma
concentration.
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--To obtain up-to-date information about the treatment of overdose, a
good resource is your certified Regional Poison Control Center. Telephone
numbers of certified poison control centers are listed in the Physicians' Desk
Reference (PDR). In managing overdosage, consider the possibility of multiple
drug overdoses, interaction among drugs, and unusual drug kinetics in your
patient.
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.
DOSAGE AND ADMINISTRATION:
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:
For sedation, the drug may be administered in single doses of 30 to 120 mg
repeated at intervals; frequency will be determined by the patient's response.
It is generally considered that no more than 400 mg of phenobarbital should be
administered during a 24-hour period.
Adults:
Daytime Sedation: 30 to 120 mg daily in 2 to 3 divided doses.
Oral Hypnotic: 100 to 200 mg.
Anticonvulsant Use--Clinical laboratory reference values should be used to
determine the therapeutic anticonvulsant level of phenobarbital in the serum. To
achieve the blood levels considered therapeutic in children, higher per-
kilogram dosages are generally necessary for phenobarbital and most other
anticonvulsants. In children and infants, phenobarbital at a loading dose of 15
to 20 mg/kg produces blood levels of about 20 mcgm/mL shortly after
administration.
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.
Children: 3 to 6 mg/kg/day.
Special Patient Population--Dosage should be reduced in the elderly or
debilitated because these patients may be more sensitive to barbiturates. Dosage
should be reduced for patients with impaired renal function or hepatic disease.
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