The following adverse reactions and their incidence were compiled from surveillance
of thousands of hospitalized patients. Because such patients may be less aware
of certain 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 reactions
estimated to occur at a rate of 1 to 3 patients per 100 is:
Less than 1 in 100 Patients. Adverse reactions estimated to occur
at a rate of less than 1 in 100 patients listed below, grouped by organ system,
and by decreasing order of occurrence are:
Nervous System: Agitation, confusion, hyperkinesia, ataxia, CNS
depression, nightmares, nervousness, psychiatric disturbance, hallucinations,
insomnia, anxiety, dizziness, thinking abnormality.
Respiratory System: Hypoventilation, apnea.
Cardiovascular System: Bradycardia, hypotension, syncope.
Digestive System: Nausea, vomiting, constipation.
Other Reported Reactions: Headache, hypersensitivity reactions
(angioedema, skin rashes, exfoliative dermatitis), fever, liver damage, megaloblastic
anemia following chronic phenobarbital use.
Drug Abuse And Dependence
Mephobarbital is a controlled substance in Narcotic Schedule IV. Barbiturates
may be habit forming. Tolerance, psychological dependence, and physical dependence
may occur especially following prolonged use of high doses of barbiturates.
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 two-fold. As this occurs, the margin between an 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 these drugs. Intensity of withdrawal
symptoms gradually declines over a period of approximately 15 days. Individuals
susceptible to a barbiturate abuse and dependence include alcoholics and opiate
abusers, as well as other sedative-hypnotic and amphetamine abusers.
Drug dependence to 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 to
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 takes an extended
period of time. One method involves substituting a 30 mg dose of phenobarbital
for each 100 mg to 200 mg dose of barbiturate that the patient has been taking.
The total daily amount of phenobarbital is then administered in 3 to 4 divided
doses, not to exceed 600 mg daily. Should signs of withdrawal occur on the first
day of treatment, a loading dose of 100 mg 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 a 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 physically dependent on barbiturates may be given phenobarbital 3 mg/kg/day
to 10 mg/kg/day. After withdrawal symptoms (hyperactivity, disturbed sleep,
tremors, hyperreflexia) are relieved, the dosage of phenobarbital should be
gradually decreased and completely withdrawn over a 2-week period.