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SEDATIVES AND HYPNOTICS, BARBITURATES The following general discussion of the barbiturates refers to their use as sedative-hypnotic agents and as anticonvulsants. In addition, barbiturates are discussed under General Anesthetics, Barbiturates. Links to Drug Comparison Tables Pharmacokinetics of Sedatives and Hypnotic Barbiturates Sedative/Hypnotic Barbiturate Drug Interactions Indications The following indications apply to most barbiturates. For specific indications, refer to the individual monographs. Ac e con l i e epi ode : Emergency control of certain acute convulsive episodes (eg, those associated with status epilepticus, cholera, eclampsia, meningitis, tetanus, and toxic reactions to strychnine or local anesthetics).1 An icon l an (mephoba bi al, phenoba bi al): Treatment of partial and generalized tonic-clonic and cortical focal seizures.1 2 3 4 5 H pno ic: Short-term treatment of insomnia, since barbiturates appear to lose their effectiveness in sleep induction and maintenance after 2 weeks. If insomnia persists, seek alternative therapy (including nondrug) for chronic insomnia.1 2 3 6 7 8 9 10 11 12 13 P eane he ic: Used as preanesthetic sedatives.1 2 3 6 7 8 9 10 11 12 13 Seda ion: Although traditionally used as nonspecific CNS depressants for daytime sedation, the barbiturates generally have been replaced by the benzodiazepines.2 3 4 15

Administration & Dosage Individualize dosage; consider patient's age, weight and condition. Use parenteral routes only when oral administration is impossible or impractical.5 In am c la (IM) injec ion: IM injection of the sodium salts should be made deeply into a large muscle. Do not exceed 5 mL at any one site because of possible tissue irritation. Monitor patient's vital signs.5 In a eno (IV): Restrict to conditions in which other routes are not feasible, either because the patient is unconscious (as in cerebral hemorrhage, eclampsia or status epilepticus), or because the patient resists (as in delirium), or because prompt action is imperative. Slow IV injection is essential; observe patients carefully during administration. Maintain blood pressure, respiratory and cardiac function, monitor vital signs, and have equipment for resuscitation and artificial ventilation available.5 Rec al admini a ion: Rectally administered barbiturates are absorbed from the colon and are used occasionally in infants for prolonged convulsive states, or when oral or parenteral administration may be undesirable. If the rectal form is not available, the soluble sodium salt may be incorporated in a retention enema.5 13 Elde l /Debili a ed: Reduce dosage because these patients may be more sensitive to barbiturates.5 Hepa ic/Renal f nc ion impai men : Reduce dosage.

Pharmacolog
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Barbiturates can produce all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia. Overdosage can produce death. These agents depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. Barbiturates have little analgesic action at subanesthetic doses and may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses. However, only phenobarbital and mephobarbital are effective as oral anticonvulsants in subhypnotic doses. Barbiturates are respiratory depressants; the degree of respiratory depression is dose-dependent. With hypnotic doses, respiratory depression is similar to that which occurs during physiologic sleep and is accompanied by a slight decrease in blood pressure and heart rate.2 3 4

Pharmacokinetics Absorption: Barbiturates are absorbed in varying degrees following oral, rectal, or parenteral administration. The salts are more rapidly absorbed than the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.2 3 4 On e : Onset of action for oral or rectal administration varies from 20 to 60 minutes. For IM administration, onset is slightly faster than the oral route. Following IV administration, onset ranges from almost immediate for pentobarbital sodium and secobarbital to 5 minutes for phenobarbital sodium. Maximal CNS depression may not occur for at least 15 minutes after IV administration of phenobarbital sodium.1 3 6 D a ion: Duration of action varies and is related to dose and to the rate at which the barbiturates are redistributed throughout the body. In the following table, the barbiturates are classified according to their duration of action. Do not use this classification to predict the exact duration of effect, but use as a guide in drug selection.

Pha macokine ic of Seda i e and H pno ic Ba bi Ba bi ae Half-life (h) Range Mephobarbital 11 to 6715 34 O al do age ange (mg)
a

ae D a ion (h)

Mean Seda i e

H pno ic

On e (min)

32 to 2004

Phenobarbital 53 to 1182 792

30 to 1202 1002 to 3206

30 to 605 6 107 to 165

Amobarbital

16 to 408

258

45 to 607 6 to 87

Butabarbital

66 to 140 1008

45 to 120

50 to 100

Pentobarbital

15 to 507

40 to 120

1007
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10 to 15 Secobarbital 15 to 4014 2814 10014

3 to 47

a b c

Total daily dose; administered in 2 to 4 divided doses. Available as injection only.

May follow dose-dependent kinetics. Mean half-life is 50 hours for 50 mg and 22 hours for 100 mg.

Distribution: Barbiturates are weak acids that are 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. The more lipid soluble the barbiturate, the more rapidly it penetrates body tissue. Barbiturates are bound to plasma and tissue proteins; the degree of binding increases directly as a function of lipid solubility.2 3 4 Phenobarbital has the lowest lipid solubility, plasma binding and brain protein binding, the longest delay in onset of activity, and the longest duration of action. Secobarbital has the highest lipid solubility, plasma protein binding and brain protein binding, the shortest delay in onset of activity, and the shortest duration of action.2 3 4 14 E cretion: 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 phenobarbital dose is eliminated unchanged in the urine, whereas the amount of other barbiturates excreted unchanged in the urine is negligible. The excretion of unmetabolized barbiturate is one feature that distinguishes the long-acting agents. The inactive metabolites of the barbiturates are excreted as conjugates of glucuronic acid.2 3 4 6

Clinical Evidence Clinical ial : Barbiturate-induced sleep reduces the amount of time spent in the rapid eye movement (REM) phase of sleep or dreaming stage. Also, Stages and V sleep are decreased. Following abrupt cessation of barbiturates used regularly, patients may experience markedly increased dreaming, nightmares or insomnia.2 3 4 Secobarbital and pentobarbital lose most of their effectiveness for inducing and maintaining sleep by the end of 2 weeks of continued drug administration, even with the use of multiple doses. Other barbiturates might also be expected to lose their effectiveness for inducing and maintaining sleep after about 2 weeks. However, definitions of tolerance vary; these two barbiturates have been given for weeks to months for chronic sedation with little tolerance developing, although decreased effects on sleep stages occur. In addition, the chronic disruption of the normal sleep pattern may make sleep less satisfying; therefore, dosages may be increased possibly resulting in enhanced tolerance. 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 agents are superior for producing sleep, while the intermediate-acting compounds are more effective in maintaining sleep, controlled studies have failed to demonstrate these differential effects.2 3 4 15 Mephobarbital has a relatively mild hypnotic effect, but exerts strong sedative effects. When used as a sedative, patients usually become more calm, cheerful and better adjusted to surroundings without clouding of mental
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faculties. It reportedly produces less sedation than phenobarbital.

Contraindications Barbiturate sensitivity; manifest or latent porphyria; marked liver function impairment; nephritic patients; patients with respiratory disease where dyspnea or obstruction is present; intra-arterial administration (consequences vary from transient pain to gangrene); subcutaneous administration (produces tissue irritation ranging from tenderness and redness to necrosis); previous addiction to the sedative/hypnotic group (ordinary doses may be ineffective and may contribute to further addiction).1 6 10 11

Warnings/Precautions Habi fo ming: Tolerance or psychological and physical dependence may occur with continued use (see Drug abuse and dependence in the Precautions section). Administer with caution, if at all, to patients who are mentally depressed, have suicidal tendencies or a history of drug abuse (eg, alcoholics, opiate abusers, other sedativehypnotic and amphetamine abusers). Limit prescribing and dispensing to the amount required for the interval until the next appointment.2 3 4 6 IV admini a ion: Too rapid administration may cause respiratory depression, apnea, laryngospasm, or vasodilation with fall in blood pressure. Parenteral solutions of barbiturates are highly alkaline. Therefore, use extreme care to avoid perivascular extravasation or intra-arterial injection. Extravascular injection may cause local tissue damage with subsequent necrosis; consequences of intra-arterial injection may vary from transient pain to gangrene of the limb. Any complaint of pain in the limb warrants stopping the injection.3 6 10 11 Phenoba bi al odi m may be administered IM or IV as an anticonvulsant for emergency use. When administered IV, it may require at least 15 minutes before reaching peak concentrations in the brain. Therefore, injecting phenobarbital sodium until the convulsions stop may cause the brain level to exceed that required to control the convulsions and may lead to severe barbiturate-induced depression.6 Pain: Exercise caution when administering to patients with acute or chronic pain, because paradoxical excitement may be induced or important symptoms may be masked. However, the use of barbiturates as sedatives in postoperative surgery and as adjuncts to cancer chemotherapy is well established.2 3 4 Sei e di o de : Status epilepticus may result from abrupt discontinuation, even when administered in small daily doses in the treatment of epilepsy.4 Effec on i amin D: Barbiturates may increase vitamin D requirements, possibly by increasing the metabolism of vitamin D via enzyme induction. Rickets and osteomalacia have been reported rarely following prolonged use of barbiturates.4 Ta a ine en i i i : Some of these products contain tartrazine, which may cause allergic-type reactions (including bronchial asthma) in susceptible individuals. Although the incidence of tartrazine sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Specific products containing tartrazine are identified in the product listings.9 Renal f nc ion impai men : Barbiturates are excreted either partially or completely unchanged in the urine and are contraindicated in patients with renal function impairment. Hepa ic f nc ion impai men : Barbiturates are metabolized primarily by hepatic microsomal enzymes. Administer
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with caution and initially in reduced doses to patients with hepatic function impairment. Do not use in patients showing premonitory signs of hepatic coma.2 3 4 Special i k pa ien : Untoward reactions may occur in the presence of fever, hyperthyroidism, diabetes mellitus, and severe anemia. Use with caution.1 Use mephoba bi al with caution in patients with myasthenia gravis and myxedema.4 D g ab e and dependence: Barbiturates may be habit forming. Tolerance, psychological dependence, and physical dependence may occur, especially following prolonged use of high doses. Doses in excess of 400 mg/day pen oba bi al or ecoba bi al for approximately 90 days are likely to produce some degree of physical dependence. A dose 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 develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than 2-fold. As this occurs, the margin between an intoxicating dosage and fatal dosage becomes smaller.2 3 4 In o ica ion: Symptoms of acute intoxication include unsteady gait, slurred speech, and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgment, irritability, insomnia, and somatic complaints. If an individual appears to be intoxicated with alcohol to a degree that is radically disproportionate to the amount of alcohol in his/her blood, suspect the use of barbiturates. The lethal dose of a barbiturate is less if accompanied with alcohol.2 3 4 Dependence: Symptoms are similar to those of chronic alcoholism and include the following: a strong desire or need to continue taking the drug; tendency to increase the dose; psychological dependence on the effects of the drug related to subjective and individual appreciation of those effects; and physical dependence on the effects of the drug requiring its presence for maintenance of homeostasis resulting in a definite, characteristic, and selflimited abstinence syndrome when the drug is withdrawn.2 3 4 Wi hd a al mp om : Withdrawal symptoms can be severe and may cause death.2 3 4 Mino mp om : These may appear 8 to 12 hours after the last dose of a barbiturate and 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.2 3 4 Majo mp om : 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 within about 15 days.2 3 4 T ea men of dependence: Treatment of dependence consists of cautious and gradual withdrawal of the drug, which takes an extended period of time. One method involves substituting 30 mg phenobarbital for each 100 to 200 mg barbiturate dose the patient is taking. The total daily amount of phenoba bi al is administered in 3 to 4 divided doses, not to exceed 600 mg/day. Should signs of withdrawal occur on the first day of treatment, administer an IM loading dose of phenobarbital 100 to 200 mg in addition to the oral dose. After stabilization on phenobarbital, decrease the total daily dose 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
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tolerated. Severely dependent individuals generally may be withdrawn over 2 to 3 weeks. Infants physically dependent on barbiturates may be given phenobarbital 3 to 10 mg/kg/day. After withdrawal symptoms (eg, hyperactivity, disturbed sleep, tremors, hyperreflexia) are relieved, gradually decrease the dosage of phenobarbital; completely withdraw over 2 weeks.1 2 3 4 Child en: In some patients, especially children, barbiturates repeatedly produce excitement rather than depression. Barbiturates may produce irritability, excitability, inappropriate tearfulness, and aggression in children. Hyperkinetic states also may be induced and are primarily related to a specific drug sensitivity. Cognitive deficits have been associated with phenobarbital use for complicated febrile seizures in children. Safety and efficacy of amobarbital (children < 6 years of age) have not been established.2 15 17 18 Elde l : May produce marked excitement, depression, and confusion in elderly patients. In some people, barbiturates repeatedly produce excitement rather than depression.2 3 4 Per the Beers list, all barbiturates (except phenoba bi al) are highly addictive and cause more adverse effects than most sedative or hypnotic drugs in elderly patients except when used to control seizures.21

Pregnanc /Lactation P egnanc : Categor D. Barbiturates may cause fetal damage when administered to a pregnant woman. Studies suggest a connection between maternal consumption of barbiturates and a higher incidence of fetal abnormalities. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise her of the potential hazards to the fetus.1 2 3 4 6 7 8 9 10 11 12 13 14 Barbiturates readily cross the placental barrier and are distributed throughout fetal tissues. Fetal blood levels approach maternal blood levels following parenteral use.2 3 4 Withdrawal symptoms occur in infants born to mothers who receive barbiturates throughout the last trimester of pregnancy. Reports include the acute withdrawal syndrome of seizures and hyperirritability from birth to a delayed onset of up to 14 days.2 3 4 An icon l an e: Because of the strong possibility of precipitating status epilepticus with attendant hypoxia and the risk to the mother and unborn child, do not discontinue anticonvulsants when used to prevent major seizures. However, consider discontinuing anticonvulsants prior to and during pregnancy when the nature, frequency and severity of the seizures do not pose a serious threat to the patient. It is not known whether even minor seizures constitute some risk to the embryo or fetus. Maternal ingestion of anticonvulsants, particularly barbiturates, may be associated with a neonatal coagulation defect that may cause bleeding, usually within 24 hours of birth. The defect is characterized by decreased levels of vitamin K-dependent clotting factors, and prolongation of prothrombin time, partial thromboplastin time or both. Give prophylactic vitamin K to the mother 1 month prior to and during delivery, and to the infant immediately after birth. Labo and Deli e : Hypnotic doses do not appear to significantly impair uterine activity during labor. Full anesthetic doses decrease the force and frequency of uterine contractions. Administration to the mother during labor may result in respiratory depression in the newborn; premature infants are particularly susceptible. If barbiturates are used during labor and delivery, have resuscitation equipment available.2 3 4
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Lac a ion: Exercise caution when administering to a breast-feeding mother, because small amounts of drug are excreted in breast milk. Drowsiness in the nursing infant has been reported.2 3 4 16

Monitoring During prolonged therapy, perform periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic systems.2 3 4

Drug Interactions Most reports of clinically significant drug interactions occurring with the barbiturates have involved phenobarbital.1 4 5

Seda i e/H pno ic Ba bi P ecipi an d g Alcohol Charcoal Objec d Barbiturates Barbiturates g

a

a e D g In e ac ion 1 2 3 4 14 20 De c ip ion

Concomitant use may produce additive CNS effects and death. Charcoal may reduce the absorption of barbiturates. Depending on the clinical situation, this will reduce their efficacy or toxicity.

Chloramphenicol Barbiturates Barbiturates Monoamine oxidase inhibitors Rifampin Valproic acid Barbiturates Barbiturates

Chloramphenicol may inhibit phenobarbital metabolism. Barbiturates may Chloramphenicol enhance chloramphenicol metabolism. MAOIs may enhance the sedative effects of barbiturates.

Barbiturates Barbiturates Anticoagulants

Rifampin induces hepatic microsomal enzymes and may decrease the effectiveness of barbiturates. Valproic acid appears to decrease barbiturate metabolism, resulting in an increased effect. Barbiturates may increase metabolism of anticoagulants, resulting in a decreased response. Patients stabilized on anticoagulants may require dosage adjustments if barbiturates are added to or withdrawn from their regimen. Pharmacokinetic parameters of certain beta-blockers (metoprolol and propranolol) may be altered by barbiturates. Timolol does not appear to be affected. Increased clonazepam clearance may occur, which may lead to lower steady-state levels and loss of efficacy.

Barbiturates

Beta blockers

Barbiturates Barbiturates Barbiturates

Carbamazepine Decreased serum carbamazepine levels may occur. Clonazepam

Contraceptives, Decreased contraceptive effect may occur due to induction of microsomal oral enzymes. Menstrual irregularities (eg, spotting, breakthrough bleeding) or pregnancy may occur. An alternate form of birth control is suggested. Corticosteroids Digitoxin Barbiturates may enhance corticosteroid metabolism through the induction of hepatic microsomal enzymes. Barbiturates may increase digitoxin metabolism.
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Barbiturates Barbiturates

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Barbiturates Barbiturates Barbiturates Barbiturates Barbiturates

Doxorubicin Doxycycline Felodipine Fenoprofen Griseofulvin

Total doxorubicin plasma clearance may be increased. Phenobarbital decreases doxycycline's half-life and serum levels, which may persist for 2 weeks after barbiturate therapy is discontinued. Felodipine plasma levels and bioavailability may be reduced. Fenoprofen bioavailability may be decreased. Phenobarbital appears to interfere with the absorption of oral griseofulvin, thus decreasing its blood level; however, the effect on therapeutic response has not been established. The effect of barbiturates on metabolism is unpredictable; monitor hydantoin and barbiturate blood levels frequently if these drugs are given concurrently. Barbiturates may decrease the antimicrobial effectiveness of metronidazole. Methadone actions may be reduced. CNS depressant effects of meperidine may be prolonged. Phenobarbital may significantly reduce the serum levels and half-life of quinidine. Barbiturates decrease theophylline levels, possibly resulting in decreased effects. The clearance of verapamil may be increased and its bioavailability decreased.

Barbiturates Barbiturates Barbiturates Barbiturates Barbiturates Barbiturates Barbiturates Barbiturates

a

Hydantoins

Methoxyflurane Enhanced renal toxicity may occur. Metronidazole Narcotics

Phenylbutazone The elimination half-life of phenylbutazone may be reduced. Quinidine Theophylline Verapamil

= object drug decreased; = object drug increased; = undetermined clinical effect.

Adverse Reactions The following adverse reactions and their incidence were from observations of hospitalized patients. Because such patients may be less aware of milder adverse reactions of barbiturates, the incidence may be higher in fully ambulatory patients.2 3 4 Cardiovascular: Bradycardia, hypotension, syncope (less than 1%).2 3 4 CNS: Somnolence (1% to 3%); abnormal thinking, agitation, anxiety, ataxia, CNS depression, confusion, dizziness, fever (especially with chronic phenobarbital use), hallucinations, headache, hyperkinesia, insomnia, nervousness, nightmares, psychiatric disturbance (less than 1%); drowsiness; lethargy; residual sedation (hangover effect); vertigo. 2 3 4 9 Emotional disturbances and phobias may be accentuated with phenobarbital use. In some patients, barbiturates repeatedly produce excitement rather than depression; the patient may appear to be inebriated. Irritability and hyperactivity can occur in children.2 3 4 Barbiturates, 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.2 3 4
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GI: Constipation, nausea, vomiting (less than 1%); liver damage, particularly with chronic phenoba bi al use (less than 1%).2 3 4 9 Hematologic: Megaloblastic anemia (rarely, following chronic phenoba bi al use).2 3 4 H persensitivit : Skin rashes, angioedema (particularly following chronic phenobarbital use) (less than 1%); exfoliative dermatitis (eg, Stevens-Johnson syndrome and toxic epidermal necrolysis) may be caused by phenobarbital and may be fatal (rare).2 3 4 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. The skin eruption may be associated with fever, delirium, and marked degenerative changes in the liver and other parenchymatous organs.2 3 4 Local: Inadvertent intra-arterial injection may produce arterial spasm with resultant thrombosis and gangrene of an extremity. Reactions range from transient pain to severe tissue necrosis and neurological deficit. Subcutaneous injection may produce tissue necrosis, pain, tenderness and redness. Injection into or near peripheral nerves may result in permanent neurological deficit. Thrombophlebitis after IV use and pain at IM injection site have been reported. Respirator : Apnea, hypoventilation (less than 1%); circulatory collapse; respiratory depression.2 3 4

Overdosage The toxic dose of barbiturates varies considerably. In general, an oral dose of 1 g produces serious poisoning in an adult. Death commonly occurs after 2 to 10 g of ingested barbiturate.2 3 4 S mp om : Onset of symptoms may not occur until several hours after ingestion. Acute barbiturate overdosage is manifested by CNS and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may show paralytic dilation), nystagmus, ataxia, oliguria, tachycardia, hypotension, lowered body temperature, and coma. Typical shock syndrome (eg, apnea, circulatory collapse, respiratory arrest, death) may occur.1 In extreme overdose, all electrical activity in the brain may cease, in which case a flat electroencephalogram normally equated with clinical death cannot be accepted. This effect is fully reversible unless hypoxic damage occurs. Consider the possibility of barbiturate intoxication even in situations that appear to involve trauma.5 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.5 T ea men : Treatment is mainly supportive. Maintain an adequate airway, with assisted respiration and oxygen administration, as necessary. Monitor vital signs and fluid balance. Refer to General Management of Acute Overdosage. General Management of Acute Overdosage 5
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Administer 30 g activated charcoal. Nasogastric administration of multiple doses of activated charcoal has been successful in accelerating the elimination of phenobarbital from the body. Consider gastric lavage with a cuffed endotracheal tube in place with the patient in the face-down position. Activated charcoal may be left in the emptied stomach and a saline cathartic administered.5 16 Administer fluid and other standard treatments for shock, if needed. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. However, diuresis and peritoneal dialysis are of little value. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenoba bi al and mephoba bi al (which is metabolized to phenobarbital).5 Hemodialysis and hemoperfusion may be used in severe barbiturate intoxication or if the patient is anuric or in shock. The patient should be rolled from side to side every 30 minutes.5

Patient Information Instruct the patient not to increase the dose of the drug without consulting a health care provider.2 3 4 Advise patients that barbiturates may impair mental or physical abilities required for the performance of potentially hazardous tasks (eg, driving, operating machinery).2 3 4 Advise patients not to consume alcohol while taking barbiturates. Concurrent use of barbiturates with other CNS depressants (eg, alcohol, narcotics, tranquilizers, antihistamines) may result in additional CNS depressant effects.2
34

Instruct patient to notify the health care provider if any of the following occur: fever; sore throat; mouth sores; easy bruising or bleeding; tiny broken blood vessels under the skin.19 Patients may use these drugs on a limited basis as a sleep aid; advise patients not to use for longer than 2 weeks.19

References 1. Phenoba bi al Injec ion [package insert]. Wyeth; March 1989. 2. Phenoba bi al Eli i and Table [package insert]. Lilly; October 1991.

3. Nemb al (pentobarbital) Injection ]package insert. Abbott; December 1991. 4. Meba al (mephobarbital) Tablets [package insert]. Winthrop; November 1987. 5. Federal Register. Class labeling guidelines for barbiturates. 11/18/80, pp 76360-76365 6. L minal (phenobarbital) Injection [package insert]. Winthrop; August 1988. 7. Nemb al (pentobarbital) Caplets [package insert]. Abbott; March 1988. 8. Am al (amobarbital) Injection [package insert]. Lilly; November 1992. 9. B i ol (butabarbital) Tablets and Elixir [package insert]. Wallace; July 1992. 10. Secoba bi al Injec ion [package insert]. Wyeth; July 1992.
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11. Pen oba bi al Injec ion [package insert]. Wyeth; January 1988. 12. Nemb al (pentobarbital) Elixir [package insert]. Abbott; March 1992. 13. Nemb al (pentobarbital) Suppositories [package insert]. Abbott; November 1990. 14. Seconal (secobarbital) Caplets [package insert]. Lilly; January 1991. 15. Hardman JG, Limbird LE, eds; Gilman AG, consulting ed. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY: McGraw-Hill; 1990. 16. Goldberg MJ, Berlinger WG. Treatment of phenobarbital overdose with activated charcoal. JAMA. 1982;247:2400-2401. PubMed 17. Livingston S, Pauli LL, Pruce I, et al. Phenobarbital vs. phenytoin for grand mal epilepsy. AFP1980 Aug;22:12327. 18. Reactions. Anticonvulsant drugs can have psychiatric effects too. 1980 Oct 10:1. 19. Covington TR, associate ed. Patient Drug Facts. St. Louis, MO: Wolters Kluwer Health; 2004. 20. Tatro DS, ed. Drug Interaction Facts. St. Louis, MO: Wolters Kluwer Health; 2004. 21. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716-2724. PubMed

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