Effects On The Body And Therapeutic Uses

Barbiturates affect all excitable tissues in the body. However, NEURONS are more sensitive to their effects than other tissues. The depth of central nervous system depression ranges from mild sedation to coma and depends on many factors including which drug is used, its dose, the route of administration, and the level of excitability present just before the barbiturate was taken. The most common uses for the barbiturates are still to promote sleep and to induce anesthesia. Barbiturate-induced sleep resembles normal sleep in many ways, but there are a few important differences. Barbiturates reduce the amount of time spent in rapid eye movement or REM sleep—a very important phase of sleep. Prolonged use of barbiturates causes restlessness during the late stages of sleep. Since the barbiturates remain in our bodies for some time after we awaken, there can be residual drowsiness that can impair judgment and distort moods for some time after the obvious sedative effects have disappeared. Curiously, some people are actually excited by barbiturates, and the individual may even appear inebriated. This paradoxical reaction often occurs in the elderly and is more common after taking phenobarbital.

The general use of barbiturates as hypnotics (SLEEPING Pills) has decreased significantly, since they have been replaced by the safer benzodiazepines. Phenobarbital and butabarbital are still available, however, as sedatives in a number of combination medications used to treat a variety of inflammatory disorders. These two drugs also are used occasionally to antagonize the unwanted overstimulation produced by ephedrine, AMPHETAMINE, and theophylline.

Since epilepsy is a condition of abnormally increased neuronal excitation, any of the barbiturates can be used to treat convulsions when given in anesthetic doses; however, phenobarbital has a selective anticonvulsant effect that makes it particularly useful in treating grand mal seizures. This selective effect is shared with mephobarbital and metharbital. Thus, phenobarbital is often used in hospital emergency rooms to treat convulsions such as those that develop during tetanus, eclampsia, status epilepticus, cerebral hemorrhage, and poisoning by convulsant drugs. The benzodiazepines are, however, gradually replacing the barbiturates in this setting as well.

It is not completely understood how barbiturates work but, in general, they act to enhance the activity of GABA on GABA-sensitive neurons by acting at the same receptor on which GABA exerts its effects (see Figure 2). GABA is a NEUROTRANSMIT-TER that normally acts to reduce the electrical activity of the brain; its action is like a brake. Thus, barbiturates enhance the braking effects of GABA to promote sedation. There is an area in the brain called the reticular activating system, which is responsible for maintaining wakefulness. Since this area has many interconnecting or polysynaptic neurons, it is the first to succumb to the barbiturates, and that is why an individual becomes tired and falls asleep after taking a barbiturate.

TABLE 1

Classification of Barbiturates on the Basis of Duration of Action

TABLE 1

Classification of Barbiturates on the Basis of Duration of Action

Drug Class and Generic Names

Trade Names

Routes of Administration*

Half-Life (in hours)

Ultrashort-Acting:

methohexital sodium

Brevital

IV

3.5-6**

thiamylal sodium

Surital

IV

t

thiopental sodium

Pentothal

IV

3-8**

Short-Acting:

butalbital

t

PO

35

hexobarbital

Sombulex

PO; IV

3-7

pentobarbital

Nembutal

PO; IM

15-48

secobarbital

Seconal

PO; IM

15-40

Intermediate-Acting:

amobarbital

Amytal

PO; IM

8-42

aprobarbital

Alurate

PO

14-34

butabarbital

Butisol

PO

34-42

talbutal

Lotusate

PO

t

Long-Acting:

phénobarbital

Luminal

PO; IV

24-96

mephobarbital

Mebaral

PO

11-67

**Values are for whole body, half-life in the brain is less than 30 minutes.

■¡■Half-life data not available for human subjects.

^Various preparations in combination with acetaminophen.

SOURCE: Rail, 1990; Csaky, 1979.

**Values are for whole body, half-life in the brain is less than 30 minutes.

■¡■Half-life data not available for human subjects.

^Various preparations in combination with acetaminophen.

SOURCE: Rail, 1990; Csaky, 1979.

lipid; when the ultrashort-acting barbiturates are given intravenously, they proceed directly to the brain to produce anesthesia and unconsciousness. After only a few minutes, however, these drugs are redistributed to the fats in the rest of the body so their concentration is reduced in the brain. Thus, recovery from IV barbiturate anesthesia can be very fast. For this reason, drugs such as methohexi-tal and thiopental are used primarily as intravenous anesthetic agents and not as sedatives.

The other longer-acting barbiturates must be metabolized by the liver into inactive compounds before the effects wane. Since these metabolites are more soluble in water, they are excreted through the kidneys and into the urine. As is the case with most drugs, metabolism and excretion is much quicker in young adults than in the elderly and infants. Plasma half-lives are also increased in pregnant women because the blood volume is expanded due to the development of the placenta and fetus.

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