Therapeutic Index

Topics: Barbiturate, Heroin, Morphine Pages: 9 (3092 words) Published: February 5, 2012
The Inaba text describes the phenomenon of "therapeutic index." Addiction to barbiturates can be critical in terms of lethality as measured by the therapeutic index. Describe how this phenomenon might lead to an accidental overdose. Why is this factor more critical with barbiturates than with other classes of depressant drugs?

Barbiturates are nonselective central nervous system (CNS) depressants, capable of producing all degrees of depression from mild sedation and hypnosis to general anesthesia, deep coma and death. The extent of CNS depression varies with the route of administration, dose and pharmacokinetic characteristics of the particular barbiturate. Patient specific factors such as age, physical or emotional state and the concomitant use of other drugs will also affect response.

The mechanism of action of barbiturates is not completely known. They may act by enhancing and/or mimicking the synaptic action of gamma-amino butyric acid (GABA), an inhibitory neurotransmitter. The sedative-hypnotic action of barbiturates may be due to an inhibition of conduction in the reticular formation resulting in a decrease in the number of impulses reaching the cerebral cortex.

Anticonvulsant activity may result from a reduction in CNS synaptic transmission and an increase in the threshold for electrical stimulation of the motor cortex. Phenobarbital is the only barbiturate with anticonvulsant activity at sub hypnotic doses.

The therapeutic index of barbiturates is narrow. Amounts needed to relieve anxiety and those causing general CNS depression are not greatly different. Therefore, the use of barbiturates as anxiolytics is almost always accompanied by some degree of impairment of cognitive function. Supratherapeutic doses lead to marked impairment of mental and motor faculties i.e. distortion of judgment, clouding of perception, slurring of speech and ataxia. In some patients however, (especially children and the elderly), drowsiness may be paradoxically preceded by transient euphoria, elation, excitement and confusion.

A greater health hazard than the opiates, barbiturates areas addicting as heroin and even more dangerous during withdrawal. - Barbiturate-related deaths average over three thousand annually; almost half of these are suicides. Although they constitute a major drug-abuse problem in schools, barbiturates are still considered "soft" drugs because they may be obtained legally, by prescription. Three hundred tons of barbiturates are produced annually in the United "states, and may' be found in one out of three medicine chests. , Of 2,500 barbiturates . synthesized, only about a dozen are commonly used. The five top barbiturate "sleepers" (sleeping pills) accounted for nineteen million prescriptions in one recent year, costing the public $16 million. The drug industry churns out an annual ten billion doses of "downers," including both barbiturates and nonbarbiturate sedative-hypnotics-or fifty for each man, woman, and child in the United States. One million people are habitual barbiturate abusers. Barbiturates are central-nervous-system depressants containing barbituric acid, or malonylurea. Three categories of the drug exist: long-acting, short-to-intermediate-acting, and ultra-short-acting. The long-acting drugs (eight to sixteen hours) are used as anti-convulsants in the treatment of epilepsy, and for controlling peptic ulcers , high blood pressure. Veronal (bar. bital), Luminal (pennobarbital), Mebaral (mephobarbital), and Gemonil (methabarbital) are in this group. The short-to-intermedlate-acting drugs (four to six hours) are sleeping -pills, the most commonly abused barbiturates, These include Alurate (aprobarbital), Amytal (amobarbital), Butisol Sodium (butabarbital), Dial (diallybarbituric acid), Nembutal (pentobarbital), Seconal (secobarbital), and Tuinal (amobarbital and secobarbital). Ultra-short-acting barbiturates (immediate but brief), used ,, either as intravenous anesthetics or as a...
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