Therapeutic Index
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
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
References: Engs, R.C. Alcohol and Other Drugs: Self Responsibility, Tichenor Publishing Company, Bloomington, IN, 1987. (c) Copyright Ruth C. Engs, Bloomington, IN, 1996 Woodard, L. L. (2009) Drug and Alcohol Abuse - A Deadly Combination. Retrieved February 2, 2012, from http://ezinearticles.com/?Drug-and-Alcohol-Abuse---A-Deadly-Combination&id=2868861