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TOLERANCE AND DEPENDENCE

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Before we move on to the central nervous system (CNS) sedatives and narcotics, we need to clarify a few terms and definitions.

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Tolerance is a physiological state characterized by a reduced drug effect with repeated use of the drug. Higher doses are needed to produce the same effect.

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Essentially, tolerance is a state of reduced effectiveness. The term does not give any indication of the mechanism involved. Tolerance could be the result of increased elimination of a drug or of reduced effectiveness of drug–receptor interaction. For some drugs, tolerance develops to one effect of the drug and not to other effects. For example, with the narcotics, tolerance is seen to the analgesic effect, but less tolerance develops to the respiratory depression.

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Cross-tolerance means that individuals tolerant to one drug will be tolerant to other drugs in the same class, but not to drugs in other classes.

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A person who is tolerant to the sedative effects of one barbiturate will be tolerant to the effect of all the barbiturates (a situation termed cross-tolerance). However, that person will not be tolerant to the sedative effects of opiates.

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Dependence is characterized by signs and symptoms of withdrawal when drug levels fall.

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Dependence can be physical, in which case the person has physical signs of withdrawal, or it can be psychological, in which case the person has psychological signs of withdrawal. There is something called cross-dependence, which is similar to cross-tolerance.

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ORGANIZATION OF CLASS

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Drugs that are classified as anxiolytics and hypnotics are used for a variety of purposes, including treatment of anxiety and epilepsy, sleep induction, and anesthesia. They are often called sedative-hypnotics or just anxiolytics.

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Cross-tolerance and cross-dependence occur between all of the CNS sedatives, including the barbiturates, benzodiazepines, and ethanol.

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This is an important feature of all the drugs in this class.

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These drugs are generally classified by chemical structure. The two largest groups of drugs are the barbiturates and benzodiazepines. There are a relatively large number of drugs in both of these groups, but (thankfully) their names are generally recognizable. The barbiturates are no longer used to treat anxiety, but it is easier to learn them in this context.

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Barbiturates Benzodiazepines Others NBBRAs

PHENOBARBITAL

THIOPENTAL

amobarbital

methohexital

pentobarbital

secobarbital

ALPRAZOLAM

DIAZEPAM

LORAZEPAM

clonazepam

clorazepate

flurazepam

oxazepam

quazepam

temazepam

triazolam

BUSPIRONE

chloral hydrate

ramelteon

zaleplon

zolpidem

eszopiclone

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Notice that the barbiturates all end in “-tal” and all, except thiopental and methohexital, end in “-barbital.” The benzodiazepines, for the most part, end in “-pam” or “-lam.” The notable exception here is chlordiazepoxide. This nomenclature makes it easy to succeed at name recognition.

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All of these drugs reduce anxiety ...

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