Tolerance & Dependence

Question 1

—is a common feature of sedative-hypnotic use.

Answer 1

Tolerance—decreased responsiveness to a drug following repeated exposure

Note: It may
result in the need for an increase in the dose required to maintainsymptomatic improvement or to promote sleep.

It is important to
recognize that partial cross-tolerance occurs between the sedativehypnotics described here and also with ethanol (see Chapter
23 )—a feature of some clinical importance, as explained below.

Question 2

The mechanisms responsible for tolerance to sedative-hypnotics are not well understood.

An increase in the rate of drug metabolism
(metabolic tolerance) may be partly responsible in the case of
chronic administration of barbiturates, but changes in responsivenessof the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics.

In the case
of benzodiazepines, the development of tolerance in animals has been associated with down-regulation of brain benzodiazepine
receptors.

Question 3

Tolerance has been reported to occur with the extended
use of______________.

Answer 3

zolpidem

Question 4

Minimal tolerance was observed with the use of
__________ over a 5-week period and__________over a 6-month
period.

Answer 4

zaleplon

eszopiclone

Question 5

The perceived desirable properties of relief of anxiety, euphoria, disinhibition, and promotion of sleep have led to the compulsive
misuse of virtually all sedative-hypnotics. (See Chapter 32 for
a detailed discussion.)

For this reason, most sedative-hypnotic
drugsare classified as____________ forprescribing
purposes in the United States.

Answer 5

Schedule III or Schedule IV drugs

Question 6

The consequences of abuse
of these agents can be defined in both psychological and physiologic
terms.

The psychological component may initially parallel
simple neurotic behavior patterns difficult to differentiate from those of the inveterate coffee drinker or cigarette smoker.

When
the pattern of sedative-hypnotic use becomes compulsive (addiction,
see Chapter 32 ), more serious complications develop, including
dependence and tolerance

Question 7

_______ can be described as an **altered physiologic state **that requires continuous drug administration to prevent an abstinence or withdrawal syndrome.

Answer 7

Dependence

Question 8

In the case of sedative-hypnotics,
this dependence is characterized by states of______________that may progress to convulsions.

Answer 8

of increased anxiety, insomnia,
and central nervous system excitability

Question 9

Most sedative-hypnotics—including benzodiazepines—
are capable of causing dependence when used on a long-term basis.
However, the severity of withdrawal symptoms differs among individual drugs and depends also on the magnitude of the dose used mmediately before cessation of use.

When higher doses of sedativehypnotics
are used, abrupt withdrawal leads to more serious withdrawal
signs. Differences in the severity of withdrawal symptoms
resulting from individual sedative-hypnotics relate in part to halflife
since drugs with long half-lives are eliminated slowly enough
to accomplish gradual withdrawal with few physical symptoms.

Question 10

The use of drugs with very short half-lives for hypnotic effects may** lead to signs** of withdrawal even between doses.

For example,_________
a benzodiazepine with a half-life of about 4 hours, has been reported to cause daytime anxiety when used to treat sleep disorders.

Answer 10

triazolam,

Question 11

The
abrupt cessation of use of zolpidem, zaleplon, or eszopiclone may
also result in withdrawal symptoms, though usually of less intensity
than those seen with benzodiazepines