CLINICAL TOXICOLOGY OF SEDATIVE-HYPNOTICS Direct Toxic Actions

Question 1

Many of the common adverse effects of sedative-hypnotics result from__________ of the central nervous system.

Answer 1

dose-related depression

Question 2

Relatively low doses may lead to ____________________________ prompting the Food and Drug Administration in
2007 to issue warnings of this potential hazard.

Answer 2

• drowsiness,
• impaired judgment,
• and diminished motor skills,
• sometimes with a significant impact
• on driving ability,
• job performance,
• and personal relationships.
• Sleep driving and other somnambulistic behavior with no memory of the event has occurred with the sedative-hypnotic drugs used in sleep disorders,

Question 3

________
may cause a significant dose-related anterograde amnesia; they can
significantly impair ability to learn new information, particularly
that involving effortful cognitive processes, while leaving the
retrieval of previously learned information intact.

Answer 3

Benzodiazepines

Question 5

This effect is utilized for uncomfortable clinical procedures, eg, endoscopy, because the patient is able to cooperate during the procedure but amnesic regarding it afterward.

The criminal use of benzodiazepines
in cases of_________ is based on their dose-dependent
amnestic effects.

Answer 5

“date rape

Question 6

​Hangover effects are not uncommon following
use of hypnotic drugs with long elimination half-lives.

Question 7

Because elderly patients are more sensitive to the effects of sedative-hypnotics, doses approximately half of those used in younger adults are safer
and usually as effective.

The most common reversible cause of confusional
states in the elderly is_____. At higher
doses, toxicity may present as lethargy or a state of exhaustion or,
alternatively, as gross symptoms equivalent to those of ethanol intoxication.

Answer 7

overuse of sedative-hypnotics

Question 8

The physician should be aware of variability among
patients in terms of doses causing adverse effects.

An increased
sensitivity to sedative-hypnotics is more common in patients with
_____________, __________ and _________

Answer 8

• cardiovascular disease,
• respiratory disease, or hepatic impairment
• and in older patients.

Question 9

Sedative-hypnotics can exacerbate breathing
problems in patients with______________ and in those with _____________

Answer 9

• ** chronic pulmonary diseas**e
• symptomatic sleep apnea.

Question 10

Sedative-hypnotics are the drugs most frequently involved in
deliberate overdoses, in part because of their general availability as
very commonly prescribed pharmacologic agents.

The ____________
are considered to be safer drugs in this respect, since they
have flatter dose-response curves.

Epidemiologic studies on the
incidence of drug-related deaths support this general assumption—eg,
0.3 deaths per million tablets of diazepam prescribed versus 11.6
deaths per million capsules of secobarbital in one study.

Answer 10

benzodiazepines

Question 11

______________
is purportedly more toxic in overdose than other benzodiazepines.
Of course, many factors other than the specific sedative-hypnotic could influence such data—particularly the presence of other central nervous system depressants, including ethanol.

Answer 11

Alprazolam

Question 12

In fact,
most serious cases of drug overdosage, intentional or accidental,
do involve polypharmacy; and when combinations of agents are
taken, the practical safety of benzodiazepines may be less than the
foregoing would imply.

Question 13

The lethal dose of any sedative-hypnotic varies with the patient
and the circumstances (see Chapter 58 ).

If discovery of the ingestion is made early and a conservative treatment regimen is started, the
outcome is rarely fatal, even following very high doses.

Question 14

On the
other hand, for most sedative-hypnotics—with the exception of ________and ______________** **that have
a similar mechanism of action—a dose as low as ten times the hypnotic dose may be fatal if the patient is not discovered or doesnot seek help in time.

Answer 14

benzodiazepines

**possibly the newer hypnotic drugs **

Question 15

With severe toxicity, the respiratory depression
from central actions of the drug may be complicated by
aspiration of gastric contents in the unattended patient—an even more likely occurrence if ethanol is present.

Question 16

Cardiovascular
depression further complicates successful resuscitation. In such
patients, treatment consists of ensuring a patent airway, with
mechanical ventilation if needed, and maintenance of plasma
volume, renal output, and cardiac function.

Use of a positive inotropic
drug such as___________, which preserves renal blood flow, is
sometimes indicated. Hemodialysis or hemoperfusion may be
used to hasten elimination of some of these drugs.

Answer 16

dopamine

Question 17

Flumazenil reverses the sedative actions of benzodiazepines,
and those of eszopiclone, zaleplon, and zolpidem, although experiencewith its use in overdose of the newer hypnotics islimited.
However, its duration of action is short, its antagonism of respiratorydepression is unpredictable, and there is a risk of precipitationof withdrawal symptoms in long-term users of benzodiazepines
(see below). Consequently, the use of flumazenil in benzodiazepine
overdose must be accompanied by adequate monitoring and
support of respiratory function.

The extensive clinical use of triazolam
has led to reports of serious central nervous system effects
including behavioral disinhibition, delirium, aggression, and violence.
Although behavioral disinhibition may occur with any
sedative-hypnotic drug, it does not appear to be more prevalent
with triazolam than with other benzodiazepines. Disinhibitory
reactions during benzodiazepine treatment are more clearly associated
with the use of very high doses and the pretreatment level of
patient hostility.

Question 18

Adverse effects of the sedative-hypnotics that are not referable to their central nervous system actions occur infrequently.

Question 19

Hypersensitivity reactions, including skin rashes, occur only **occasionally **with most drugs of this class.

Reports of teratogenicity
leading to fetal deformation following use of certain benzodiazepines have resulted in FDA assignment of individual benzodiazepines
to either __________ in terms of pregnancy risk.

Answer 19

category D or X

Question 20

Most
barbiturates are FDA pregnancy ____________.

Answer 20

category D

Question 21

Eszopiclone, ramelteon,
zaleplon, and zolpidemare __________.

Answer 21

category C,

Question 22

While _____________ is a
pregnancy category B drug.

Answer 22

buspirone

Question 23

Because __________enhance porphyrin
synthesis, they are absolutely contraindicated in patients with a
history of acute intermittent porphyria, variegate porphyria,
hereditary coproporphyria, or symptomatic porphyria.

Answer 23

barbiturates