Sedative-hypnotics can cause dose-dependent depression of the central nervous system, leading to drowsiness, impaired judgment, and diminished motor skills. This can significantly impact driving, work performance, and relationships. At higher doses, sedative-hypnotics may cause lethargy or exhaustion and exacerbate breathing problems. Long-term use can lead to tolerance, dependence, and potentially life-threatening withdrawal symptoms when discontinued. Sedative-hypnotics frequently interact with other central nervous system depressants in an additive manner, enhancing depression and potentially leading to serious consequences if not properly managed.

1. Your logo
Clinical toxicology of
sedative-hypnotics
Domina Petric, MD

2. Direct toxic actions
Many of the common adverse effects of
sedative-hypnotics result from dose-related
depression of the CNS.
Relatively low doses may lead to drowsiness,
impaired judgment and diminished motor skills.
This can lead to a significant impact on driving
ability, job performance and personal
relationships.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

3. Direct toxic actions
 Sleep driving and other somnambulistic behavior with no
memory of the event have occurred with the sedative-
hypnotic drugs.
 Benzodiazepines may cause a significant dose-related
anterograde amnesia.
 They can significantly impair ability to learn new
information, particularly that involving effortful cognitive
processes.
 Retrieval of previously learned information is intact with
benzodiazepines.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

4. Direct toxic actions
 The criminal use of benzodiazepines in cases of ˝date
rape˝ is based on their dose-dependent amnestic effects.
 Hangover effects are not uncommon following use of
hypnotic drugs with long elimination half-lives.
 Elderly patients are more sensitive to the effects of
sedative-hypnotics.
 Doses approximately half of those used in younger
adults are safer for elderly patients and usually as
effective.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

5. Direct toxic actions
 The most common reversible cause of confusional states
in the elderly is overuse of sedative-hypnotics.
 At higher doses, toxicity may present as lethargy or a
state of exhaustion.
 An increased sensitivity to sedative-hypnotics is more
common in patients with cardiovascular disease,
respiratory disease and hepatic impairment.
 Sedative-hypnotics can exacerbate breathing problems
in patients with chronic pulmonary disease and in those
with symptomatic sleep apnea.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

6. Direct toxic actions
Sedative-hypnotics are the drugs most frequently
involved in deliberate overdoses.
The benzodiazepines are considered to be safer drugs
than barbiturates.
Alprazolam is more toxic in overdose than other
benzodiazepines.
Most serious cases of drug overdosage, intentional or
accidental, involve polypharmacy.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

7. Direct toxic actions
 With high doses and severe toxicity, the respiratory depression from
central actions of the drug may be complicated by aspiration of
gastric contents in the unattended patient.
 This is more likely if ethanol is also present in the blood of the
patient.
 Cardiovascular depression further complicates successful
resuscitation.
 Airway, mechanical ventilation, maintenance of plasma volume,
renal output and cardiac function!
 Use of dopamine or other inotropic drug is sometimes indicated to
preserve renal blood flow.
 Hemodialysis or hemoperfusion may be used to hasten elimination
of some of these drugs.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

8. Direct toxic actions
Flumazenil reverses the sedative actions of benzodiazepines and
those of eszopiclone, zaleplon and zolpidem.
Duration of action is short and its antagonism of respiratory
depression is unpredictable.
There is a risk of precipitation of withdrawal symptoms in long-term
users of benzodiazepines.
The use of flumazenil in benzodiazepine overdose must be
accompanied by adequate monitoring and support of respiratory
function.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

9. Direct toxic actions
The extensive clinical use of triazolam may lead to
serious CNS effects: behavioral disinhibition, delirium,
aggression and violence.
Behavioral disinhibition may occur with any sedative-
hypnotic drug.
Disinhibitory reactions during benzodiazepine treatment
are more clearly associated with the use of very high
doses and the pretreatment level of patient´s hostility.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

10. Direct toxic actions
 Hypersensitivity reactions, including skin rashes, occur only
occasionally with sedative-hypnotics.
FDA pregnancy category:
 for individual benzodiazepines is either D or X
 most barbiturates are D
 eszopiclone, ramelteon, zaleplon and zolpidem are C
 buspirone is B
Barbiturates enhance porphyrin synthesis and are absolutely
contraindicated in patients with a history of acute intermittent
porphyria, variegate porphyria, hereditary coproporphyria and
symptomatic porphyria.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

11. Alterations in drug response
Depending on the dosage and the duration of use,
tolerance occurs in varying degrees to many of the
pharmacologic effects of sedative-hypnotics.
The lethal dose range is not altered significantly by the
long-term use of sedative-hypnotics.
Cross-tolerance between the different sedative
hypnotics, including ethanol, can lead to an
unsatisfactory therapeutic response.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

12. Alterations in drug response
 With the long-term use of sedative-hypnotics, especially if
doses are increased, a state of dependence can occur.
 Withdrawal from a sedative-hypnotic can have severe and life-
threatening manifestations.
 Withdrawal symptoms range from restlessness, anxiety,
weakness and orthostatic hypotension to hyperactive reflexes
and generalized seizures.
 Symptoms of withdrawal are usually more severe following
discontinuance of sedative-hypnotics with shorter half-lives.
 Eszopiclone, zolpidem and zaleplon are exceptions.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

13. Alterations in drug response
Symptoms of withdrawal syndrome are less
pronounced with longer-acting drugs.
Cross-dependence is the ability of one drug to
suppress abstinence symptoms from
discontinuance of another drug.
It is quite marked among sedative-hypnotics.
Longer-acting drugs such as chlordiazepoxide,
diazepam and phenobarbital can be used to alleviate
withdrawal symptoms of shorter-acting drugs,
including ethanol.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

14. Drug interactions
 The most common drug interactions are interactions with other CNS
depressant drugs.
 That leads to additive effects, which can be useful in anesthesia
practice.
 Such interactions, if not anticipated, can lead to serious
consequences: enhanced depression with concomitant use of many
other drugs.
 Additive effects can be predicted with concomitant use of alcoholic
beverages, opioid analgesics, anticonvulsants and phenothiazines.
 Less obvious, but very important, is enhanced CNS depression with
a variety of antihistamines, antihypertensive agents and
antidepressant drugs of the tricyclic class.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.

15. Literature
Katzung, Masters, Trevor.
Basic and clinical
pharmacology.
Katzung, Masters, Trevor. Basic and
clinical pharmacology.