Sedative and Hypnotic Drugs

Question 1

Generally, which suffix correlates with Benzodiazepines?

What are 2 exceptions?

Answer 1

-pam/lam

Chlordiazepoxide
Chlorazepate

Question 2

What is the Benzodiazepine antagonist?

Answer 2

Flumazenil

Question 3

What is the suffix for Barbiturates?

Answer 3

-tal

Question 4

Which Benzos are considered short, intermediate and long acting?

Answer 4

Short acting: Triazolam

Intermediate acting: Alprazolam

Long acting: Flurazepam

Question 5

Which Barbiturates are considered ultra-short acting, short acting and long acting?

Answer 5

Ultra-short acting: Thiopental

Short acting: Secobarbital

Long acting: Phenobarbital

Question 6

What is the progression of CNS effects of ingested drugs?

Answer 6

Sedation -> Hyponosis -> Anesthesia -> Coma

Question 7

What is the MOA of Benzodiazepines?

What is there a risk of?

Answer 7

Binds to GABAA receptor and enhances GABA’s effects (shifts dose-response curve left).
-increase Cl- influx, hyperpolarization, and decreased number of APs.

Dependence and tolerance.

Question 8

What are the advantages and disadvantages to treating anxiety with Benzodiazepines?

Answer 8

Advantages: high therapeutic index, antidote available if overdose, low risk of drug-drug interactions, minimal CVS effects.

Disadvantages: risk of dependence, CNS depression.

Question 9

Under which circumstances are Benzodiazepines more likely to cause cumulative effects?

Answer 9

When taken as multiple doses, due to long half-life.

Question 10

Which drug is bound to serum albumin (80%) most of the time in vitro?

Answer 10

Alprazolam

Question 11

Which CYP metabolizes Alprazolam?

What is it used for?

Answer 11

CYP3A4

Management of anxiety disorder or short-term relief of anxiety symptoms. Can also be used for panic disorder, w/ or w/o agoraphobia.

Question 12

In which patients is Alprazolam contraindicated? (3)

Answer 12

Paatients w/ a known sensitivity to the drug or other Benzos.

Patients with acute narrow angle glaucoma.

Ketoconozole and Itraconozole (because they impair oxidative metabolism by CYP3A).

Question 13

Which warnings are associated with Alprazolam?

Answer 13

Dependence and withdrawal reactions, including seizures.

Question 14

Which drug is given IM/IV for preoperative sedation/anxiolysis/amnesia?

What is the black box warning?

Answer 14

Midazolam

IV Midazolam has been associated w/ respiratory depression and arrest, especially used in non-critical care settings.

Question 15

Diazepam’s effects are the result of facilitation of what?

What is the half-life and elimination process?

Answer 15

GABA (inhibitory NT)

Initial distribution phase is followed by prolonged terminal elimination phase (half-life up to 48 hrs.). The terminal elimination half-life of the active metabolite N-desmethyldiazepam can be up to 100 hrs.**

Question 16

What happens to the half-life of Diazepam in patients with mild to moderate cirrhosis?

Answer 16

It increases, possibly from 2 to 5-fold.

Question 17

What are the indications for Diazepam?

Answer 17

Management of anxiety disorders or short-term relief of symptoms.

May improve symptoms in acute alcohol withdrawal.

Question 18

What are the contraindications of Diazepam?

Answer 18

Patients with a known hypersensitivity to the drug.

Pediatric patients < 6 mo.

Patients with myasthenia gravis, severe respiratory insufficiency, hepatic insufficiency and sleep apnea.

Patients with acute narrow-angle glaucoma.

Question 19

What is the warning associated with Diazepam?

Answer 19

NOT recommended in the treatment of psychotic patients.

Question 20

Indication for Oxazapam:

Answer 20

Treatment of anxiety, anxiety w/ depression and acute alcohol withdrawal.

Question 21

Indication for Triazolam:

What is the black box warning?

Answer 21

Short-term relief of insomnia (7-10 days).

BB warning: concomitant use in patients with opioids may cause severe sedation, respiratory depression, coma and death.

Question 22

Indications for Chlordiazepoxide (3)

What is the black box warning?

Answer 22

(1) Management of anxiety disorders or short-term relief of symptoms of anxiety, (2) acute alcohol withdrawal symptoms, and (3) pre-op apprehension and anxiety.

Concomitant use with opioids may cause severe sedation, respiratory depression, coma and death.

Question 23

Indications for Flurazepam:

What should be done if symptoms do not improve?

Answer 23

Used for the treatment of insomnia characterized by trouble falling asleep, frequent awakenings and early awakenings.

Failure of insomnia to remit after 7-10 days may indicate a primary pyschiatric medical illness that should be evaluated.

Question 24

What are the indications for Lorazepam? (2)

Answer 24

Treatment of epilepsy.

Used before surgery and medical procedures to relieve pre-op anxiety.

Question 25

What are the indications for Flumazenil? (2) What is the black box warning?

Answer 25

- Complete or partial reversal of sedative effects of Benzos in cases where general anesthesia has been induced/maintained w/ Benzos. - Management of Benzo overdose. May cause seizures.

Question 26

How is Thiopental given? What are the indications? (5)

Answer 26

Only IV. Sole anesthetic for brief (< 15 min) procedures. To supplement regional anesthesia. To provide hypnosis during balanced anesthesia. To control convulsive states. In neurosurgical patients with elevated intracranial pressures.

Question 27

What are the adverse reactions of Thiopental?

Answer 27

Respiratory depression, myocardial depression, arrhythmias, prolonged somnolence, sneezing, coughing, etc.

Question 28

What are the indications for Secobarbital? (2) What is the warning?

Answer 28

Hyponotic, for short-term insomnia, because it loses its effectiveness after 2 wks. Preanesthetic. If insomnia does not remit after 7-10 days of treatment may suggest a primary psychiatric disorder.

Question 29

What is the indication of Phenobarbital? Who is it contraindicated in? What is the warning? It has been shown to...

Answer 29

Use as a sedative or hypnotic. Patients with a barbiturate sensitivity and in patients with a history of porphyria. If insomnia does not remit after 7-10 days of treatment may suggest a primary psychiatric disorder. Induces liver microsomal enzymes, thus increasing metabolism of other meds.

Question 30

In general, what is the risk of giving Benzos for insomnia? What is the benefit of using Zolpidem, Zaleplon and Eszopiclone?

Answer 30

May cause daytime sedation and patients may develop anterograde amnesia and tolerance. They are highly effective, rapid onset and with minimal hangover effects. Zolpidem is given for sustained sleep maintenance. Eszopiclone has a longer half-life.

Question 31

What is the MOA of Ramelteon? What is the indication?

Answer 31

Agonist at MT1 and MT2 melatonin receptors. Treatment of insomnia characterized by difficulty with sleep onset.

Question 32

What is the MOA of newer sleep aids (Zolpidem, Zaleplon and Eszopiclone)? What is a benefit of using them?

Answer 32

Binds to GABAA receptors w/ a1-subunit. -increased Cl- influx, increased hyperpolarization, and decreased APs (CNS depression). There are minimal depressive effects on organ systems.

Question 33

Buspirone is used for: How long does it take to work? What is the benefit of using it? Metabolized by...

Answer 33

Treatment of generalized anxiety disorder. May take more than a week. Does not cause sedation, euphoria, hypnosis, etc. CYP3A4

Question 34

What is the MOA for Zaleplon? What is the indication? What is the warning associated with it?

Answer 34

It is a non-benzo with a unique structure that interacts with GABA-BZ complex. Short-term treatment for short-term treatment of insomnia. If insomnia does not remit after 7-10 days of treatment may suggest a primary psychiatric disorder.

Question 35

What is the indication for Zolpidem? Who is it contraindicated in? What drugs may interact with it? What are the warnings? (2)

Answer 35

Short-term treatment of insomnia characterized by trouble initiating sleep. It has been shown to decrease sleep latency for up to 35 days. Patients with known hypersensitivity to zolpidem tartate or other active ingredients. CNS depressants. If insomnia does not remit after 7-10 days of treatment may suggest a primary psychiatric disorder. Worsening depression or suicidal thinking may occur.

Question 36

What is the indication for Eszopiclone? What is the warning? What are the adverse reactions?

Answer 36

Treatment of insomnia and improve sleep maintenance. It is a CNS depressant. Unpleasant taste, HA, somnolence, respiratory infection, dizziness, dry mouth, etc.

Question 37

How does Meprobamate work? What is the indication?

Answer 37

It slows brain activity to allow for relaxation. Anxiety treatment or short-term relief of anxiety symptoms.

Question 38

What is the indication for chloral hydrate?

Answer 38

Short-term use as a sedative or sleep medicine. May be used to treat alcohol withdrawal symptoms, or to treat withdrawal from other meds.

Question 39

Which drugs are strictly used for insomnia? (9)

Answer 39

``` Triazolam Flurazepam Secobarbital Phenobarbital Zolpidem Zaleplon Eszopiclone Ramelteon Chloral hydrate ```