Sedatives / Hypnotics

Question 1

General characteristics of sedatives

Answer 1

Anxiolytics
Reduce anxiety, exert calming effect. Minimal effects on motor / cognitive functions.
Anticonvulsant effects.

Question 2

General characteristics of hypnotics

Answer 2

Produce drowsiness and promote onset / maintenance of sleep

Anticonvulsant effects

Question 3

What are the 2 main classes of sedatives / hypnotics?

Answer 3

Benzos and barbiturates

Question 4

Benzos
General mechanism
Effects
Length of use
Adverse rxns

Answer 4

• Positive modulators at GABAa receptors. Increase affinity of GABAa receptor for GABA and increase freq of GABA-induced Cl channel opening, but do NOT directly activate receptor.
• Able to produce sedating, hypnotic, anxiolytic, amnesiac, spasmolytic, and antiseizure effects, but unable to produce anesthesia / coma.
• May slightly lower BP.
• Do NOT depress respiration or induce CYP enzymes.
• Only indicated for short-term use (2-4 weeks)
• Adverse effects –
• CNS: drowsiness, ataxia, slurred speech
• Doseage should be tapered to avoid insomnia, anxiety, and seizures (withdrawal syndrome)
• May cause paradoxical excitement in kids and elderly
• Avoid during pregnancy. Category D / X.

Question 5

General mechanism of barbiturates

Answer 5

• Increase duration of GABA channel opening and directly activate receptor at high concentrations.
• Able to produce anesthesia / coma at high doses.
• Can depress respiration and induce CYP enzymes.

Question 6

Diazepam
Brand name
Type of drug
Use
2 metabolites
Why does diazepam have a longer duration of action than oxazepam?
Adverse rxns
Precautions

Answer 6

• Valium
• Benzo
• Use – short term management of anxiety disorders and acute alcohol withdrawal. Also acts as muscle relaxant for seizure disorders, cerebral palsy, stroke, and MS
• Mechansim – increases affinity of GABAa receptor for GABA and increases freq of GABA-induced Cl channel opening.
• 2 metabolites, desmethyldiazepam and oxazepam, are active. Diazepam has a longer duration of action than oxazepam b/c it is further upstream in terms of metabolism.
• Adverse rxns – see above
• Precautions – avoid during pregnancy and breastfeeding

Question 7

Lorazepam
Brand name
Type of drug
Main diff from diazepam
Use
Mechanism
Adverse rxns

Answer 7

• Ativan
• Benzo
• Main diff from diazepam – No active metabolites. Doesn’t produce a hangover / drowsiness. More potent.
• Use – anxiety disorder, preop sedation, anterograde amnesia, sedation for critical care. DOC for status epilepticus
• Mechanism – Increases affinity of GABAa receptor for GABA and increases freq of GABA-induced Cl channel opening.
• Adverse rxns – see above

Question 8

Flumazenil
Type of drug
Use
Mechanism
Pharmacokinetics
Precaution

Answer 8

• Short acting benzo
• Use – treats benzo overdose or reverses benzo sedation during anesthesia. Also antagonizes zolpidem and eszopiclone. No effect on barbiturates.
• Mechanism – competes w/ benzo for binding to GABAa receptor
• Short half life. May need repeated doses.
• Precaution – may precipitate benzo withdrawal syndrome (anxiety, insomnia, seizures)

Question 9

Buspirone
Type of drug
Effects
Good for which population?
Use
Mechanism
Pharmacokinetics
Time of onset
Precautions

Answer 9

• Non-benzo anxiolytic that produces no hypnosis, anticonvulstant effects, or psychomotor impairment. Reduce anxiety w/o effecting GABA. Good in pregnant women or other people who can’t tolerate benzos.
• Use – treats GAD
• Mechanism – Partial agonist at 5HT1a receptors. Moderate affinity and partial agonist at D2 receptors.
• Low bioavailability.
• Significant latency, taking 2-6 weeks to work. Not good for acute anxiety.
• Precautions
• Taper off benzos as buspirone is initiated.
• Renal insufficiency
• Hepatic disease

Question 10

Transient insomnia
Length
Cause
Tx

Answer 10

Lasts less than 3 days.
Caused by brief environmental / situational stressor.
May respond to sleep hygiene rules

Question 11

Short-term insomnia
Length
Cause
Tx

Answer 11

3 days to 3 weeks.
Caused by stressors.
Tx w/ intermittent use of hypnotics for 7-10 days

Question 12

Long-term insomnia

Cause

Answer 12

Lasts more than 3 weeks.
Caused by major psychiatric illness (mania), sleep apnea, or chronic medical illnesses (CHF). May also be due to “learned” insomnia.

Question 13

Zolpidem
Brand name
Type of drug
Use
Mechanism
Adverse rxns

Answer 13

• Ambien
• Non-benzo sedative / hypnotic
• Use – short term tx of insomnia (7-10 days)
• Mechanism – Modulates GABAa receptor complex
• Adverse rxns: overall well-tolerated (no hangover effect). Rebound insomnia. Sleep walking.

Question 14

Eszopicolone
Brand name
Type of drug
Comparison to zolpidem
Use
Mechanism
Adverse rxns

Answer 14

• Lunesta
• Non-benzo sedative / hypnotic.
• More potent than zolpidem.
• Use – 1st drug approved for long-term treatment of insomnia (>6 months)
• Mechanism – modulates GABAa receptor complex
• Adverse rxns – well tolerated overall (no hangover). Rebound insomnia, anxiety, unpleasant taste, xerostomia.

Question 15

Aprazolam
Brand name
Type of drug

Answer 15

Xanax

Potent benzo

Question 16

Clonazepam
Type of drug
Use

Answer 16

Long-acting benzo
Used for seizures and panic disorder.
Tolerance may develop to anti-seizure effects.

Question 17

Midazolam

Use

Answer 17

Preanesthetic / intraoperative med, conscious sedation, amnesia for minor surgical / diagnostic procedures

Question 18

Oxazepam

Use

Answer 18

Used for acute anxiety, anxiety associated w/ depression, tension, agitation, and irritability in older pxs

Question 19

Other indications for sedatives / hypnotics

Answer 19

Adjunct to anesthesia, seizures, muscle relaxation, alcohol withdrawal.