Sedative Hypnotic Drugs

Sedative-Hypnotic Drugs depress CNS function in a...

Non-selective manner that are primarily used t treat anxiety + insomnia

At lower hypnotic drug doses, the drugs tend to produce…

Calmness (reduced anxiety) or drowsiness (sedation) and initiate normal state of sleep (hypnosis)

At higher hypnotic drug doses, the drugs tend to produce

State of general anesthesia, coma, fatal respiratory depression and death

Sedative-Hypnotic Drugs Chain

Alertness → Sedation → Hypnosis → General Anesthesia → Coma → Death

Sedative-Hypnotic Drug Examples

Benzodiazepines + BZD-Like Drugs + Barbiturates

BZD Drug Example

Diazepam + Lorazepam + Midazolam (Date-Rape Drugs)

BZD-Like Drug Examples

Zolpidem + Eszopiclone (in combination with alcohol, CNS depressant effects are potentiated)

Melatonin Agonist Drug Example

Ramelteon

Partial Serotonin Agonist Drug Example

Buspirone

BZD + BZX-Like Drugs

Treats insomnia + anxiety, induces anesthesia, manages seizure disorders + muscle spasms + panic disorder + alcohol withdrawal

Most Familiar Member of BZD + BZD-Like Drugs

Diazepam

Most Prescribed BZD + BZD-Like Drugs

Lorazepam + Alprazolam

Compared to Barbiturates, BZDs are…

Safer, potential abuse is lower, produce less tolerance, fewer drug interactions, suicide potential lower, intensity of respiratory depression is lower

BZD MOA

Bind to GABA receptors in this protein complex l/t potentiation of inhibitory effects of GABA

BZD have a more specific

Anxiolytic effect than other sedatives such as barbituates

BZD CNS Pharmacological Actions

Reduce anxiety, promote sleep (sedation), produce hypnosis, skeletal muscle relaxation, anticonvulsants

BZD CVS Pharmacological Actions

Profound hypotension + cardiac arrest (intravenously)

BZD Respiratory Pharmacological Actions

May worsen hypoventilation + hypoxemia in COPD patients

Long–Acting BZDs

Diazepam (lasts 1-3 days)

Intermediate-Acting BZDs

Alprazolam + Lorazepam (lasts 10-20 hours)

Short-Acting BZDs

Lasts 3-8 hours

BZDs Therapeutic Uses

Anxiety, insomnia, seizure disorder, muscle spasms, alcohol withdrawal, perioperative applications

Anterograde Amnesia

Loss of ability to create new memories after the event that caused amnesia, l/t partial or complete inability to recall the recent past

BZD CNS Adverse Effects

Anterograde amnesia, sleep driving, sleep eating (avoid concurrent use of other CNS depressants like alcohol), muscle weakness

BZD Abuse Potential

Less severe compared to barbiturates, dependence can occur with chronic administration as well as tolerance

BZD Respiratory Adverse Effects

Severe respiratory depression may occur on IV-injection

BZD + Pregnancy

Linked to teratogenicity

Acute Toxicity of BZDs

Profound hypotensive, respiratory arrest, cardiac arrest upon IV administration

BZD Toxicity Treatment

Flumazenil (reverses the sedative effects but may not reverse respiratory depression)

Sedative chloral hydrate lethally occurs when combined with…

Clonazepam + Lorazepam + Oxazepam

Zolpidem

Binds to BZD-receptors to facilitate GABA-mediated inhibition (minimal muscle relaxant effects, minimal anticonvulsant effects, less risk of developing tolerance + dependence), should avoid alcohol

Zolpidem Side Effects

Amnesia, sleep-walking, binge eating, depression + suicide ideation

Zalepon

Potentiates GABA-receptor activity, prolonged use doesn’t appear to cause tolerance, but physical dependence is minimal

Eszopiclone

Potentiates GABA receptor activity, has a bitter aftertaste 

Ramelteon

Not controlled substance, activates melatonin receptors, approved for chronic insomnia, should be avoided in severe hepatic impairment

Buspirone

Stimulates 5-HT receptors (lacks muscle relaxant, amnestic, anticonvulsant, hypnotic effects), treatment of generalized anxiety disorder (GAD) 

Buspirone Side Effects

Nausea, dizziness, headache, insomnia, suicide ideation

Advantages of Buspirone over BZDs

Doesn’t interact with alcohol

Disadvantages of Buspirone

Slow onset of 2-4 weeks, should be taken as prescribed (no PRN use)

Barbiturates

Originate from barbituric acid, small therapeutic index, potential for addiction + drug abuse, powerful respiratory depression

Barbiturate Drug Example

Thiopental aka “Truth Serum”

Barbiturates MOA

Binds to GABA receptor-chloride channel complex

CNS Depression of Barbiturates

Produces dose-dependent degrees of depression -> low doses cause sedating effect, moderate doses cause sleep then anaesthesia, higher doses cause coma + death

What should you avoid when taking barbiturates?

Avoid concurrent use of other CNS depressants such as alcohol

Respiratory Effects on Barbiturates

Depression of both respiratory drive + mechanisms responsible for rhythmic character

Thiopental (Truth Serum) Pharmacokinetics

Ultra-short acting (20 minutes) duration of action

Therapeutic Uses of Thiopental

Induction of anesthesia

Barbiturates Adverse Effects

Addiction, drug hangover (drowsiness, decreased motor function, anterograde amnesia), N/V, bradycardia, respiratory depression

Acute Toxicity on Barbiturates

Respiratory depression, coma, pinpoint pupils (unlike BZDs, there is no specific antidote)

Drugs Used for Treatment of Insomnia

BZDs, BZD-like drugs, melatonin agonists, partial serotonin receptor agonists

What antidepressants are used for the treatment of insomnia?

Trazodone + Doxepin (both have strong sedative actions)