Sedative-Hypnotics Overview

Sedative-Hypnotics

• Sedative-hypnotic agents are central nervous system depressants.
• The degree of CNS depression a drug produces depends on the dose.
• Low doses of these agents reduce anxiety, promote relaxation, and induce mild sedation. Higher doses can induce sleep or general anesthesia.
• Interactions with other CNS depressants (alcohol, antihistamines) can be dangerous.
• Sedative-hypnotic drugs generally decrease excitatory neurotransmitter (glutamate) activity and increase inhibitory signaling (GABA).
• This leads to increased synaptic inhibition and reduced neuronal firing.

Mechanism of Action for Sedative-Hypnotics

• Most sedative-hypnotic drugs decrease glutamate (excitatory neurotransmitter) nerve firing by increasing inhibitory signaling.
• Inhibitory signals from GABA neurons increase, and glutamate nerve firing decreases.

Benzodiazepines

• Commonly prescribed drugs globally.
• Routes of administration: capsule, tablet, intravenous, or intranasal.
• Mechanism of action: activation of benzodiazepine receptors increases the frequency of chloride channel opening. This enhances GABA's inhibitory effects.
• Therapeutic effects: relaxation, calmness, relief of anxiety, reduced aggression, produces muscle relaxation, & seizure-preventing effects.
• Lethality of overdose is rare.
• Antidote: Flumazenil
• Adverse effects in short-term use: drowsiness, lethargy, impaired thinking/memory, respiratory depression (especially with rapid administration).
• Adverse effects in long-term use: symptoms of chronic sedative-hypnotic intoxication (impaired thinking, poor memory, disorientation, coordination problems, slurred speech).
• Adverse effects in specific populations: pregnant women, nursing mothers (can cross placenta/enter breast milk), older adults (slower metabolism potentially leading to over-sedation).

Barbiturates

• Class of sedative-hypnotic drugs.
• Replaced by safer alternatives due to higher risk of overdose.
• Mechanism of action: increase the duration of chloride channel opening, enhancing GABA's inhibitory effects.
• Therapeutic uses: epilepsy, anesthesia, anti-anxiety, sedation/hypnosis.
• Adverse effects: short-term use (suppresses REM sleep, low doses may cause mild euphoria, dizziness), long-term use (chronic inebriation leads to impairment in memory, judgment, and thinking, mood swings, and depression).
• High lethality.

Zopiclone and Benzodiazepine-like Drugs

• Benzodiazepine-like drugs also bind to GABA receptors.
• Zopiclone and other benzodiazepine-like drugs cause sedation.
• They disturb sleep patterns less than benzodiazepines.
• They should be used cautiously in older adults.

Alcohol

• Ethanol, one of the three most used non-medicinal drugs in Canada (along with caffeine and nicotine).
• Common misuse due to availability and societal acceptance.
• Absorption is rapid, mostly from the small intestine.
• Distribution is widespread throughout the body's water compartments (including the brain, placenta, and fetus).
• Metabolism: 95% biotransformed in the liver, remaining 5% in breath, urine, and sweat.
• Rate of ethanol metabolism is relatively constant, independent of BAC.
• Effects depend on dose: low doses cause sedation, higher doses induce impairment, unconsciousness and death at extremely high doses.
• Symptoms of chronic high dose use include cognitive problems, mood swings, and depression.

Cannabis (Marijuana)

• Cannabis sativa contains psychoactive compounds, including THC.
• Legal in Canada since 2018
• THC binds to cannabinoid receptors (CB1&2).
• Short-term effects include relaxation, drowsiness, euphoria, impaired coordination, and altered perception.
• Long-term use can potentially lead to cognitive impairments, and psychological problems.

Opioids

• Derived from opium poppy. Morphine is the most useful opioid.

• Endogenous Opioids: Produced by the body (enkephalins, endorphins).

• Natural Opioids: Morphine, codeine.

• Semi-synthetic Opioids (Examples): Hydromorphone, diacetylmorphine.

• Synthetic Opioids: Fentanyl.

• Mechanism of action: Bind to opioid receptors (mu, kappa, delta) in the CNS, blocking pain signals and reducing emotional responses.

• Effects: pain relief, sedation, euphoria.

• Potential for misuse, tolerance, withdrawal, addiction.

This quiz covers the essential concepts of sedative-hypnotic agents, their mechanisms of action, and the role of benzodiazepines in treatment. Explore how these central nervous system depressants affect neurotransmitter activity and doses necessary for different therapeutic effects. Test your understanding of safety considerations and drug interactions.