Sedatives and Hypnotics

Action of sedatives

Decrease excitement and activity, produce drowsiness, facilitate onset and maintenance of sleep state

What is the mechanism of action for sedatives and hypnotics

Inhibit neural excitation → Enhance GABA Cl channel, inhibit excitatory AMPA/kinate receptor, inhibit glutamate release, NDMAr antagonist

How do sedatives (benzodiazepine) act on the GABA system

Bind to GABA alpha subunit → Causes hyperpolarization by keeping Cl- channel open → Higher inhibition

What are the ADME of benzodiazepines

Absorbed completely and metabolized by CYP3A4, CYP2C19

What is the effect of benzodiazepines on sleep

Decrease sleep latency and awakening, REM is shortened, increase number of cycles in REM

What is the effect of high dose benzodiazepines on lung

Decrease hypoxic, hypercapnic drive, decrease muscle tone, promote sleep apnea in REM sleep

What is the effect of propofol and barbiturates on CVS

Decrease ABP

What is the effect of ketamine on CVS

Preserve cardiac function

What are benzodiazepines used for

Antianxiety, anticonvulsants, preanesthesia, insomnia, alcohol withdrawal syndrome → Diazepam, midazolams

What are the adverse effects of benzodiazepines

CNS toxicity increase with age, residual daytime sleepiness, IMPAIR DRIVING and psychomotor skill when combined with alcohol

What benzodiazepines can be used for insomnia, antianxiety, and anticonvulsant

Clonazepam, lorazepam, diazepam, midazolam

What benzodiazepines can be used for agoraphobic, insomnia, anxiety

Alprazolam

What is flumazenil

Benzodiazepines receptor ANTAGONIST; IV only → competitively bind to GABAa

How do differing doses of barbiturates change its effect

Small dose: increase reaction to pain

Anesthetic dose (thiopental): decrease pain perception

What is the effect of chronic administration of barbiturates

Increase tolerance: Euphoric, sedative, hypnotic effects → Therapeutic index decrease

Effect of barbiturates on CVS

Decrease blood pressure, decrease RBF, decrease CBF; can depress contractility in high doses

What are the uses of phenobarbital and thiopentone

Phenobarbital: First line anticonvulsant

Thiopentone: Anesthesia, emergency seizure and intracranial pressure drug

Untoward effect of barbiturates

Paradoxical excitement, hypersensitivity

Signs of toxicity from barbiturates

Severe respiratory depression, cardiac contractility decrease, coma

What happens when phenobarbital, pentobarbital interact with CYP3A4 inducer

Accelerate metabolism of drug → Less effect

What is propofol (mechanism of action, adverse effect)

Enhance GABA cl channel opening; rapid onset/offset; adverse effects: dose dependent decrease ABP, respiratory depression, pain on injection

What is ketamine (mechanism of action, adverse effect)

NDMAr antagonist, analgesic effect; adverse effect: dissociative hypnosis, adverse psychological effect, minimal effect on respiration, preserve CVS

What is dexmedetomidine (mechanism of action, adverse effect)

Alpha 2 adrenergic agonist at LC; sedation, analgesia, hypnosis effects