Sedative Hypnotics Flashcards
Which type of drug has more pronounced depression of the CNS? Sedative or hypnotic?
Hypnotic - can be achieved by increasing dose of sedative as well
Name the 5 major classes of drugs used as hypnotics
Benzodiazepines Barbiturates NBBRAs - nonbenzo benzo receptor agonists 5-HT1A partial agonists MT (melatonin) receptor agonists
Which type of sedative hypnotic drug shows a nonlinear dose-response curve? Why is this important?
Benzos
Increasing dose eventually tapers off the sedation effects so they are safer drugs. Older drugs showing linear curve could produce anesthesia or even coma and death with increasing dose
MOA of benzos
Bind GABAa receptors at BZ1 or BZ2 which functions as a chloride channel and increase its activity by causing more frequent channel openings. They reduce the EC50 of the GABA induced Cl- influx
Agonists at the benzo receptors produce what two important clinical effects?
Anxiolytic (anti-anxiety) and anticonvulsant
-azolam or -azepam is the common ending for what class of drugs?
Benzos
What is the method of delivery for benzos? How do they distribute?
Oral - highly lipophilic and distribute throughout body
Name the 2 short acting benzos
Oxazepam and triazolam
Name the three intermediate acting benzos
Alprazolam
Lorazepam
Temazepam
Name the two long acting benzos
Diazepam
Flurazepam
What enzyme catalyzes phase I reactions of benzos? After this, how are they excreted?
CYP3A4
Conjugated and excreted in urine
Name three benzos that are NOT metabolized by the P450 system
Oxazepam
Lorazepam
Temazepam
Skip phase I reactions and are conjugated directly
Which benzo is metabolized in liver to active metabolites that can vary in half lives between 30 and 100 hours?
Flurazepam
What is the role of benzos in treating anxiety?
They are only given short term, 4-6 weeks, while waiting for the SSRI to take effect
Which benzo is useful in treating muscle spasms and can be used in MS and cerebral palsy?
Diazepam
Which benzo is used to treat epileptic seizures?
Clonazepam
Name the two benzos used to treat status epilepticus
Diazepam and lorazepam
State where brain is constantly having a seizure
Which two benzos can be used in managing alcohol withdrawal?
Diazepam and oxazepam
Name a benzo for each category used in sleep disorders: long, intermediate, and short acting
Long: Flurazepam
Intermed: Temazepam
Short: triazolam
Patient taking a sleep aid presets with anxiety, irritability, rage, and hostility. What type of drug was she most likely taking?
Benzo - can cause paradoxical effects
Barbiturates also do this
Name the only two class of drugs where abrupt withdrawal can kill you
Benzos and barbiturates
What does flumazenil do? Two adverse effects?
It is the only benzo receptor antagonist - used in benzo overdose
Can cause withdrawal in the physiologically dependent
Can lead to seizures if the benzo was being used to treat them
-barbital is the common ending for what type of drug? What is the only one of its class without this ending?
Barbiturate
Thiopental
MOA of barbiturates?
Like benzos, act at GABAa receptors (but bind at a different site)
But they also bind less specifically than benzos so they also block glutamate receptors and sodium channels
Explain how barbiturates can lead to death by respiratory failure
They suppress the hypoxic and chemoreceptor response to CO2. So impulse to breathe is blocked
What actions do barbiturates have on CYP enzymes?
They are CYP inducers
Which barbiturate is still used IV to induce anesthesia?
Ultra short acting thiopental
Which barbiturate has anticonvulsant properties and is still used to treat tonic-clonic seizures, status epilepticus, and eclampsia?
Phenobarbital
Which sedative drug can be used to treat hyperbillirubinemia and kernicterus in the neonate?
Phenobarbital
Which sedative class of drug is contraindicated in patients with porphyria?
Barbiturates - increase porphyrin synthesis
Which sedative class of drug can cause hangover effects?
Barbiturates
Which sedative class of drug can cause hyperalgesia?
Barbiturates
Which class of sedative drug, if given rapidly by IV can lead to cardiovascular collapse?
Barbiturates
Which class of sedative drugs ONLY acts at the BZ1 subtype receptor? What receptor? What effect is not seen due to the lack of BZ2 binding?
NBBRAs - non-benzo benzo receptor agonists
GABAa receptor
BZ2 is responsible for minimizing muscle convulsants, so the NBBRAs aren’t used as muscle relaxants
What two sedative drugs are prescribed for patients having trouble with sleep initiation but not maintenance? Which has the shorter duration of action?
Zolpidem - NBBRA (1.5-3.5)
Zaleplon - NBBRA - shorter half life (1hr)
Name the three NBBRAs
Zolpiden
Zaleplon
Eszopiclone
“z” drugs
Which sedative drug is approved for improving sleep maintenance?
Eszopiclone - NBBRA (6 hour half life)
Which class of sedative drug is ONLY an anxiolytic and has no hypnotic, anticonvulsant, or muscle relaxant properties? Name the drug
5-HT1A partial agonists
Buspirone
Which sedative drug has no interactions with alcohol, no interactions with other sedatives, and has no withdrawal on abrupt discontinuation?
5-HT1A partial agonists
Buspirone
What drug acts at MT1 and MT2 receptors to treat insomnia with difficulty of sleep onset? What receptor are these?
Ramelteon - melatonin receptor agonist
What antihistamine with antiemetic properties is also approved for relief of anxiety?
Hydroxyzine
What drug is commonly used to treat performance anxiety?
Propranolol
Used for Mild Situational Insomnia
Diphenhydramine
Doxylamine
