Chapter 29: Sedative And Hypnoics Flashcards
Sedative-Hypnotic Drugs
Drugs that depress central nervous system (CNS) function
Primarily used to treat anxiety and insomnia
Antianxiety agents or anxiolytics
Distinction between antianxiety effects and hypnotic effects is often a matter of dosage
Been around since 1950s
Valium was first
Benzodiazepines
Benzodiazepine-like drugs
Barbiturates
Benzodiazepines and Benzodiazepine Receptor Agonists
Drugs of choice to treat insomnia and anxiety
Used to induce general anesthesia
Used to manage seizure disorders, muscle spasms, panic disorder, and withdrawal from alcohol
Most familiar member: Diazepam [Valium]
Most prescribed: Lorazepam and alprazolam
Safer than general CNS depressants
Lower potential for abuse
Produce less tolerance and physical dependence
Fewer drug interactions
Benzodiazepines: overview pharm effects
Central nervous system: Reduce anxiety and promote sleep
Cardiovascular system: Oral versus intravenous
Oral little to no effect
IV –hypotension
Respiratory system: Weak respiratory depressants
May be a problem with underlying dz like COPD
Muscle relaxation
SE: confusion, anterograde amnesia –affects hippocampus and cerebral cortex
Benzo pharmaco
Absorption and distribution -Cross BBB
Metabolism -Active metabolites –can have action of the drug long after it is gone
Time course of action
Benzo therapeutic uses
Anxiety
First choice
Insomnia
Decrease latency time to fall asleep and decrease night time wake ups
Seizure disorders
Muscle spasm
Valium
Alcohol withdrawal
Valium
Perioperative applications
Benzo ADR
CNS depression
Anterograde amnesia
Imapired recall after taking meds
Esp with halcyon
Sleep driving
Paradoxical effects
Excitation
Respiratory depression
Abuse
Sched 4
Use in pregnancy and lactation
Can cross placenta
Other adverse effects
Lighthead, difficulty c [ ], drowsiness, Incorrdinatation
Benzo drug interactions
If other CNS depressants are taken –alc, opioids, barbiturates increase resp depression
Do not accel metabolism of other drugs, do not induce any hepatic cyp drug metabolism activities
Benzo tolerance and dependence
Tolerance
With prolonged use, tolerance develops to some effects but not others
Tolerance to anti sz
No tolerance to anti anxiety and hypotonics
s/sx of withdrawal are worse with benzos that have short duration of action
Physical dependence
Can cause physical dependence, but the incidence of substantial dependence is low
Dependence greater with Xanax ER
Benzo acute tox
Oral overdose: Drowsiness, lethargy, and confusion
Intravenous toxicity: Life-threatening reactions, profound hypotension, respiratory arrest, and cardiac arrest
General treatment measures
Oral: Gastric lavage, activated charcoal, saline cathartic, and dialysis
Treatment with flumazenil
Competitive benzodiazepine receptor antagonist
Reverses the sedative effects of benzodiazepines but may not reverse respiratory depression
Approved for benzodiazepine overdose and for reversing the effects of benzodiazepines after general anesthesia
Benzo admin
Routes
Oral
Parenteral (intramuscular and intravenous)
For sleep -> short term, not routine monitoring. Don’t use for sleep apnea or sleep driving ( complex behaviors)
Benzo like drugs Zolpidem [Ambien]
Zolpidem [Ambien]
Sedative-hypnotic
Most widely used hypnotic
Short-term management of insomnia
Long term use: No apparent tolerance or increase in adverse effects
Side effects: Daytime drowsiness and dizziness
Sched 4
1-2% of pop get daytime drowsiness
Do reound insomnia when d/c
Peak 2 hr
Half life of 2.5 hr
Benzo like Zaleplon [Sonata]
New class of hypnotics, pyrazolopyrimidines
Short-term management of insomnia
Prolonged use does not appear to cause tolerance
Most common side effects: Headache, nausea, drowsiness, dizziness, myalgia, and abdominal pain
Benzo like drugs Eszopiclone [Lunesta]
The S-isomer of zopiclone
For treatment of insomnia
No limitation on how long it can be used
Most common adverse effect: Bitter aftertaste
Other common side effects: Headache (from higher dosing), somnolence, dizziness, and dry mouth
Not any safer than others
Manu did a 6 month study which is why no limitation
May have complex behaviour
Peak 1-2 hr half life 6 hr
Ramelteon: Melatonin Agonist
Brand name: Rozerem
Relatively new hypnotic
Not a controlled substance
Activation of melatonin receptors
Approved for chronic insomnia: Difficulty with sleep onset but not with sleep maintenance
Rapid onset (about 30 min)
Difficulty with sleep onset not maintenance
Superior to melatonin bc it doesn’t activate m3 receptors (reg other systems besides sleep)
Slective to mt and mt 2 receptors (selective for sleep
Barbiturates
Cause tolerance and dependence
High abuse potential
Multiple drug interactions
Powerful respiratory depressants that can be fatal with overdose
Barbiturates are used much less than they were in the past because they have been replaced by newer and safer drugs, primarily the benzodiazepines and the benzodiazepine-like drugs (such as zolpidem)
Been around for 100 y
Non selective cns depressants
No longer used for anxiety or insomnia
