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
3 classifications of barbs
Ultrashort-acting (thiopental)
Short- to intermediate-acting (secobarbital)
Long-acting (phenobarbital)
Anti sz
Barb MOA
Binds to the GABA receptor–chloride channel complex
Can readily cause death with OD bc you have a llot of the potential for CNS depressany
Barb pharm effects
CNS depression
Cardiovascular effects
Hypotension
Barb tolerance and physical dependence
Tolerance
Develops to many—but not all—of the CNS effects
Very little tolerance develops to respiratory depression
Physical dependence
Aburpt withdrawal is more dangerous than withdrawal from opioids
75% will experience delirium with withdrawal
Barb pharmacokinetics
Lipid solubility has a significant impact
Rapid onset and brief duration
Barb uses
Seizure disorders –Pb
Induction of anesthesia
Insomnia
Other uses
Barb drug interactions
CNS depressants
Interactions that result from the induction of drug-metabolizing enzymes
Chloral hydrate
Meprobamate
Barb adr
Respiratory depression
Suicide
Abuse
High potential
Sche 3
Rare use in medical usage
Barb acute tox
Symptoms
Respiratory depression
Coma
Pinpoint pupils
Treatment
Maintain body heat
Support blood pressure
Removal of barbiturate from the body: Activated charcoal
Maintenance of an adequate oxygen supply to the brain
Barb admin
Oral
Intravenous
Intramuscular
Mgmt of insomnia
Sleep physiology
Sleep phases
Basic management principles
Cause-specific therapy
Nondrug therapy
Drugs used for treatment
Hypnotic drugs
Transient for most
~ 80 % of people have short term 10% have chronic
Drugs for insomnia should be short term taken 2-3 weeks then reassess
Avoid escalating doseages –can lead to tolerance
Sleep physiology
Rapid-eye-movement (REM) sleep
Non–rapid-eye-movement (NREM) sleep
Stages I and II: Relatively light sleep
Stages III and IV: Deep sleep
Basic insomnia mgmt principles
Cause-specific therapy
Treatment is highly dependent on the cause
Nondrug therapy
Turn off blue screens
Therapy with hypnotic drugs
Edu pt on sleep hygiene
Drugs used or tx of insomnia
Benzodiazepines
Benzodiazepine-like drugs: Zolpidem, zaleplon, and eszopiclone
Ramelteon –for people having difficulting falling asleep
Drugs used for insomnia: AD
Trazodone [Oleptro]
Atypical antidepressant with strong sedative actions
Can decrease sleep latency and prolong sleep duration
Does not cause tolerance or physical dependence
Doxepin
Old tricyclic antidepressant with strong sedative actions
Used to treat patients who have trouble staying asleep
Drugs used for insomnia: antihistamines
Diphenhydramine
Doxylamine
Can be purchased without a prescription
Less effective than others
Tolerance develops quickly (in 1 to 2 wk)
Adverse effects: Daytime drowsiness and anticholinergic effects
Drugs for insomnia: other
Melatonin appears to be moderately effective
REG CIRC RHYTHM
Good for jet lag and insomnia
Peak 2-4 an
Starting dose 0.3-1 mg tab taken about 1-2h before bed
Hasten sleep onset and rem sleep
Long term low dose (less than 2 mg) have no side effects
Have have SE with high doses short term: hang over, nightmares, HA
Valerian root, chamomile, passionflower, lemon balm, and lavender have very mild sedative effects; proof of benefits for insomnia is lacking
