sedatives/hypnotics/anxiolytics Flashcards
sedative def.
calms anxiety, decreases excitement and activity, does not produce drowsiness or impair performance
hypnotic
induces sleep, implies restful, refreshing sleep, not “hypnotized”, natural sleep
anxiolytic
antianxiety, relieves anxiety without sleep or sedation (not all are sedative)
narcotic
actually means “sleep producing”, refers to opiods or illegal drugs
the reticular formation
contains dopamine, adrenergic, serotonergic and cholinergic neurons; regulates the sleep-wake cycle
factors that regulate sleep
age, sleep history, drug ingestion, circadian rhythms
benzodiazepine chemistry
annealating the 1-2 bond with an electron rich ring (triazole or imidazole) yields high affinity and decreased t1/2
no ring = antagonist
long acting benzos
accumulation, active metabolites
short acting benzos
midazolam, anasthetic
bezodiazepine antagonist
flumazenil
no phenyl ring
used to treat benzo overdose
SE: induce convulsions and panic attacks in those that are benzo dependent
Z-hypnotics
zolpidem, zaleplon, eszopiclone (long term use) 3A4 to some extent oversode treatment (flumazenil) SE: daytime drowsniness, dizziness, ataxia, NV, doing activities in sleep
illicit use of sedative-hypnotics
benzos:
flunitrazepam (“roofies”), clonazepam
nonbenzos: zolpidem
barbituates compared to benzos
“worse at everything”
benzo and barbituate binding
benzos are only allosteric
barbituates are allosteric and orthosteric
GHB
not common, used to next day wakefulness
melatonin agonists
ramelteon, tasimelteon
preferred over melatonin because FDA approved
buspirone
anxiety tx
longer onset of action ~ weeks (dont use for an acute situation)
used for: GAD, social anxiety, comorbid depression, adjunct in OCD, PTSD; not good for panic disorders
propranolol
uses: social anxiety, PTSD
tolerance and withdrawl from benzos
normal: Cl- moves through
add benzo acutely: more Cl- moves through: hyperpolarized
chronic: downregulation of receptors, return to baseline
withdrawl: not enough Cl- is coming in, neurons being firing
DSM 5 for generalized anxiety
Excessive worry around a number of life events that is difficult to control, present for at least 6 months
generalized anxiety disorder treatment
SSRI (first line) x 2-4 weeks for initial onset of symptom relief, take 6-8 weeks to see full impact (paroxetine and escitalopram are FDA approved; any can be used - lower doses and slower titrations that depression)
SNRIs can be helpful: duloxetine and venlafaxine are FDA approved (useful for concomitant pain syndrome)
Benzodiazepines are used for bridge therapy until other meds kick in; if used longer than 30-60 days, must be tapered to avoid withdrawal (seizures)
Buspirone: dosed high enough (15 TID) and patient is aware of how long it takes to work
social anxiety disorder epidemiology
Persistent fear about social and/or performance situations in which the patient fears embarrassment or humiliation that is unreasonable; duration at least 6 months
Social Anxiety Disorder Treatment
SSRI are first line: paroxetine and sertraline are FDA-approved (any can be used)
SNRI: may be useful for failure of SSRI: Venlafaxine is FDA-approved (any can be used)
Beta-blockers: may be useful for non-generalized, performance-related SAD
Panic Disorder etiology
Recurrent, unexpected panic attacks
Panic Attack: abrupt surge of intense fear or discomfort that reaches a peak in minutes and is accompanied by at least 4 physical and psychological symptoms
May lead to agoraphobia: isolating themselves in a safe place
panic disorder treatments
SSRIs are first-line maintenance therapy: most are FDA approved
SNRIs: Venlafaxine approved, Duloxetine has good clinical data
TCAs, mirtazapine, MAO-inhibitors: show efficacy similar to SSRIs but have worse side effects
Benzodiazepines should NOT be considered for maintenance therapy unless after several treatment failures (clonazepam and alprazolam FDA approved)
OCD
Obsessions: recurrent thoughts or images that are intrusive and cause anxiety
Compulsions: repetitive behavior or mental acts performed in response to obsession
Must cause marked distress and take more than 1 hours per day or interfere significantly with functioning
OCD treatment
SSRIs are first-line treatment for OCD; most are FDA approved
Failure of a few trials of SSRIs, can try clomipramine (TCA)
Venlafaxine XR has been studied with effectiveness
Antipsychotics can be considered for augmentation therapy with antidepressants
PTSD
Exposure to real or threatened death, serious injury, or sexual violence leading to distressing memories, avoidance of associated stimuli, negative alterations in mood, or marked alterations in reactivity or arousal
PTSD treatment
SSRIs/SNRIs are first-line treatment - With multiple failed trials, can consider mirtazapine
Prazosin may be helpful for sleep or nightmares (10mg/day)
Benzodiazepines are NOT recommended for PTSD
Substance abuse disorders should be treated simultaneously
PTSD prevention
Beta-blockers and opioids have been studied in civilian and combat trauma surviviors (give everyone in an IED attack morphine)
Varying degrees of success
Selected Drug Therapy Issues in Anxiety Disorders
Jitteriness: results from the use SSRIs and SNRIs - Lower doses than depression doses and slower dose titration
Onset of action for SSRIs/SNRIs is 2-4 weeks with maximal response at 6-8 weeks and withdrawl symptoms (flu like symptoms)
Abrupt discontinuation of benzodiazepines can be life-threatening
nonpharm anxiety counseling
Psychotherapy and cognitive behavioral therapy are mainstays of treatment
Drug therapy often helps the effectiveness of these modalities
insomnia
Difficulty with sleep initiation, sleep maintenance, and/or early-morning awakening
Takes place at least 3 weeks per night and present for at least 3 months
insomnia treatment
First line is non-pharmacological! - Behavior therapy: stimulus control, sleep restriction, relaxation, Sleep hygiene principles are necessary
The Z-hypnotics: Zolpidem has several dosage forms, including a sublingual form (Intermezzo), Eszopiclone: FDA-approved for long-term use (6 months)
Benzodiazepines: temazepam is most common, Longer-acting agents (diazepam, chlordiazepoxide) cause significant daytime hangover, Any benzodiazepine can be used for insomnia, Must consider taper to discontinue to avoid life-threatening withdrawal
Melatonin agonists are useful for sleep latency (staying asleep)
Doxepin: lower, branded dose of doxepin = same side effects, suicidality warning, and sleep behavior warning
All medications FDA-approved for sleep have sleep behavior warning
Suvorexant (Belsomra)
Selective dual orexin receptor antagonist = blocking the wake promoting neuropeptides orexin to suppress “wake drive”
Daytime somnolence risk: 10mg dose carries risk for impaired driving; patients taking 20mg should be warned against daytime driving
Should NOT be used in patients with narcolepsy (absolutely CI, patients already don’t have enough orexin)
3A4 inhibitor
sleep apnea
Breathing related sleep disorders are divided into obstructive sleep apnea, central sleep apnea, and sleep-related hypoventilation
Patients must have evidence of at least 5 obstructive apneas per hour of sleep confirmed by polysomnography
sleep apnea treatment
Weight loss
Initially CPAP: continuous positive airway pressure
Excessive daytime sleepiness: modafinil or armodafinil
Surgery is an option
Ensure that obstructive apnea is addressed before recommending sedative/hypnotic drug therapy
narcolepsy
Cataplexy: emotional response (tearfulness, laughter), losing muscle tone - Sodium oxybate (Xyrem) = Gamma-hydroxy butyrate: Dosed twice nightly, must set alarm to take 2nd dose, Black Box Warning: respiratory depression and misuse risk
Excessive daytime sleepiness: Methylphenidate, dextroamphetamine, mixed amphetamine salts, Modafinil/ amodafinil, Sodium oxybate, Selegiline
Shift Work Sleep Disorder
Problem for those working night shifts or those with changing shifts throughout the week
Sleep hygiene may be helpful: black-out curtains, noise markers
Drug Therapy: focuses on improving wakefulness during wake time
Modafinil and armodafinil are drugs of choice
Restless Leg Syndrome
Urge to move the legs in response to an uncomfortable or unpleasant sensation that begins/worsens during periods of rest, partially or completely relieved by movement, worse in the evening/night
Dopamine agonists are first line: pramipexole and ropinirole
Levodopa/carbidopa can be considered
Gabapentin encarbil: unclear benefit/risk
Others: opioids not recommended, iron supplementation has little evidence, and clonazepam may be considered
GAD treatment overview
SSRI
SNRI
buspirone/benzos
SAD treatment overview
SSRI
SNRI
BB
phenelzine
panic disorder treatment overview
SSRI
SNRI
TCAs, MAOIs, Mirtazapine
OCD treatment overview
SSRI
clomipramine
venlafaxine XR
augment: antipsychotics
PTSD treatment overview
SSRI/SNRI
mirtazapine
nightmares: prazosin
sleep apnea treatment overview
weight loss/CPAP
modafinil/armodafinil (daytime sleepiness
insomnia treatment overview
nonpharm Z-hypnotics benzos melatonin agonists doxepin
narcolepsy treatment ovreview
cataplexy: Xyrem
daytime sleepiness: stimulants, modafinil/armodafinil, Xyrem
