anxiety/insomnia drugs Flashcards
Generalized Anxiety Disorder:
6 months or more of excessive worry or anxiety, generally with an unidentified cause.
panic disorder
periods of sudden, intense fear or terror and feelings of impending doom.
social anxiety disorder
persistent fear and anxiety in social or performance situations that are recognized as excessive or unreasonable. These situations are either avoided or endured with intense anxiety.
agoraphobia
intense fear in at least 2 settings (public transportation, open spaces, closed spaces, standing in line, being in a crowd, being outside the home alone)
PTSD
follows a traumatic event, characterized by increased arousal and avoidance of stimuli that approximate the original traumatic event
OCD
Obsessive or intrusive thoughts that cannot be controlled and are repetitive. (e.g., washing hands, combing hair, cleaning house)
3 groups of Pharmacotherapeutic Options for Anxiety & Related Disorders
- benzodiazepines
- non-benzos: anti-depressants, buspirone
- MISC: BBs, MAOIs, antihistamines, barbituates, antipyschotics
sedative vs hypnotic drugs
sedative: anxiolytic (calming) effect but ideally don’t produce sleep (no CNS depression)
hypnotic: low doses = encourage drowsiness- onset and maintenance of sleep. CNS depression
Most sedatives will first cause _____
Then, at higher doses, produce ______
sedation
hypnosis
what are the benzodiazepine drugs?
all end in “pam” or “lam”
include xanax, versed, valium, klonopin, etc.
benzos are schedule __ substances
schedule IV- hold potential for addiction and OD (MUST give naloxone when prescribing this)
5 properties shared by benzos (to varying degrees)
Anxiolytic Hypnotic Muscle relaxation Anticonvulsant Amnesic actions ( agent: versed)
what does binding of GABA to GABAa receptor cause?
increase CL- through the channel = hyperpolarization =makes it harder to cell to depolarize = reduces neuronal excitability (calming effect)
(inhibitory in action)
what is the MOA of benzos ?
increase Cl- flow through channel by binding alpha and gamma GABA subunits = reduce neuronal excitability
what is the distribution of benzo drugs?
large distribution b/c they are lipophilic
effect of individual benzo agents depends on what 4 factors?
- receptor affinity
- lipid solubility
- metabolism
- half-life
what is the significance of receptor affinity for benzo agents?
high potency = higher GABAa affinity = more intense withdrawal symptoms
(alprazolam, lorazepam)
what is the significance of lipid solubility for benzo agents?
higher lipophilic = more rapid onset and may wear off quicker
(midazolam)
lower lipophilic = more sustained effect
(clonazepam)
what is the significance of metabolism for benzo agents? what are the three types ?
- oxidative metabolism (majority)
- have active metabolites that extend DOA
- glucoronidation (LOT: lorazepam, oxazepam, temazepam)
why are the LOT agents safer benzos for elderly to use?
they undergo glucoronidation (not converted to active metabolites- excreted unchanged in urine) = less likely to accumulate to toxic levels
what is the significance of half life for benzo agents?
Extended in hepatic and renal dysfunction and the elderly
two agents with low potency and short half life (<12 hrs) ?
xanax (alprazolam) and versed (midazolam)
two agents with intermediate halfe like and potency?
klonapin (clonazepam) and ativan (lorazepam)
what agent has long half life (>40hrs ) and high potency?
valium (diazepam )
short half life/ low potency vs long half life/high potency (kinda weeds)
Short half-life/high potency (for acute management)
- Rapid acting agents for quick relief of symptoms
- Tolerance develops quickly
- Withdrawal problems common
- Interdose breakthrough symptoms occur
Long half-life/low potency: “hangover” effect in morning
Accumulate in older adults
what are the short acting benzos? (4)
Short Acting: “ATOM” Alprazolam Triazolam Oxazepam Midazolam
what are the intermediate acting benzos (3) ?
Intermediate Acting: “TLC”
Temazepam
Lorazepam
Clonazepam
what are the long acting benzos (4)?
Long Acting: “CDeF” Clorazepate Chlordiazepoxide Diazepam Flurazepam
with increased doses, benzos can cause what ADRs?
- drowsy/lethargy
- Impaired motor coordination, dizziness, vertigo, slurred speech, blurry vision, mood swings, euphoria, hostile or erratic behavior
- respiratory depression
Benzos with longer 1/2 life have what major concern?
accumulation =delayed symptoms of over-medication.
respiratory depression from Benzos are ____-dependent, exacerbated when administered with ____, _____ or _____?
Dose dependent, exacerbated when administered with opioids, alcohol or given to patients with COPD
how can you avoid residual daytime sedation with benzos? how to avoid rebound insomnia?
daytime sedation- use lowest effective dose
rebound insomnia- when discontinuing, taper
what is anterograde amnesia? what can cause it?
benzos: impaired memory and recall
3 cautions for using benzos in elderly
Memory problems
Increase the risk of falls
Drug accumulation (particularly those with long ½ lives)
what drugs have tolerance and dependence cautions?
benzos
abuse potential of benzos is low in patients using it for what? why?
Abuse potential is low in patients with true generalized anxiety disorder
Patients usually do not escalate dose because tolerance to the anxiolytic action is not prominent
what is the OD antidote for Benzos?
Flumazenil : Competitively inhibits the activity at the benzodiazepine receptor site on the GABAA receptor complex.
onset and DOA of flumazenil
Onset: 1-2 minutes, DOA: 60 minutes ( may have to repeat dose. shorter 1/2 like than benzo (benzo can outlast the antidote)
what drug class is effective for several anxiety disorders & agents of choice for long-term treatment of anxiety?
SSRIs
what drug class have preventive efficacy for panic disorder and anxiolytic activity?
TCAs
what must you look out for when starting someone on an anti-depressant? (SSRI, TCA, effexor, cymbalta)?
may initially cause worsening anxiety - full benefit takes weeks (just like when txting depression)
anti-depressants for anxiety use:
_______ approved for the treatment of generalized anxiety and social anxiety disorder
______approved for generalized anxiety disorder
effexor
cymbalta
MOA of buspirone
MOA: 5-HT1A (serotonin) & dopamine receptors agonist
Upon activation, 5-HT1A receptors inhibit firing of 5-HT neurons
what is the main drawback of buspirone (buspar)?
long onset of axn (3-4weeks): don’t use for acute anxiety!
what can you as “bridge-therapy” when putting someone on buspirone (buspar) ?
short-term benzos
how can beta-blockers be used for anxiety?
-block the peripheral symptoms of panic disorder or performance anxiety (e.g., propranolol for public speaking)
how can MAOIs be used for anxiety?
- panic disorder when the patient also has atypical depression.
- *not commonly used because of serious ADRs
how can anti-histamines be used for anxiety? what are the two agents?
Those with sedating properties can reduce anxiety and often tried in patients with substance abuse issues
Hydroxyzine (Atarax & Vistaril)
Diphenhydramine (Benadryl)
what is a narrow-therapeutic drug with no ceiling that is RARELY used for anxiety?
barbituates
generalized anxiety disorder: what are your 3 drug txt options ?
- 1st line: antidepressants: SSRIs, SNRIs
- acute episode or bridge therapy: benzos
- when you can’t use benzos: buspirone
* USE ALL THREE with cognitive behavior therapy
panic disorder: what are your 2 drug txt options
- 1st line: anti-depressants: SSRI
- high-potency Benzos (alprazolam, lorazepam)
* BOTH with cognitive behavior therapy
OCD: drug txt options
SSRIs and clomipramine (Anafranil)
*BOTH in high doses with cognitive behavioral therapy
PTSD: drug txt options
1st line: SSRI
- then txt specific symptoms:
txting specific symptoms of PTSD: explosive behavior, nightmares, aggression/anger/depression, pyschotic
explosive: BBs
nightmares: prazosin
aggression/anger/depression: valproic acid, carbamazepine, lamotrigine, topiramate
Psychotic symptoms – olanzapine, quetiapine, risperidone
txting social anxiety disorder: 2 drugs, how long do you wait for full effect?
SSRI &SNRI
- takes 12 weeks for response
how do you treat specific phobias?
Not treated with medications
- Systematic desensitization and other behavioral approaches often effective
serotonin is converted into _______ in the _________ ______during sleep
melatonin in pineal gland
The _______ ________ _______ maintains wakefulness, and when activity declines, sleep occurs.
reticular activating system
what are the 5 NTs involved in sleep? which for dreaming? which for non-dreaming sleep?
NE, 5-HT, acetylcholine, histamine, and neuropeptides
NE is involved in dreaming, and 5-HT is active during non-dreaming sleep
do you want to impact the sleep cycle with meds?
NO!- just want to induce or keep them asleep
what are the stages in the sleep cycle?
Wakefulness Non-REM sleep Stage 1 Stage 2 Stages 3 & 4 (delta sleep) REM sleep
what are the 3 types of insomnia?
Transient
Short term
Chronic
transient insomnia : define and txt
most associated with acute stressors, resolves when stressors removed.
Pharmacotherapy may be used for a few days until situations resolves
short term insomnia : define and txt
associated with acute stressor, but it is of an ongoing nature.
Recommend avoiding stimulants (caffeine), pharmacotherapy for 7-10 days
chronic insomnia
cause can be underlying medical or psychiatric cause, or behavioral problem
what kind of agents do you want if you have problems initiating sleep? what about maintaining sleep?
PROBLEMS STARTING SLEEP- AGENT WITH QUICK ONSET AND SHORT DOA
PROBLEMS MAINTAINING SLEEP - LONGER DOA ( onset doesn’t matter as much)
insomnia: which benzo agent is short acting?
triazolam
insomnia: which benzo is long-acting?
flurazepam and quazepam
what are the 3 non-benzos for insomnia? which can be used for sleep onset, maintenance and chronic therapy?
Zolpidem (Ambien)- onset and maintenance
Zaleplon (Sonata)- onset
Eszopiclone (Lunesta)- onset, maintanance and chronic therapy
what is the melatonin receptor 1&2 agonist for insomnia?
Ramelteon (Rozerem)- for chronic
tricyclic antidepressant for insomnia
Doxepin (Silenor)- for maintenance
*“hangover” effect next morning
orexin receptor antagonist for insomnia
Suvorexant (Belsomra)- for maintenance
block orexin that normally promotes wakefulness
non-benzo MOA for insomnia? which receptor does it bind to? which does it NOT bind to?
Selectively bind to benzodiazepine receptor 1 (BZ1) enhancing the activity of GABA = decr. neuron excitability = sedation
* NO BZ2 receptor activity
Minimal anxiolytic, muscle relaxation and anticonvulsant properties
why are non-benzo agents replacing Benzos for insomnia txt?
Preferred because they don’t affect sleep architecture, just decrease sleep latency
Have less adverse effects compared to older agents
- HA, dizziness, daytime somnolence, GI complaints
what drug Can be effective, helpful in managing insomnia associated with SSRI?
trazodone
what 4 drugs may CAUSE insomnia?
SSRIs / SNRIs
stimulants (methylphenidate)
glucocorticoids
opiods (w. chronic use)
what delays abs. of non-benzo sleep aids?
food
for what patients is the 1/2 life extended for non-benzo sleep aids ?
renal and liver disease
which non-benzo may have a hangover effect?
lunesta b/c of the very long DOA
what is the boxed warning for non-benzo sleep aids?
increase risky behavior that can lead to death. patients may not remember driving, eating, sex, etc.
what is the difference for men and women in terms of taking non-benzo sleep aids?
women have a lower max dose allowed
what patient population must you warn about OTC diphenhydramine for sleep? why?
Use caution in elderly patients because anticholinergic action can worsen dementia or other medical conditions
Which adverse effect of zolpidem carries the greatest potential for harm?
Abnormal behaviors while asleep
