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154 Cards in this Set

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Which age groups are most affected by insomnia?
Young adults and middled aged more than kids or adolescents
Define Insomnia
Difficulty falling asleep or staying asleep
Describe which gender is more likely to be affected by insomnia
Women!
What do 40% of all insomnia patients also have?
Some psychiatric illness.
Define Sleep continuity
Overall balance of sleep and wakefulness
Define Sleep Latency
"Amount of time required to fall asleep"
Define Intermittent wakefulness
Amount of awake time after initial sleep onset
Define Sleep Efficiency
The ratio of accrual time spent asleep to time spent in bed
Dyssomnia
Abnormalities in the amount, quality or timing of sleep
Define Parasomnia
Abnormal behavorial or physiological events occurring in association with sleep, specific sleep stages or sleep-wake transitions
Normal duration of sleep
7-8 hours
Describe REM Sleep
Rapid eye movement
a-Circulation to brain increases
b-Electrical and metabolic activity increases
c-Vivid dreams
d-Heart rate and respiratory rate fluctuate
e-Reduction in muscle tone
Describe Non-REM sleep
a- 4 stages (I-IV)
b- Low levels of metabolic and electrical activity
c- Dreams more purposeful and logical
What part of the brain regulates circadian rhythm?
Suprachiasmatic nucleus
Melatonin is released from where and is responsible for what?
It is released from the pineal gland and promotes sleep onset
Many middle aged adults and elderly have both reduced quantity and quality of sleep due to declining levels of what?
Melatonin
What are some drugs that could cause sleep disorders?
Anticonvulsants, Central Adrenergic blockers, diuretics, SSRIs, Corticosteroids and CNS stimulants
Describe Primary Insomnia
An endogenous disorder thought to be due to structural or neurochemical etiology that results in complaints for at least one month that impacts social, occupational or other components of living and other diseases are ruled out.
Complications of Insomnia
1.Increased mortality risk
2.Reduced work/school performance
3.Motor vehicle accidents
4.Psychological disturbances
5.Social problems
Nightmare disorder, sleep terror disorder, sleepwalking are classified as what type of sleep disorders?
Parasomnia
Narcolepsy is classified as what type of sleep disorder?
Dysomnia
Describe Transient Insomnia
Generally the result of an acute stressor and lasts 2-3 days
Describe Short-term insomnia
Lasts up to 3 weeks, may be associated with situational, personal or acute medical stress
Describe Chronic Insomnia
Symptoms persisting beyond 3 weeks that may be associated with a stressful situation, medical condition or a conditioned arousal response to sleep attempts
Sleep disorder Treatment Goals
1.Restore restful sleep
2.Enable functional daytime activity
3.Improve quality of life
4.Reduce morbidity/mortality
Describe the place in therapy for NON-pharmacological therapy
It should always precede or accompany pharmacological therapy
Should Rx's be used in anticipation of difficulty sleeping?
No, just when it occurs
Describe the guidelines regarding sedative-hypnotics in those with transient insomnia
They should be used very carefully as to avoid next day performance impairment
Describe the guidelines regarding sedative-hypnotic use in those with short-term insomnia
Use them intermittently, skip 1-2 nights of medications after 1-2 nights of sleep)
Describe the overall treatment principles in terms of Chronic Insomnia
1.Look for other causes!
2.Reinforce sleep hygiene
3.Limit use of sedatives to 1/3 nights to prevent tolerance and dependence
If a patient has a long sleep latency, which type of agent should be used?
A rapid onset agent
If a patient has a problem with sleep maintenance, which type of agent should be used?
One with a long duration
Name the main Non-Pharm therapies
1.Sleep hygiene
2.Stimulus control therapy
3.Sleep restriction
4.Relaxation tehrapy
5.Cognitive restructuring
6.Paradoxical intention
Describe Sleep Hygiene
1.Exercise 3-4x per week, but not within 3 hours of bedtime
2.Maintain a dark, quiet sleep environment
3.Avoid use of tobacco, alcohol or caffeine
4.Avoid large quantities of liquids near bedtime
Describe Stimulus Control Therapy
1.Regular wake/sleep times
2.Limit sleep to restful sleep
3.Only go to bed when sleepy
4.Use bed only for sleep and intimacy
5.No reading/watching TV in bed
6.If can not sleep, leave bed and engage in a restful activity
7.Avoid daytime naps (If unavoidable, nap before 3pm)
Describe Sleep Restriction Non-Pharm therapy
1.Total sleep time kept at a minimum of 5 hours
2.Goal is to reduce time spent awake in bed
3.As the time asleep to time in bed ratio (sleep efficiency ratio) reaches 85%, 15-20 min are added to time allowed in bed.
Describe Relaxation therapy non-Pharm therapy
1.coordinated by psychologist and lasts 6-8 weeks
2.Imagery training, meditation, progressive muscle relaxation
Describe Cognitive restructuring
Using a psychologist, thoughts that prohibit sleep (i.e. worry or perfectionism) are corrected
Describe the Paradoxical intention sleep method
Patients are instructed to try staying awake to avoid worrying about falling asleep.
ADR of OTC Antihistamines
1.Hangover effect - sedation the day after taking medication (MAY CAUSE FALLS IN ELDERLY)
2.Anticholinergic effects
3.Paradoxical stimulation in kids
4.Tolerance after 4 days of use
Describe effectiveness of OTC Antihistamines
Useful in mild, transient insomnia, but less than BZDs. Decreases sleep latency, reduces number of awakenings and increases total sleep
Diphenhydramine DOSE
50mg at HS
Doxylamine DOSE
25mg at HS
Advantage of Doxylamine over Diphenhydramine
Doxylamine has a shorter half life, therefore will have less of a hangover effect
BZD MOA
Binds to BZD-1 and BZD-2 receptors and enhances GABA actions.
BZD ADRs
1.Hangover effect
2.Anterograde amnesia
3.tolerance
4.Abuse
5.Respiratory depression
6.Prego Cat D or X
7.Reduce stage 3 and 4 sleepa nd REM sleep
Describe aspects of the hangover effect often observed with BZD use
Long acting BZDs such as Flurazepam and Quazepam are culprits due to accumulation of active metabolites.
Which BZDs should be avoided in elderly and why?
Long acting agents because of the risk of falls
Which BZDs are the longest acting?
Flurazepam and Quazepam
In treating Insomnia with BZDs, why would a long acting BZD actually be preferred?
If the patient has comcomitant anxiety, this can help maintain duration throughout the next day.
Which BZD is especially bad with the anterograde amnesia?
Triazolam, due to its rapid onset and short half-life
Describe the tolerance ADR associated with BZDs
Tolerance can develop within 1-2 weeks of continuous use of a short acting agent and 1-3 months for a longer acting agents
Why should BZDs be used VERY carefully in those with sleep apnea?
They are notorious for causing respiratory depression
Are BZDs safe in breastfeeding women?
No
Regarding BZD Metabolism, which type of BZDs are preferred in those who are elderly or have hepatic dysfunction or are taking meds that alter CYP Fx?
Those that are conjugated via glucuronidation
BZD drug interactions
1.Ethanol/Barbiturates - Additive sedation and respiratory depression.
2.Any meds that interact with 3A4 can alter BZDs if they also are metabolized by it.
Describe BZD withdrawal symptoms
Anxiety
Nausea
Vomiting
Tremors
Seizures
Rebound insomnia
(Short/Long) acting BZDs are associated with more severe withdrawal symptoms.
Short
Describe the effectiveness of BZDs in treating insomnia
-Decreased sleep latency
-Indicated for TRANSIENT/SHORT-TERM
-Shorter acting agents are preferred for sleep-onset problems and longer acting are used for maintenance
Which types of insomnia are BZDs most effective for?
Transient and Short-Term
For the insomnia lecture, which two BZDs are Glucuronidated and not metabolized via CYP 3A4?
Lorazepam and Temazepam
Clonazepam Onset?
Intermediate
Clonazepam
Duration?
Long
Clonazepam
Metabolism
CYP3A4
Flurazepam - Onset
Fast
Flurazepam - Duration
Long
Flurazepam - Metabolism
CYP3A4
Active metabolites
Quazepam - Onset
Fast
Quazepam - Duration
Long
Quazepam - Metabolism
CYP3A4
Active Metabolites
Estazolam - Onset
Intermediate
Estazolam - Duration
Intermediate
Estazolam - Metabolism
CYP 3A4
Lorazepam - Onset
Intermediate
Lorazepam Duration
Intermediate
Lorazepam Metabolism
Glucuronidation
Temazepam - Onset
Intermediate
Temazepam - Duration
Intermediate
Temazepam - Metabolism
Glucuronidation
Triazolam - Onset
Very Fast
Triazolam - Duration
Short acting
Triazolam - Metabolism
CYP3A4
3 Long acting BZDs
C - Clonazepam
F - Flurazepam
Q - Quazepam
Can't Flee Quickly
2 Fast onset BZDs
Flurazepam and Quazepam
Fastest onset BZD
Triazolam
Short acting BZD
Triazolam
Zolpidem Dosing
10mg QHS
Elderly/HepImp:5mg
20mg=More side effects
Zolpidem CR Dosing
12.5mg QHS
Elderly/HepImp:6.26mg
Zolpidem MOA
Selectively acts on BZD-1 with little anxiolytic, anticonvulsant or muscle relaxant activity
Zolpidem MOA
Minimal tolerance/rebound effects vs BZDs
Drowsiness, Amnesia, HA and GI complaints
Describe the effectiveness of Zolpidem
Comparable to BZDs for reducing SLEEP LATENCY (due to rapid onset) and increasing total sleep time and efficiency without messing up architexture
Zaleplon Dose
10mg QHS
5mg if elderly
Zaleplon MOA
Selective for BZD-1 receptor without anxiolytic, anticonvulsant or muscle relaxant properties
Zaleplon ADR
Dizziness, HA, Somnolence
NO SIGNIFICANT REPORTS OF HANGOVER, TOLERANCE OR WITHDRAWAL
2 Major drug interations with Zoleplon
Cimetidine Increase Zaleplon due to CYP3A4 inhibition, lower dose to 5mg
Rifampin can reduce zaleplon dose, consider alternative sleep aid
Describe effectiveness of Zaleplon
Has a short half life, so good for REDUCING SLEEP LATENCY, but NOT for reducing nocturnal awakenings or increasing total sleep time.
MAY BE USED IF PATIENT WAKES UP IN MIDDLE OF NIGHT AND 4 HOURS OF USEABLE TIME STILL OCCURS (NO HANGOVER EFFECT STILL!)
Does Zaleplon or zolpidem modify the sleep architexture?
No
Eszopiclone (Lunesta) Dose
2mg QHS
1mg in elderly
May increase to 3mg if persistant
Eszopiclone MOA
Selectively acts on BZD-1 with little anxiolytic, muscle relaxant or anticonvulsant properties
Esczopiclone ADR
HA, somnolence, unpleasant taste.
NO REPORTS OF TOLERANCE, WITHDRAWAL OR HANGOVER
Eszopiclone Drug interactions
CYP3A4 Inhibitors, start with 1mg if strong inhibitor is also being taken
Examples of Strong CYP3A4 inhibitors
Clarithromycin, Ketoconazole, Nefazodone
Describe effectiveness of Eszopiclone
REDUCES SLEEP LATENCY
IMPROVED MAINTENANCE WITH NO MODIFICAITON OF SLEEP ARCHITEXTURE
OF BZD-1 selective agents, which has the shortest half life?
Zaleplon (Sonata), thus is used to reduce sleep latency
FDA Indication for Zaleplon
Sleep initiation
FDA Indication for Eszopiclone (Lunesta)
Insomnia and Chronic Insomnia
Zolpidem (BRAND)
Ambien
Zaleplon (BRAND)
Sonata
Eszopiclone (BRAND)
Lunesta
Ambien GEN
Zolpidem
Sonata GEN
Zaleplon
Lunesta GEN
Eszopiclone
Ramelteon (BRAND)
Rozerem
Rozerem GEN
Ramelteon
Ramelteon DOSE
8mg QHS
Caution in hepaticImp
Do not use if severe hepatic
Ramelteon MOA
Agonist at MT-1 and MT-2 receptors and is for SLEEP INITIATION
Ramelteon ADR
Dizziness
Ramelteon Drug Interaction
Fluvoxamine - Can increase serum concentrations dramatically, thus don't use both
Ramelteon Effectiveness
Useful for patients with prolonged sleep latencies (Reduces by 10-15minutes).
Can be used for long term, not a controlled substance.
NO EVIDENCE OF WITHDRAWAL OR TOLERANCE
May have a role for substance abusers with insomnia
Discuss use of Chloral Hydrate
TRANSIENT
Chloral hydrate DOSE
500-1000mg PO or PR 15-30 minutes before bedtime
Chloral Hydrate MOA
Unknown depressant
Chloral Hydrate ADR
Where to begin...
Active metabolites can cause N/V/D, exacerbate respiratory and CV conditions.
MAY CAUSE HYPERBILIRUBINEMIA
Describe effectiveness of Chloral Hydrate
Rapid onset/Moderate duration.
Tolerance/Adverse effects limit use to 2-7 days.
Useful for Peds (10-40mg/kg)
Barbiturate ADR
Respiratory depression, CNS depression, bradycardia, hypotension
Effectiveness of Barbiturates
High risk of CNS/RESP depression vs. BZDS without advantage
When are ADs warranted in the treatment of insomnia?
Only when patients have depression, another indication or patient has insomnia and cannot take a BZD
TCA MOA
Blocks reuptake of NE and 5-HT
TCA ADR
Hangover
Falls inelderly
Anticholinergic
Cardiac conduction abnormalities
Describe TCA Effectiveness
Often used in non-depressed patients, but not well studied. Useful if patient has depression or neuropathic pain or co-moribidities
Melatonin ADRs
Vasoconstriction
Enhance immune function (No immunosuppressive co-therapy)
NO PREGO/Lactating
What can cause Circadian Rhythm sleep disorders?
1. Discrepancy is present between patients sleep-wake cycle and external demands for periods of sleep and wake or JET LAG or SHIFT WORK
Describe Light therapy for Circadian disorders
Bright light during the day, dark environment while sleeping
Describe how to minimize jet lag symptoms
1.If travel <7 days, then keep original time zone patterns.
2.If travel >7 days, attempt to alter sleep schedule gradually.
Describe Pharm Tx for Circadian disorders
1.Short acting BZDs
2.Zaleplon and zolpidem preferred
3.Ramelteon being studied
4.Melatonin is commonly used
Define sleep apnea
10 second cessation of airflow into the mouth or nose
What agents should be avoided in patients with sleep apnea?
CNS depressants (BZDs or Opioids), THEY ARE LETHAL
What is Modafinil use for?
Sleep apnea, helps those with daytime sleepiness despite CPAP.
CPAP
Continuous positive airway pressure is a standard treatment for patients with Obstructive sleap apnea
Modafanil ADR
HA, Nausea, Nervousness
Hypnagogic
At threshold of sleep
Describe the Narcolepsy Tetrad
1.Sleep attacks
2.Cataplexy
3.Hypnagogic hallucinations
4.Sleep paralysis
Describe Cataplexy
Sudden loss of muscle tone, can be precipitated by intense emotions, most narcolepsy patients have this
Non-pharm Tx for Narcolepsy
2 or more daytime naps for 15 minutes recommended
Describe the Pharm Tx for EDS (Excessive daytime sleepiness) for narcolepsy patients
Modafinil
Does Modafinil help with cataplexy?
Nope
What are the most effective agents for the treatment of cataplexy?
TCAs and Fluoxetine
OR
GHB
Sodium Oxybate(GHB) MOA
In terms of treating Cataplexy, its unknown. It binds to GABAb and specific receptors and does some stuff, who knows?
ADR of Sodium Oxybate
HA, Nausea, Dizzines
Etiology of Restless Leg Syndrome
Decreased D2 binding in the striatum of patients
Describe RLS
Abnormal feeling in the limbs (typically calfs) urging patients to keep legs moving. Sx are relieved by walking or moving legs
Non-Rx Treatment of RLS
Exercise, impove nutrition, sleep hygiene
Rx therapy for RLS
Mild: BZDs (Caution: Short-acting can cause wandering)
Opiates can work, tolerance though...
DA agonists (Must titrate)
Ropinirole
Pramipexole
Pergoloide
What is one problem with using Dopamine agonists to treat RLS?
May exacerbate insomnia