Sleep Disorders 06
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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
-
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