Insomnia, Drowsiness, & Fatigue Flashcards
What is insomnia?
- Insomnia is a disorder of difficulty falling asleep, staying asleep or waking up too early and unable to return, or not getting a quality sleep even after sleeping an adequate number of hours.
- Insomnia is one of the most common patient complaints that we see in pharmacy settings
How does insomnia impact the health care setting?
- It costs our health system about $20 billion – over $100 billion a year
- Small number of patients consult with their healthcare provider, usually patients prefer to come to the pharmacy and pick up over the counter medications to help them. That’s when our role as pharmacists come in play. We need to engage with our patient to recognize if they’re insomnia is something we can recommend an over counter medication for or refer the patient to a healthcare provider for further evaluation.
How much sleep does the average adult in the US get?
Adults in the U.S. usually get about 6.9 hours/day on workdays & 7.6 hours on non workdays
In 2015:
* About 34% experienced 1 or more sleeping related problem during the last 7 days
* And 13% rarely/never get a good night sleep
* And about 20% of U.S. adults use insomnia medications in a given month
* Of those 20%, about 60% of medications are OTCs – antihistamines
What is the healthy amount of sleep for a 4-12 month old infant?
12-16 hours (including naps)
How many hours of sleep does a 1-2 y.o. need?
11-14 hours (including naps)
How many hours of sleep do 3-5 y.o. need?
10-13 hrs of sleep (including naps)
How many hours do 6-12 y.o. need?
9-12 hours
How many hours of sleep do 13-18 y.o. need?
8-10 hours
How many hours of sleep do over 18 y.o. need?
7 hours or more
What are risk factors for insomnia?
Risk Factors:
* Age – older adults are at a higher risk of experiencing insomnia.
* We also see higher risks with females.
* Also some medical and psychiatric condition could put the patient at a higher risk.
* Shift work (like working night shifts or working both day and night shifts like our patient in the case)
* Stressful event like divorce, financial struggles, death of a family members or an upcoming hard exam.
* Also patient with limited financial and educational resources have higher risks.
What medical disorders put you at higher risk for insomnia?
Among the medical conditions we see a higher risk of insomnia is associated with:
* Arthritis
* Benign prostatic hyperplasia
* Diabetes
* Incontinence that could cause the patients to wake up in the middle of the night to go to the bathroom in the middle of the night
* Acid reflexes
* Irritable bowel syndrome
* Peptic ulcer disease that could cause heart burn and discomfort that wakes up the patient in the middle of the night and sometimes can cause uncomfortable cough.
* Some of those conditions can cause patients to wake up in the middle of the night to go to the bathroom such as BPH, DM, and incontinence as well.
* Also, heart failure can cause shortness of breath and difficulty sleep just like COPD and asthma.
* Psychiatric disorders: anxiety, depression, substance use disorder
* Sleep disorders: obstructive sleep apnea, psychophysiological insomnia, RLS, shift work sleep disorder
* Other conditions- menopause, pregnancy
Which drugs cause drug-induced insomnia?
Alcohol
Anticholinesterase inhibitors (e.g. donepezil)
Antidepressants (Fluoxetine, bupropion)
Diuretics
Stimulants (amphetamines, methylphenidate, phentermine, atomoxetine)
Caffeine
Steroids
Decongestants (pseudoephedrine)
Varenicline
Aripiprazole
Which drugs produce withdrawal insomnia?
Alcohol
Amphetamines
Antihistamines (1st gen)
Barbiturates
Benzodiazepines
Illicit drugs (e.g. cocaine, marijuana, phencyclidine)
Monoamine oxidase inhibitors
Opiates
Tricyclics antidepressants
What is the difference between drug-induced insomnia and a medication that could cause withdrawal insomnia once the pt stops taking them?
Drug-induced insomnia occurs when a substance directly interferes with sleep while it is actively in the system, such as stimulants disrupting normal sleep patterns. Withdrawal insomnia, on the other hand, happens when stopping or reducing a drug that the body has adapted to, leading to sleep disturbances as the brain adjusts to the absence of the substance.
What are the 5 stages of the sleep cycle?
- Stage I Sleep: transitional
- Stage II Sleep: intermediate
- Stage III and IV: deep sleep or delta sleep
- Stage V: REM (rapid eye movement). Neither light nor deep sleep stage and has high dream activity
Cycle is about 90-120 mins long
Each night the body undergoes about 3-7 cycles
Stage I-IV are not REM sleep stages
List the sleep promoting neurotransmitters.
Adenosine
Melatonin
GABA
List the wake promoting neurotransmitters.
Norepinephrine
Serotonin
Histamine
Dopamine
Acetylcholine
Orexin
What are the three main classifications for primary insomnia?
Idiopathic, paradoxical, psychophysiological
Differentiate between idiopathic, paradoxical, psychophysiological insomnia.
- Idiopathic insomnia is an insomnia that begins in early childhood and has no identifiable causes – it is also known as childhood onset insomnia
- Paradoxical insomnia is a rare sleep disorder that causes people to feel they are awake while they are asleep. The causes are unclear but active brain activity during sleep may play a role in sleep walking
- Psychophysiological insomnia is the most common type of chronic insomnia that caused by a combination of psychological factors, such as anxiety about sleep, negative conditioning and learned sleeplessness and physiological factors including physiological arousal
What are other types of insomnia? (2 more)
Adjustment insomnia (short-term)
* inadequate sleep hygiene, acute stressors (acute medical illness, acute anxiety, travel, hospitalization, divorce, or death of a beloved one)
Secondary Insomnia
* another sleep disorder, general condition, psychiatric condition, substance use disorder, or medications
What are the characteristics of short-term insomnia?
- Symptoms less than 3 months
- 30% to 50%
What are the characteristics of chronic insomnia?
- Symptoms ≥ 3 times/week for ≥ 3 months
- 5% – 10%
What are characteristics of recurrent insomnia?
Symptoms ≥ 2 within 1 year
What is needed to diagnose a patient with chronic insomnia disorder?
Diagnostic criteria:
Dissatisfaction with sleep quality or quantity with ≥ 1 of following:
* Difficulty initiating sleep
* Difficulty maintaining sleep
* Early morning awakening with inability to fall back asleep
Significant distress or impairment of functioning (social, academic, behavioral, etc.)
* ≥ 3 nights/week
* ≥ 3 months
Not due to:
* Other sleep disorder
* Co-existing medical condition
* Lack of opportunity to sleep
* Medication or substance use
How do we measure insomnia?
- One option is a sleep diary or log
What are some sleep goals?
- The Sleep Latency (SL) or Sleep Onset Latency (SOL)– time to fall asleep after lights out– should be less than 30 mins
- Limited number of awakening and lower duration if incidence occurs
- We want a wake after sleep onset (WASO =sum of awake times from sleep onset to final awakening time) to be less than 30 mins.
- We want to increase the total time in bed (TIB)
- We want a total sleep time of greater than 6 hours. (TST)
- We want a sleep efficiency score (SE) of 80-85%
SE= TST/(TIB x 100)
What are the sumptoms of insomnia?
- Sleep-onset – difficulty initiating sleep
- Sleep maintenance – difficulty staying asleep throughout the night
- Early morning awakening & inability to fall back asleep
- Poor sleep quality caused by disturbing dreams
What are symptoms of sleep depravation?
- Fatigue
- Drowsiness
- Anxiety
- Irritability
- Depression
- Decreased concentration
- Memory impairment
What are the complications associated with insomnia and sleep deprivation?
Poor quality of life
High morbidity & mortality rates
* CVD
* Pain syndromes
* Depression
* Anxiety
* Substance use disorder
What are nonpharmacological methods to treating insomnia?
- Guidelines recommend Cognitive Behavioral Therapy (CBT) as a 1st line therapy
- Addresses dysfunctional behaviors and beliefs
- Combination of sleep restriction, sleep hygiene, stimulus control, paradoxical intention and cognitive restructuring
Sleep Restrictions:
* Limiting time spent in bed to only sleeping hours
* Dark, comfortable, and quiet bedroom
Sleep Hygiene: addressing environmental factors
* Avoid alcohol, caffeinated beverages, and stimulants prior to bedtime
* Avoid exercising prior to bedtime
* Turn the face of the clock to avoid anxiety over falling asleep
* Avoid heavy meals before bedtime
* Create bedtime rituals (e.g. relax on soft music, mild stretching, yoga, or pleasurable reading)
Stimulus Control: Alter sleep-wake schedules:
* Going to bed when sleepy
* Reserve bed for sleep (no TV in the bedroom)
* If unable to sleep, get up and do something to take your mind off sleeping for 10-15 mins, return only if sleepy
* Daily wake-up time that is the same regardless of how much sleep was obtained the previous night
* Avoid napping during the day or limit to 30 mins
Paradoxical Intention:
* Try to stay awake instead of falling asleep to alleviate not falling asleep anxiety
* Helps reducing the stress and makes it easier to fall asleep
Cognitive Restructuring:
* CBT focused on individual’s unique causes of insomnia
What are natural products we can use to treat insomnia?
Melatonin
* Possibly effective
* Side effects: rare, daytime sleepiness, headache, nausea & dizziness
* Notes: If used chronically, endogenous melatonin can decrease leading to dependence
* QHS
* For jetlag: 0.5-2 mg taken pre-flight and 5 mg post flight
* Possibly safe when using low oral doses for short term in children
Valerian
* Possibly effective
* Side Effects: Sedation, CNS depressant, Headache
* Risk with concurrent CNS depressants
* Other uses: anxiety, depression
* Avoid using in pregnancy and lactation
Ashwagandha
* Possibly effective
* N/V/D
* GI Upset
* Do not use in pregnancy and lactation
Chamomile
* Insufficient evidence
* Side effects: Allergic rxn
* Cross sensitivity w/ ragweed asters, and artichoke
When was the final monograph on nonprescription sleeps aids issued by the FDA?
1989
* Antihistamine diphenhydramine hydrochloride or diphenhydramine citrate salts
* Only sleep aids considered safe and effective for self administration
Which first generation antihistamines may help with insomnia?
Diphenhydramine (Benadryl, ZzzQuil, store brands)
Rx & OTC
* MOA: Competitively block histamine-1 receptors
* 50 mg po qhs
* Do not use in children younger than 6 y.o.
* General side effects: Sedation, Cognitive impairment
* Peripheral anticholinergic side effects: dry mouth, urinary retention (men with BPH have difficulty urinating), dry/blurred vision, constipation, seizures/arrhythmias (higher doses).
* Avoid in men with BPH and flaucoma
* Causes paradoxical excitation in young children
Doxylamine (Unisom, SleepTabs, Sleep Aid, store brands)
OTC
* MOA: Competitively block histamine-1 receptors
* 25 mg po qhs
* Do not use in children younger than 12 y.o.
* General side effects: Sedation, Cognitive impairment
* Peripheral anticholinergic side effects: dry mouth, urinary retention (men with BPH have difficulty urinating), dry/blurred vision, constipation, seizures/arrhythmias (higher doses).
* Avoid in men with BPH and flaucoma
* Causes paradoxical excitation in young children
* Be aware: some OTC Unisom product contains diphenhydramine
How is diphenhydramine relevant to insomnia?
- Tx for occasional insomnia
- Decreases sleep latency
- Improves sleep quality
- Max sedating effect 1-3 hours
- CYP2D6 inhibitor–>many drug interactions
List some common drug interactions that diphenhydramine has.
- Acetylcholinesterase inhibitors- Diminish the therapeutic effects of each other (Monitor)
- Aripiprazole- Increase serum levels (Monitor)
- Buprenorphine- Enhance the CNS depressant effect of buprenorphine (Monitor, dose adjustments may be needed)
- GI agents (prokinetic)- Diminish of the therapeutic effect of the GI agents (Monitor)
- Metoprolol- Increase serum level of metoprolol and cause negative chronotropic effects, especially in women (Alternative therapy)
- Opioid agonist- Enhance the CNS depressant of opioids (Avoid use togther)
- QT prolonging agents- Additive QT prolongation effect (Unless contraindicated, co administer with caution)
- Tamoxifen- Decrease serum concentration of endoxifen (active metabolite of tamoxifen) (Consider alternative therapy w/ less CYP2D6 activity if possible)
Define each component of ADME for diphenhydramine.
Absorption
* Well GI absorption
* Bioavailability 42% to 62%
Distribution
* 1-4 hours
* Volume of distribution: Children: 22 L/kg, Adults 17 L/kg, older adults: 14 L/kg
Metabolism
* Metabolized in the liver by CYP2D6
* Significant first-pass metabolism
Elimination
* t1/2: 2.4 to 9.3 hours
* Excreted renally
Define each component of ADME for Doxylamine.
Absorption
* 2-2.4 hours
* Pediatrics: 1-2 hrs
Distribution
* 2-4 hours
Metabolism
* Hepatic (liver)
Elimination
* t1/2: 10-12 hours
* Excreted renally
Explain how first-generation anti-histamines are processed in the body.
- For only short-term use. No more than 7-10 days
- Tolerance to sedative effects can develop after 10 days of use
- Recommend an “off night” after taking for 3 consecutive days
- Avoid in older adults
- Counseling (avoid taking with EtOH bc of additive CNS depression effect, avoid engaging in tasks that need full attention until medication effect is known)
What are special populations to consider and potentially refer?
Refer:
* less than 12 y.o. or greater than or equal to 65 y.o.
* Pregnant or breastfeeding
* Frequent nocturnal awakenings or early morning awakenings
* Chronic insomnia (greater than or equal to 3 months)
* Secondary insomnia to a general medical or psychiatric condition
* Significant disturbances as defined by sleep onset-latency, wake after sleep onset, sleep efficiency, and/or total sleep time
* >10 days of self treating
Considerations
* Pregnancy (benefit vs risk)
* lactation (CNS adverse effect, 2nd gen antihistamine recommended)
* Children and adolesents (paradoxial excitement, anticholinergic toxicity)
* Older adults (Beers criteria: avoid 1st gen in pts over 65, non rx recommended)
What is drowsiness?
unusual feelings of sleepiness and lethargy making it hard to stay focused and alert
Can be acute or chronic
What is fatigue?
Fatigue is consistently feeling tired or exhausted and rest doesn’t improve it.
Can be acute or chronic
What does drowsiness and fatigue impact?
- Productivity
- Mood
- Overall health
What negative outcome can fatigue and drowsiness lead to (especially in younger adults)?
Increased incidences of motor vehicle crashes in young drivers due to sleeping < 6 hours/night
What are risk factors for drowsiness and fatigue?
- Sleep duration and quality
- Lifestyle- diet and exercise
- Overexitation
- Medications
- Comorbities
- Sedating agent’s susceptibility
What medications cause drowsiness and fatigue?
- CNS depressants (Antihistamines, Antipsychotics, Antiepiletics, Opioids)
- Dopamine antagonists
- Antibiotics
- Antihypertensives
What comorbities related to drowsiness and fatigue?
- Depression and grief
- Cancer
- Anemia
- Hypothyroidism
- Chronic pain
- Iron deficiency
How do fatigue and drowsiness work on a pathophysiological level?
Essentially, it means that the longer we stay awake after our last sleep, the sleepier we feel. This increase in sleepiness is part of the body’s natural homeostatic process, which balances sleep and wakefulness. As we go without sleep, our need for rest builds up, leading to a stronger urge to sleep the longer we stay awake.
How might drowsiness present?
- Foggy or woozy
- Dozing off
- Responsive but not fully alert
- Dream like thoughts
What are treatment options for fatigue?
- Caffeine
- Nonprescription caffeine containing products
- Adequate sleep/sleep hygiene
- Assess any dryg induced drowsiness and fatigue
- Chronic symptoms (sleep 7-8 hours) medical referral
What are natural products that help reduce drowsiness and fatigue?
- Ginseng–> boosts physical and mental energy and produces a sense of wellbeing. HW, it also increases the risk of bleeding.
- Caffeine containing supplements–> kola nut, Guarana, Yerba mate, Cocoa, Green and black tea, Kombucha. HW, Green tea extract is linked to liver damage in body building products.
What is the most common CNS stimulant?
Caffeine
What is the recommended daily consumption of caffeine?
- F–> 151 mg
- M–> 196 mg
What are sources of caffeine?
- Coffee, tea, soft drinks
- Energy drinks are the most common way of consumption for younger populations
What is the mechanism of action (MOA) for caffeine?
- Phosphodiesterase inhibitors–> increase 3’ and 5’ cyclic adenosine menophosphate–> prevent apnea
CNS stimulant
* Increases the sensitivity of medullary respiratory center to carbon dioxide
* Stimulates central inspiratory drive
* Enhance contraction of skeletal muslces including diaphragm
What are adverse events of caffeine?
- Headache
- Nervousness
- Dizziness
- Anxiety
- Irritability
- Insomnia
- Tachycardia
Dose related: high bp
What will an abrupt discontinuation of caffeine do in those who drink 100-200 mg daily?
- Headache
- Fatigue
- Decreased concentration
- Irritability
Describe the components of ADME for caffeine.
Absorption
* Onset of action is 15 mins
* Peak concentration: 30-120 mins
Distribution
* Volume of distribution: 0.6 L/kg
* Protein binging: 36%
Metabolism
* Hepatic by CYP1A2
* Active metabolite theophylline
Excretion
* t1/2: 5 hours
* Excreted via urine
What are common drug interactions with caffeine?
Adenosine–> Diminish the therapeutic effect of adenosine–> Monitor for decreased effect of adenosine. Cardiac facilities may ask patients to avoid caffeine 12-24 hours prior to nuclear stress test
Atomoxetine–> Increase hypertensive or tachycardic effect of caffeine–> monitor
Ciprofloxacin–> Increase serum concentration of caffeine–> monitor
Linezolid–> Enhance hypertensive effect of caffeine–> Reduce caffeine dose, monitor BP
Lithium–> Decreases serum concentration of lithium–> monitor
Theophylline–> Increases plasma concentration of theophylline–> Avoid using together or maintain consistent intake of caffeine. Monitor theophylline trough levels
Tizanidine—> Increases serum concentration of tizanidine—> Avoid using together if possible. If not possible, initiate tizanidine at 2 mg and increase 2-4 mg increments based on patient response. Monitor for adverse events
Tobacco—> Tobacco decreases serum concentration of caffeine–> monitor
What are special populations to consider with drowsiness and fatigue, which may lead to referral?
Refer:
* less than 12 y.o.
* Pregnant or breastfeeding
* Heart disease
* Anxiety disorder
* Medication induced drowsiness
* Persistent symptoms after 7-10 days of self treatment
* Chronic fatigue
Special Populations:
* Pregnancy (caffeine crosses placenta)
* Lactation (caffeine passes through breast milk, infants unable to metabolize caffeine)
* Children and Adolescents (higher risk of CV and CNS adverse effect, no caffeine containing products either for under 12)
