medication review presentation

General Considerations

This lecture will cover medications commonly taken by sleep lab patients that are known to have effects on sleep

The purpose of this lecture is not to memorize the generic and trade name of every medication our patients may ever take!

General Considerations Medication classes that will be covered:

Sedatives and hypnoticsStimulantsPsychiatric medicationsPain medicationsAntiepilepticsRLS/PLMD medicationsCardiovascular medicationsRespiratory medicationsCold medications and antihistaminesRecreational drugs

General Considerations 3.1 billion prescriptions were written in

2002 in the US alone Nearly half of all Americans are currently

prescribed at least one medication Most patients seen at the sleep lab are

under the influence of prescribed medicationsIt’s important to know and understand

patients’ medication lists (even OTC drugs) to correctly read and score studies, and also for the sake of safety

General Considerations

584 prescription and OTC drugs list sleepiness as a side effect

Of the 20 most commonly prescribed medications in the US, at least half are known to affect sleep

20 most commonly prescribed brand-name medications

20 most commonly prescribed generic medications

General Considerations The effects many medications have on

sleep are largely unknownEven highly controlled studies have

produced differing results

Several factors limit the understanding of how different medications affect sleep and wakefulness:Limited researchInconsistent findingsPopulation differencesAcute vs. chronic effects

General Considerations The more medications a patient is on,

the higher the chance of clinically significant interactions

Physicians should always be aware of a patient’s medications and instruct the patient and tech as to their use before and during the PSGAny changes to a patient’s regular

medication routine should be clearly indicated on the study order or history

General Considerations Abbreviations:

SOL – sleep onset latency○ Some charts will use “SL” instead

ROL – REM onset latency○ Some charts will use “RL” instead

TST – total sleep timeSWS – slow-wave sleepWASO – wake after sleep onsetEDS – excessive daytime sleepiness

I will try to give both generic and trade namesTrade names will always be capitalized

Sedatives and Hypnotics

Sedatives are prescribed to treat anxiety, and hypnotics are prescribed to treat insomniaNearly identical in how they function and are

often used interchangeably

Have a history of limited efficacy, serious side effects, addiction, and lethal toxicity in overdoseLong-term use can lead to tolerance and

actually cause insomnia

Sedatives and Hypnotics All classes bind to GABA receptors in

the brain, inhibiting internal and external influences from disrupting sleepBasically “protect” sleep from things such as

worries, noise, and painTreating OSA-induced EDS with sedatives

can decrease respiratory drive and increase prevalence of OSA, actually worsening sleep

Beware that the effects of multiple sedatives may be more than additive

Sedatives and Hypnotics

3 main categories of hypnotics:BarbituratesBenzodiazepinesNon-benzodiazepines

Barbiturates Widely used until the 1960s, but were often

abused and had a high danger of overdose Examples:

Trade name Generic name

Luminal phenobarbital

Nembutal pentobarbital

Quaalude, Sopor methaqualone

Doriden glutethimide

Placidyl ethchlorvynol

Nodudor methyprylon

Barbiturates Biggest effect seen on sleep is that they’re

very sedating Increase TST, decrease REM, increase

spindle frequency and density, increase SWSPhenobarbital (Luminal) may actually suppress

SWS

Can decrease respiratory drive and increase prevalence of OSA

May exacerbate respiratory failure in patients with COPD, CSA, or restrictive lung disease

Benzodiazepines Became available in the 1970s, and have less

overdose and abuse potential than barbiturates

Bind to a broad range of GABA receptors and have a widespread sedating effect

Examples:


Ativan lorazepam

Klonopin clonazepam

Dalmare flurazepam

Valium diazepam

Xanax alprazolam

Halcion triazolam

Tranzene clorazepate

Benzodiazepines Tend to lose efficacy with prolonged use Decrease WASO, increase TST,

increase stages N1 and N2, increase spindle frequency/density, decrease SWS, decrease REMClonazepam (Klonopin) may actually

increase SWS

Are also sometimes used to treat PLMD Clonazepam (Klonopin) is also used to

treat REM behavior disorder

Benzodiazepines Have similar respiratory effects as

barbiturates:Can cause respiratory depression, causing or

worsening OSACan exacerbate respiratory failure in patients with

COPD, CSA, or restrictive lung disease

Withdrawal can cause REM rebound Flurazepam (Dalmare), diazepam (Valium),

and clorazepate (Tranzene) have almost 11 day half-livesEffects may be seen long after being discontinued

Non-benzodiazepines Bind preferentially to GABAA receptors

and have a less widespread effect than benzodiazepines

Examples:Trade name Generic name

Ambien zolpidem

Benadryl diphenhydramine (also an antihistamine)

Sonata zaleplon

Lunesta eszopiclone

Rozerem ramelteon

BuSpar buspirone

Non-benzodiazepines Have a relatively short half-life, and have the

fewest side effects of all hypnoticsBuspirone (BuSpar) in particular has been studied and

found to have no effects on sleep architecture or daytime alertness

Zolpidem (Ambien) and eszopiclone (Lunesta) have greatest sleep-inducing efficacy, but zaleplon (Sonata) has fewest side effects

Zaleplon (Sonata) may increase ROL and SWS Conflicting studies have shown that zolpidem

(Ambien) can either suppress or increase SWS No REM rebound occurs after discontinuing

Stimulants

Increase CNS activation to promote alertness

Used to treat narcolepsy, hypersomnia, ADHD, obesity, and even the common cold

Many of the same medications are used to treat both narcolepsy and ADHD

Stimulants


Provigil Modafinil

Nuvigil Armodafinil

Strattera atomexetine

Adderall amphetamine

Dexedrine dextroamphetamine

Desoxyn methamphetamine

Concerta, Ritalin methylphenidate


Didrex benzphetamine

Desoxyn methamphetamine

Adipex phentermine

Meridia sibutramine

Example narcolepsy/hypersomnia/ADHD medications: Example appetite suppressants:

Stimulants Most have high potential for abuse and

can cause personality changes, tremor, hypertension, headaches, and GERD

Newer stimulants modafinil (Provigil) and armodafinil (Nuvigil) are distinct from the amphetamines and have a much lower abuse potentialNow usually the first route of treatment for

narcolepsy

Stimulants

Any medications that increase alertness have the risk of causing insomnia

Increase SOL, ROL, WASO, arousals, and stages N1 and N2

Decrease SWS, REM, and TST

Stimulants Common dose-dependent side effects

may also interfere with sleep:AnxietyHeadacheIrritabilityHeart palpitationsTremors

Sudden withdrawal from any stimulant substance may cause profound sleepinessBeware of how stimulant withdrawal may

affect MSLTs

Antidepressants

Four main classes:SSRIs and SNRIsTricyclicsMAOIsAtypical antidepressants

Each class affects neurotransmitters in different ways

Each has its own set of side effects, which range from stimulating to sedating

Antidepressants Most antidepressants affect the

neurotransmitters norepinephrine, serotonin, acetylcholine, and dopamineAll are known to play an important role in the

sleep-wake cycle

15% of those who take antidepressants report disrupted sleep or daytime fatigue

Many are sedating, but stopping them prior to a PSG is not always practical or safe

Almost all classes have been known to exacerbate PLMD

SSRIs and SNRIs Selective serotonin reuptake inhibitors

affect the neurotransmitter serotoninSNRIs affect both serotonin and

norepinephrine, and have similar sleep effects to SSRIs


Prozac fluoxetine

Zoloft sertraline

Celexa citalopram

Lexapro escitalopram

Paxil paroxetine

Luvox fluvoxamine


Cymbalta duloxetine

Effexor venlafaxine

Example SSRIs: Example SNRIs:

SSRIs and SNRIs Generally have the mildest side effects of

all antidepressants SSRIs tend to be stimulating, and can

cause mild-moderate insomniaFluoxetine (Prozac) is the most sleep-disruptive

Can also cause drowsiness in some individualsMostly seen with paroxetine (Paxil) and

fluvoxamine (Luvox)

Decrease TST, increase WASO, decrease REM, and increase PLMDFluoxetine (Prozac) can also decrease SWS

SSRIs and SNRIs Tend to be respiratory stimulants and

can improve OSA Can cause SEMs to occur during most

of the night, even long after cessation of drug useMost prevalent with fluoxetine (Prozac),

paroxetine (Paxil), and sertraline (Zoloft)Less prevalent with citalopram (Celexa) and

escitalopram (Lexapro)“Prozac eyes” are often so rapid that they

can easily be mistaken for REMs.

SSRIs and SNRIs MSLT of a patient taking 20mg

fluoxetine daily (30 seconds)

SSRIs and SNRIs Same patient and epoch (120 seconds)

SSRIs and SNRIs Most increase ROL and decrease REM by

about 30%Knowing this is important for correct interpretation

REM suppression was once believed to be an important part of treatment

Because of their stimulating effects, SSRIs and SNRIs can worsen REM behavior disorder

Despite the sleep disruption caused by these drugs, patients report sleeping better subjectively

Tricyclics Have a broader effect on neurotransmitters

Alter norepinephrine, histamine, and acetylcholine activity

Examples:


Elavil amitriptyline

Norpramin desipramine

Pamelor nortriptyline

Sinequan doxepin

Tofranil imipramine

Vivactil protriptyline

Tricyclics

Mildly-moderately sedating Improve sleep but cause EDS

Protriptyline (Vivactil) less sedating than others

Increase TST, decrease WASO, increase SWS, decrease REM, and increase PLMD

MAOIs

Monoamine oxidase inhibitors are the oldest antidepressants, and have greatest effects on sleep

Examples:


Marplan isocarboxazid

Nardil phenelzine

Parnate tranylcypromine

MAOIs

Tend to be sedating, but can also cause insomnia

Suppress REM, but effect is more sustained than with SSRIs

Cause increased WASO, decreased TST, and markedly reduced REM

Atypical Antidepressants

Work through a variety of mechanisms and affect multiple neurotransmitters, so effects on sleep are less known

Examples:


Desyrel trazodone

Serzone nefazodone

Remeron mirtazapine

Wellbutrin bupropion

Atypical Antidepressants Trazodone (Desyrel) and nefazodone

(Serzone) are considered serotonin antagonist and reuptake inhibitorsCan cause EDS, but may improve sleepIncrease TST and SWSConflicting results on REM effects

Mirtazapine (Remeron) is a norepinephrine and specific serotonin antagonistAlso causes sedation and EDS but enhances

sleepIncreases TST, decreases SOL

Atypical Antidepressants Bupropion (Wellbutrin), as well as the

tricyclic protryiptiline (Vivactil), are norepinephrine and dopamine reuptake inhibitorsMost alerting of antidepressants, and can

cause insomniaActually increase REM and don’t exacerbate

PLMD

St. John’s Wort is an herb taken by some for depressionHas been shown to increase SWS

Antidepressants

Antipsychotics Lithium has traditionally been the drug of

choice for treating bipolar disorderTrade names include Cibalith, Eskalith,

Lithane, and LithobidThe seizure medication divalproex

(Depakote) is also prescribed to treat the manic phase of bipolar disorder

Tends to be sedating, causing EDS but improving sleep

Reduces REM, increases SWS and the prevalence of arousal disorders such as night terrors and somnambulism

Antipsychotics Common antipsychotics which are prescribed

for schizophrenia, other psychoses, and occasionally bipolar disorder:

Characterized mainly by their sedative effectChlorpromazine (Thorazine) can cause an increase in

SWS; diffuse, slower activity in the EEG; and a decrease in spindle activity


Thorazine chlorpromazine

Haldol haloperidol

Mellaril thioridazine

Risperdal risperidone

Seroquel quetiapine

Zyprexa olanzapine

Chantix

Smoking cessation aid that works by blocking nicotine receptors in the brainMakes smoking have less of a pleasurable

effect

Known to cause insomnia and vivid, unusual dreams

Watch for symptoms of stimulant withdrawal

Pain Medications Many prescription pain medications are

either narcotics or barbiturates Are often VERY sedating Examples:


Vicodin, Lortab hydrocodone

Darvocet propoxyphrene

Demerol meperidine

Methadone methadone

Percocet oxycodone

Norgesic orphenadrine

--- morphine

--- codeine

Pain Medications

Decrease SOL and WASO, increase TST, may decrease SWS and REM

May decrease alpha, and can cause slower, diffuse EEG

Can depress respiratory system and increase severity of OSA

Have been known to cause confusion in elderly patients

Aspirin (ASA or acetylsalicylic acid) in an NSAID taken for pain or to prevent heart attackMain effect on sleep is a decrease in SWS

Antiepileptic and Neuromuscular Medications

Prescribed to treat epileptic seizures as well as muscle pain caused by injury

Include both muscle relaxants and anticonvulsants

Example muscle relaxants:


Flexeril cyclobenzaprine

Soma carisoprodol

Antiepileptic and Neuromuscular Medications Example anticonvulsants:

Topiramate (Topamax) is also prescribed to treat migraine headaches

Divalproex (Depakote) is also prescribed for bipolar disorder


Depakote divalproex

Dilantin phenytoin

Neurontin gabapentin

Tegretol carbamazepine

Topamax topiramate

Keppra levetiracetam

Antiepileptic and Neuromuscular Medications

Tend to be very sedating Phenytoin (Dilantin) may increase

SWS, decrease alpha, and cause diffuse, slower EEG activity

Anticonvulsants also tend to reduce REM

RLS/PLMD Medications Restless leg syndrome and periodic limb

movement disorder occur in up to 15% of the populationOften occur comorbidly

Frequency of RLS/PLMD increases with age

Historically treated with benzodiazepines, particularly clonazepam (Klonopin)

Newer drugs affect mainly dopamine receptors

RLS/PLMD Medications Examples:

Carbidopa and levodopa (Sinemet) have been reported to induce vivid dreams or nightmares, hallucinations, vocalizations, and somnambulism

○ Rarely used due to the potential for tachyphylaxis and augmentation of symptoms


Sinemet carbidopa/levodopa

Permax pergolide

Mirapex pramipexole

Requip repinirole

Eldepryl selegiline

RLS/PLMD Medications Tend to reduce SWS and REM

Conflicting studies have shown levodopa either increases or decreases REM

Common side effects are nausea and headache, which may also interfere with sleep

Usually improve sleep quality and decrease arousals

Pramipexole (Mirapex) was originally developed to treat Parkinson’s DiseaseMay cause sudden attacks of uncontrollable

sleepiness in some individuals

Antihypertensives Different classes have

different methods of action, but the desired effect is to lower blood pressureClasses include

diuretics, beta-blockers, alpha-beta-blockers, ACE inhibitors, calcium channel blockers, and vasodilators

Examples:


Inderal propranolol

Tenormin atenolol

Lopressor metoprolol

--- pindolol

--- reserpine

Catapres clonidine

Coreg carvedilol

Cozaar losartan

Privinil, Zestril lisinopril

Antihypertensives

May suppress REM and increase SWS Have been reported to cause insomnia,

nightmares, vivid dreams, hallucinations, vocalizations, somnambulism, and EDSMost sleep effects seen with clonidine

(Catapres)Fewest sleep effects seen with atenolol

(Tenormin)

Diuretics

Work by stimulating the kidneys to excrete more sodium into the urineThis draws excess fluid out of cells so it can

be eliminated from the body

Although mainly prescribed to treat high blood pressure, are also commonly used to treat edema caused by heart failure, kidney disease, or liver cirrhosis

Diuretics Examples:

The main effect on sleep is excessive urination, which can cause frequent nocturnal awakenings

A possible side effect is potassium deficiency, which can cause nocturnal cramping of the calf muscles


Bumex bumetanide

Zaroxolyn metolazone

Aquazide, Microzide hydrochlorothiazide (HCTZ)

Lasix furosemide

Hypolipidemics

Work to lower cholesterol by blocking its production by or absorption into the body

Along with antihypertensives, are some of the most common drugs taken by sleep lab patients

Hypolipidemics Examples:

No consistent findings on sleep and wakefulness Insomnia reported rarely with atorvastatin (Lipitor) and

lovastatin (Mevacor, Altoprev)


Caduet amlodipine/atorvastatin

Vytorin ezetimibe/simvastatin

Zetia ezetimibe

Tricor fenofibrate

Lipitor atorvastatin

Mevacor, Altoprev lovastatin

Pravachol pravastatin

Crestor rosuvastatin

Zocor simvastatin

Antiarrhythmatics Work by slowing down the heart rate to

treat fast arrhythmias such as atrial fibrillation, atrial flutter, ventricular fibrillation, and ventricular tachycardia

Includes a vast array of medications that work through a variety of mechanisms

How they affect sleep has been largely inconclusive

Atrialfibrillation

Antiarrhythmatics

Examples:


--- quinidine

Tambocor flecainide

Rythmol propafenone

Ethmozine moricizine

Calan verapamil

Cardizem diltiazem

Procardia nifedipine

Lanoxin digoxin

Coumadin warfarin

Antiarrhythmatics

Most common complaint is daytime fatigue

Most important thing to be aware of with these drugs is that they indicate the patient has a documented history of cardiac arrhythmias, so be very vigilant!

Respiratory Medications The most common respiratory conditions

that require long-term medication are asthma and COPD

Examples:

Theophylline (Aerolate) is chemically related to caffeine, and doses are usually high enough to disrupt sleep


Proventil, Ventolin albuterol

Maxair pirbuterol

Aerolate theophylline

--- aminophylline

Atrovent ipratropium

Respiratory Medications Work by stimulating the central nervous

system, which can cause insomnia, especially if taken shortly before bedtime

Corticosteroids like prednisone are prescribed for asthma as well as for joint pain and inflammationCan cause jitters and insomniaIncrease appetite and can cause fluid

retention○ Any weight gain can increase the risk of OSA

Decongestants Work by reducing blood flow to the mucus

membranes so that less mucus is produced

Examples include oxymetazoline (Afrin), phenylphrine (Contac-D, Sudafed PE), and phenylpropanolamine (Phenyldrine), but most common decongestant is pseudoephedrine

Pseudoephedrine can be found in:Actifed, Advil Cold & Sinus, Aleve Cold & Sinus,

DayQuil, NyQuil, Dimetapp, Robitussin, Sudafed, Triaminic, Tylenol Cold, and most drugs that end in “-D”

Decongestants

Most cause some degree of CNS stimulation, which may result in insomniaParticularly true w/ drugs containing

pseudoephedrine

Pseudoephedrine has been reported to induce hallucinations, vocalizations, and somnambulismEphedrine in brain = adrenaline in body

Antihistamines Work by blocking histamine, a

neurotransmitter that’s responsible for allergy symptoms but that also promotes wakefulness

Examples:Trade name Generic name

Zyrtec cetirizine

Astelin azelastine

Benadryl diphenhydramine

Allegra fexofenadine

Claritin, Alavert loratadine

Clarinex desloratadine

Dramamine dimenhydrinate

Antihistamines Tend to be sedating, and can cause

drowsinessDiphenhydramine (Benadryl) also used as a

sleep aid

Shorten SOL, decrease REM, decrease arousals, and increase TSTNewer antihistamines such as cetirizine

(Zyrtec) have fewer side effects

Taking antihistamines before bed can result in a dry mouth and drowsiness upon awakening

Cold Medications and Antihistamines Many cold medications contain an antihistamine

as well as a decongestant, so side effects may be unpredictable and can vary greatly from one patient to the next

Most cold medications

are available OTC, so

they’re readily

accessible to patients

Alcohol

Affects GABA receptors in the brain Consumed close to bedtime, can

initially be very sedatingAt least 25% of insomniacs report

using alcohol as a sleep aidThose with greater trouble sleeping

are more likely to have diagnosable alcoholism

Alcohol In the first half of the night, NREM is

increased and REM is reduced In the second half of the night,

withdrawal symptoms occur, particularly in heavy drinkersShallow, disrupted sleep; late-night REM

rebound; nightmares; sympathetic nervous system arousal; tachycardia; sweating

Decreases SOL and REM, increased WASO (especially in second half of the night)

Alcohol Relaxes muscles of the upper

airwayThis can cause or worsen snoring and

OSA Alcoholics often report insomnia,

hypersomnia, circadian rhythm disturbances, and parasomniasRecovering alcoholics may have

abnormal sleep patterns for years after becoming sober

Caffeine Binds to adenosine receptors

in the brain, blocking the

sleep-inducing neurotransmitter

adenosine from having an effect Consumption of large amounts may lead

to restlessness, nervousness, excitement, insomnia, flushed face, and GI problems1000mg can produce insomnia, dyspnea,

delirium, and arrhythmiasDoses above 5000mg can be fatal

Caffeine Because it’s so prevalent,

it’s easy to ingest large amounts unintentionally.

Caffeine Chronic daily use leads to tolerance and

dependence Half-life is 3-7 hours, so even caffeine

consumed in the afternoon can disrupt sleep at nightEffect more pronounced in children, pregnant

women, the elderly, and people with hypothyroidism

Increases arousals, decreases TST and SWS Beware that caffeine is present in many

headache medications (e.g., Excedrin Migraine)

Nicotine Approximately 23% of adults in the US use

nicotine products Conflicting reports on how it affects sleep

May be sedating in lower doses but altering in higher doses

Also conflicting reports on how it affects REMSome reports have shown an increase while

others have shown a decrease

Nicotine patches deliver small doses of nicotine into the bloodstream around the clockCan cause insomnia and disturbing dreams

Other Recreational Drugs Marijuana (tetrahydracannibinol)

Effects on sleep very similar to alcoholMay induce sleepiness

OpiatesMay induce sleepiness but cause

REM suppressionCan increase SWS and prevalence of

night terrors and somnambulism

Other Recreational Drugs Amphetamines

Can be useful as prescription stimulants, but some forms (particularly methamphetamine) have a high abuse potential when used as recreational drugs

Effects tend to be dose-dependent, so recreational users may have even more disturbed sleep than those who take prescription amphetamines as prescribed

Helpful Hints Drugs that can cause nightmares or

vivid dreams:Antihistamines, benzodiazepines, beta-

blockers, dopaminergics, isotretinoin, ofloxacin, naproxen, thiothixene, verapamil, varenicline

Drugs that can cause excessive daytime sleepiness:Antihistamines, antihypertensives, anti-

nausea agents, dopamine agonists, antiepileptics

Helpful Hints

Drugs that can cause insomnia:Amphetamines,

antiretrovirals, anti-influenza drugs, cholesterol-lowering drugs, corticosteroids

Helpful Hints Following are some tips for

recognizing the class of unfamiliar drugs

Some precautions:These only work on generic names, as

trademarked drugs are often named arbitrarily and for marketing purposes

These tips aren’t applicable in all cases – they’re a general trend, not a hard and fast rule

Helpful Hints

Generic drug names that: Are usually:

Contain “barb” Barbiturates

End in “-pam” or “-lam” Benzodiazepines

Contain “amphetamine” Amphetamines

End in “-oxetine” or “-pram” SSRI antidepressants

End in “-triptyline” Tricyclic antidepressants

Start or end with “lith” Lithium preparations

End in “-dopa” Dopaminergic Parkinson’s drugs

End in “-lol’ Beta-blockers

Contain “statin" Cholesterol-lowering statins

End in “-buterol” or “-phylline” Respiratory medications

Conclusion The vast array of substances available

to our patients will continually challenge our ability to interpret PSGs

As technologists, we must remain aware of the latest trends in the use and abuse of various drugs

We must know if and how each PSG might be affected by a patient’s medications, including those NOT taken the night of the study

Questions,Concerns,Feedback

Should you have any questions or feedback regarding this presentation please feel free to contact our program director, Jennifer Brickner-York, at [email protected].

Thank You.

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Lenik, S.H. (2009). Handbook for sleep medicine technologists. Denver, CO: Outskirts Press.

Neubauer, D.N. (2008). Medication effects on sleep. (2008). ACCP Sleep Medicine Review Board syllabus book, ed. C.W. Atwood.

Pandi-Perumal, S.R., Ruoti, R.R., & Kramer, M. (Eds.). (2007). Sleep and psychosomatic medicine. Boca Raton, FL: Informa Healthcare.

Silverman, H.M. (1998). The pill book. New York, NY: Bantam.

medication review presentation

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