335 notecards = 84 pages (4 cards per page)
Intrusive REM sleep episodes can occur during the day with fragmented sleep at night is referred to as what?
What are the 4 characteristic symptoms of Narcolepsy?
Weakness or loss of muscle tone is known as what?
Imagined sensations that occur while a person is falling asleep are known as what
Muscle paralysis upon wakening is known as what?
Narcolepsy's pathophysiology is still unclear, but appears to involve what system?
Orexin peptides are released from where?
Orexin acts on what 2 receptors?
Orexin acts on its receptors to promote what?
Orexin is also involved in what other functions?
What is the pathophysiology of Narcolepsy?
Pharmacological intervention of narcolepsy is what?
Is there a cure for narcolepsy?
No (treated pharmacologically)
What drugs help treat EDS?
What is the brand name of Modafinil?
What is the R-isomer of modafinil?
What is the brand name of Armodafinil?
What is the MOA for Modafinil and Armodafinil?
What are some other stimulants used to help treat EDS?
What are the MOA of Amphetamine and Methylphenidate?
Increase catecholamine neurotransmission that leads to wakefulness and alertness
Between Modafinil and Armodafinil, which has the longer duration of action?
Armodafinil ( R-isomer)
Modafinil appears to be more selective in what area of the brain?
sleep/wake cycle of the hypothalamus
Which drug selectively binds to and inhibits DAT and NET?
What is the brand name of Solriamfetol?
What is the drug class of Sunosi?
Dopamine/Norepinephrine reuptake inhibitor
Sunosi improves what?
Sunosi reduces what?
What form of GHB is gamma-hydroxybutyric acid?
What form of GHB is gamma-hydroxybutyrate, sodium salt or sodium oxybate?
What is the brand name of Sodium Oxypate?
What is the drug of abuse that is used as a date rape drug?
What is Xyrem used to treat?
Pharmacological effects of sodium oxybate are due to weak agonist actions at which receptor?
GABAB is what kind of receptor?
heterodimer (has R1 and R2 subunit)
GABAB is linked to which G protein?
Xyrem acts as an agonist at pre- and postsynaptic GABAB receptors and increases what?
GABAB receptors are found in high concentrations of which parts of the brain?
Xyrem causes slow inhibitory postsynaptic potential by activating what channels?
Xyrem causes inhibition of what?
voltage gated Calcium channels (decreasing the release of neurotransmitter)
Nightly doses of Sodium Oxybate (Xyrem) cause:
List some clinical uses of sedative-hypnotics:
These drugs decrease activity, calm, and reduce anxiety:
What is the MAIN indication of sedatives?
These drug produce drowsiness, facilitate onset and maintenance of sleep:
What is the MAIN indication of hypnotics?
True or False: A drug with a narrow therapeutic index have a greater risk for unwanted SE.
List examples of wake-promoting neurotransmitters:
Wake-promoting transmitters are balanced by what?
sleep promoting transmitters (especially GABA)
What area of the hypothalamus is known as a "sleep-promoter" area?
VLPO (Ventrolateral preoptic area)
The VLPO projects inhibitory GABAergic neurons to the wake-promoting centers that include which parts of the brain?
What drives regulate the balance between sleep and wakefulness?
The sleep-promoting areas and neurotransmitters predominate with GABA tone is known as what?
The wake-promoting histamine and other neurotransmitters predominate with activation of wake-promoting neurotransmitter centers and also the cortex is known as what?
What is the brand name of alprazolam?
What is the brand name of clonazepam?
What is the brand name of clorazepate?
What is the generic for Valium?
What is the generic for ativan?
What is the brand name of Quazepam?
What is the generic of temazepam?
What is the brand name of Triazolam?
What is the target receptor of benzodiazepines (BZD)?
What subunits are required for BZD activity?
BZDs bind to a specific recognition/receptor site located between which subunits?
alpha and gamma
Do BZD bind to the same site as GABA?
No (allosteric site between alpha and gamma subunit)
Positive allosteric modulation of GABAA receptors do what?
Alpha-1 receptors associated with BZD are associated with what?
Alpha-2 receptors associated with BZD are associated with what?
List some areas that BZD receptors are found in the CNS:
The vast majority of BZD receptors are which type?
Which CNS effect is undetermined in regards to BZD receptors?
BZD have what effects on sleep stages (sleeping state)?
What is the time it takes to fall asleep known as?
BZD have an increase in what stage of sleep?
What sleep time is reduced with the use of a BZD?
True or False: The number of REM cycles increases with the use of a BZD.
The effects of sleep stages are reduced with the what of benzodiazepines?
A BZD can have what organ system effects?
What are the respiratory system effects of a BZD?
What are the CV system effects of a BZD?
A BZD can suppress what area of the brain?
Which BZD is a prodrug that is converted to active metabolite in gastric juice?
A BZD is highly what?
protein bound (70-99%)
Plasma free drug concentration of a BZD is equivalent to what?
Why are benzodiazepines rapidly uptaken into the brain?
Benzodiazepines are redistributed into what other tissues?
The metabolism of a BZD is associated with what CYP enzymes?
Which benzodiazepines are not hepatically metabolized?
What are the phase 1 reactions associated with a BZD?
Many phase 1 metabolites are what?
What are the phase 2 reactions of a BZD?
Which benzodiazepines posses the major route of metabolism via glucuronidation (phase 2)?
Which BZD has a preferred pathway of glucuronidation?
Inactive metabolites are produced by which phase of metabolism in regards to a BZD?
What kind of excretion is associated with phase 2 metabolism of a BZD?
Temazepam is slowly converted into what by CYP (phase 1) metabolism?
If temazepam undergoes CYP metabolism into Oxazepam, what is the next step of metabolism?
List examples of inhibitors of CYP3A4 that can influence concentration of BZDs:
A BZD with a shorter half-life may result in what SE?
A BZD with a longer half-life may result in what SE?
A BZD can be grouped by it's what?
Which drug is a competitive antagonist at BZ receptor binding site?
Flumazenil is administered by which route only?
IV only (extensive first pass)
How long do the effects of Flumazenil last?
Flumazenil is used for which indications?
Flumazenil may cause what?
Flumazenil is NOT intended for the overdose of which drugs?
Novel Benzodiazepine Receptor Agonists are known as what?
What are the 3 Z drugs?
What is the brand name of Zolpidem?
What is the brand name of Zaleplon?
What is the brand name of Eszopliclone?
What are the indications of BZDAs (Z drugs)?
Short or long term relief of insomnia
BZDAs decrease what?
BZDAs have minimal effects on what?
Tolerance and dependence may occur with the long-term use of which drugs?
BZDAs (Z drugs)
Z drugs are agonists that have high affinity for which subunit GABA-A receptors and bind to the BZD recognition site?
Which drug can be used to reverse the effects of Z drugs?
The absorption of Zolpidem is slowed with what?
Ambien is extensively metabolized by which CYP?
Late night administration of Zolpidem may cause what?
Eszopliclone is the active enantiomer of what?
zopliclone (not used in U.S.)
Lunesta undergoes which metabolism?
Which drug requires IMMEDIATE use at bedtime?
Sonata is mostly metabolized by what?
hepatic aldehyde oxidase (to a lesser extent by CYP3A4)
What is the brand name of Ramelteon?
What is the drug class of Rozarem?
Melatonin receptor agonist
Rozerem binds to which receptors?
MT1 and MT2 receptors are found where?
The MT1 receptor promotes what?
The MT2 receptor does what?
regulates circadian rhythm
Ramelteon is more selective for which receptor?
Ramelteon has a what?
Ramelteon decreases what?
Ramelteon has no what?
Ramelteon has significant what metabolism?
What is the main metabolism assoc. w/ Ramelteon?
Which metabolism is also involved with Ramelteon?
Ramelteon has potential drug-drug interactions when used with what of the CYP1A2 and CYP2C9 enzymes?
Which drug is used for Non-24-Hour Sleep-Wake Disorder?
What is the brand name of Tasimelteon?
What is the drug class of Hetlioz?
Melatonin receptor agonist
Hetlioz activates the MT1 and MT2 receptors, however has higher affinity for which receptors?
What are the major metabolizers associated with Hetlioz?
Hetlioz has potential drug-drug interactions with which inhibitors?
Hetlioz has potential drug-drug interactions with which inducers?
What is the brand name of Suvorexant?
Which drugs are considered Novel hypnotic drugs?
What is the drug class of Belsomra?
Orexin receptor antagonist
Orexin 1 receptor is a GPCR coupled to which G protein?
Orexin 2 is GPCR coupled to which G protein?
Gq and/or Gi
Orexin peptides are AKA what?
The metabolism of Belsomra is primarily by what?
CYP3A4 (excreted in feces)
What are the SE of Belsomra?
Orexin peptides are released from where?
Orexin peptides act on their receptors to promote what?
Orexin peptides are also involved in what other functions?
OX1 and OX2 are found in wake promoting areas such as the:
Which drugs reversibly depress the activity of excitable tissues?
What is the brand name of Amobarbital?
What is the brand name of Phenobarbital?
What is the brand name of Butabarbital?
What is the brand name of Pentobarbital?
What are the brand names of Secobarbital?
What is the brand name of Methohexital?
Barbiturates enhance what?
Which subunits are required for barbiturate binding?
True or False: Barbiturates increase the duration of channel opening.
Barbiturates inhibit which receptors?
AMPA (Glutamate ionotropic receptors)
In the PNS, barbiturates depress what?
What effects to barbiturates have on sleep stages?
True or False: Barbiturates have significant CV system effects at therapeutic doses.
False; only at high doses
Barbiturates in high doses can have what effect on the CV system?
In hypnotic doses, what are the effects of barbiturates on the respiratory system?
In high doses of barbiturates, what is the effect on the respiratory system?
Respiratory drive eliminated (drug suppresses medullary causing breathing to stop = fatal)
Chronic administration of barbiturates have what effects on the liver?
True or False: Chronic use of barbiturates can affect other drugs in the body by decreasing their strength/effectiveness.
Which miscellaneous agent is converted to the active compound: trichloroethanol, by alcohol dehydrogenase, and has similar actions to barbiturates?
Which miscellaneous agent is approved only for anxiety (nighttime sedative) and has actions similar to BZDs?
Chloral hydrate adverse GI effects on a what?
empty stomach (needs to be taken with food)
List some examples of OTC sleep meds:
What drug class are Diphenhydramine and Doxylamine?
H1 receptor antagonists
What SE do Diphenhydramine and Doxylamine produce?
What are the 2 stages of the sleep cycle?
NREM sleep occurs how long after falling asleep?
less than 45 min
When does REM sleep first occur?
70-90 min after falling asleep
How long does REM sleep last initially?
5-7 minutes (progressively becomes longer)
What is the average amount of sleep required for adults?
Sleep facilitates what things?
Which gender predominates in having insomnia?
Insomnia is characterized by what?
Insomnia that is less than 1 week and is self limiting is which class?
What are some causes of Transient insomnia?
Short-term Insomnia is considered how long?
Short-term insomnia is causes by what?
More severe stressors
Chronic insomnia is considered to last how long?
> 3 weeks/ 1 month to years
Chronic insomnia is frequently comorbid with what conditions?
List the stimulus control counseling points for non-pharm therapy for sleep disorders:
List the Good sleep hygiene counseling points for non-pharm therapy for sleep disorders:
Are there guidelines for chronic insomnia?
What is the MOA for antihistamines used for sleep disorders?
Blocks histamine1 and muscarinic receptors
What are some OTC antihistamines indicated for sleep?
What is the dosing regimen for Diphenhydramine for sleep?
25-50 mg QHS
What is the dosing regimen for Doxylamine for sleep?
25-100 mg QHS
What is the maximum duration for antihistamines used for sleep?
14 consecutive nights
List some contraindications for antihistamines used for sleep:
For special populations of patients (pregnancy, children, geriatrics, etc.) what should be recommended regarding oral antihistamines for sleep?
Refer them to healthcare provider
If a patient is recommended to take melatonin, when should they take the medicine?
1 hour prior to bedtime
If a patient is taking Valerian root for sleep, how long should they take it before bed?
How long would it take for Valerian root to reach optimal effect?
Why should Valerian root NOT be recommended for sleep?
Teratogenic and hepatic toxicity
What is a central nervous system stimulant and depressant?
BZDRA bind to which receptors in the brain?
Traditional BZDs increase what stage of sleep?
Traditional BZDs decrease which sleep stages?
Traditional BZDs should be avoided in which patients?
Long term efficacy is not established for traditional BZDs, therefore should be used for how long?
List some adverse effects of traditional BZDs:
Which Z drug has rapid onset, and the shortest half life?
Zaleplon selectively binds to which receptor?
Zaleplon is BEST used as a sleep aid for what?
Plasma levels are increased with the use of Zaleplon and which drug?
Cimetidine (CYP inhibitor)
Plasma levels are decreased with the use of Zaleplon and which drug?
Rifampin (CYP inducer)
Zolpidem binds to receptor?
What is the maximum strength of Zalpleon or Zolpidem in elderly patients?
Zolpidem has what kind of half-life?
Intermediate (6-8 hours)
What is the maximum initiation strength of Zolpidem for women?
5 mg (due to next morning impairment --> may titrate up to 10 mg PRN)
Which Z drug has a rapid onset, longer half-life, duration?
Lunesta is a better option for what?
Lunesta may be taken for up to how long?
What are the doses of Lunesta?
1, 2, or 3 mg
What is the max dose of Lunesta for elderly patients?
What is the most unique SE of Lunesta?
Unpleasant taste (metallic taste)
Rozerem is selective for which receptors?
Rozerem regulates what?
How many active metabolites does Rozerem have?
How is Rozerem taken?
8 mg within 30 min of bedtime on empty stomach
Rozerem is viable option for what patients?
Those who have history of substance abuse
True or False: Rozerem has no next day somnolence or withdrawal effects.
Rozerem is metabolized primarily by which enzyme?
Which patients would need a higher dose of Rozerem?
Smokers (smoking is CYP1A2 inducer)
What is the brand name of Suvorexant?
What is the drug class of Belsomra?
Orexin receptor antagonist
Orexin helps regulate what?
What is the dosing of Belsomra?
10-20 mg 20 minutes before bed
Which drugs are alternatives for patients with nonrestorative sleep who should not receive benzodiazepines?
Are lower or higher doses of antidepressants used for sleep?
List some TCAs used for sleep:
What is the downfall of antidepressants used for sleep?
Significant daytime sedation and side effects
Which antidepressant results in daytime sedation and weight gain?
What is a 2nd line drug for transient/short-term insomnia?
What is the dosing for Trazodone for insomnia?
25-100 mg at bedtime
Trazodone may be used for insomnia that is induced with other drugs. What are other drugs that can induce this insomnia (antidepressants)?
What are the SE associated with taking Trazodone for insomnia?
Orthostasis is associated with which receptor?
What are the Guidelines for pharmacists related to BZDRAs for transient or short-term insomnia?
What is defined as no air flow at the nose and mouth for at least 10 seconds?
How many episodes/hour is mild sleep apnea?
How many episodes/hour is severe sleep apnea?
> 30 episodes/hour
How many episodes/hour is moderate sleep apnea?
What are the components of obstructive sleep apnea (OSA)?
What are the components of central sleep apnea (CSA)?
What are some complications of OSA?
What are symptoms of OSA?
What is the pathophysiology of OSA?
Airflow ceases --> episode stops by a reflex action from the decrease in O2 --> arousal --> breathing resumes
What is the treatment for OSA?
Which drug is used to promote wakefulness with OSA?
What are some stimulants that are used for Narcolepsy?
What is the standard treatment for EDS associated with Narcolepsy?
Modafinil is what enzyme inducer?
Modafinil is what enzyme inhibitor?
What are the most effective agents for cataplexy associated with narcolepsy?
True or False: The dosing of Fluoxetine for cataplexy associated with narcolepsy is the same dosing as depression.
Which drug is effective for hypersomnia and cataplexy?
What is the dosing of Sodium oxybate?
2.25 grams 2-4 hours before bedtime and 2.25 grams right at bedtime
What is the dosing of Sunosi for narcolepsy?
75 mg daily
What is the dosing of Sunosi for OSA?
37.5 mg daily
What is the max dose of Sunosi?
150 mg daily
Sunosi must be avoided how long before bedtime?
9 hours (TAKE IN THE MORNING)
The sleep-wake cycle is under what?
Circadian rhythm sleep disorders present with what 2 disorders (either/or)
insomnia or hypersomnia
What are 2 common examples of circadian sleep disorders?
What is the first drug to treat circadian rhythm sleep disorder in the blind?
Sleep disturbance assoc. w/ jet lag typically lasts how long?
Which travel is associated with a longer duration of jet lag?
What treatments (short-term) are used for jet lag?
Insomnia or excessive sleepiness that occurs because of working shifts during normal sleep time is known as what?
Shift work sleep disorder
What are the treatments for SWSD?
Parethesias usually felt deep in calf muscles with urge to keep limbs in motion is known as what?
Ekbom syndrome is associated with what sleep disorder?
Restless leg syndrome (RLS)
What are the symptoms of RLS?
Which drugs are first line therapy for RLS?
Which DA agonists are FDA approved for RLS?
Ropinirole and Pramipexole are indicated also for what?
If frequent awakenings occur with RLS, what drugs are used?
What is the most frequently studied sedative hypnotic associated with RLS?
Clonazepam (0.5-2 mg)
What are other drugs used for RLS that have a shorter half-life and lack carry over sedation?
What drug can be used for painful RLS?
Gabapentin (300-900 mg near bedtime)
Abnormal behavior or physiologic events that either occur during sleep or are exaggerated by sleep are known as what?
List some examples of Parasomnias:
Which drug is the treatment of choice for REM behavior disorder?
Sleep walking and sleep terrors may be treated with what drugs?
Alpha-2 on GABAA is responsible for what?
Alpha-3 on GABAA is responsible for what?
muscle relaxant effects
Alpha-5 on GABAA is responsible for what?
Alpha-1 on GABAA is responsible for what?
Picotoxin is a toxin that derives from a plant or shrub that causes what?
Picotoxin inhibits what?
Barbituate binding on AMPA receptors results in what?
Blocking the channel
Thiobarbituates are not useful for insomnia, but are useful for what?
Anesthesia (sulfur group present)
Which 2 BZDs have major metabolite half-lives and therefore would not be ideal for everyday use for someone who goes to work every day?
BZDs that are metabolized at the top of their structures will have what?
Longer 1/2 lives
BZDs that have the 4th ring at the top causing metabolism to occur at the bottom of the structure will have what?
Shorter 1/2 lives
Which BZD possesses a Nitro group (N2O) and therefore is 7-10 times more potent than other BZDs?
Flunitrazepam causes what?
Which Z drug has the greatest potency?
Zolpidem is highly selective for which subunit?
The p-CH3 groups on FRAR and PAR of zolpidem are responsible for what?
The removal of imidazole N of ERR of zolpidem leads to what?
complete loss of selectivity
The antiplanar (AP) region of zolpidem is responsible for what?
binding affinity and selectivity
Which enzyme is responsible for giving us the primary active metabolite in Zolpidem?
What inhibits alcohol dehydrogenase?
Which drug's binding site overlaps BZ site, but does not act like classical BZ's?
Lunesta has a high affinity for which subunits?
Which Z drug is structurally unrelated to the others?
Sonata has an affinity for which subunits?
Sonata has a weak SAR, but what distinct group on its structure seems to be important for binding?
What is the major metabolism route for Sonata?
Chloral hydrate is used for which patients?
What is the prolonged active metabolite of Chloral hydrate?
What converts chloral into trichloroethanol?
H1 receptors are highly localized where?
Do H1 receptor antagonists that don't penetrate the brain cause sleepiness?
Suvorexant (Belsomra) is heavily oxidized by what?