CNS Exam 3

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1

Intrusive REM sleep episodes can occur during the day with fragmented sleep at night is referred to as what?

Narcolepsy

2

What are the 4 characteristic symptoms of Narcolepsy?

  • Excessive daytime sleepiness
  • Cataplexy
  • Hypnagogic hallucinations that occur at sleep onset
  • Sleep paralysis
3

Weakness or loss of muscle tone is known as what?

Cataplexy

4

Imagined sensations that occur while a person is falling asleep are known as what

Hypnagogic hallucinations

5

Muscle paralysis upon wakening is known as what?

Sleep paralysis

6

Narcolepsy's pathophysiology is still unclear, but appears to involve what system?

hypocretin-orexin system

7

Orexin peptides are released from where?

lateral hypothalamus

8

Orexin acts on what 2 receptors?

  • OX1
  • OX2
9

Orexin acts on its receptors to promote what?

wakefulness

10

Orexin is also involved in what other functions?

  • eating
  • reward
11

What is the pathophysiology of Narcolepsy?

  • Loss of the hypocretin-orexin system in many narcoleptic patients
    • Decreased orexin neurons in lateral and posterior hypothalamus
    • Reduced orexin levels in CSF and brain tissue
12

Pharmacological intervention of narcolepsy is what?

symptomatic

13

Is there a cure for narcolepsy?

No (treated pharmacologically)

14

What drugs help treat EDS?

Stimulants

15

What is the brand name of Modafinil?

Provigil

16

What is the R-isomer of modafinil?

Nuvigil

17

What is the brand name of Armodafinil?

Nuvigil

18

What is the MOA for Modafinil and Armodafinil?

  • Unknown, possibly DAT inhibition
  • In preclinical studies, increases in NE, DA, H neurotransmission have been observed
19

What are some other stimulants used to help treat EDS?

  • Amphetamine
  • Methylphenidate
20

What are the MOA of Amphetamine and Methylphenidate?

Increase catecholamine neurotransmission that leads to wakefulness and alertness

21

Between Modafinil and Armodafinil, which has the longer duration of action?

Armodafinil ( R-isomer)

22

Modafinil appears to be more selective in what area of the brain?

sleep/wake cycle of the hypothalamus

23

Which drug selectively binds to and inhibits DAT and NET?

Solriamfetol

24

What is the brand name of Solriamfetol?

Sunosi

25

What is the drug class of Sunosi?

Dopamine/Norepinephrine reuptake inhibitor

26

Sunosi improves what?

wakefulness

27

Sunosi reduces what?

  • excessive daytime sleepiness (EDS)
28

What form of GHB is gamma-hydroxybutyric acid?

Endogenous

29

What form of GHB is gamma-hydroxybutyrate, sodium salt or sodium oxybate?

Therapeutic

30

What is the brand name of Sodium Oxypate?

Xyrem

31

What is the drug of abuse that is used as a date rape drug?

Illicit GHB

32

What is Xyrem used to treat?

  • Cataplexy
  • EDS
    • in Narcolepsy patients
33

Pharmacological effects of sodium oxybate are due to weak agonist actions at which receptor?

GABAB

34

GABAB is what kind of receptor?

heterodimer (has R1 and R2 subunit)

35

GABAB is linked to which G protein?

Gi

36

Xyrem acts as an agonist at pre- and postsynaptic GABAB receptors and increases what?

inhibitory transmission

37

GABAB receptors are found in high concentrations of which parts of the brain?

  • hippocampus
  • cortex
  • thalamus
38

Xyrem causes slow inhibitory postsynaptic potential by activating what channels?

K+

39

Xyrem causes inhibition of what?

voltage gated Calcium channels (decreasing the release of neurotransmitter)

40

Nightly doses of Sodium Oxybate (Xyrem) cause:

  • Reduction of transitions between wakefulness and REM sleep during the day
  • Reduction of cataplexy during the day
  • Reduction of nocturnal awakenings
  • Increase in slow wave sleep
41

List some clinical uses of sedative-hypnotics:

  • Insomnia
  • Anxiety
  • Sedation and amnesia before and during medical procedures
  • Epilepsy and seizures
42

These drugs decrease activity, calm, and reduce anxiety:

Sedatives

43

What is the MAIN indication of sedatives?

Anxiety

44

These drug produce drowsiness, facilitate onset and maintenance of sleep:

Hypnotics

45

What is the MAIN indication of hypnotics?

Insomnia

46

True or False: A drug with a narrow therapeutic index have a greater risk for unwanted SE.

True

47

List examples of wake-promoting neurotransmitters:

  • Histamine
  • NE
48

Wake-promoting transmitters are balanced by what?

sleep promoting transmitters (especially GABA)

49

What area of the hypothalamus is known as a "sleep-promoter" area?

VLPO (Ventrolateral preoptic area)

50

The VLPO projects inhibitory GABAergic neurons to the wake-promoting centers that include which parts of the brain?

  • tuberomamillary nucleus
  • locus coeruleus
51

What drives regulate the balance between sleep and wakefulness?

  • Circadian
  • homeostatic
52

The sleep-promoting areas and neurotransmitters predominate with GABA tone is known as what?

"off switch"

53

The wake-promoting histamine and other neurotransmitters predominate with activation of wake-promoting neurotransmitter centers and also the cortex is known as what?

"on-switch"

54

What is the brand name of alprazolam?

Xanax

55

What is the brand name of clonazepam?

Klonopin

56

What is the brand name of clorazepate?

Tranxene

57

What is the generic for Valium?

diazepam

58

What is the generic for ativan?

Lorazepam

59

What is the brand name of Quazepam?

Doral

60

What is the generic of temazepam?

Restoril

61

What is the brand name of Triazolam?

Halcion

62

What is the target receptor of benzodiazepines (BZD)?

GABAA receptor

63

What subunits are required for BZD activity?

  • alpha
  • beta
  • gamma
64

BZDs bind to a specific recognition/receptor site located between which subunits?

alpha and gamma

65

Do BZD bind to the same site as GABA?

No (allosteric site between alpha and gamma subunit)

66

Positive allosteric modulation of GABAA receptors do what?

  • Enhance GABA binding
  • Increase in frequency of channel openings
67

Alpha-1 receptors associated with BZD are associated with what?

  • somnolence/sleepiness
  • amnesia
68

Alpha-2 receptors associated with BZD are associated with what?

  • anxiolytic effects
  • muscle relaxation
69

List some areas that BZD receptors are found in the CNS:

  • amygdala
  • brainstem
  • hippocampus
  • hypothalamus
  • prefrontal cortex
  • thalamus
  • SC
70

The vast majority of BZD receptors are which type?

alpha-1

71

Which CNS effect is undetermined in regards to BZD receptors?

Anticonvulsant

72

BZD have what effects on sleep stages (sleeping state)?

  • Decreased sleep latency
  • Decreased number of awakenings
73

What is the time it takes to fall asleep known as?

Sleep latency

74

BZD have an increase in what stage of sleep?

stage 2

75

What sleep time is reduced with the use of a BZD?

  • slow wave
  • REM
76

True or False: The number of REM cycles increases with the use of a BZD.

True

77

The effects of sleep stages are reduced with the what of benzodiazepines?

chronic use

78

A BZD can have what organ system effects?

  • Respiratory
  • CV
79

What are the respiratory system effects of a BZD?

  • Depression in patients with pulmonary disease
  • worsen sleep-related breathing disorders
80

What are the CV system effects of a BZD?

  • Minor in healthy subjects
  • depression in patients with impaired CV function
81

A BZD can suppress what area of the brain?

hypothalamus

82

Which BZD is a prodrug that is converted to active metabolite in gastric juice?

Clorazepate

83

A BZD is highly what?

protein bound (70-99%)

84

Plasma free drug concentration of a BZD is equivalent to what?

CSF concentration

85

Why are benzodiazepines rapidly uptaken into the brain?

Their lipophilicity

86

Benzodiazepines are redistributed into what other tissues?

  • Muscle
  • fat
    • bc of their lipophilicity
87

The metabolism of a BZD is associated with what CYP enzymes?

  • CYP3A4 (mostly)
  • CYP2C19
88

Which benzodiazepines are not hepatically metabolized?

  • lorazepam
  • oxazepam
  • temazepam
89

What are the phase 1 reactions associated with a BZD?

  • N-dealkylation (stage 1)- pretty quick rxn
  • Hydroxylation (stage 2)- little slower rxn
90

Many phase 1 metabolites are what?

active

91

What are the phase 2 reactions of a BZD?

Glucuronide conjugation

92

Which benzodiazepines posses the major route of metabolism via glucuronidation (phase 2)?

  • lorazepam
  • oxazepam
93

Which BZD has a preferred pathway of glucuronidation?

Temazepam

94

Inactive metabolites are produced by which phase of metabolism in regards to a BZD?

Phase II

95

What kind of excretion is associated with phase 2 metabolism of a BZD?

Renal excretion

96

Temazepam is slowly converted into what by CYP (phase 1) metabolism?

Oxazepam

97

If temazepam undergoes CYP metabolism into Oxazepam, what is the next step of metabolism?

Glucuronidation

98

List examples of inhibitors of CYP3A4 that can influence concentration of BZDs:

  • Macrolides
    • Erythromycin
    • Clarithromycin
  • Ritonavir
  • Antifungals
    • Itraconazole
    • Ketoconazole
  • Nefazodone
  • Grapefruit juice
99

A BZD with a shorter half-life may result in what SE?

Rebound insomnia

100

A BZD with a longer half-life may result in what SE?

Hang-over sleepiness

101

A BZD can be grouped by it's what?

half-life

102

Which drug is a competitive antagonist at BZ receptor binding site?

Flumazenil

103

Flumazenil is administered by which route only?

IV only (extensive first pass)

104

How long do the effects of Flumazenil last?

30-60 min

105

Flumazenil is used for which indications?

  • Overdose of BZD
  • Reversal of BZD agonist effects
106

Flumazenil may cause what?

seizures

107

Flumazenil is NOT intended for the overdose of which drugs?

  • Barbiturates
  • TCAs
108

Novel Benzodiazepine Receptor Agonists are known as what?

Z drugs

109

What are the 3 Z drugs?

  • Zolpidem
  • Zaleplon
  • Eszopiclone
110

What is the brand name of Zolpidem?

Ambien

111

What is the brand name of Zaleplon?

Sonata

112

What is the brand name of Eszopliclone?

Lunesta

113

What are the indications of BZDAs (Z drugs)?

Short or long term relief of insomnia

114

BZDAs decrease what?

sleep latency

115

BZDAs have minimal effects on what?

sleep stages

116

Tolerance and dependence may occur with the long-term use of which drugs?

BZDAs (Z drugs)

117

Z drugs are agonists that have high affinity for which subunit GABA-A receptors and bind to the BZD recognition site?

α1 subunit

118

Which drug can be used to reverse the effects of Z drugs?

Flumazenil

119

The absorption of Zolpidem is slowed with what?

food

120

Ambien is extensively metabolized by which CYP?

3A4

121

Late night administration of Zolpidem may cause what?

  • drowsiness
  • delayed reaction time
  • amnesia
122

Eszopliclone is the active enantiomer of what?

zopliclone (not used in U.S.)

123

Lunesta undergoes which metabolism?

  • CYP3A4
  • 2E1
124

Which drug requires IMMEDIATE use at bedtime?

Zaleplon (Sonata)

125

Sonata is mostly metabolized by what?

hepatic aldehyde oxidase (to a lesser extent by CYP3A4)

126

What is the brand name of Ramelteon?

Rozarem

127

What is the drug class of Rozarem?

Melatonin receptor agonist

128

Rozerem binds to which receptors?

  • MT1
  • MT2
129

MT1 and MT2 receptors are found where?

suprachiasmatic nucleus

130

The MT1 receptor promotes what?

sleep onset

131

The MT2 receptor does what?

regulates circadian rhythm

132

Ramelteon is more selective for which receptor?

MT1

133

Ramelteon has a what?

active metabolite

134

Ramelteon decreases what?

sleep latency

135

Ramelteon has no what?

  • rebound insomnia
  • withdrawal symptoms
136

Ramelteon has significant what metabolism?

first-pass

137

What is the main metabolism assoc. w/ Ramelteon?

CYP1A2

138

Which metabolism is also involved with Ramelteon?

CYP2C9

139

Ramelteon has potential drug-drug interactions when used with what of the CYP1A2 and CYP2C9 enzymes?

inhibitors

140

Which drug is used for Non-24-Hour Sleep-Wake Disorder?

Tasimelteon

141

What is the brand name of Tasimelteon?

Hetlioz

142

What is the drug class of Hetlioz?

Melatonin receptor agonist

143

Hetlioz activates the MT1 and MT2 receptors, however has higher affinity for which receptors?

MT2

144

What are the major metabolizers associated with Hetlioz?

  • CYP1A2
  • CYP3A4
145

Hetlioz has potential drug-drug interactions with which inhibitors?

CYP1A2

146

Hetlioz has potential drug-drug interactions with which inducers?

CYP3A4

147

What is the brand name of Suvorexant?

Belsomra

148

Which drugs are considered Novel hypnotic drugs?

  • Tasimelteon (Hetlioz)
  • Suvorexant (Belsomra)
149

What is the drug class of Belsomra?

Orexin receptor antagonist

150

Orexin 1 receptor is a GPCR coupled to which G protein?

Gq

151

Orexin 2 is GPCR coupled to which G protein?

Gq and/or Gi

152
  • Suvorexant competes with WHAT and binds to orexin receptors

orexin

153

Orexin peptides are AKA what?

hypocretins

154

The metabolism of Belsomra is primarily by what?

CYP3A4 (excreted in feces)

155

What are the SE of Belsomra?

  • somnolence
  • signs of narcolepsy (RARE)
156

Orexin peptides are released from where?

lateral hypothalamus

157

Orexin peptides act on their receptors to promote what?

wakefulness

158

Orexin peptides are also involved in what other functions?

  • eating
  • reward
159

OX1 and OX2 are found in wake promoting areas such as the:

  • locus coeruleus
  • tuberomamillary nucleus
160

Which drugs reversibly depress the activity of excitable tissues?

Barbiturates

161

What is the brand name of Amobarbital?

Amytal

162

What is the brand name of Phenobarbital?

Luminal

163

What is the brand name of Butabarbital?

Butisol

164

What is the brand name of Pentobarbital?

Nembutal

165

What are the brand names of Secobarbital?

  • Seconal
  • Tuinal
166

What is the brand name of Methohexital?

Brevital

167

Barbiturates enhance what?

GABA binding

168

Which subunits are required for barbiturate binding?

  • alpha
  • beta
169

True or False: Barbiturates increase the duration of channel opening.

True

170

Barbiturates inhibit which receptors?

AMPA (Glutamate ionotropic receptors)

171

In the PNS, barbiturates depress what?

  • ganglionic and neuromuscular transmission
    • reduce activity of nicotinic receptors (found on NMJ and Ganglion)
172

What effects to barbiturates have on sleep stages?

  • Decreased sleep latency
  • Decreased number of awakenings
  • Slow wave and REM sleep reduced
173

True or False: Barbiturates have significant CV system effects at therapeutic doses.

False; only at high doses

174

Barbiturates in high doses can have what effect on the CV system?

  • Decreased HR and BP
  • Depression of CV reflexes in CHF
175

In hypnotic doses, what are the effects of barbiturates on the respiratory system?

  • Decrease respiratory drive
176

In high doses of barbiturates, what is the effect on the respiratory system?

Respiratory drive eliminated (drug suppresses medullary causing breathing to stop = fatal)

177

Chronic administration of barbiturates have what effects on the liver?

  • Increase in CYP 450 oxidase activity
  • Increase in glucuronyl transferase activity
  • Increase in δ-aminolevulinic acid (ALA) synthetase
178

True or False: Chronic use of barbiturates can affect other drugs in the body by decreasing their strength/effectiveness.

True

179

Which miscellaneous agent is converted to the active compound: trichloroethanol, by alcohol dehydrogenase, and has similar actions to barbiturates?

Chloral hydrate

180

Which miscellaneous agent is approved only for anxiety (nighttime sedative) and has actions similar to BZDs?

Meprobamate

181

Chloral hydrate adverse GI effects on a what?

empty stomach (needs to be taken with food)

182

List some examples of OTC sleep meds:

  • Diphenhydramine (Benadryl, Unisom SleepGels, SleepMelts)
  • Doxylamine (Unisom SleepTabs)
183

What drug class are Diphenhydramine and Doxylamine?

H1 receptor antagonists

184

What SE do Diphenhydramine and Doxylamine produce?

anticholinergic

185

What are the 2 stages of the sleep cycle?

  • NREM
  • REM
186

NREM sleep occurs how long after falling asleep?

less than 45 min

187

When does REM sleep first occur?

70-90 min after falling asleep

188

How long does REM sleep last initially?

5-7 minutes (progressively becomes longer)

189

What is the average amount of sleep required for adults?

7-9 hours

190

Sleep facilitates what things?

  • Hormone release
  • Memory consolidation
  • Tissue repair
191

Which gender predominates in having insomnia?

Women

192

Insomnia is characterized by what?

  • Difficulty falling asleep
  • Difficulty maintaining sleep
  • Experiencing non-restorative sleep
  • Causes significant stress or
    impairment in function
193

Insomnia that is less than 1 week and is self limiting is which class?

Transient

194

What are some causes of Transient insomnia?

  • Acute life stress
  • medical illness
  • anxiety
  • poor sleep habits or travel
195

Short-term Insomnia is considered how long?

1-3 weeks

196

Short-term insomnia is causes by what?

More severe stressors

197

Chronic insomnia is considered to last how long?

> 3 weeks/ 1 month to years

198

Chronic insomnia is frequently comorbid with what conditions?

psychiatric/medical conditions

199

List the stimulus control counseling points for non-pharm therapy for sleep disorders:

  • Establish a regular sleep pattern: Go to bed and arise at about the same time daily, even on the weekends
  • Sleep only as much as necessary, go to bed only when sleepy and use bed for sleeping or intimacy only
  • If unable to fall asleep (within 20-30 minutes), do not continue to try to sleep; rather, perform a relaxing activity until you feel tired
  • Avoid daytime napping
  • Schedule “worry time” during the day
200

List the Good sleep hygiene counseling points for non-pharm therapy for sleep disorders:

  • Exercise regularly (3-4x/week) but not within 2–4 hours of bedtime
  • Make the bedroom comfortable for sleeping. Avoid temperature extremes, noise, and light
  • Avoid using caffeine, alcohol, or nicotine for at least 4–6 hours before bedtime
  • If hungry, eat a light snack, but avoid eating meals within 2 hours before bedtime and avoid drinking large quantities of liquid
  • Engage in “relaxing and enjoyable activities” before bedtime
201

Are there guidelines for chronic insomnia?

No

202

What is the MOA for antihistamines used for sleep disorders?

Blocks histamine1 and muscarinic receptors

203

What are some OTC antihistamines indicated for sleep?

  • Diphenhydramine (only FDA approved)
  • Doxylamine
204

What is the dosing regimen for Diphenhydramine for sleep?

25-50 mg QHS

205

What is the dosing regimen for Doxylamine for sleep?

25-100 mg QHS

206

What is the maximum duration for antihistamines used for sleep?

14 consecutive nights

207

List some contraindications for antihistamines used for sleep:

  • Angle closure glaucoma
  • Male patients of advanced age
  • CV disease
  • Dementia
208

For special populations of patients (pregnancy, children, geriatrics, etc.) what should be recommended regarding oral antihistamines for sleep?

Refer them to healthcare provider

209

If a patient is recommended to take melatonin, when should they take the medicine?

1 hour prior to bedtime

210

If a patient is taking Valerian root for sleep, how long should they take it before bed?

1/2-2 hours

211

How long would it take for Valerian root to reach optimal effect?

2-4 weeks

212

Why should Valerian root NOT be recommended for sleep?

Teratogenic and hepatic toxicity

213

What is a central nervous system stimulant and depressant?

Alcohol

214

BZDRA bind to which receptors in the brain?

GABAA

215

Traditional BZDs increase what stage of sleep?

stage 2

216

Traditional BZDs decrease which sleep stages?

  • REM
  • Stage 3
  • Stage 4
217

Traditional BZDs should be avoided in which patients?

  • Pregnant
  • History of substance abuse
218

Long term efficacy is not established for traditional BZDs, therefore should be used for how long?

14-28 days

219

List some adverse effects of traditional BZDs:

  • Dose dependent
  • Greatest potential for daytime sedation with high doses and long or intermediate half-lives and in elderly
  • Anterograde amnesia
  • Rebound insomnia
220

Which Z drug has rapid onset, and the shortest half life?

Zaleplon

221

Zaleplon selectively binds to which receptor?

BZ-1

222

Zaleplon is BEST used as a sleep aid for what?

middle-of-the-night awakenings

223

Plasma levels are increased with the use of Zaleplon and which drug?

Cimetidine (CYP inhibitor)

224

Plasma levels are decreased with the use of Zaleplon and which drug?

Rifampin (CYP inducer)

225

Zolpidem binds to receptor?

BZ-1

226

What is the maximum strength of Zalpleon or Zolpidem in elderly patients?

5 mg

227

Zolpidem has what kind of half-life?

Intermediate (6-8 hours)

228

What is the maximum initiation strength of Zolpidem for women?

5 mg (due to next morning impairment --> may titrate up to 10 mg PRN)

229

Which Z drug has a rapid onset, longer half-life, duration?

Eszopiclone

230

Lunesta is a better option for what?

  • sleep maintenance insomnia
  • early morning awakenings
231

Lunesta may be taken for up to how long?

6 months

232

What are the doses of Lunesta?

1, 2, or 3 mg

233

What is the max dose of Lunesta for elderly patients?

2 mg

234

What is the most unique SE of Lunesta?

Unpleasant taste (metallic taste)

235

Rozerem is selective for which receptors?

  • MT1
  • MT2
236

Rozerem regulates what?

  • Circadian rhythm
  • Sleep onset
237

How many active metabolites does Rozerem have?

1

238

How is Rozerem taken?

8 mg within 30 min of bedtime on empty stomach

239

Rozerem is viable option for what patients?

Those who have history of substance abuse

240

True or False: Rozerem has no next day somnolence or withdrawal effects.

True

241

Rozerem is metabolized primarily by which enzyme?

CYP1A2

242

Which patients would need a higher dose of Rozerem?

Smokers (smoking is CYP1A2 inducer)

243

What is the brand name of Suvorexant?

Belsomra

244

What is the drug class of Belsomra?

Orexin receptor antagonist

245

Orexin helps regulate what?

Wakefulness

246

What is the dosing of Belsomra?

10-20 mg 20 minutes before bed

247

Which drugs are alternatives for patients with nonrestorative sleep who should not receive benzodiazepines?

Antidepressants

248

Are lower or higher doses of antidepressants used for sleep?

Lower

249

List some TCAs used for sleep:

  • Amitriptyline
  • Nortriptyline
  • Doxepin
250

What is the downfall of antidepressants used for sleep?

Significant daytime sedation and side effects

251

Which antidepressant results in daytime sedation and weight gain?

Mirtazepine

252

What is a 2nd line drug for transient/short-term insomnia?

Trazodone

253

What is the dosing for Trazodone for insomnia?

25-100 mg at bedtime

254

Trazodone may be used for insomnia that is induced with other drugs. What are other drugs that can induce this insomnia (antidepressants)?

  • SSRI
  • Bupropion
255

What are the SE associated with taking Trazodone for insomnia?

  • Carry over sedation
  • Orthostasis (dizziness, blood pressure bottoms)
  • Priapism (erection lasting more than 4 hours)
256

Orthostasis is associated with which receptor?

alpha-1

257

What are the Guidelines for pharmacists related to BZDRAs for transient or short-term insomnia?

  • BZDRAs 3-4 nights/week for 3-4 weeks (short term)
  • Monitor
    • Falling asleep (in < 2 hours), maintaining sleep, rest, daytime fatigue, and concentration
    • Tolerance and dependence
  • Rebound insomnia or withdrawal effects
    • Taper dose (slowly pull Pt. off)
  • Consider special populations
  • Ramelteon now alternative first line
258

What is defined as no air flow at the nose and mouth for at least 10 seconds?

Sleep Apnea

259

How many episodes/hour is mild sleep apnea?

5-15 episodes/hour

260

How many episodes/hour is severe sleep apnea?

> 30 episodes/hour

261

How many episodes/hour is moderate sleep apnea?

15-30 episodes/hour

262

What are the components of obstructive sleep apnea (OSA)?

  • Caused by upper airway collapse and obstruction
  • Loud snores or brief gasps that alternate with episodes of silence that lasts 20-30 second
  • Disturbs partner; subject is often unaware
  • Cessation of breathing 60-90 seconds with cyanosis
  • Most subjects are overweight
263

What are the components of central sleep apnea (CSA)?

  • Temporary loss of respiration during sleep- impaired respiratory drive
  • Treatment is with PAP and ventilatory O2
264

What are some complications of OSA?

  • Arrhythmias
  • hypertension
  • pulmonary heart disease
  • sudden death
265

What are symptoms of OSA?

  • Daytime headache
  • poor memory
  • irritability
266

What is the pathophysiology of OSA?

Airflow ceases --> episode stops by a reflex action from the decrease in O2 --> arousal --> breathing resumes

267

What is the treatment for OSA?

  • Nonpharmacologic: Weight loss, removal of obstruction (e.g. tonsillectomy)
  • No drug therapy
268

Which drug is used to promote wakefulness with OSA?

Modafinil

269

What are some stimulants that are used for Narcolepsy?

  • Dextroamphetamine
  • Methylphenidate
270

What is the standard treatment for EDS associated with Narcolepsy?

Modafinil

271

Modafinil is what enzyme inducer?

CYP3A4

272

Modafinil is what enzyme inhibitor?

CYP2C19

273

What are the most effective agents for cataplexy associated with narcolepsy?

  • TCAs
  • Venlafaxine
  • Fluoxetine
274

True or False: The dosing of Fluoxetine for cataplexy associated with narcolepsy is the same dosing as depression.

True

275

Which drug is effective for hypersomnia and cataplexy?

Selegiline

276

What is the dosing of Sodium oxybate?

2.25 grams 2-4 hours before bedtime and 2.25 grams right at bedtime

277

What is the dosing of Sunosi for narcolepsy?

75 mg daily

278

What is the dosing of Sunosi for OSA?

37.5 mg daily

279

What is the max dose of Sunosi?

150 mg daily

280

Sunosi must be avoided how long before bedtime?

9 hours (TAKE IN THE MORNING)

281

The sleep-wake cycle is under what?

Circadian control

282

Circadian rhythm sleep disorders present with what 2 disorders (either/or)

insomnia or hypersomnia

283

What are 2 common examples of circadian sleep disorders?

  • Jet lag
  • Shirt work sleep disorder (SWSD)
284

What is the first drug to treat circadian rhythm sleep disorder in the blind?

Tasimelteon (Hetlioz)

285

Sleep disturbance assoc. w/ jet lag typically lasts how long?

2-3 days

286

Which travel is associated with a longer duration of jet lag?

Eastward

287

What treatments (short-term) are used for jet lag?

  • Short-acting benzodiazepine receptor agonists
  • Ramelteon
  • Melatonin 0.5-5 mg at bedtime
288

Insomnia or excessive sleepiness that occurs because of working shifts during normal sleep time is known as what?

Shift work sleep disorder

289

What are the treatments for SWSD?

  • Short-acting benzodiazepine receptor agonists
  • Melatonin
  • Ramelteon
  • Modafinil FDA approved to improve wakefulness
290

Parethesias usually felt deep in calf muscles with urge to keep limbs in motion is known as what?

Ekbom syndrome

291

Ekbom syndrome is associated with what sleep disorder?

Restless leg syndrome (RLS)

292

What are the symptoms of RLS?

  • Urge to move limbs usually associated with uncomfortable and unpleasant sensations
  • Begin or worsen during rest/inactivity
  • Exclusively present or worse in evening/night
  • Temporarily relieved by movement
293

Which drugs are first line therapy for RLS?

Dopamine agonists

294

Which DA agonists are FDA approved for RLS?

  • Ropinirole
  • Pramipexole
    • lower doses
295

Ropinirole and Pramipexole are indicated also for what?

Parkinson's disease

296

If frequent awakenings occur with RLS, what drugs are used?

Sedative hypnotics

297

What is the most frequently studied sedative hypnotic associated with RLS?

Clonazepam (0.5-2 mg)

298

What are other drugs used for RLS that have a shorter half-life and lack carry over sedation?

  • Zolpidem
  • Zaleplon
  • Triazolam
299

What drug can be used for painful RLS?

Gabapentin (300-900 mg near bedtime)

300

Abnormal behavior or physiologic events that either occur during sleep or are exaggerated by sleep are known as what?

Parasomnias

301

List some examples of Parasomnias:

  • Sleep walking and sleep terrors
  • Sleep talking
  • REM behavior disorders and nightmares
  • Enuresis (urinating in sleep) and bruxism (grinding teeth)
302

Which drug is the treatment of choice for REM behavior disorder?

Clonazepam

303

Sleep walking and sleep terrors may be treated with what drugs?

  • SSRIs
  • BZDs
  • TCAs
304

Alpha-2 on GABAA is responsible for what?

anxiolytic effects

305

Alpha-3 on GABAA is responsible for what?

muscle relaxant effects

306

Alpha-5 on GABAA is responsible for what?

anticonvulsant effects

307

Alpha-1 on GABAA is responsible for what?

Somnolence effects

308

Picotoxin is a toxin that derives from a plant or shrub that causes what?

Convulsions

309

Picotoxin inhibits what?

GABA function

310

Barbituate binding on AMPA receptors results in what?

Blocking the channel

311

Thiobarbituates are not useful for insomnia, but are useful for what?

Anesthesia (sulfur group present)

312

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?

  • Quazepam
  • Flurazepam
313

BZDs that are metabolized at the top of their structures will have what?

Longer 1/2 lives

314

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

315

Which BZD possesses a Nitro group (N2O) and therefore is 7-10 times more potent than other BZDs?

Flunitrazepam

316

Flunitrazepam causes what?

Anterograde amnesia

317

Which Z drug has the greatest potency?

Zolpidem

318

Zolpidem is highly selective for which subunit?

alpha-1

319

The p-CH3 groups on FRAR and PAR of zolpidem are responsible for what?

alpha-1 selectivity

320

The removal of imidazole N of ERR of zolpidem leads to what?

complete loss of selectivity

321

The antiplanar (AP) region of zolpidem is responsible for what?

binding affinity and selectivity

322

Which enzyme is responsible for giving us the primary active metabolite in Zolpidem?

Alcohol dehydrogenase

323

What inhibits alcohol dehydrogenase?

Disulferism (Antabuse)

324

Which drug's binding site overlaps BZ site, but does not act like classical BZ's?

Eszipiclone (Lunesta)

325

Lunesta has a high affinity for which subunits?

  • alpha-1
  • alpha-3
326

Which Z drug is structurally unrelated to the others?

Zaleplon (Sonata)

327

Sonata has an affinity for which subunits?

  • alpha 1 (high)
  • alpha 5 (some)
328

Sonata has a weak SAR, but what distinct group on its structure seems to be important for binding?

CN

329

What is the major metabolism route for Sonata?

Aldehyde oxidase

330

Chloral hydrate is used for which patients?

Pediatrics

331

What is the prolonged active metabolite of Chloral hydrate?

trichloroethanol

332

What converts chloral into trichloroethanol?

alcohol dehydrogenase

333

H1 receptors are highly localized where?

  • Hypothalamus
    • Tuberomammillary nucleus
    • suprachiasmatic nucleus
334

Do H1 receptor antagonists that don't penetrate the brain cause sleepiness?

NO

335

Suvorexant (Belsomra) is heavily oxidized by what?

CYP3A4