4.5 Pharmacology of anxiolytics and sedative hypnotics

Question 1

Where are the GABAb receptor located?

Answer 1

• Brain
• Limbic system

Question 2

How does GABAb receptor have inhibitory effects on the pre- and post- synapses?

Answer 2

• Presynaptic: decrease Ca2+ conductance
• Postsynaptic: Increase K conductance

Question 3

What drug is a GABAb receptor agonist?

Answer 3

Xyrem (sodium oxybate salt of GHB)

Question 4

What are the two classes of Xyrem and what are their uses?

Answer 4

• C1: illicit use
• C3: Medical use (liquid)

Question 5

Who is xyrem available to?

Answer 5

Available only to prescribers enrolled in xyrem pt success program

Question 6

What does the use of xyrem w concomitant stimulant lead to?

Answer 6

• Decrease excessive daytime sleepiness
• Increase daytime wakefulness

Question 7

What effect does GHB have on the CNS?

Answer 7

Can cause CNS depression

Question 8

What is the severity of GHB’s CNS depression dependent on?

Answer 8

Dose dependent

Question 9

What is an issue regarding GHB for sleep?

Answer 9

Pts often awaken spontaneously and require another dose in middle of night

Question 10

What are acute SE/AEs of GHB?

Answer 10

• CNS depression: dizziness, drowsiness, coma
• Loss of consciousness and reflexes
• Amnesia
• N/V, headache
• Seizures
• Death

Question 11

What is GHB used as and why?

Answer 11

Used only as supportive tx bc there is no antagonist to counteract effects

Question 12

What drugs are melatonin agonist?

Answer 12

• Ramelteon (rozerem)
• Tasimelteon (hetlioz)

Question 13

What is the MOA of ramelteon (rozerem)?

Answer 13

High affinity for MT1 and MT2 melatonin receptors

Question 14

Why is ramelteon’s (rozerem) MOA the way it is?

Answer 14

• MT1 and MT2 melatonin receptors are on suprachiasmatic nucleus (SCN) which serves as “master clock” by regulating circadian rhythms

Question 15

How is ramelteon (rozerem) metabolized?

Answer 15

CYP1A2 substrate

Question 16

What is ramelteon (rozerem) used for?

Answer 16

Tx of insomnia characterized by difficulty w sleep onset

Question 17

Does ramelteon (rozerem) have abuse potential?

Answer 17

• Non-controlled substance sleep aid
• No abuse, withdrawal, or dependency

Question 18

What is a risk for ramelteon (rozerem)?

Answer 18

Negligible risk for next day “hangover” effects

Question 19

What is the MOA of tasimelteon (hetlioz)?

Answer 19

High affinity for MT1 and MT2 melatonin receptors (same as ramelteon)

Question 20

What is tasimelteon (hetlioz) used for?

Answer 20

Tx of non 24 hr sleep wake disorder

Question 21

What is special about tasimelteon (hetlioz)?

Answer 21

It is an orphan drug

Question 22

Where is the oxerin/hypocretin system located?

Answer 22

Hypothalamus

Question 23

What is the MOA of suvorexant (belsomra)?

Answer 23

• High affinity antagonist for OX1 and OX2 orexin receptors
• Decrease arousal and attention via receptors in locus coeruleus and raphe
• Produce rewarding stimuli via receptors that modulate mesolimbic projections between VTA and nucleus accumbens

Question 24

What is suvorexant (belsomra) used for?

Answer 24

Tx of insomnia

Question 25

What is a possible SE with suvorexant (belsomra)?

Answer 25

Morning impairment likely/possible (use lowest dose possible)

Question 26

What did the FDA require for labeling on all sleep disorder drugs?

Answer 26

Include: - Sleep driving - Cooking and eating food and making phone calls while sleeping

Question 27

What is tryptophan?

Answer 27

A 5HT precursor dietary supplement

Question 28

What is an issue w tryptophan?

Answer 28

- Withdrawn from market - Caused eosinophilia-myalgia syndrome

Question 29

What is melatonin?

Answer 29

A nutraceutical

Question 30

What is melatonin used for?

Answer 30

Insomnia, sleep disturbances

Question 31

What is a SE w melatonin?

Answer 31

Drowsiness

Question 32

What is lemon balm?

Answer 32

A sedative herb

Question 33

What is a caution w lemon balm?

Answer 33

Use w caution in pts w thyroid problems

Question 34

What is valerian?

Answer 34

A sedative herb

Question 35

What is valerian used for?

Answer 35

Insomnia

Question 36

What has been noted w valerian use?

Answer 36

Hepatotoxicity

Question 37

What is chamomile?

Answer 37

A mild sedative herb

Question 38

What are cautions w chamomile?

Answer 38

- Avoid use in pts w a ragweed allergy - Use w caution in pts using P450 substrates

Question 39

What is kava kava?

Answer 39

A sedative herb

Question 40

What is kava kava used for?

Answer 40

Insomnia

Question 41

What is a possible problem w kava kava?

Answer 41

Possibly hepatotoxic

Question 42

What is the incidence and severity of sedative hypnotics overdose?

Answer 42

- Incidence: commonly encountered in emergency room - Benzos or z-hypnotics in combination w other agents

Question 43

What are causes of sedative hypnotics overdose?

Answer 43

- Suicide and suicide attempts - Drug abuse

Question 44

What are s/sxs of sedative hypnotics overdose?

Answer 44

- Depressed respiration - Decreased BP and reflexes - Hypothermia

Question 45

What are txs for sedative hypnotics overdose?

Answer 45

- Supportive tx: flumazenil for benzos or z-hypnotics - Maintain respiration - Maintain CV function

Question 46

When should tx for anxiety be considered?

Answer 46

- Interferes w normal life - Interferes w another disease

Question 47

What drugs can induce anxiety?

Answer 47

- Cocaine - Beta agonists - Psychostimulants like caffeine - Corticosteroids

Question 48

What diseases can induce anxiety?

Answer 48

- CHF - COPD - Diagnosis of terminal disease

Question 49

Withdrawal of what meds can induce anxiety?

Answer 49

- Antidepressants - Anxiolytics - Drugs of abuse

Question 50

What neurotransmitters can cause anxiety?

Answer 50

NE and serotonin

Question 51

How does NE cause anxiety?

Answer 51

- Overactive locus coeruleus releases NE -> stimulates autonomic nervous system -> projects to amygdala (fear center) - Dysregulated in GAD and other anxiety disorders

Question 52

How is the GABAergic system involved in controlling/causing anxiety?

Answer 52

- Normally counteracts/balances stimulatory effects of excess NE - Hypothesis is reduced GABAergic signaling causes anxiety

Question 53

How is serotonin involved in anxiety?

Answer 53

May involve amygdala and balance w NE

Question 54

Which serotonin targeting drugs have efficacy in GAD, panic disorder, OCD, social anxiety?

Answer 54

- Drugs that target multiple receptors/SSRIs - Partial agonists of 5HT1A receptors effective

Question 55

What are the drug txs for anxiety?

Answer 55

- Benzos (quick acting, effective) - Antidepressants (SSRIs, SNRIs, TCAs: take weeks; ketamine nasal spray: new breakthrough, very quick acting) - Buspirone (buspar) - BBs

Question 56

What is the pharmacological profile of buspirone (buspar)?

Answer 56

- Partial agonist on brain for 5HT1A receptors - Moderate affinity for brain dopamine D2 receptors

Question 57

What is buspirone's (buspar) onset of action compared to benzos?

Answer 57

Longer (adaptive response)

Question 58

What is the abuse potential of buspirone (buspar)?

Answer 58

- Low abuse potential - Little to no withdrawal

Question 59

What are uses of buspirone (buspar)?

Answer 59

- GAD, social anxiety, comorbid depression - Adjunct use w OCD, PTSD

Question 60

What is buspirone (buspar) not good for?

Answer 60

Panic disorders (use benzos instead)

Question 61

What are propranolol's use?

Answer 61

- Social anxiety: decreased peripheral sxs of anxiety - PTSD nightmares

Question 62

What are monitoring parameters of propranolol?

Answer 62

Monitoring CV: - HR - BP

Question 63

What are SEs of propranolol?

Answer 63

- Hallucinations - Vivid dreams - Lethargy - Impotence

Question 64

What meds are misc anxiolytics?

Answer 64

- Hydroxyzine (vistaril): histamine H1 antagonist - Clonidine (catapres): alpha2 agonist