E1: Sedative-hypnotics And Anxiolytics

Question 1

What kind of drugs are used for short term treatment of insomnia?

Answer 1

Sedative hypnotics

Question 2

What is the DOC for enuresis?

Answer 2

TCAs

Question 3

What kind of channels are GABA receptors?

Answer 3

Cl channels

Question 4

What does activation of GABAa receptors do?

Answer 4

Causes depression of electrical activity, which decreases anxiety and promotes sleep

Question 5

What is the MOA of barbiturates?

Answer 5

-Binds to GABA receptor and stimulates Cl influx, which produces inhibition independent of GABA

Question 6

What are the effects of barbiturates?

Answer 6

• Marked CNS depressant, hypnosis

- cause euphoria

Question 7

What kind of drug is phenobarbital?

What is it commonly used for?

Answer 7

• Long acting barbiturates

- often used as anticonvulsants

Question 8

How are barbiturates metabolized?

Answer 8

• metabolized by the liver

- induces CYP450s with chronic use

Question 9

What are the side effects of barbiturates?

Answer 9

• CNS depression: drowsiness, mood distortion, impaired judgment
• Paradoxical excitement
• vertigo, n/v/d
• severe physiological and psychological dependence

Question 10

What are the contraindications of barbiturates?

Answer 10

• porphyria: enhance porphyrins synthesis
• pulmonary insufficiency: may cause respiratory depression
• Supra-additive effects

Question 11

Why are barbiturates dangerous drugs?

Answer 11

They do not have a ceiling effect and have a low margin of safety
-Supra-additive effects with alcohol

Question 12

What are the most commonly used group of anxiolytics and sedative-hypnotics?

Answer 12

Benzodiazepines

Question 13

How are benzodiazepines metabolized?

Answer 13

-metabolized by CYP34A in the liver where it is converted to active metabolites

Question 14

Which benzos have a long duration of action?

Answer 14

Diazepam and flurazepam

Question 15

Which benzos have and intermediate duration of action?

Answer 15

Alprazolam and oxazepam/lorazepam

Question 16

Which benzo has a short duration of action?

Answer 16

Midazolam

Question 17

What is the MOA of Benzos?

Answer 17

• Bind to specific sites of the GABAa receptor, increases affinity of the receptor to GABA prolonging its action
• effect is dependent on GABA

Question 18

Are benzos or barbiturates safer? Why?

Answer 18

Benzos are safer because they have a ceiling effect

Question 19

What is the DOC for anxiety?

Answer 19

Benzos

Question 20

What are the anxiety disorders that benzos are not used for?

Answer 20

• OCD
• Agoraphobia and panic disorders
• post traumatic stress
• anxiety and children and adolescents

Question 21

What benzos are commonly used for insomnia?

Answer 21

Flurazepam and temazepam

Question 22

What benzos are commonly used for status epilepticus?

Answer 22

Diazepam and lorazepam

Question 23

Which benzo is used in preparation for anesthesia for short surgical procedures?

Answer 23

Midazolam

Question 24

Which benzo causes anterograde amnesia?

Answer 24

Midazolam

Question 25

Which benzo is often used for muscle relaxation?

Answer 25

Diazepam

Question 26

Which Benzos can be given to provide a tapered withdrawal?

Answer 26

Chlordiazepoxide, diazepam, and lorazepam

Question 27

What are the side effects of Benzodiazepines?

Answer 27

- CNS depression: dizziness, sedation, confusion - Paradoxical excitement - Supra-additive effects - sleep related behaviors

Question 28

What is paradoxical excitement?

Answer 28

-stimulation, hyperactivity, and aggressive behavior that may occur due to dis-inhibition of suppressed behavior, common in the elderly

Question 29

What are the contraindications to Benzodiazepines?

Answer 29

- Should not be given during pregnancy unless absolutely necessary - sleep apnea - elderly

Question 30

What is important to remember about Benzodiazepines and withdrawal?

Answer 30

- Abrupt discontinuation can cause rebound increases in insomnia and anxiety - BZs should be tapered very slowly following chronic use

Question 31

What kind of drug is Flumazenil?

Answer 31

Benzodiazepine antagonist

Question 32

What is the MOA of Flumazenil?

Answer 32

-Competes with BZs for GABA receptor and reverses the effects of BZs

Question 33

What is the major adverse effect of Flumazenil?

Answer 33

- Triggers withdrawal and seizures in patients who are physically dependent upon BZs - do not used in patients with history of seizures

Question 34

What are the “Z” drugs?

Answer 34

Zolpidem (ambien), Zaleplon (Sonata), and Eszopiclone (lunesta)

Question 35

What is the MOA of the “Z” drugs?

Answer 35

Bind to the BZ1 subtype of the GABA receptor to increase GABA mediated inhibition

Question 36

Which of the “z” drugs has a long half life?

Answer 36

Eszopiclone

Question 37

What are the side effects of the “z” drugs?

Answer 37

- High margin of safety - Diarrhea and nausea - sleep related behavior - rebound insomnia - Withdrawal symptoms

Question 38

What is the MOA of Suvorexant?

Answer 38

- Antagonist at orexin receptors | - Orexins are involved in regulating the sleep wake cycle and promote wakefulness

Question 39

How is suvorexant metabolized?

Answer 39

Metabolized by CYP3A4

Question 40

What are the contraindications for suvorexant?

Answer 40

Narcolepsy

Question 41

What is the MOA of Ramelteon?

Answer 41

- melatonin analogue, resets the sleep wake cycle | - promotes sleepiness with no GABA effect

Question 42

How is Ramelteon metabolized?

Answer 42

CYP450 in the liver

Question 43

What are the side effects of Ramelteon?

Answer 43

- Additive sedation with alcohol and other sedative hypnotics - drowsiness, dizziness, and nausea

Question 44

When is Benadryl indicated for insomnia?

Answer 44

Useful for occasional insomnia and are especially useful in someone who has been addicted to Benzos or alcohol

Question 45

What is the MOA of Chloral Hydrate?

Answer 45

-Acts similarly to barbiturates on GABAa receptor, converted to trichloroethanol which causes sedation

Question 46

Is chloral hydrate a safe drug?

Answer 46

No it has a low margin of safety, high doses induce respiratory and vasomotor depression

Question 47

What are the side effects of Chloral hydrate?

Answer 47

- gastric irritation, nausea, vomiting, and cardiac arrhythmias - long term use may cause liver damage and fatal intoxication

Question 48

What is the use of Buspirone?

Answer 48

Relieves anxiety without producing sedation

Question 49

What is the MOA of Buspirone?

Answer 49

Partial agonist at the postsynaptic serotonin receptor | -Full agonist for presynaptic serotoninc receptors

Question 50

How is Buspirone metabolized?

Answer 50

CYP3A4 in the liver