Sedative-Hypnotics

Question 1

What are the sedatives that target GABA-A receptors?

Answer 1

• Benzodiazepines
• Non-benzodiazepine Agonists
• Barbiturates
• Ethanol

Question 2

GABA-A Receptors

Answer 2

Ionotropic receptors that cause Cl- channels to open leading to inhibitory synaptic potentials

Question 3

GABA-B Receptors

Answer 3

Metabotropic G-protein linked receptors that act on presynaptic terminals and regulate the release of GABA or other NTs

Question 4

What is the most abundant GABA-A configuration?

Answer 4

2-alpha
2-beta
1-gamma

Question 5

What is the binding site on GABA-A for GABA?

Answer 5

Alpha/beta interface - normally 2 sites

Question 6

What is the binding site on GABA-A for benzodiazepines, imidazopyridines and pyrrolopyrazines?

Answer 6

Alpha/gamma interface

Question 7

What are the BZ1 selective class of drugs?

Answer 7

Non-benzodiazepines

• Imidazopyridines
• Pyrrolopyrazines

Question 8

Benzodiazepine MOA

Answer 8

Binding of the drug acts as a positive allosteric regulator that increases GABA affinity for GABA-A receptor and increases the frequency of Cl- channel opening - more inhibitory signal

Question 9

Where do the barbiturates bind?

Answer 9

Bind to parts of GABA-A separate from BZ sites and lead to increased DURATION of Cl- channel opening rather than frequency

Question 10

What suffices are indicative of benzodiazepines?

Answer 10

• AM
• PAM
• LAM

Question 11

What are the indications for benzodiazepines?

Answer 11

• Anxiety
• Sleep disorders
• Anticonvulsant
• Treatment for EtOH withdrawal

Question 12

What are the contraindications of benzodiazepines?

Answer 12

Significant pulmonary illness or CNS depression

Question 13

Benzodiazepines are highly _______.

Answer 13

Protein-bound

Question 14

What happens to the half life of diazepam as the age of patients increases?

Answer 14

It will increase due to the decreased hepatic function

Question 15

What are the benzodiazepines that go directly to phase II metabolism in the liver?

Answer 15

LOT
Lorazepam
Oxazepam
Temazepam

Question 16

What are the benzodiazepines with the shortest half lives?

Answer 16

LOT
Lorazepam
Oxazepam
Temazepam

Question 17

Benzodiazepine SE

Answer 17

• Amnesia
• Confusion
• Dizziness
• Allergic Reaction
• Tolerance
• Dependence

Question 18

What is the tolerance that is developed to benzodiazepines?

Answer 18

Tolerance is only developed to the sedative effects, NOT the anti-anxiety effects

Question 19

What are the imidazopyridines?

Answer 19

Zolpidem

Zaleplon

Question 20

What are the pyrrolpyrazines?

Answer 20

Eszopiclone

Question 21

Non-benzodiazepine MOA

Answer 21

Bind selectively to BZ1 and positively modulates GABA-A action

Question 22

Non-benzodiazepine SE

Answer 22

• Similar to benzodiazepines
• Sleep-driving/eating
• Anterograde amnesia

Question 23

Which of the non-benzodiazepines has the longest half life?

Answer 23

Eszopiclone

Question 24

What are the barbituates?

Answer 24

Penobarbital
Methohexital
Thiopental

-AL suffix

Question 25

Barbituate MOA

Answer 25

Binds to GABA-A at distinct regions from BZ1/2 and increase duration of Cl- channel opening - at high doses they can directly open Cl- channels

Question 26

What are the short acting barbiturates?

Answer 26

Thiopental and Mexihexital

Question 27

What are the long acting barbiturates?

Answer 27

Phenobarbital

Question 28

Barbituate SE

Answer 28

- Respiratory Depressant - Death from OD - Withdrawal - Tolerance due to CYP450 induction

Question 29

Ramelteon MOA

Answer 29

Melatonin agonist that binds MT1 and 2 receptors with higher affinity that melatonin - no BZ binding

Question 30

Ramelteon SE

Answer 30

- Headache - Fatigue - Dizziness

Question 31

What is a major advantage of ramelteon?

Answer 31

No physical dependence or withdrawal symptoms

Question 32

Do benzodiazepines cure insomnia?

Answer 32

No, they will only resolve the symptoms for as long as they are taken.

Question 33

Valeriana officinalis - Herbal MOA

Answer 33

Mediate GABA release and inhibit its breakdown - can be used to treat insomnia for up to 4 weeks

Question 34

Chamomile - Herbal MOA

Answer 34

Benzodiazepine agonist

Question 35

Passion Flower - Herbal MOA

Answer 35

Benzodiazepine partial agonist

Question 36

Buspirone MOA

Answer 36

5-HT1A partial agonist

Question 37

Buspirone SE

Answer 37

- Headaches - Dizziness - Sedation

Question 38

Buspirone Contraindications

Answer 38

DO NOT USE alongside a MAO-I

Question 39

Buspirone Indications

Answer 39

- Major depression | - Anxiety disorders

Question 40

What are advantages of buspirone over benzodiazepines?

Answer 40

- NO risk of dependence | - NO sexual dysfunction

Question 41

Sedative (Anxiolytic)

Answer 41

Reduces anxiety and exerts a calming effect

Question 42

Hypnotic

Answer 42

Produces drowsiness and facilitates the onset and maintenance of sleep

Question 43

Where is GABA synthesized?

Answer 43

Nucleus Accumbens

Question 44

Which GABA receptors do all sedatives act on?

Answer 44

GABA-A

Question 45

What drug classes does BZ1 bind?

Answer 45

- Benzodiazepines - Imidazopyridines - Pyrrolopyrazines

Question 46

What drug classes does BZ2 bind?

Answer 46

- Benzodiazepines

Question 47

Flumazenil MOA

Answer 47

Competitive antagonist of BZ1 and 2 site and blocks the actions of drugs that act at these sites

Question 48

Benzodiazepine Indications

Answer 48

Anxiety, Insomnia, Anesthesia, Alcohol Withdrawal, Seizures

Question 49

What are the benzodiazepines with long half lives?

Answer 49

- Chlordiazepoxide - Diazepam - Flurazepam

Question 50

What is the metabolism of zaleplon inhibited by?

Answer 50

Cimetidine