Pharmaclogy - Sedatives and Hypnotics

Question 1

What is a sedative?

Answer 1

Sedative = calming = anxiolytic effect (ideally with little effect on motor or mental functions)

Question 2

What is a hypnotic?

Answer 2

Hypnotic = induce sleep

more pronounced CNS depression than sedation; can be achieved with most sedative drugs simply by increasing dose

Question 3

MOA: Sedatives and Hypnotics

Answer 3

bind to some site on

GABA-A Receptor complex and potentiate GABA-mediated inhibition

Question 4

GABA-A receptos is what kind of channel?

Answer 4

Chloride

Question 5

Where do benzodiazepines bind to the GABA-A receptor?

Answer 5

binding site between α1 – γ2 sub-units

Question 6

Where do barbituates bind to the GABA-A receptor?

Answer 6

bind to α or β sub-unit

Question 7

Where does ethanol bind to the GABA-A receptor?

Answer 7

binds to α

Question 8

T/F: Most benzodiazepines bind to both GABA-A receptor subtypes.

Answer 8

True

omega-1 and omega-2

Question 9

What is the “ceiling effect” of benzos?

Answer 9

Increasing doses do not produce respiratory arrest/coma, whereas barbs and alcohol can induce full CNS depression

Question 10

T/F: In high doses, barbituates and alcohol can directly open chloride channels, resulting in full CNS depression (total GABA rush)

Answer 10

True

Question 11

Give the class:
Diazepam
Chlordiazepoxide 
Lorazepam 
Flurazepam 
Alprazolam
Midazolam i.v. or i.m.
Triazolam

Answer 11

Benzodiazepines

Question 12

Most benzos are metabolized how?

Answer 12

most benzos undergo microsomal oxidation (Phase I, via P450 system; particularly CYP3A4 and CYP2C19, with only modest P450 induction), and subsequent conjugation

Question 13

What is the half life of flurazepam?

Answer 13

74 hours

Question 14

Which benzo has the shortest half life?

Answer 14

Midazolam, 1.9 hrs

Question 15

How is Zolpidem different from the more traditional benzodiazepines?

Answer 15

Zolpidem is specific for BDZ1 agonist (omega-1) whereas traditional benzos act on both omega 1 and 2.

This results in sedation w/o muscle relaxation/anticonvulsant activity

Question 16

Use: Flumazenil

Answer 16

Benzo-antagonist

Use to reverse overdoses of benzos

Question 17

What is the half life of phenobarbital?

Answer 17

4-5 days

less lipid soluble therefore slower onset

Question 18

What is a barbituate commonly used to induce anesthesia due to its lipid solubulity and subsequent “fast on fast off” character?

Answer 18

Thiopental

known for its rapid redistribution

Question 19

Does buspirone interact with the GABA-A complex?

Answer 19

No

Relieves anxiety w/o marked sedation

Question 20

Use: alprazolam

Answer 20

Anti-anxiety;

shorter-acting benzo

Question 21

Use: Lorazepam

Answer 21

Anti-anxietyl
Anti-convulsant
shorter-acting benzo

Question 22

Use: Triazolam

Answer 22

Induce sleep;

very short-acting benzo

Question 23

Use: Zolpidem

Answer 23

Induce sleep, a “pseudo-benzo”

Question 24

What benzo is used in anesthesia to produce anterograde amnesia?

Answer 24

Midazolam

very short-acting benzo

Question 25

Use: Diazepam

Answer 25

Anticonvulsant;

muscle relaxer

Question 26

Use: Phenobarbital

Answer 26

Anticonvulsant

Question 27

Name 3 adverse effects of the sedatives-hypnotics classes.

Answer 27

1. drowsiness & “hangover”
2. falls! – especially in the elderly - use caution – it is easy to produce confusion, sedation, unsteadiness with these drugs in the elderly
3. dose-related CNS depression
   (additive CNS depression with more than one agent)
4. tolerance = common feature of sedative-hypnotic drug use -cross tolerance
   - metabolic tolerance - induce enzymes (notably with barbiturates and alcohol)
   - dynamic tolerance - decreased CNS responsiveness (receptor down-regulation)
5. psychologic & physiologic dependence is significant problem;

Note: abrupt withdrawal can be life-threatening, notably with non-benzo seditive-hypnotics (e.g. alcohol and barbiturates)