Pharmacology of Sedative-Hypnotic Drugs

Question 1

Name some common uses for sedative-hypnotic drugs

Answer 1

• induce sleep
• treat anxiety
• muscle relaxation - (often, diazepam)
• anticonvulsant
• pre-anesthetic
• recreation

Question 2

What is the main mechanism of action for most sedative-hypnotic drugs?

Answer 2

Sedative-Hypnotic drugs bind to GABA-A Receptor-chloride ion channel complex and POTENTIATE GABA-mediated inhibition

Question 3

Why do benzodiazepines have a ceiling effect while barbiturates (and EtOH) can be lethal?

Answer 3

All 3 drug classes augment the action of GABA; however in high doses barbs and alcohol can also directly open Cl- channel, which may lead to full CNS depression and death.

Question 4

Newer benzos that are selective for the BDZ1 (omega 1) receptor are primarily used for what purpose?

Answer 4

“pseudo-benzos”- used as sleeping pills

Ex/ Zolpidem (ambien) and Escopiclone (lunesta)

Question 5

What is flumazenil used for?

Answer 5

it is a synthetic benzodiazepine-antagonist–> used to reverse overdose of benzos.

Question 6

Which barbiturate is sometimes used for induction of anesthesia?

Answer 6

Thiopental- highly lipid soluble, fast-on, fast-off (rapid distribution into tissues)

Question 7

What are the 7 benzodiazepenes that are “GABA-a agonists” and their half-lives?

Answer 7

Diazepam-43 hrs (metabolite to 100 hrs)
Chlordiazepoxide- 10 hrs (metabolite to 100 hrs)
Lorazepam-14 hrs
Flurazepam- 74 hrs (metabolites to 100hrs)
Alprazolam- 12 hrs
Midazolam- 1.9 hrs
Triazolam- 2.9 hrs

Question 8

What disorders can all benzos be used to treat?

Answer 8

short term depression, bipolar

Question 9

Which benzos can be used as anticonvulsants?

Answer 9

Diazepam (also muscle relaxant)

Lorazepam

Question 10

Which benzos can be used for sedation?

Answer 10

lorazepam, alprazolam, triazolam (to induce sleep)

Question 11

Which of the benzos is used for anesthesia because of its calming effects and production of anterograde amnesia?

Answer 11

Midazolam

Question 12

What are some of the side effects of benzodiazepenes?

Answer 12

• daytime sedation and drowsiness
• anterograde amnesia
• synergistic depression of CNS with other drugs
• psychologic and physiologic dependence (chronic use)

Question 13

What are some side effects of zolpidem?

Answer 13

sleep walking

next morning impairment

Question 14

What are some side effects of Flumazenil?

Answer 14

• withdrawal
• seizures if its a mixed overdose
• not uniform in the reversal of respiratory depression

Question 15

What is the mechanism of action of the barbiturates (thiopental and phenobarbital)?

Answer 15

GABAa agonist

Question 16

What is the mechanism of action of busiprone?

Answer 16

partial agonist of 5HT1a

Question 17

What is phenobarbital used for?

Answer 17

antiepileptic and anticonvulsant

Question 18

What is Busiprone used for?

Answer 18

anxiolytic without marked sedation

Question 19

What are the side effects of the barbiturates (phenobarbital and thiopental)?

Answer 19

• daytime sedation and drowsiness
• dose-dependent depression of CNS
• psychologic and physiologic dependence (chronic use)
• abrupt withdrawal is life threatening