Benzodiazepine Class (Dr. E's lecture)

Question 1

What are the 5 pharmacological effects of Benzos?

Answer 1

Anxiolysis
Sedation
Anterograde Amnesia
Anticonvulsant Actions
Muscle Relaxation (Spinal Level)

Question 2

Do Benzos produce skeletal muscle relaxation? Is this good for surgery?

Answer 2

do NOT produce skeletal muscle relaxation adequate for surgery

Question 3

Action of Benzos does NOT alter the dose of _________ _________ required.

Answer 3

muscle relaxants

Question 4

What is the potential for tolerance/abuse in Benzos?

Answer 4

LESS than that for opioids and Barbs b/c there is a ceiling effect

Question 5

Is there an issue for OD?

Answer 5

Greater margin of safety in OD

Question 6

What are the effects of Benzos on hepatic enzymes?

Answer 6

DO NOT induce hepatic enzymes

Question 7

What drugs have Benzos replace? What for? Which benzo is the main one used?

Answer 7

Replaced Barbiturates for premeds and MAC (Sedation) –> MIDAZOLAM

Question 8

What do the Benzos as a class have that makes them well liked for their sedative qualities?

Answer 8

Have a SPECIFIC Antagonist- Flumazenil

Question 9

What is the structure of the Benzos?

Answer 9

Benzene Ring
fused with a 7-membered diazepine ring
-opens at physiologic pH and is activated

Question 10

What is the MOA of the Benzos?

Answer 10

• Facilitate the action of GABA at the GABAa receptor
• DO NOT activate GABAa receptor
• Increase affinity/potency of GABA for GABAa receptor
• FACILITATE, DO NOT activate!

Question 11

Describe the GABAa receptor. (with affinity of GABA binding to GABAa receptor)

Answer 11

• opening of Cl gated channels
• increases Cl conductance
• hyperpolarization of the POST-synaptic membrane
• increases resistance of post-synaptic membrane to excitation

Question 12

Do Benzos act pre- or post- synaptically?

Answer 12

POST SYNAPTICALLY

Question 13

Which subunits does GABA bind to on the GABAa receptor

Answer 13

alpha subunits

Question 14

What subunits do the Benzos bind to on the GABAa receptor?

Answer 14

gamma

Question 15

What is the principal inhibitory neurotransmitter in the CNS?

Answer 15

GABA

Question 16

Mostly, the GABAa receptors are found where? minimal effects where?

Answer 16

postsynaptic membranes in the CNS!- minimal effects OUTSIDE the CNS!!!!

Question 17

Describe the 2 different Alpha subunits of the GABAa receptor and the effects when a ligand is bound to them.

Answer 17

Alpha 1 subunit

• Sedative effects
• Most Abundant (60% in the CNS are this type)
• Cortex and Thalamus (they integrate pain and stress)

Alpha 2 subunit

• Anxiolytic effects
• Hippocampus and Amygdala (memory and emotion/behavior)

Question 18

What are the main differences between the Benzodiazepine drugs? (hint, there are 3)

Answer 18

1. Potency (receptor binding affinity)
2. Lipid Solubility (ability to cross the BBB, and redistribute to peripheral tissues)
3. Pharmacokinetics (uptake, distribution, metabolism, and elimination)

Question 19

In general Benzos are highly _______ _______ AND highly ________ to ________ _________

Answer 19

Lipid soluble

bound to plasma proteins (like albumin)

Question 20

Which of the Benzos is water soluble in preparation?

Answer 20

Midazolam/ Versed

Question 21

Which is the most potent Benzo?

Answer 21

Lorazepam/Ativan: 5 - 10 x potency of Diazepam

Question 22

Which benzo is the most potent amnestic used in anesthetic practice?

Answer 22

Lorazepam/Ativan