IV anes - BZD

Question 1

What is the MOA of BZDs?

Answer 1

Increases the frequency of chloride channel opening by binding to GABA

Question 2

What causes midazolam to be water soluble at a low ph?

Answer 2

The imidazole ring

Question 3

What causes diazepam and lorazepam IV to irritate the veins?

Answer 3

Propylene glycol. It is added because diazepam and lorazepam are insoluble in water

Question 4

What route are diazepam and lorazepam best absorbed?

Answer 4

Orally thru GI tract

Question 5

Which two BZDs are absorbed well IM?

Answer 5

Lorazepam and midazolam

Question 6

What happens to the imidazole ring of midazolam at physiologic ph?

Answer 6

It closes which increases its lipid solubility

Question 7

What are the differences in brain solubility in the three BZDs?

Answer 7

Diazepam is relatively lipid soluble and readily penetrates the bbb
Lorazepam moderately - slow uptake in the brain

Question 8

What mechanism is responsible for awakening from a BZD?

Answer 8

Redistribution

Question 9

How long does it take for peak plasma levels when absorbed orally?

Answer 9

1-2h

Question 10

How protein bound are the BZDs?

Answer 10

90-98%

Question 11

How are they biotransformed ?

Answer 11

Phase I metabolism

Question 12

What BZD has active phase I metabolites?

Answer 12

Diazepam

Question 13

What is the elimination half life of diazepam and why?

Answer 13

30 hours because it has a low hepatic extraction ratio and a large Vd (high lipid solubility)

Question 14

What is the elimination half life of lorazepam?

Answer 14

15
It’s lower lipid solubility make it have a smaller Vd
It has a low hepatic extraction ratio
Clinical duration is longer due to increased receptor affinity in most patients

Question 15

What is the elimination half life of midazolam?

Answer 15

2 hours

Even though it has a large Vd, it has a high hepatic extraction ratio

Question 16

How are the metabolites of BZDs excreted?

Answer 16

In the urine

Question 17

What condition can lead to prolonged sedation in patients receiving midazolam?

Answer 17

Kidney failure due to the accumulation do the conjugated metabolite - alphahydroxymidazolam

Question 18

What are the CV effects of BZDs?

Answer 18

Decreased arterial blood pressure, cardiac output, SVR

Question 19

What are the respiratory effects of BZDs?

Answer 19

Depress the ventilatory response to CO2

Question 20

What are the cerebral effects of BZDs?

Answer 20

Decrease CMRO2, CBF and ICP

Question 21

What drugs reduce the metabolism of diazepam?

Answer 21

Cimetidine, erthromycin,

Question 22

What drug increases the free drug concentration of diazepam?

Answer 22

Heparin by displacing diazepam from protein binding sites

Question 23

How do BZDs affect the MAC of a volatile anesthetic?

Answer 23

Reduces it by 30%

Question 24

What is the bioavailability of midazolam from greatest to least?

Answer 24

IV > IM > intra nasal > rectal > oral

Question 25

What do BZDs bind in the blood?

Answer 25

Albumin

Question 26

What adjustments need to be made in dosing with hypoalbuminemia?

Answer 26

You must lower the dosing because hypoalbuminemia increases the free fraction of BZDs.

Question 27

What is the principal pathway of biorransformation for lorazepam?

Answer 27

Glucoronidation

Question 28

What is unique about the metabolism or midazolam?

Answer 28

It’s metabolite have 30% potency of the primary drug