PK/PD ICU

Question 1

What must be true about renal function to use Cockcroft-Gault and other equations?

Answer 1

must be stable

Question 2

What type of dose should not be adjusted in AKI?

Answer 2

loading dose

Question 3

What can increase hepatic blood flow and metabolism?

Answer 3

1. early sepsis–> increased CO
2. vasodilators
3. inotropes
4. TBI
5. burn injuries

Question 4

What can decrease hepatic blood flow and metabolism?

Answer 4

1. vasopressors
2. hypovolemic shock
3. decreased cardiac output CO
4. mechanical ventilation

Question 5

What is augmented renal clearance?

Answer 5

kidney hyperfiltration above baseline leads to subtherapeutic concentrations
males CrCl: >130
females CrCl: >120

Question 6

Why do critically ill patients tend to have decreased absorption due to decreased perfusion/blood flow?

Answer 6

the body shunts blood to vital organs

Question 7

What dosage form can volume overload and edema effect the absorption of?

Answer 7

SQ
IM

Question 8

What do we base loading doses off of?

Answer 8

Volume of distribution

Question 9

What are causes of changes in distribution?

Answer 9

1. fluid volume- edema, third spacing
2. capillary permeability- third spacing
3. lipophilic drugs have wider distribution

Question 10

When Vd increases, what happens to drugs at their target tissues?

Answer 10

decrease concentrations

Question 11

What happens to patients with lower levels of albumin when taking highly protein-bound drugs?

Answer 11

higher level of free, active drug –> supratherapeutic concentrations

Question 12

What is the normal range of albumin?

Answer 12

3.5-5

Question 13

What is hypoalbuminemia?

Answer 13

<2.5

Question 14

What is the total PHT range?

Answer 14

10-20

Question 15

What is the free PHT range?

Answer 15

1-2

Question 16

When do we use the adjusted PHT equation?

Answer 16

low albumin and only have a total level
ALWAYS use free PHT level if you have it

Question 17

What is the adjusted PHT equation?

Answer 17

(Z x serum albumin) + 0.1

Question 18

How is Z determined for the PHT equation?

Answer 18

Z= 0.2 in patients with hypoalbuminemia
Z= 0.1 in patients with hypoalbuminemia and ESRD or HD-dependent

Question 19

What is the total range for Valproic Acid?

Answer 19

50-100

Question 20

What is the free range for valproic acid?

Answer 20

6-22

Question 21

How does hypoalbuminemia effect hydrophilic antibiotic dosing?

Answer 21

Increased fraction of free drug- increased clearance
Vd will increase- decreased drug to target tissues
–> underdosing

Question 22

How are alternative ways to dose antibiotics in hypoalbuminemia?

Answer 22

1. loading doses/ aggressive initial regimen
2. extended infusion time for t>MIC (time-dependent antibiotics)

Question 23

What is ECMO?

Answer 23

device used in cardiac/respiratory failure that directly removes CO2 from the blood and oxygenates it as it passes through the circuit

Question 24

How does ECMO affect drugs?

Answer 24

highly protein-bound and highly lipophilic drugs tend to become sequestered in the ECMO circuit leading to lower systemic concentrations

Question 25

Which highly lipophilic drugs may be effected by increased Vd and also may become sequestered due to ECMO?

Answer 25

1. Fentanyl 2. Propofol 3. Midazolam 4. Fluoroquinolones 5. Piperacillin/Tazobactam 6. Ceftriaxone 7. Vancomycin

Question 26

What should all patients on ECMO have?

Answer 26

DVT treatment (preferably IV heparin)

Question 27

What is important when applying literature to critically ill patients?

Answer 27

seeing if the patient population was or included critically ill patients

Question 28

What is the duration of action of single IV doses of drugs in critically ill patients a function of?

Answer 28

distribution > clearance