PK/PD ICU Flashcards
What must be true about renal function to use Cockcroft-Gault and other equations?
must be stable
What type of dose should not be adjusted in AKI?
loading dose
What can increase hepatic blood flow and metabolism?
- early sepsis–> increased CO
- vasodilators
- inotropes
- TBI
- burn injuries
What can decrease hepatic blood flow and metabolism?
- vasopressors
- hypovolemic shock
- decreased cardiac output CO
- mechanical ventilation
What is augmented renal clearance?
kidney hyperfiltration above baseline leads to subtherapeutic concentrations
males CrCl: >130
females CrCl: >120
Why do critically ill patients tend to have decreased absorption due to decreased perfusion/blood flow?
the body shunts blood to vital organs
What dosage form can volume overload and edema effect the absorption of?
SQ
IM
What do we base loading doses off of?
Volume of distribution
What are causes of changes in distribution?
- fluid volume- edema, third spacing
- capillary permeability- third spacing
- lipophilic drugs have wider distribution
When Vd increases, what happens to drugs at their target tissues?
decrease concentrations
What happens to patients with lower levels of albumin when taking highly protein-bound drugs?
higher level of free, active drug –> supratherapeutic concentrations
What is the normal range of albumin?
3.5-5
What is hypoalbuminemia?
<2.5
What is the total PHT range?
10-20
What is the free PHT range?
1-2
When do we use the adjusted PHT equation?
low albumin and only have a total level
ALWAYS use free PHT level if you have it
What is the adjusted PHT equation?
(Z x serum albumin) + 0.1
How is Z determined for the PHT equation?
Z= 0.2 in patients with hypoalbuminemia
Z= 0.1 in patients with hypoalbuminemia and ESRD or HD-dependent
What is the total range for Valproic Acid?
50-100
What is the free range for valproic acid?
6-22
How does hypoalbuminemia effect hydrophilic antibiotic dosing?
Increased fraction of free drug- increased clearance
Vd will increase- decreased drug to target tissues
–> underdosing
How are alternative ways to dose antibiotics in hypoalbuminemia?
- loading doses/ aggressive initial regimen
- extended infusion time for t>MIC (time-dependent antibiotics)
What is ECMO?
device used in cardiac/respiratory failure that directly removes CO2 from the blood and oxygenates it as it passes through the circuit
How does ECMO affect drugs?
highly protein-bound and highly lipophilic drugs tend to become sequestered in the ECMO circuit leading to lower systemic concentrations
Which highly lipophilic drugs may be effected by increased Vd and also may become sequestered due to ECMO?
- Fentanyl
- Propofol
- Midazolam
- Fluoroquinolones
- Piperacillin/Tazobactam
- Ceftriaxone
- Vancomycin
What should all patients on ECMO have?
DVT treatment (preferably IV heparin)
What is important when applying literature to critically ill patients?
seeing if the patient population was or included critically ill patients
What is the duration of action of single IV doses of drugs in critically ill patients a function of?
distribution > clearance
