CPB (Pharm)

Question 1

What is the difference between pharmacokinetics and pharmacodynamics?

Answer 1

Kinetics = how the body affects the drug (i.e. absorption, delivery, distribution, metabolism, and elimination); Dynamics = how the drug affects the body (i.e. receptor affinity, drug concentration etc.)

Question 2

What is the hepatic extraction ratio?

Answer 2

Fraction of drug contained in arterial blood that is removed as it passes through the liver; High ratio = dependent on liver flow for elimination; Low ratio = dependent on extrahepatic cellular processes for clearance (not affected as much by flow)

Question 3

How does hemodilution affect the body in terms of pharmacokinetics and pharmacodynamics?

Answer 3

Decreased hematocrit + increased plasma volume + decrease in plasma protein concentration + reduced RBC concentration + reduction in free concentration of drugs

Question 4

How does hemodilution affect protein binding of drugs?

Answer 4

Decrease in plasma protein concentration leads to a shift in bound:free drug ratio; drugs with high plasma protein binding will have a larger increase in free fraction with hemodilution from CPB

Question 5

How does heparin affect protein binding?

Answer 5

Heparin results in lipoprotein lipase and hepatic lipase release which hydrolyzes triglycerides into fatty acids -> these bind competitively to plasma proteins and results in displacement of bound drugs

Question 6

How does reduced perfusion on CPB affect the drugs we give on CPB?

Answer 6

High liver extraction ratio drugs are more affected (i.e. propofol, fentanyl); also vasoconstriction drugs may further reduce regional flow

Question 7

How does rewarming and restoration of normal cardiac flow after CPB affect drug distribution?

Answer 7

Drugs that were trapped in previously poorly perfused areas are redistributed

Question 8

How does hypothermia affect pharmacodynamics and pharmacokinetics of drugs on CPB?

Answer 8

Peripheral vasoconstriction (decreases absorption of drugs) + fluid extravasation (drugs move from central to peripheral compartments) + decreased enzyme function decreases breakdown and increases elimination half-life

Question 9

How does hyperthermia affect drugs on CPB?

Answer 9

Increased rate of biotransformation and other metabolic processes

Question 10

How does acidosis affect drug distribution?

Answer 10

Acidosis while on CPB can cause basic drugs to be “trapped” in the acidic cellular micro-environments

Question 11

How do the lungs affect drug metabolism and uptake?

Answer 11

Lungs are a reservoir for basic drugs (lidocaine, fentanyl, propranolol); if administered during CPB there will be higher blood concentrations since the lungs are out of the equation

Question 12

How does the CPB equipment affect drug levels?

Answer 12

Oxygenators bind lipophilic agents (volatile agents, propofol, opioids) + hemofiltration can potentially remove drugs

Question 13

What factors affect free drug concentration at receptor sites?

Answer 13

Distribution of drug to receptor area (i.e. protein binding, tissue binding like digitalis, and age) + rate of free drug uptake from plasma + equilibration across plasma membrane

Question 14

How does heart failure affect hemodynamics?

Answer 14

Reduction in cellular levels of cAMP which is associated with down-regulated beta1-adrenergic receptors

Question 15

How is protein binding affected by CPB?

Answer 15

Increased alpha-1 acid glycoprotein (AGP) secondary to SIRS in setting of CPB results in reduced free drug concentration (highly protein bound drugs more affected)

Question 16

How does hypothermia affect pharmacodynamics of drugs on CPB?

Answer 16

Transformation of receptor subtypes + alterations in receptor affinity (decreased opiate binding during hypothermia) + decreased MAC requirement of iso + rewarming = increased anesthetic requirements

Question 17

Is anesthetic requirements increased or decreased on CPB?

Answer 17

Decreased: possibly due to CPB induced neurologic injury (microembolic load, cerebral edema, brain inflammation, decreased CYP450 activity, increased ICP)

Question 18

How is the acid-base system affected when on CPB?

Answer 18

Usually get acidotic due to ischemia -> diminishes body’s response to endogenous and exogenous catecholamines + affects degree of ionization of drugs

Question 19

How are Ca, Mg, and K levels affected on CPB?

Answer 19

Decreased Ca, decreased Mg, initially decreased K on CPB then increased 2/2 cardioplegia

Question 20

How is beta-adrenergic receptor function affected by CPB?

Answer 20

It is impaired following CPB (possibly 2/2 ischemia-reperfusion injury, acute receptor desensitization, or decrease in GRK activity)

Question 21

Should you give corticosteroids on CPB?

Answer 21

No positive effect on major clinical outcomes; possible small reduction in risk of postop atrial fibrillation (both in SIRS trial and DECS trial)

Question 22

What happens to opioids on CPB?

Answer 22

Hypothermia prolongs elimination half-time so decreased clearance of fentanyl + sequestration of fentanyl (and sufentanil) occurs in the lungs once coming off CPB

Question 23

How are benzos affected on CPB?

Answer 23

Benzos are highly protein bound (>90%) so depends highly on protein binding (i.e. acid/base status)

Question 24

How does hypothermia affect propofol levels?

Answer 24

Increase in plasma levels (but returns after rewarming)

Question 25

What happens with propofol use in the postop period?

Answer 25

Usually exhibits prolonged elimination half-time and reduced clearance (likely 2/2 decreased hepatic clearance and prolonged half-time due to altered tissue perfusion)

Question 26

How are volatile anesthetics affected by CPB?

Answer 26

Net neutral change in B/G coefficient (B/G increased by cooling but decreased by hemodilution) + increased solubility in tissue due to hypothermia (increases depth) + uptake by oxygenator

Question 27

How does CPB affect neuromuscular blockade?

Answer 27

Overall, CPB causes NMB requirements to be reduced even though there is potentiation of NMB due to acidosis, hypothermia, and hemodilution; rocuronium is protein bound so affected by levels of albumin

Question 28

How does heparin plasma levels change with CPB?

Answer 28

3 compartment model: Rapid initial disappearance (endothelial uptake) + saturable clearance (reticuloendothelial system and uptake into monocytes) + exponential first-order decay (renal clearance)

Question 29

Do you need more or less lidocaine on CPB?

Answer 29

More; significant sequestration in lungs + increased alpha-1 acid glycoprotein causes less free drug levels