CPB (Pharm) Flashcards
What is the difference between pharmacokinetics and pharmacodynamics?
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.)
What is the hepatic extraction ratio?
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)
How does hemodilution affect the body in terms of pharmacokinetics and pharmacodynamics?
Decreased hematocrit + increased plasma volume + decrease in plasma protein concentration + reduced RBC concentration + reduction in free concentration of drugs
How does hemodilution affect protein binding of drugs?
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
How does heparin affect protein binding?
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
How does reduced perfusion on CPB affect the drugs we give on CPB?
High liver extraction ratio drugs are more affected (i.e. propofol, fentanyl); also vasoconstriction drugs may further reduce regional flow
How does rewarming and restoration of normal cardiac flow after CPB affect drug distribution?
Drugs that were trapped in previously poorly perfused areas are redistributed
How does hypothermia affect pharmacodynamics and pharmacokinetics of drugs on CPB?
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
How does hyperthermia affect drugs on CPB?
Increased rate of biotransformation and other metabolic processes
How does acidosis affect drug distribution?
Acidosis while on CPB can cause basic drugs to be “trapped” in the acidic cellular micro-environments
How do the lungs affect drug metabolism and uptake?
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
How does the CPB equipment affect drug levels?
Oxygenators bind lipophilic agents (volatile agents, propofol, opioids) + hemofiltration can potentially remove drugs
What factors affect free drug concentration at receptor sites?
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
How does heart failure affect hemodynamics?
Reduction in cellular levels of cAMP which is associated with down-regulated beta1-adrenergic receptors
How is protein binding affected by CPB?
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)
How does hypothermia affect pharmacodynamics of drugs on CPB?
Transformation of receptor subtypes + alterations in receptor affinity (decreased opiate binding during hypothermia) + decreased MAC requirement of iso + rewarming = increased anesthetic requirements
Is anesthetic requirements increased or decreased on CPB?
Decreased: possibly due to CPB induced neurologic injury (microembolic load, cerebral edema, brain inflammation, decreased CYP450 activity, increased ICP)
How is the acid-base system affected when on CPB?
Usually get acidotic due to ischemia -> diminishes body’s response to endogenous and exogenous catecholamines + affects degree of ionization of drugs
How are Ca, Mg, and K levels affected on CPB?
Decreased Ca, decreased Mg, initially decreased K on CPB then increased 2/2 cardioplegia
How is beta-adrenergic receptor function affected by CPB?
It is impaired following CPB (possibly 2/2 ischemia-reperfusion injury, acute receptor desensitization, or decrease in GRK activity)
Should you give corticosteroids on CPB?
No positive effect on major clinical outcomes; possible small reduction in risk of postop atrial fibrillation (both in SIRS trial and DECS trial)
What happens to opioids on CPB?
Hypothermia prolongs elimination half-time so decreased clearance of fentanyl + sequestration of fentanyl (and sufentanil) occurs in the lungs once coming off CPB
How are benzos affected on CPB?
Benzos are highly protein bound (>90%) so depends highly on protein binding (i.e. acid/base status)
How does hypothermia affect propofol levels?
Increase in plasma levels (but returns after rewarming)
What happens with propofol use in the postop period?
Usually exhibits prolonged elimination half-time and reduced clearance (likely 2/2 decreased hepatic clearance and prolonged half-time due to altered tissue perfusion)
How are volatile anesthetics affected by CPB?
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
How does CPB affect neuromuscular blockade?
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
How does heparin plasma levels change with CPB?
3 compartment model: Rapid initial disappearance (endothelial uptake) + saturable clearance (reticuloendothelial system and uptake into monocytes) + exponential first-order decay (renal clearance)
Do you need more or less lidocaine on CPB?
More; significant sequestration in lungs + increased alpha-1 acid glycoprotein causes less free drug levels
