Elimination Equations and Related Application Flashcards
State the clearance equation:
Total Cl = Hepatic Cl + Renal Cl
What is the equation for total clearance?
Total Cl = Hepatic Cl + Renal Cl
What are the main organs responsible for elimination?
The liver and the kidneys
What is the extraction ratio? What equations is it associated with?
A value that defines the proportion of blood through an eliminating organ that is cleared of a given drug.
Clorgan = Qorgan*Eorgan
E = (∆C)/Centering = Rate of elimination/Centering
What are the two forms of drug elimination? Define them:
Excretion: Irreversible loss of chemically unchanged drug
Metabolism: Conversion of the drug into a different chemical species
What are the two forms of drug elimination? What organs are mainly responsible for each?
Excretion - Kidneys
Metabolism - Liver
What is the rate of elimination equation?
Rate of elimination = Clearance*Drug conc.
dA/dt = Cl*C
Define clearance. Define elimination rate. How do they differ?
The capacity of the body to eliminate a given drug.
The rate at which a given drug is eliminated by the body.
Clearance describes the amount of plasma that is cleared of a drug whereas the elimination rate describes how much drug is eliminated from the plasma in a given amount of time.
What is required for a steady state to be achieved in a dose regimen?
The rate in and rate out of a drug must be equal.
What is the steady state dose regimen equation?
Rate in = Rate out
Dose/time = Cl*C
ONLY where the concentration is Css
What is the general dose regimen equation?
Rate in = Rate out
Dose/time = Cl*C
What is meant by clearance being additive? Relate this to the total elimination rate.
The clearance of one organ or tissue adds to that of others.
The total elimination rate describes the sum of elimination rates by each organ.
Define the additivity of clearance as an equation.
Total Clearance = Clearance “A” + Clearance “B”
What organ is the exception to the additivity of clearance? Why?
The lungs since blood does not pass through the lungs in such a simple linear manner as the rest of the body.
What family of enzymes is responsible for the majority of drug oxidation and reduction reactions in the liver?
Cytochrome P450 enzymes.
What are cytochrome P450 enzymes? Why are they important?
A family of metabolic enzymes in the liver.
They’re important because they’re responsible for a large amount of drug clearance in the body.
What are the 5 key points of drug metabolism?
- Substrate specificity of drugs
- Affected by Michaelis-Menten kinetics
- Drug metabolism can saturate (at high conc.)
- Drug interactions can cause enz inhibition or induction
- Genetic variability can influence metabolism
What defines the upper limit of drug’s clearance if it has a high extraction ratio?
The amount of organ blood flow.
What is the renal clearance equation?
Clr = Clfiltration +Cl secretion - Clreabsorption
What three mechanisms are involved in renal secretion?
- Filtration
- Secretion
- Tubular reabsorption
State the renal clearance equation:
Clr = Clfiltration +Cl secretion - Clreabsorption
Why can’t the extraction ratio be greater than 1? Why is this useful to know?
It means you’re excreting more than 100% of the drug in your bloodstream.
It helps let you know if you’ve messed up the calculations.
What causes most drugs to be reabsorbed by the kidneys?
They are passively reabsorbed as solutes of water.
Which two kidney processes increase renal clearance?
Which process decreases it?
Filtration and secretion.
Reabsorption.
