Excretion Lecture Flashcards
Define elimination
Irreversible loss of drug from the body via either of the processes of metabolism or excretion
Define metabolism
Loss of drug from the body by chemical conversion
- Primarily occurs in the liver
Define excretion
Loss of drug from the body by diffusion, filtration, evaporation or transport process
- Primarily occurs in the kidney or liver
Define pharmacokinetics
Expresses the rate of elimination of a drug as the change in drug concentration with the passage of time: dc/dt-C^n= -kC^n
n= 0 is zero order
n= 1 is first order
Define rate constant
Function of the slope of the elimination line seen when fall in drug conc is plotted vs time
Define volume of distribution
Apparent volume into which a drug “appears” to be dissolved, if the conc is mearsured in the blood
Define half life
Amount of time require for the concentration of the drug to fall by one-half in the blood stream
Define clearance
Amount of blood “cleared” of the drug by a define process in a unit of time
- Refers to the body’s ability to rid itself of a drug, waste or other substance
= rate of elimination/drug concentration
Zero order kinetics?
C^0 = 1; rate of elimination is unrelated to concentration
First order kinetics?
C^1 = C; rate of elimination is dependent on concentration
Define total clearance
sum of all possible routes of metabolism and excretion of the substance being considered
Define metabolic clearance
liver metabolism + other organ metabolism
Define excretory clearance
Renal and biliary + other excretion
Define renal clearance
Action of the kidneys only
Define hepatic clearance
Action of the liver only
What are metabolic and transport processes mediated by?
Enzymes or transporters which can be saturated at a given drug concetration
What are three processes involved in renal excretion?
Glomerular filtration
Tubular reabsorption
Tubular secretion
Define glomerular filtration
Filtration based on size
- Plasma like filtration
- 5,000-20,000 MW
- – which is why we do not lose drugs that are bound to albumin because they are too large to be filtered
Define tubular reabsorption
Removes useful solutes and returns them to the blood stream
Define tubular secretion
Removes wastes from the blood and secretes them into the filtrate –> Increases the loss
Why for many drugs (Ceftazidime and Cefepime) is there clearance greatly dependent upon renal function?
Bc it varies with GFR
- Reduced GFR occurs with aging and a number of diseases leading to dramatic delay of drug clearance for the body
Renal clearance can also be effected by?
Amount of free drug in plasma because that is the drug available for glomerular filtration and secretion
What is renal tubular reabsorption?
99% of filtered fluid is reabsorbed in the renal tubules
- Passive diffusion and active transport
What are factors that influence reabsorption?
Urine flow: too rapid may not have time to catch the stuff it needs
Urine pH: can make a molecule into something that cannot be reabsorped
Lipophilicity of a drug:
Transport modulation: drugs can modify transports so things are not lost or lost
