Clearance Flashcards
Define/ describe pharmacokinetics
The movement of drugs within the body. It is the science linking dose and concentration (in the body). The two main pharmacokinetic properties of a drug are clearance and volume of distribution
Define/ describe pharmacodynamics
Is the effect of drugs and their mechanisms of action. The science linking concentration and effect is pharmacodynamics. The two main pharmacodynamic properties of drugs are the maximum effect (Emax), and the concentration producing 50% of the maximum effect (C50)
Define clearance
Clearance describes the relationship between concentration (plasma) and the rate of elimination of drug from the body.
i.e. it describes the volume of plasma per which a drug is completely removed per unit of time.
Formula describing clearance
Rate out= CL * Concentration
Describe target concentration
When concentration of the drug in the body is producing the right balance between benefits and adverse effects.
Maintenance dose is predicted based on what values?
Target concentration and clearance
Key factor determining the magnitude of clearance
The blood flow to the organ. Liver blood flow 90L/h/70kg. Kidneys have a blood flow of 70L/h/70 kg
What is the clearance of morphine dependant on and what is it?
Clearance mostly in the liver so blood flow to the liver is an important determinant of morphine clearance. 60 L/h
What is the clearance of nitroglycerine?
Breaks down in many body tissues so clearance not directly related to the blood flow of one organ. It is 150 L/h
What is the clearance of gentamicin?
Eliminated mainly by GF so clearance is 6L/h
What is the clearance of theophylline
Mainly metabolised in the liver but at a low rate compared with liver blood flow, only a small fraction is extracted as blood passes through the liver. 3L/h
Clearance of warfarin
Liver. 3l/day
Describe constant clearance
When drug clearance is independent of concentration or organ blood flow, synonyms are linear and first order.
Most drug metabolism is considered constant as concentrations are so small they don’t reach Vmax (where enzyme metabolism no longer occurs due to saturation).
Clearance is constant when clearance by GF as you can’t saturate GF
Describe concentration dependant clearance
When clearance depends on the concentration of the drug. Synonyms are mixed-order, non-linear and Michaelis-Lenten
Two examples of mixed order clearance
Renal tubular secretion- whereby kidney tubules are saturable; penicillin is excreted via tubular secretion thus is mixed-order.
Metabolism of phenytoin is saturable at doses close to those that are used clinically
If drug concentration is small in relation to Km what will the elimination rate be?
First order/ linear
If the drug concentration is large in relation to Km what will the elimination rate be?
Zero order/ non-linear
If clearances is flow dependant what organ is it typically associated with?
The liver
Formula for maintenance dose
Maintenance dose rate= CL*Target concentration
Three mechanisms for enhancing elimination in poisoning
Heamodialysis
Haemoperfusion
Gut adsorption
What is the livers upper limit of clearance
90L/h (equal to liver blood flow)
What is the kidneys upper limit of clearance
70L/h (equal to renal blood flow)
Why is the clearance of glyceryl trinitrate greater than blood flow to liver/kidneys
It is 150L/h. Because it is a very unstable molecule that breaks down in plasma and all throughout the body
Where is clearance of digoxin and what is it?
Largely glomerular filtration, some liver. 9L/hr
