Pharmacology Basics (Compartments, Kinetics, Receptors etc) Flashcards
Define Vd
The theoretical volume into which a drug must disperse to produce the measured plasma concentration.
Calculated by Dose/ Conc (time zero)
What factors determine Vd?
Lipid solubility
Percentage plasma protein binding
Percentage tissue protein binding
Blood flow to various tissues
Define clearance?
In the units mls/ minute.
Is the volume of plasma completely cleared of a substance per unit time.
It is additive of all the systems involved participating, including kidney, liver, lungs.
Used to describe first order kinetics
How do you derive clearance?
From a concentration- time graph,
Cl = Dose/ AUC
Equations that you can use for calculating Clearance?
Cl = rate of elimination/ plasma concentration
Cl = Vd x k (elimination rate constant)
Cl = Vd x (0.693/ t half)
What is half life?
The time taken for the plasma concentration to fall to half its value.
Can be derived from concentration-time graph
After 5 half lives 98% complete.
How are Vd, Cl and t1/2 interrelated?
Vd is proportional to t1/2 x Cl
How can Vd, Cl and t1/2 be used to explain the clinical differences between fentanyl and alfentanil?
Fent is more lipid soluble, more potent therefore used in smaller doses than alfentanil.
More lipid soluble = higher Vd of fent
The differences of onset and offset can be explained by the pKa values, Fent pKa 8.4, Alf 6.4. Therefore alfentanil more unionised at physiological pH.
Clearance of alfentanil is less than fentanyl, but due to smaller Vd still offset is faster.
What is first order kinetics?
Elimination of the drug is occurring because the enzymes are not saturated.
Therefore, a constant portion of drug is eliminated from the body per unit time. The rate of elimination is directly proportional the concentration of the drug present at that time.
Exponential decay graph.
Eg. most drugs at clinical doses.
What is zero order kinetics?
The enzymes within this elimination process are saturated, therefore a constant amount of drug is eliminated per unit time.
The rate of elimination from constant.
Linear graph.
Eg. Ethanol, Phenytoin, Thiopentone
What is the Michaelis-Menton equation?
V =
Km + [S]
V = velocity Vmax = maximal rate of reaction S = substrate Km = michaelis constant, which is the substrate concentration at which V = 1/2V max
What is the Michaelis-Menten kinetics?
This describes the kinetics of the body’s enzymes and are used to predict the rate of reaction between an enzyme and and substrate to form a product.
How can Michaelis Menton kinetics be used in clinical practice?
At low substrate concentrations, rate of reaction is proportional to concentration of substrate.
At high concentrations, rate of reaction is proprotional to the maximal rate of reaction.
Graph, is plotted as substrate conc (x) against velocity (y). Changes from first order kinetics to zero order kinetics.
