Drug Distribution Flashcards
What does drug distribution refer to?
The Reversible Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body (for example, fat, muscle, and brain tissue).
What does tissue distribution depend on?
Plasma protein binding Tissue perfusion Membrane characteristics Blood-brain barrier Blood-testes/ovary barrier Lipid soluble drugs Actively transported Transport mechanisms Diseases and other drugs (esp renal failure, liver disease, obesity) Elimination
What can be said about an unbound drug (not bound to plasma protein)?
Only unbound drug is biologically active.
What can change the amount of bound drug?
Renal failure Hypoalbuminaemia Pregnancy Other drugs Saturability of binding
When does protein binding matter?
When there is a very large percentage of the drug that is bound to plasma proteins - a small increase in unbound level has a massive percentage change of the free drug level (4% to 6% means a 50% increase in free drug levels)
What are the parameters of the therapeutic range?
volume of distribution, clearance and half-life
What is the volume of distribution?
The volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration.
What does a greater Vd indicate?
the greater the ability of the drug to diffuse into and through membranes
What is the Vd in theory
42L (in equal distribution in the body)
What is the definition of clearance?
The theoretical volume of fluid from which a drug is completely removed over a period of time.
What is the measurement of clearance?
Measured in units of time (ml/min)
What does clearance depend on?
Dependent on concentration and urine flow rate for renal clearance.
Dependent on metabolism and biliary excretion for hepatic clearance.
What is the definition of half life?
The time taken for the drug concentration in the blood to decline to half of the current value.
What is half life dependant on?
Volume of distribution and rate of clearance.
What is the result of prolongation of the half life of a drug?
Will increase the toxicity of a drug.
Due to reduction in clearance
Due to a large volume of distribution (amiodarone)