Drug distribution and excretion Flashcards
Distribution
Reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the body eg muscle, fat, brain
What 6 things effect tissue distribution?
Disease and other drugs tissue perfusion Membrane characteristics Plasma protein binding Elimination Transport mechanism
Membrane characteristics
Blood-brain barrier
Blood testes-ovary barrier, lipid soluble drug, active transport
Plasma protein binding
Drug bound to albumin eg phenytoin
Binding is reversible and can be changed in response to renal failure, pregnancy etc.
Is an unbound drug active or inactive
Active
What 3 things effect the therapeutic range
- Clearance
- Volume of distribution
- Half life
Clearance (ml/min)
Theoretical volume of fluid from which a drug is completely removed over a period of time
What is clearance dependent on?
- Metabolism and biliary secretion
- Concentration and urine flow
Volume of distribution (Vd)
Volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration
What does a greater Vd mean?
Greater ability to diffuse into/through membrane
What should the Vd be?
42L
Half life (t1/2)
Time taken for the drug concentration in the blood to decline to half of current value
Depends on Vd and clearance
What does an increased half life mean?
Increased toxicity
To have an effect what should a drugs concentration and half life be?
- Steady concentration between therapeutic range
- 4-5 half lives before stabilisation
Drug elimination
Removal of active drug and metabolites from body
Determines length of action
