Drug Distribution Flashcards
Define drug distribution:
Reversible transfer of drug between blood/extravascular fluids and tissues
What effects tissue distribution of drug:
- Plasma binding Protein
- Tissue Perfusion
- Membrane characteristics
- Transport Mechanisms
- Effected by diseases & other drugs
- Elimination
What type of Membrane characteristics affect tissue distribution of drugs:
Blood-Brain barrier
Testes/Ovary/Placenta barrier, resistance to many substances attempting to cross
Tight cell junction prevents paracellular movement
What are plasma binding proteins?
Plasma proteins - albumin binds to drugs making them biologically inactive
What effects the level of bound drug:
Renal Failure
Hypoalbuminemia (not enough albumin)
Pregnancy
Other drugs
Saturability of Binding
When is the level of bound drug relevant?
When above 90% of drug is bound to plasma binding proteins
Why are high plasma protein binding levels imporant?
If bound drug is, e.g 98%, change to 96% is a 100% increase in active drug levels
What 3 mechanisms affect renal drug excretion:
- Glomerular Filtration
- Passive Tubular Filtration
- Active Tubular Secretion
What is filtered at the glomerulus?
(filtering unit of kidney)
Unbound drugs
How can the drug prevent glomerular filtration?
Drug particle size & charge
How does filtration rate affect drug clearance rate?
Increased filtration rate increases drug clearance rate
In passive tubular filtration how does drug conc change?
Further down the kidney tubules the more concentrated the filtrate
Therefore drug is more concentrated
What happens to some of the drug in passive tubular filtration?
Reabsorbed by passive diffusion, only unionised drug is reabsorbed
What does active tubular secretion mainly excrete?
Protein bound cationic (+ve) & anionic (-ve) drugs.
What is a zero order reaction
Reactions where rate is not affected by concentration of drug used
What is t1/2
Half life
Time take for drug to reach half its concentration in the blood
What is Vd
Volume of distribution
Volume of plasma necessary to account for total amount of drug in patient’s body
What is clearance
Rate drug is removed from plasma over concentration of drug in plasma
What determines clearance
Ability of body to clear drug from plasma is:
Renal clearance +
Hepatic clearance +
Clearance from all other tissues
What determines where a drug end ups
Drug Lipophalicity - different for different membranes
If not lipophilic - availability of transport proteins
