Factors Affecting Drug Distribution Flashcards
Factors affecting drug distribution
Rate at which drug is distributed
Drugs bind reversibly to plasma proteins
Size of drug molecules
Lipid solubility
Rate at which a drug is distributed to various organs depends on what?
Proportion of cardiac output received by the organs
What are highly perfused tissues?
Brain
Heart
Liver
Kidney
What are slow and less highly perfused tissues?
Skin
Adipose tissue
Drugs bind reversibly to plasma proteins (albumin)
- Plasma protein binding is saturable meaning?
Drugs may be displaced from plasma binding sites by other drugs having a higher affinity for such sites
Drugs bind reversibly to plasma proteins (albumin)
- Increase in free (active) concentration of displaced drug
Leads to increased tissue concentration and pharmacological effect
Drug distribution is affected by?
Size of the drug molecules
Lipid solubility of a drug affects the extent of distribution.
- This is true for what type of drug?
Psychoactive drugs crossing the BBB to produce effects in the CNS
What is the BBB?
Tight junctions btwn the capillary endothelial cells and by the presence of glial cells surrounding the capillaries, restricting the penetration of polar molecules into the neurons
Two processes responsible for the decline of plasma drug concentration over time?
Metabolism
Excretion
Metabolism (or biotransformation)
Enzymatic process converting drugs to either active or inactive metabolities
Example of active drug
Prodrug
Metabolism
- where does it take place?
Liver
Metabolism
- where else could it take place?
Gut
Kidneys
Brain
Lungs
Metabolism
- what is the primary purpose of drug metabolism?
Inactive drugs by generating more water-soluble (polar) metabolites that can be readily excreted by the kidneys
