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
Biotransformation help the excretion of drugs by?
Kidneys
Reabsorption from where increases the duration of action of lipid-soluble substances?
Proximal tubule
What are prodrugs?
Drugs administered as inactive compounds and are subsequently metabolized to active metabolites
What are examples of prodrugs?
L-Dopa- dopamine
Heroin- morphine
Prednisone- prednisolone
Codeine- morphine
With quantal dose-response curves, the response elicited with each dose of drugs is described as how?
Cumulative percentage of subjects exhibiting a defined all-or-none effect
Therapeutic Index
Measure of drug safety (drug with a larger therapeutic index is safer than one with a lower therapeutic index)
Examples of drugs with low therapeutic index
Lithium
Warfarin
Phenytoin
Digoxin
Theophylline
Examples of drugs with low therapeutic index pt 2?
Aminoglycoside antibiotics and some cancer chemotherapy agents
