Drug Distribution Flashcards
Name the factors that affect drug distribution
Cardiac output and blood flow, Plasma binding protein, lipid solubility, degree of drug ionisation, pH of compartments and capillary permeability
Describe the binding of drugs to the plasma protein albumin
Lipid soluble proteins bind non specifically however weak acid drugs bind to a specific, saturable site so there is high competition.
What occurs to the level of free drug with hypo/hyper albumin levels and name an example of cause.
Hyperalbuminemia - Dehydration, causes free drug levels to decrease.
Hypoalbuminemia - Burns, causes increase in free drug levels
Describe how lipid solubility affects drug distribution
Hydrophilic drugs are soluble in aqueous, polar media so the rate of distribution depends on diffusion characteristics of the drug.
Lipophilic drugs - Soluble in fats/non-polar medias so rate of distribution depends on the rate of delivery to tissue.
Describe how pH and drug ionisation effects drug distribution
pH of compartment affects the degree of ionisation (ration of ionised to unionised). Ionised drugs have low lipid solubility so cannot diffuse across cell membranes.
Describe how capillary diffusion affects drug distribution
The properties of the capillaries that feed the tissue will influence the ability of drugs to distribute out into the tissue
Describe features of blood brain barrier and how bacterial meningitis effects this
Very tight barrier that only allowed very lipophilic drugs through. Meningitis increases the BBB permeability which allows the bacteria to reach the CNS however also means antibiotics can pass through the BB
Name some other specalised barriers
Placenta - Tight endothelial cell junctions which makes it partially protective except with lipid soluble drugs and unionised weak acids and bases.
Chronic abscess - Avascular compartments meaning it is very difficult for drugs to reach it.
Lung infection - Local low pressure of O2 but high CO2 causes reflex vasocontraction which again reduced the amount of blood flow to the area.
How is the apparent volume of distribution calculated?
Total amount of drug in body / Blood plasma conc of drug.
What is the apparent volume of distribution?
Theoretical volume required to account to the amount of drug in the body. It may not always be physiologically possible.
What is the single compartment model of distribution
It assumes rapid mixing of drug in the plasma
Describe the two compartment model of distribution
IV dose quickly travels to the central compartment (blood and well perfused tissues) and takes longer to travel to the peripheral compartments (poorly perfused tissue eg, fat) however once in the peripheral compartments, drugs tend to accumulate here and take longer to excrete.
What causes the volume of distribution to vary?
Height, weight, age, fluid accumulation and accumulation of fat
What is the clinical relevance of the apparent volume of distribution (Vd)?
Because it equals total amount of drug/plasma conc then you can rearrange this equations to figure out how much drug you need to give to reach a certain plasma concentration, if you know the Vd of the drug.
