Drug Distribution Flashcards
what factors affect the distribution of drugs?
- cardiac output and blood flow
- plasma protein binding- albumin
- lipid solubility
- degree of ionisation of drug
- pH of compartments
- capillary permeability
- sepsis and shock alter permeability of normally thick membranes
what drugs bind to albumin?
lipophilic drugs bind non-specifically to albumin and use it as a transport system round the body
how does albumin binding affect drug function?
drugs not bound to albumin will be able to diffuse across membranes whereas drugs bound will not and will therefore not be able to function
what factors affect albumin production?
burns and renal disease and malnutrition all lead to decrease in production of albumin
What effect does a decreased albumin production have on drug distribution?
less albumin so less available for drug molecules to bind to therefore more drug is likely to get out of vascular compartment and into tissue
How do hydrophilic drugs cross membranes?
more soluble in polar and aqueous media so do not get across the membrane very easily. specific transport mechanisms in membranes are required
how does drug ionisation affect drug distribution?
can only cross the membrane is unionised, how lipophilic drug is is negligible.
ionised drugs will not diffuse across the membrane and can hence become trapped
how do drug molecules diffuse across capillaries? what features exist in capillary wall to accommodate diffusion?
- large lipophilic sometimes pass through fused invaginations of capillary wall
- fenestration allows small lipophilic molecules through easily
- larger lipophilic molecules get through sinusoids or discontinuous capillaries
what is the blood brain barrier? what is its function?
- adaptation of the normal endothelial layer
- Normal endothelial cells prevent vascular entry and ready exchange into the brain
what conditions can the BBB pose a problem for drugs?
meningits- inflammation of the meninges which can be caused by bacterial infection. Need to get antibiotics in to kill bacteria yet BBB normally prevents antibiotics getting into CSF
How is the BBB exploited during meningitis in order to get antibiotics through it to kill bacteria? what is also the problem with this
- during meningitis there is a weakening of the BBB hence you are able to get antibiotics in to treat the infection
- can let other drugs have access to the CSF which you wouldn’t normally want to
what difficulties to drugs are posed by the placenta?
- tight endothelial cell junctions which protect the maternal and foetal capillaries
- lipid soluble drugs cross it
- weak acids and bases can potentially accumulate in the foetal circulation
what difficulties to drug distribution are posed by chronic abbesses?
- acidified area where you can’t get accumulation of drug in
- avascular region so causes problems distributing drug to that area
rowdies lung infection pose difficulties to drug distribution?
- area of lung not perfused for a reason, area of low oxygen saturation because capillaries are not doing their function so blood flow restricted to that area
- if infection in that area then blood flow is reduced and tricky to distribute drug there
what can affect the volume of distribution of a drug?
wellbeing of patient
