F10 Drug disposition Flashcards
what does disposition mean?
- what happens to a drug after administration (ADME)
- where and how is it absorbed
- how quickly it is absorbed
- how much riches the systemic circulation
- where it goes in the body
- whether it accumulates in certain tissues
- how it is cleared by metabolism and excretion
what factors are important to the absorption of a drug?
- formulation
- acidic or basic?
where are most drugs absorbed and how is this area adapted for absorption?
- small intestine
- long residence time
- large surface area
- good blood supply
- transporters for active transport
- favourable pH
- microbiome
- incomplete absorption
what is the hepatic portal system?
- network of blood vessels that cover the stomach and small intestines
- carry absorbed nutrients (and drugs) from the gut straight to the liver first
- essentially, hepatic portal veins take the blood from the small intestine and spleen to the liver first before the rest of the circulation
where do drugs go first after crossing the gut epithelium?
the hepatic portal system
what does the hepatic portal system allow for?
- a ‘first pass’ through the liver
- allows metabolism of drug as it diffuses through to the hepatic vein before it reaches the systemic circulation
what is bioavailability? how is it measured?
a measure of how much drug that is administered reaches the systemic circulation
- fraction
- percentage
describe the systemic circulation structure and functions
- closed system of arteries, capillaries and veins
- oxygenation and nutrient supply to tissues
- clearance of waste products
- once drug has gone through the liver, it circulates everywhere
why does capillary structure vary between tissues?
the structure determines how much drug will cross the endothelial cells
what are the 3 structure types of capillaries?
- continuous
- fenestrated
- discontinuous
describe continuous capillary
- have no gaps within cells
- solutes pass through intercellular clefts
- consists of basement membrane, pericytes and endothelial cells
describe fenestrated capillary
- have ‘windows’ within endothelial cells
- solutes can diffuse out
- small pores
- found in the kidneys
describe discontinuous capillary. where are they found?
- have large gaps between and within cells and discontinuous basement membrane
- free movement of even large solutes
- have larger pores than the fenestrated capillaries
- found in the liver, bone marrow etc.
describe exchange in the brain
- gaps in the blood brain barrier are tightly packed so they are shut and the hydrophilic drugs can’t cross through the gaps
- therefore, the hydrophilic drug must be transported with the blood flow
- brain also has extra layer of cells in the capillary called astrocytes
what is a favourable environment for lipophilic drugs in the body?
- adipocytes
- they are filled with lipid vacuoles where lipophilic drugs can accumulate and stay there
- this occurs in the systemic circulation to the adipose tissue
