F10. Drug disposition

Question 1

what is drug disposition?

Answer 1

-defines what happens to drug after administration
-overview of all ADME processes
ONE NOTE

Question 2

Describe small intestine

Answer 2

-most drugs are absorbed in the small intestine
-Long residence time
-Large surface area
-Good blood supply
-Transporters for active transport
-Favourable pH
-Microbiome
-Incomplete absorption

Question 3

Describe the hepatic portal system

Answer 3

-After crossing the gut epithelium the drug
enters 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

Question 4

Describe first pass metabolism

Answer 4

-“First pass” through the liver from the hepatic portal system
allows metabolism of drug as it diffuses through to the hepatic vein
-Some of the administered dose may be lost
-Other routes of administration avoid this problem

Question 5

What is bioavailability?

Answer 5

a measure of how much drug that is administered reaches the systemic circulation

Question 6

Describe systemic circulation

Answer 6

-Closed system of arteries,
capillaries and veins
-Oxygenation and nutrient
supply to tissues
-Clearance of waste
products
-Once drug is through the
liver it circulates
everywhere

Question 7

Describe continuous structure of capillaries

Answer 7

-Continuous have no gaps within cells
-Solutes must pass through intercellular clefts

Question 8

Describe fenestrated structure of capillaries

Answer 8

-Fenestrated have “windows” within endothelial cells
-Solutes can diffuse out

Question 9

Describe discontinuous structure of capillaries

Answer 9

-Discontinuous have large gaps between and within cells and discontinuous basement membrane
-Free movement of even large solutes

Question 10

How do drugs flow to lean tissues?

Answer 10

-As blood flows through most tissues (muscle, skin, lungs, heart etc.)
hydrophilic drug will escape through intercellular gaps.
-Lipophilic drug can freely escape between and across cells
ONE NOTE

Question 11

How do drugs flow to the brain?

Answer 11

-The brain has a specialised structure known as the blood brain
barrier which tightly regulates exchange of solutes
-Hydrophilic drug must be transported
ONE NOTE

Question 12

Describe how drugs flow to the adipose tissue

Answer 12

Adipocytes are filled with lipid vacuoles, where lipophilic drugs can accumulate
ONE NOTE

Question 13

Describe drug clearance

Answer 13

-Every pass through the
circulatory system means a
pass through the liver and
kidneys
-Drug is cleared or “extracted”
on each pass
-Extraction ratio and
clearance can be calculated

Question 14

Describe drug passing through the liver

Answer 14

-Hepatocytes metabolise drug
with CYP450 and UGT enzymes
-Reduced concentration of
parent drug on exit
-Metabolites also released
-May be pharmacologically active
-Some drugs may also be
excreted in bile
-Passive filtration and
active secretion clear drug
to urine
-Metabolites from liver are
more water soluble, and also
cleared
-Final elimination step
ONE NOTE

Question 15

Describe measures of elimination

Answer 15

Half life:
-Time taken for plasma concentration to decrease by half
Clearance:
-The apparent volume of plasma cleared of drug in a unit of time
Extraction ratio:
-The plasma concentration after passage through the organ divided by the concentration before entry (i.e. fraction lost)