Drug Distribution - Protein Binding

Question 1

Paracellular

Answer 1

In between cells

Question 2

Transcellular

Answer 2

Through the cells -diffusion, active transport pinocytosis

Question 3

solute carriers for weak acids and week bases

Answer 3

Organic anion transporters (drugs that are weak acids)
Organic cation transporters (drugs that are weak buses)

Question 4

P-gp transporters are examples of what type of active transport?

Answer 4

ATP - binding cassettes

Question 5

Why are certain barriers more permeable?

Answer 5

To allow substances to be metabolised (liver endothelium) and eliminated (renal endothelium in glomermus)

Question 6

Other barriers are much less permeable. Why?

Answer 6

To protect sensitive organs from circulating chemicals or pathogens

Question 7

Permeability can be affected by?

Answer 7

Cell type
Number of cell layers
Junctions between calls

Question 8

It drug is ionised it is lipid(soluble/insoluble)?

Answer 8

Lipid insoluble

Question 9

It drug is unionised it is lipid(soluble/insoluble)?

Answer 9

Lipid soluble

Question 10

When does pKa=pH?

Answer 10

When 50% of the drug is ionised and 50% is unionised

Question 11

Medications such as reflux disease or gastric ulcers can be treated using what inhibitors? And how?

Answer 11

Proton pump inhibitors by increasing gastric pH (reduces acidity)

Question 12

Plasma proteins are?

Answer 12

Major transporters of endogenous lipids and steroid hormones

Question 13

Most common plasma protein?

Answer 13

Albumin 55%

Question 14

Plasma proteins (examples)

Answer 14

Albumin 55%
Globulin 38%
Fibrinogen 7%
Others <1%

Question 15

Drugs can exist in 2 forms

Answer 15

Bound and unbound forms

Question 16

Drugs can bind to plasma proteins. Can be reversible reaction why?

Answer 16

Drug will unbind for metabolism and excretion

Question 17

What is the importance of protein binding?

Answer 17

Proteins are too large to pass through most epithelia /endothelia
Only free drug can bind their site of action

Question 18

Implications on bound proteins

Answer 18

Typically remain in the blood
Unable to exert their pharmacological effect
Can’t be metabolised or excreted
Becomes stored in a reservoir and can impact Vd

Question 19

Heavily protein bound drugs have longer / shorter half life

Answer 19

Longer

Question 20

Characteristics of albumin

Answer 20

Negatively charged
High affinity for acidic drugs but has low capacity
Low affinity for basicdrugs but has a high capacity

Question 21

Drug and protein concentration graph:
Bound protein may plateau why?

Answer 21

Plasma proteins become saturated which result in increase unbound fraction as the concentration of the drug increases (all the plasma proteins have been taken up)

Question 22

Some drugs bind readily to substances outside of the bloodstream which is?

Answer 22

Tissue binding

Question 23

Examples of tissue binding

Answer 23

Fat, bones muscle

Question 24

Information of tissue binding because?

Answer 24

It requires solid tissue samples to test

Question 25

What type of drugs will bind extensively to fat stores?(hydrophilic/lipophicic)

Answer 25

Highly lipophilic drugs

Question 26

If someone is overweight, the plasma concentration is less why?

Answer 26

Because the drug goes to store within fatty tissue and not within the plasma

Question 27

Osteoporosis is caused by?

Answer 27

Increase resorption causing thinning of bones and increased risk of fractures

Question 28

Bisphosphonates work by?

Answer 28

Binding to calcium in bones and inhibits resorption

Question 29

Resorption is a process in which?

Answer 29

A substance, such as tissue, is lost by being destroyed and then absorbed by the body

Question 30

Osteoclasts break down tissue in bones and release the minerals. Resulting in?

Answer 30

A transfer of calcium from bone tissue to the blood