Drug Distribution - Protein Binding Flashcards
Paracellular
In between cells
Transcellular
Through the cells -diffusion, active transport pinocytosis
solute carriers for weak acids and week bases
Organic anion transporters (drugs that are weak acids)
Organic cation transporters (drugs that are weak buses)
P-gp transporters are examples of what type of active transport?
ATP - binding cassettes
Why are certain barriers more permeable?
To allow substances to be metabolised (liver endothelium) and eliminated (renal endothelium in glomermus)
Other barriers are much less permeable. Why?
To protect sensitive organs from circulating chemicals or pathogens
Permeability can be affected by?
Cell type
Number of cell layers
Junctions between calls
It drug is ionised it is lipid(soluble/insoluble)?
Lipid insoluble
It drug is unionised it is lipid(soluble/insoluble)?
Lipid soluble
When does pKa=pH?
When 50% of the drug is ionised and 50% is unionised
Medications such as reflux disease or gastric ulcers can be treated using what inhibitors? And how?
Proton pump inhibitors by increasing gastric pH (reduces acidity)
Plasma proteins are?
Major transporters of endogenous lipids and steroid hormones
Most common plasma protein?
Albumin 55%
Plasma proteins (examples)
Albumin 55%
Globulin 38%
Fibrinogen 7%
Others <1%
Drugs can exist in 2 forms
Bound and unbound forms
Drugs can bind to plasma proteins. Can be reversible reaction why?
Drug will unbind for metabolism and excretion
What is the importance of protein binding?
Proteins are too large to pass through most epithelia /endothelia
Only free drug can bind their site of action
Implications on bound proteins
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
Heavily protein bound drugs have longer / shorter half life
Longer
Characteristics of albumin
Negatively charged
High affinity for acidic drugs but has low capacity
Low affinity for basicdrugs but has a high capacity
Drug and protein concentration graph:
Bound protein may plateau why?
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)
Some drugs bind readily to substances outside of the bloodstream which is?
Tissue binding
Examples of tissue binding
Fat, bones muscle
Information of tissue binding because?
It requires solid tissue samples to test
What type of drugs will bind extensively to fat stores?(hydrophilic/lipophicic)
Highly lipophilic drugs
If someone is overweight, the plasma concentration is less why?
Because the drug goes to store within fatty tissue and not within the plasma
Osteoporosis is caused by?
Increase resorption causing thinning of bones and increased risk of fractures
Bisphosphonates work by?
Binding to calcium in bones and inhibits resorption
Resorption is a process in which?
A substance, such as tissue, is lost by being destroyed and then absorbed by the body
Osteoclasts break down tissue in bones and release the minerals. Resulting in?
A transfer of calcium from bone tissue to the blood
