Unit 2 - Pharmacokinetics - distribution Flashcards
What is drug distribution? (Definition)
Movement of a drug from the bloodstream into:
1) various tissues of the body
2) The site of target cells/tissues
Drug distribution is the combination of two factors, these are?
Perfusion
Permeability
Perfusion can also be referred to as?
Blood flow
Permeability can also be referred to as?
The nature of the biological membrane
An organ with high ______ ________ will have more exposure to the drug.
Blood perfusion
An organ whose capillaries’ membranes are ________ will have _____ concentration of the drug than the organ with high membrane _________ capillaries
restricted
less
permeability
Provide, in order, from highest to lowest, amount of blood flow to organs. (no need to give an actual value)
Kidneys, liver, heart, brain, skin, muscle, fat
Blood perfusion to each organ is ______.
varied
What are commonly mentioned proteins in the bloodstream?
Albumins, immunoglobulins, fibrinogens
What is the main buffering system of the blood?
bicarbonate buffer system
When thinking about distribution, one must also consider drug interactions with blood-borne ________.
proteins
Drugs may be bound to plasma proteins such as albumin in the blood.
Why is this important?
Only free (unbound) drug can cross membranes, bind to receptors and be excreted by the kidney.
Interactions of drugs with plasma proteins are of what type?
Low affinity, high capacity
Give an example of a drug that binds strongly to plasma proteins.
Heparin and warfarin (both anticoagulants)
What does warfarin do?
inhibits fibrinogen conversion to fibrin, decrease coagulation potential
What is an issue related to warfarin and bound/free drugs?
Toxic dose and effective dose of warfarin are very close.
If a person takes warfarin but then suffers an infection and needs to take another drug, this drug might displace it off of serum proteins, increasing serum concentration.
This can lead to toxicity.
Only the _______ ______ form can penetrate into the target site.
The ______ form cannot.
free drug
bound
Drugs that bind tightly to blood proteins are limited in what way?
Permeability limited, rather than perfusion limited.
They are limited in their ability to cross a membrane and bind to their targets.
Describe the binding of drugs to macromolecules (plasma proteins).
- Consists of inter-molecular forces (ionic, vdw, hydrogen)
- Reversible
- Non-specific
What does the non-specific nature of binding of drugs with macromolecules mean?
One drug can replace another (in binding the macromolecule)
What would happen if warfarin and sulphonamides are administered together?
The plasma level of warfarin might be toxic, leading to fatal haemorrhage.
The interaction of a drug with a plasma protein tends to be on the ______ of the protein.
surface
What are human (body) factors that affect drug distribution?
Blood flow - perfusion
Capillary permeability
Biomolecules
How does blood flow/perfusion affect drug distribution?
The amount of dedicated blood flow to a certain organ will affect how much of the drug is delivered there.
Describe how capillary permeability affects drug distribution
Differences in capillary structure will affect how the drug can travel to the target site.
Describe how biomolecules affect drug distribution.
Biomolecules in the blood or in the target tissue can have proteins that will bind to the drug.
Describe compartmentalization.
Each organ/tissue contains different biomolecules and cell types that could effect the distribution (retention) of a drug.
Once in the tissue, there are three things that can affect drug retention. What are they?
1 - Tissue protein binding
2 - intracellular/tissue fluid pH
3 - lipids of fat cells can bind to the drug
What are drug properties that will affect drug distribution?
- Pka (ionization, charged or uncharged
- Water and lipid solubility (P-value)
- Binding to serum proteins and/or tissue-specific biomolecules
What are the different factors that affect drug distribution?
Human Body
- blood flow
- capillary permeability
- biomolecules
Drug properties
- pKa
- P-value
- binding to serum proteins and/or tissue specific biomolecules
