Drug Distribution Flashcards
How do drugs cross the epithelium / endothelium?
- Paracellular
- Transcellular ( Diffusion / Active Transport / Pinocytosis )
What are the two substances which aid with active transport?
Solute Carriers (Organic Anion / Cation Transporters) ATP - Binding Cassettes (P - Glycoprotein)
Which barrier is more permeable to allow substances to be metabolised?
Liver Endothelium
Which barrier is more permeable to allow substances to be eliminated?
Renal Endothelium in the Glomerulus
What state would lipid insoluble substances be in?
Ionised State
What state would lipid soluble substances be in?
Unionised State
What is pKa?
Hydrogen Ion Concentration at which:
50% of the drug is ionised
50% of the drug is unionised
What is protein binding?
Drugs can bind to plasma proteins.
Is a reversible reaction therefore can be bound and unbound.
What is the purpose of plasma proteins?
Major transporters of endogenous lipids and steroid hormones.
Why is protein binding important?
Some proteins are TOO LARGE to pass through most endothelia and epithelia and only free drugs can bind o their site of action.
What happens to bound proteins?
They remain in the blood and are unable to exert their pharmacological effect.
CAN NOT be metabolised or excreted.
Which drugs can reach an equilibrium across different compartments?
Unbound drugs can reach an equilibrium across different compartments.
Which drugs can’t reach an equilibrium across different compartments?
Bound drugs can’t reach an equilibrium across different compartments.
Which drugs act as a reservoir?
Bound Proteins.
What effect does protein binding have on a drug’s half - life?
Heavily protein bound drugs have a LONGER half - life.
What factors affect protein binding?
- Affinity of drug to protein binding sites.
- Drug Concentration.
- Plasma Protein Concentration.
What is the most important plasma protein for drug binding?
Albumin
Why is albumin the most important plasma protein?
Negatively charged
High affinity for acidic drugs BUT has a low capacity.
Low affinity for basic drugs BUT has a high capacity.
At higher dosages, some drugs begin to show an upward curve.
Why is this?
Plasma proteins become saturated.
Where are highly lipophilic drugs more likely to bind?
Extensively to fat stores.
Where does tissue binding occur a lot?
- Fat
- Bone
- Muscle
How does drug distribution occur in overweight patients?
They have a greater ratio of lipid levels to other body tissue.
Drug which are HIGHLY LIPID BOUND will be distribute more freely in overweight patients.
How does osteoporosis occur?
Increased resorption and thus bones begin to thin.
INCREASES RISK OF FRACTURES.
What is the purpose of bisphosphonates?
Binds to calcium in bones and inhibits resorption.
