Drug Distribution Flashcards
What affects tissue distribution?
- Plasma protein binding (the degree to which the drug is bound to it)
- Tissue perfusion
- Membrane characteristics
- Transport mechanisms
- Disease and other drugs
- Elimination
How does plasma protein affect tissue distribution?
- The amount of bound drug can be affected by:
- Renal failure
- Pregnancy
- Hypoalbuminaemia
- Other drugs
- Satruation
In plasma protein binding, what part is biologically active?
The unbound drug only
When is plasma protein important?
- The drug must be more than 90% bound and the tissue distribution small.
- I.e. if the drug is 96% protein bound then only 4% of the drug is free and available for action. If the unbound level changes to 6% then plasma levels of free drug will increase by 50%
Define volume distribution
The theoretical volume that is necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.
The greater the Volume distribution…
the greater the ability of the drug to diffuse into and through membranes
Define clearance
The theoritical volume from which a drug is completely removed over a period of time
What is clearance dependent on?
-Concentration, urine flow rate for renal clearance, metabolism, biliary excretion for hepatic clearance
Define drug elimination
The removal of active drugs and metabolites from the body
What is drug elimination made up of?
- Drug metabolism (usually in the liver)
- Drug excretion (usually kidney but also gut and lung)
What are the three principle mechanisms of drug excretion?
- Glomerular filtration
- Active tubular secretion
- Passive tubular reabsorption
How are many drugs distributed around the body?
- Many drugs bind to proteins in the plasma such as albumin, lipoproteins or alpha1-glycoprotein
- Binding is reversible
What happens in glomerular filtration?
- The glomerulus is a cluster of capillaries around the end of a kidney tubule
- Filters 190l of fluid a day
- All unbound drugs will be filtered at the glomerulus as long as their molecular size, charge or shape are not excessively large
What happens in active tubular secretion?
- acidic and basic compounds are actively secreted into the proximal tubule
- Most importnat system for eliminating protein bound cationic and anionic drugs
What are the drugs present in Passive Tubular Reabsorption?
- As the filtrate moves down the renal tubule, any drug that is present is concentrated.
- Only UN-IONISED such as weak acids are reabsorbed
What does Passive Tubular Reabsorption allow?
-Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation
Where does Passive Tubular Reabsorption occur?
-distal tubule and collecting duct
Why is the distribution of drug not uniform throughout the body?
the different tissues receive the drug from plasma at different rates and different extents.
What is distribution half life?
the time taken for 50% of the drug present in plasma to distribute outside the bloodstream.
What are barriers to drug distribution?
- blood brain barrier
- placenta
- testis
What are barriers to drug distribution?
- blood brain barrier
- placenta
- testis
How are drugs secreted into the bile?
-drugs may be passively or actively secreted into the bile
-biliary secretion accounts for 5-95% of drug elimation
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What may happen in Biliary Secretion of drugs?
- many drugs are then reabsorbed from the bole into the blood circulation. This is called Enter-Hepatic Circulation.
- it continues until the drug is metabolised in the liver or excreted by the kidneys
What are the four stages of drugs within the body?
Absorption, distribution, metabolism, excretion
Where are drugs easily and less easily distributed?
- easily distributed to the kidney, liver and heart
- distributed in small quantities through less perfused tissues like muscle and fat
