Drug Distribution Flashcards
What must a drug do to be active in the body?
Move from circulation to tissues
What 7 things affect a drugs ability to move from the circulation to the tissues?
- Plasma protein binding
- Tissue perfusion
- Membrane characteristics
- Transport mechanisms
- Diseases
- Other drugs
- Elimination
What does the binding of a drug in the plasma do to it?
- Renders it inactive
What plasma protein do drugs commonly bind to
Albumin
What 5 things can the act of binding be affected by?
- Renal failure
- Hyperalbumaemia
- Pregnancy
- Other drugs
- Free unbound albumin
What proportion of protein must be bound to allow the saturability of binding to play a role?
- 90%
Why is it 90%?
- If the bound albumin is 98% and changes to 96% then is a 100% increase of active drug
What membrane characteristics can result in decreased drug distribution?
- Blood brain barrier
- Blood-testes/ovary barrier
What 3 mechanisms does excretion of the drug in the kidneys depend on?
- Glomerular filtration
- Passive tubular reabsorption
- Active tubular secretion
What is glomerular filtration with regards to drugs?
- Unbound drugs filtered at the glomerulus
How can glomerular filtration be affected?
- Size and charge of the drug
- Renal failure
- Bound to a protein
What is passive tubular reabsorption?
- When the filtrate from the glomerulus moves down the tubules its conc increases
- The body reabsorbs some of this drug through passive diffusion
What type of drugs ONLY can be reabsorbed this way?
Un-ionised
What condition can affect passive tubular reabsorption?
Renal failure
What is active tubular secretion with regards to drugs
- When some drugs are actively secreted into the proximal kidney tubules
What is active tubular secretion the main method of excretion of?
- Protein bound cationic
- Anionic drugs
What other factors determine the pharmacological actions of the drug?
- Half life
- Maximum plasma concentration
- Time to maximum plasma concentration
Shortened “maximum plasma concentration”
Cmax
Shortened “half life”
- t(1/2)
Shortened “time to max plasma concentration”
Tmax
What will the area under the plasma concentration against time curve tell you?
- Bioavailability or systemic availability
- Extent of absorption
What does the apparent volume of distribution (Vd) tell you?
A rough indication into overall distribution of a drug in the body
What can the fact that some drugs are accumulated in specific tissue lead to?
Local toxicity
What does the presence of renal disease increase the probability of occurring with most drugs?
- Toxic side effects
What should be altered when renal failure is present?
- Reduction in dose
- Increase in dosing interval
When would you use therapeutic drug monitoring?
When using a drug with a narrow therapeutic index
What are some sites where selective accumulation may occur?
- Bone
- Eye
- Kidney
- Lung
- Fat
