Pharmacokinetics 2 Flashcards
What is distribution?
Process by which the drug is transferred reversibly from the circulation into the tissues as concentrations in the blood increase, and from the tissues into blood when the blood concentrations decrease during elimination.
Distribution of the drug into intracellular, interstitial and vascular compartments.
List methods by which drugs pass through membranes
Diffusion
Facilitated diffusion
Active transport
Describe plasma protein binding
Drugs bind non specifically to albumin in plasmsa
Reversible reaction
Drug + Protein - Drug protein complex
Reversible and saturable
Which part of the drug exerts the clinical effect according to the plasma protein binding hypothesis?
Unbound or free fraction distributes
Unbound portion is responsible for the clinical effect
Give some examples of high protein bound drugs
Warfarin Phenytoin Sulphonamides Ibuprofen Salicylates Furosemide
When can the protein binding become a problem?
When interaction occurs- the two drugs compete with one another and toxicity may occur
How does distribution occur?
Most drugs transfer by passive diffusion
Across capillary walls down a concentration gradient
Into interstitial fluid until concentration of free drug molecules in interstitial is equal to that in plasma
List some factors that influence drug distribution
Drug physicochemical properties:
- Lipid solubility
- Water solubility
Drug particle size
Drug protein bonding
The environment- blood flow and pH
What is the apparent volume of distribution?
A concept that seeks to predict how extensively a drug is distributed throughout the body
Volume into which a drug appears to be distributed with a concentration equal to plasma
How do you calculate apparent volume of distribution?
Vd= Dose (mg) / Concentration (mg/L)
What happens to a drug with low volume of distribution?
Remains in the plasma
What happens to a drug with high volume of distribution?
Distributes to the cells
What do we mean if a drug has a low volume of distribution?
Highly protein bound so retained in plasma
What do we mean if a drug has a medium volume of distribution?
Water soluble drugs, low lipid solubility
Distributes into interstitial fluid but not cells
Dose on ideal body weight to avoid toxicity
What do we mean if a drug has a high volume of distribution?
Fat soluble drug distributes into the tissues
