Lecture 14 Flashcards
Explain the distribution of pharmokinetics
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.
What are the two passages of drugs across membranes
Passive transport (Most drugs)
Active transport
Describe plasma protein binding
Drugs bind non-specifically to albumin in plasma
Drug + ProteinDrug–Protein complex
Reversible and saturable
Unbound or free fraction distributes
Unbound portion is responsible for the clinical effect
Name six protein bound drugs
Warfarin
Phenytoin
Sulphonamides
Ibuprofen
Salicylates
Furosemide
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
What are the factors that influence drug distribution?
Drug physicochemical properties
Lipid solubility
Water solubility
Drug particle size
Drug protein binding
The environment – blood flow; pH
What is the apparent volume of distribution and its equation?
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 that of plasma.
Vd=Dose (mg)/Concentration (mg/L)
What does a low Vd mean?
Vd<10L (warfarin)
Highly protein bound drug so retained in plasma
What does a medial Vd mean?
Vd10-30L (gentamicin)
Water soluble drugs, low lipid solubility,
Distributes into interstitial fluid but not cells
Dose on Ideal Body Weight to avoid toxicity
What does a high Vd mean?
Vd>100L (amiodarone)
Fat soluble drug distributes into tissues
