Pharmacokinetics

• what are the two plasma proteins found in the blood which bind drug molecules ?

  Albumin

  a1-acid glycoprotein
• how many binding sites does albumin protein have ?

  two
• albumin can bind two drug molecules at the same time. Explain how increasing the concentration of one drug can increase the therapeutic effect of the other drug.

  More of drug to bind to albumin, therefore increases the free plasma concentration of the other drug
• which drug is pharmacologically active ?

  the unbound drug
• what is the normal range of albumin ?


  3.4-5.4 g/l
• what is the normal range of a-acid glycoprotein ?

  0.04-0.12g/dL
• why might a patient with low albumin (renal impairment) experience toxicity ?

  some total concentration, higher concentration of unbound drug so increased therapeutic effect
• where do lipophilic/ unionised drugs partition ?

  they partition into lipid spaces of tissues such as the cell membrane and body fat
• where do acidic drugs bind ?

  to extracellular proteins
• why do weak acids accumulate in compartments with high pH ?

  they are lionised so cannot pass through the lipophilic cell membrane
• what are the two ways drug cross lipid membranes ?

  passive diffusion

  carrier-mediated diffusion
• what does urinary alkanisation do to the excretion of weak bases ?

  they are unionised, so reduces their excretion as they can diffuse through lipophilic cell membranes back into the blood
• what does the amount of drug that is bound to protein depend on ?

  the concentration of free drug

  its affinity for the binding sites

  the concentration of protein
• what is the affect of protein binding on drug elimination/metabolism ?

  slows it down
• where can hydrophobic drugs accumulate ?

  in body fat
• why are drugs delivered slowly to fat ?

  it has low blood supply
• what is the definition of absorption ?

  the passage of a drug from its site of administration into the plasma
• name the factors affecting gastrointestinal absorption

  • gut content (fed vs fasted)
  • gastrointestinal motility
  • splanchnic blood flow
  • particle size and formulation
  • drug-drug interactions
  • drug-drug competition for transporters
• why does food allow plasma drug concentrations to be increased ?

  eating increases splanchnic blood flow
• what is T max ?

  the time after dosing at which the plasma concentration of drug is at its maximal, C max
• why might a mixture of slow and fast release particles be included in a capsule ?

  to produce rapid but sustained absorption
• what is the plasma concentrations like for a drug with higher bioavailability ?

  higher peak plasma concentrations
• where can drugs be metabolised reducing bioavailability?

  by enzymes in the liver or gut wall
• why might bioavailability be low ?

  metabolism

  absorption is incomplete
• what is the absorption like from the gut for strong acids or bases ?

  poor as they are ionised
• what are the two forms that drug molecules exist ?

  bound and unbound
• what form of the drug is able to move through the body compartments ?

  unbound drug
• what Is extracellular fluid ?

  comprises the blood plasma, interstitial fluid and lymph (all body fluid outside of cells)
• what is transcellular fluid ?

  all the fluid formed by the transport activities of cells
• what is the intracellular fluid ?

  the sum of the fluid contents of all the cells in the body
• how can drugs pass into different fluids/compartments ?

  pass through a cellular barrier
• what are the different compartments that drugs can reach ?

  plasma (5% of body weight)

  interstitial fluid (16%)

  intracellular fluid (35%)

  transcellular fluid (2%)

  fat (20%)
• why can the bound drug not be pharmacologically active ?

  it cannot pass through cell membranes
• why do lipophilic drugs accumulate in fatty tissues ?

  they can cross membranes easily
• where do hydrophilic drugs tend to accumulate (hint: they are less lipophilic) ?

  aqueous compartments (e.g the blood plasma and interstitial fluid)
• How do organs with low blood flow differ in the way that they receive drugs compared to organs with high blood flow ?

  they receive drugs less quickly
• which drugs can pass the BBB more easily ?

  lipophilic drugs in the unionised form as they are less polar and water soluble
• how are drugs which cannot move via passive diffusion transported into cells ?

  facilitated diffusion

  active transport

  endocytosis/exocytosis -engulf drugs into cells by forming a vesicle around them
• what is metabolism ?

  it is the biotransformation of a drug into another chemical species
• what is excretion ?

  irreversible loss of drug from the systemic blood (movement out of the body)