How does protein binding affect volume of distribution?
Decreased plasma protein binding leads to an increase in free plasma fraction causing an increase in volume of distribution and a shorter elimination half life. The increase in the apparent volume of distribution and the shorter elimination half life cause a decrease in total plasma concentration.
How does protein binding affect drug activity?
Protein-binding may affect drug activity in one of two ways: either by changing the effective concentration of the drug at its site of action or by changing the rate at which the drug is eliminated, thus affecting the length of time for which effective concentrations are maintained.
What can increase volume of distribution?
Volume of distribution may be increased by kidney failure (due to fluid retention) and liver failure (due to altered body fluid and plasma protein binding)….Equations
- VP = plasma volume.
- VT = apparent tissue volume.
- fu = fraction unbound in plasma.
- fuT = fraction unbound in tissue.
How does protein binding affect pharmacokinetics?
Protein binding can influence the drug’s biological half-life. The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form. Since the unbound form is being metabolized and/or excreted from the body, the bound fraction will be released in order to maintain equilibrium.
What affects volume of distribution?
The major determinants of Vd are drug properties which affect protein binding and tissue binding. These consist of molecule size, charge, pKa, and the lipid/water partition coefficient.
Which compartment do protein bound drugs distribute to?
As most drugs bind to albumin, both the bound fraction and the binding constant decrease with increasing temperature. The unbound drug molecules are the ones that diffuse from the intravascular compartment into tissues.
What is the effect of protein binding on drugs quizlet?
When Drug B is added, it will compete with Drug A for available protein binding sites and, in addition, may displace some of Drug A from sites already occupied. The result will be an increase in levels of free (unbound) Drug A and this increases the risk of toxicity.
How does volume of distribution affect bioavailability?
Extrapolating from the equation, a drug with a larger Vd will have a larger distribution outside of the central compartment (plasma systemic circulation). It is important to consider how the relative breadth of a drug’s volume of distribution might affect the drug’s potential bioavailability.
What affects protein binding?
The concentration of several plasma proteins can be altered by many factors, including stress, surgery, liver or kidney dysfunction, and pregnancy. In such circumstances, free drug concentrations are a more accurate index of clinical effect than are total concentrations.
What factors affect protein binding?
Protein binding by this method can be affected by drug stability, radioactive tracer purity, time of equilibration, dilution, temperature, pH, buffer composition, and colloidal osmotic fluid shifts caused by plasma proteins.