Volume of Distribution Protein Binding Concepts

Name the forces involved in protein binding:

• electrostatic attraction

• Van De Waal’s forces

• Hydrogen bonding

Which acidic drugs will bind to albumins?

• penicillins

• sulfonamides

• salicylates

• barbiturates

• phenylbutazone

• etc.

What basic drugs will bind to globulins and lipoproteins?

• propranolol

• adenosine

• quinacrine

• quinine

• digitoxin

• etc.

How does protein binding affect drug distribution?

V_d is a result of a tug of war between blood and tissue: if tissue “pulls harder” a drug will have a larger volume of distribution

To calculate protein binding effects on volume of distribution:

V = V_p + V_t x (f_u / f_ut)

True or False: Only free drugs interacts with the receptor in protein binding

True; when a drug is bound to plasma proteins, it becomes inactive since its not acting as a reservoir that slowly releases free drugs

When does competition occur between drugs for binding in albumin binding sites?

only if one drug is approaching 1.2 mmol/L and if the binding affinity is also high

If a drug is highly protein bound (f_u < 0.1) and the protein binding site is away from saturation:

use f_u’ = P_t / P_t’ x f_u

How do plasma and tissue binding of a drug differ?

tissue binding of a drug can’t be measured directly since handling of the tissue results in disruption of the binding