Medications bound to protein have the following effect:
A. Enhancement of drug availability.
B. Rapid distribution of the drug to receptor sites.
C. The more drug bound to protein, the less available for the desired effect.
D. Increased metabolism of the drug by the liver.
Correct Answer: C. The more drug bound to protein, the less available for the desired effect.
Only an unbound drug can be distributed to active receptor sites. Therefore, the more of a drug that is bound to protein, the less it is available for the desired drug effect. Less drug is available if bound to protein. Metabolism would not be increased. The liver will first have to remove the drug from the protein molecule before metabolism can occur. The protein is then free to return to circulation and be used again.
Option A: Protein binding can enhance or detract from a drug’s performance. As a general rule, agents that are minimally protein bound penetrate tissue better than those that are highly bound, but they are excreted much faster. Among drugs that are less than 80-85 percent protein-bound, differences appear to be of slight clinical importance.
Option B: Distribution to receptor sites is irrelevant since the drug bound to protein cannot bind with a receptor site. Agents that are highly protein-bound may, however, differ markedly from those that are minimally bound in terms of tissue penetration and half-life. Drugs may bind to a wide variety of plasma proteins, including albumin.
Option D: In the body, a drug may be protein-bound or free. Only free drugs can act at its pharmacologically active sites, eg., receptors, cross into other fluid compartments, or be eliminated. In the clinical setting, the free concentration of a drug at receptor sites in plasma more closely correlates with the effect than is the total concentration in plasma. Any reduction in plasma protein binding increases the amount of drug available to act on receptors, possibly leading to greater effect or an increased possibility of toxicity.