What factor primarily contributes to tachyphylaxis in drug administration?

Tachyphylaxis refers to the rapid decrease in response to a drug after its administration, and it often occurs after repeated use over a short period. The primary factor contributing to this phenomenon is the repeated administration of the drug. When a drug is given multiple times, the body's receptors may become desensitized or downregulated, leading to diminished efficacy.

For instance, if a medication is administered frequently, the body may quickly adapt to its presence, resulting in less pronounced effects each time it is given. This can be seen with certain medications like opioids or some sympathomimetics, where over time, the usual dose may not achieve the desired therapeutic effect, necessitating higher doses to achieve similar results. This effect is particularly relevant in local anesthesia as well, where repeated injections may lead to a reduced effectiveness due to receptor desensitization.

While increased metabolism and decreased plasma concentration can affect drug levels and response, they do not primarily explain tachyphylaxis. Similarly, increased receptor sensitivity would actually lead to a heightened response, which contradicts the concept of tachyphylaxis. Thus, the key factor at play here is the repeated administration of the drug leading to rapid desensitization.