1.10 Therapeutic Levels

Now that the concepts of dose-response, onset, peak, and duration have been discussed, it is important to understand the therapeutic window and therapeutic index.

Therapeutic Window

For every drug, there exists a dose that is minimally effective (the Effective Concentration) and another dose that is toxic (the Toxic Concentration). Between these doses is the therapeutic window, where the safest and most effective treatment will occur. For example, see Figure 1.9^[1] for an illustration of the therapeutic window for warfarin, a medication used to prevent blood clotting. Too much warfarin administered causes bleeding and vitamin K is required as an antidote. Conversely, not enough warfarin administered for a client’s condition can cause clotting. Think of the therapeutic window (the green area on the graph) as the “perfect dose,” where clotting is prevented and yet bleeding does not occur.

The effect of warfarin is monitored using a blood test called international normalized ration (INR). For clients receiving warfarin, nurses vigilantly monitor their INR levels to ensure the dosage appropriately reaches their therapeutic window and does not place them at risk for bleeding or clotting.

Peak and Trough Levels

Now let’s apply the idea of therapeutic window to the administration of medications requiring the monitoring of peak and trough levels, which is commonly required in the administration of specific IV antibiotics. The dosage of these medications is titrated, meaning adjusted for safety, to achieve a desired therapeutic effect for the client. Titration is accomplished by closely monitoring the peak and trough levels of the medication. A drug is said to be within the “therapeutic window” when the serum blood levels of an active drug remain consistently above the level of effective concentration (so that the medication is achieving its desired therapeutic effect) and consistently below the toxic level (so that no toxic effects are occurring).

A peak drug level is drawn after the medication is administered and is known to be at the highest level in the bloodstream. A trough level is drawn when the drug is at its lowest in the bloodstream, right before the next scheduled dose is given. Medications have a predicted reference range of normal values for peak and trough levels. These numbers assist the pharmacist and provider in gauging how the body is metabolizing, protein-binding, and excreting the drug and are used to adjust the prescribed dose to keep the medication within the therapeutic window. When administering IV medications that require peak or trough levels, it is vital for the nurse to plan the administration of the medication according to the timing of these blood draws.^[2]

Therapeutic Index

The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of drug that produces a therapeutic effect versus the amount of drug that produces a toxic effect.

• A large (or high) therapeutic index number means there is a wide therapeutic window between the effective concentration and the toxic concentration of a medication, so the drug is relatively safe.
• A small (or low) therapeutic index number means there is a narrow therapeutic window between the effective concentration and the toxic concentration. A drug with a narrow therapeutic range (i.e., having little difference between toxic and therapeutic doses) often has the dosage titrated according to measurements of the actual blood levels achieved in the person taking it.

For example, phenytoin has a narrow therapeutic index between the effective and toxic concentrations. Clients who start taking phenytoin to control seizures have frequent peak and trough drug levels to ensure they achieve steady state with a therapeutic dose to prevent seizures without reaching toxic levels.