Concentration and Drug Effect Study Notes

Administrative Details

• Last day to turn in Unit $5$ Late Work: $05/06$.
• LT $8.1$: Understand how drugs act in the body.
• Content Check $8.1.1$ and Day $2$ Takeaway: Due Monday $04/27$.

Challenges in Measuring Drug Activity

• It is difficult and often physically impossible to measure the amount of drug at the site of action due to its small size or unknown location.
• Factors influencing drug movement from administration to the site of action include Absorption, Elimination, and Membrane permeability.

Dose-Response and Potency

• Dose-Response Curve: Shows that response increases as dosage increases, although human variability means individuals respond differently to the same dose.
• $EC_{50}$ (Half-Maximal Effective Concentration): The concentration producing $50\%$ of a compound's maximum effect. It is a key measure of potency.
• Potency: Changes are evaluated on a $\log_{10}$ scale; a lower $EC_{50}$ indicates higher potency.

Blood Concentration-Time Profiles

• Rationale: Blood is the monitoring fluid of choice because it circulates through the entire body and is usually in rapid equilibrium with the site of action.
• Minimum Effective Concentration (MEC): The concentration needed for a drug to produce a response. This marks the onset of action.
• Minimum Toxic Concentration (MTC): The upper concentration limit beyond which undesired or toxic effects occur.
• Therapeutic Window: The range between the MEC and the MTC where the patient receives maximum benefit with minimum risk.
• Narrow Therapeutic Index (NTI): Refers to drugs where small differences in blood concentration or dose lead to serious therapeutic failures or reactions.
• Duration of Action: The amount of time the drug concentration remains above the MEC.

Clinical Applications and Exceptions

• Applications: Evaluating product performance, monitoring patient therapy, and assessing human variability (age, gender, nationality, or disease).
• Exceptions: A blood concentration-time profile does not always reflect effect if action is delayed by hours or days, or if the drug does not depend on blood concentration to produce an effect.

Warm Up Questions & Discussion

• 1. You take an antihistamine to relieve your allergy symptoms, but it makes you feel incredibly tired. Which of these is the therapeutic effect and which is the side effect?
  • Relief of allergy symptoms is the therapeutic effect; tiredness is the side effect.
• 2. A patient assumes that if taking $1$ pill makes their pain go away a little bit, taking $10$ pills will make it go away completely. Explain why increasing the dosage of a drug will eventually stop increasing its effect.
  • The effect will eventually plateau because the physiological mechanisms or receptors responsible for the drug's action become saturated.
• 3. Why do doctors often tell patients to gradually discontinue an antagonist drug rather than stopping it abruptly?
  • To prevent adverse reactions or rebound effects associated with immediate cessation of the drug's blockade.