Affinity, Efficacy and Potency

• Affinity is a measure of how avidly a drug binds to its receptor
• Affinity can be measured by the dissociation constant K_D:

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• K_D is the molar drug concentration at which 50% of its receptors are occupied in equilibrium (mmol/L)
• A lower K_D implies a higher affinity

• Efficacy (intrinsic activity) is a measure of the magnitude of the effect once the drug is bound
• It is measured between 1 (maximal effect) and -1 (maximal opposite effect)

• Potency is a measure of the quantity of a drug to produce the maximum clinical effect
• Potency is compared using the median effective concentration (EC₅₀) or the median effective dose (ED₅₀)

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• EC₅₀ is the concentration of a drug that induces a response of 50% (i.e. halfway between baseline and maximum)
• It is a laboratory result after a test using a single set of parameters or on a single animal model
• A drug with a lower EC₅₀ is more potent
• A graph of drug concentration vs. percentage maximal response is a rectangular hyperbola, similar to the K_D graph above

• ED₅₀ is the dose of a drug that induces a specific response in 50% of a population to whom it is administered
• It is a measure of potency when the drug is administered to a population
• A drug with a lower ED₅₀ is more potent
• A graph of dose vs. percentage of population response is the quantal dose-response curve, the typical dose-response curve:

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• Semi-logarithmic transformation of this curve gives the log(dose)-response curve, and the graph becomes sigmoidal:

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• This is a reference log(dose)-response curve for a full agonist
• The linearity of the steep part of the log(dose)-response curve makes assessment of dose and response easier, and therefore comparisons between drugs easier

• LD₅₀ is the dose of a drug that is lethal in 50% of a population to whom it is administered
• This gives rise to the therapeutic index:
• The therapeutic index is the ratio of LD₅₀ to ED₅₀
• It is a balance between a drug's toxic effects and its beneficial effects

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• The ED₉₅ is plotted to demonstrate that a dose high enough to cause the specific response in 95% of a population may also cause toxic or lethal effects in a small portion of the population
• Examples of drugs with narrow therapeutic indices include:
• Theophylline
• Digoxin
• Phenytoin
• Lithium