3. Factors Contributing to Drug Effect

The Effect a Drug may have is Dependent on a Variety of Factors:

1. Drug dosage: effect of drug increases with increased amount of drug up to the POINT OF RECEPTOR SATURATION
2. Number of Receptors: receptors may be differentially expressed in one tissue to the next and, therefore, mediate different levels of biological responses.
   • Example: Beta-1 receptors are most concentrated in the heart; therefore, beta-1 agonists produce the greatest effects in the heart. Beta-2 receptors are most expressed in the bronchioles of the lungs and the arteries of skeletal muscle; therefore, beta-2 agonists produce the greatest effects in these tissues and organs.
3. Disease states: disease states can effect drug pharmacology
   • Example: pharmacokinetics of a drug change dramatically in a patient with chronic kidney disease
     • Digoxin’s volume of distribution decreases when one has chronic kidney disease [CKD]. Clearance also decreases causing digoxin’s half-life to increase, meaning that patient with CKD actually needs a lower dose than a patient with normal functioning kidney to achieve safe and effective digoxin levels.
4. Drug Efficacy/Intrinsic activity: ability to activate or block a receptor: maximum effect a drug can produce regardless of the dose
5. Drug Potency/Affinity: rate of drug-receptor binding and drug-receptor release: amount of drug needed to produce a particular effect: drug affinity for receptor:
   See below: the more potent the drug the quicker it binds its receptor (forward rate) and the slower it releases from its receptor (reverse rate).

Efficacy vs Potency: As drug efficacy increases, so does the maximal biological response it can produce. Efficacy cannot be changed by increasing the dose beyond that which elicits a maximal response, since it is an inherent characteristic of the drug. While potency is also an intrinsic property of a given drug, effects of the drug may be increased by using higher doses because potency refers to the rate of drug-receptor binding and dissociation whereas efficacy refers to the resultant biological response.

EFFICACY of a drug is therefore more important clinically than

POTENCY since one could manipulate the drug dose to produce the desirable response in case of a drug with low potency but a drug with low efficacy could not be manipulated in the same way.

Spare Receptors: often times occupation of only a fraction of receptors is necessary for obtaining a maximal response. In this case the remaining unbound receptors are known as spare receptors. This means that there can be a reduction in receptors (up to a limit!!!) without a corresponding decrease in the maximal response.