Beyond single stressors/stimuli in adaptive physiology: Dose-response relationships and translational challenges

Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...

The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response...

Pharmacodynamics explores the relationship between drug concentration and its effect. In a quantal response drug, the duration of action better correlates with drug concentration, while for graded effect drugs, the intensity of response is more relevant. This intensity depends on the dose, drug removal rate, and the region of the concentration–response curve.The concentration–response curve can be divided into three regions. Region 3 (80–100% maximum response) demonstrates...

A drug’s dosage and pharmacokinetic properties determine how quickly it acts, how intense its effects are, and how long it lasts. Higher doses increase drug concentration at receptor sites, producing a hyperbolic curve when pharmacologic response is plotted against drug dose. Converting this scale to a log-linear format results in a sigmoidal curve, better representing dose–response relationships.For drugs following a one-compartment model, the pharmacologic response is directly...

The pharmacokinetic-pharmacodynamic (PK-PD) relationship describes the intricate link between drug exposure, efficacy, and toxicity, forming the foundation for optimal dosing regimens. This relationship uses mathematical modeling to characterize drug concentration-effect dynamics, ensuring precise therapeutic outcomes.Exposure represents the pharmacokinetic aspect of the PK-PD relationship, denoting the drug amount that elicits a biological response. It is typically quantified by administered...

The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it...