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Dose-Response Relationship: Potency and Efficacy01:22

Dose-Response Relationship: Potency and Efficacy

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 produces...
Dose-Response Relationship: Overview01:03

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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...
Dose Response Curve: Conventional Versus Nonmonotonic01:21

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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 relationships...
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Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...
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Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
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Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...

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The DOse REsponse Multicentre International Collaborative Initiative (DO-RE-MI).

G Monti1, M Herrera, D Kindgen-Milles

  • 1Department of Anesthesiology and Intensive Care, Hospital Niguarda, Milan, Italy, and Anesthesiology Clinic, University of Düsseldorf, Germany. Gianpaola.monti@ospedaleniguarda.it

Contributions to Nephrology
|April 28, 2007
PubMed
Summary

Practices for renal replacement therapy (RRT) in the ICU vary widely. This study found that continuous venovenous hemodiafiltration (CVVHDF) is most common, but delivered doses often fall short of recommended levels, impacting patient outcomes.

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Area of Science:

  • Nephrology
  • Intensive Care Medicine
  • Clinical Research

Background:

  • Current practices for renal replacement therapy (RRT) in intensive care units (ICUs) are not well-defined.
  • The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) survey investigates RRT modality selection and performance.
  • This study reports preliminary findings from the first year of recruitment.

Purpose of the Study:

  • To describe current practices in RRT selection and delivery in ICUs.
  • To analyze the delivered RRT dose in relation to patient outcomes.
  • To identify factors contributing to RRT downtime.

Main Methods:

  • An observational, multinational survey (DO-RE-MI) involving 431 patients across 25 centers in 5 countries.
  • Data collected via electronic case report forms (CRFs) on patient demographics, RRT initiation criteria, modality used, delivered dose, and downtime.
  • Analysis of RRT modalities including continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous hemofiltration (CVVH), intermittent hemodialysis (IHD), and high-volume hemofiltration (HVHF).

Main Results:

  • Continuous venovenous hemodiafiltration (CVVHDF) was the most utilized RRT modality (49%), despite significant variability in delivered doses.
  • The RIFLE criteria (38%) and elevated urea/creatinine levels were primary indicators for initiating RRT.
  • Circuit clotting (74%) was the leading cause of RRT interruptions, contributing to significant downtime (8-28%).

Conclusions:

  • Significant variability exists in RRT modality selection and delivered doses across ICUs.
  • CVVHDF is the predominant RRT method, but delivered doses frequently deviate from the target of 35 ml/h/kg.
  • Circuit clotting and clinical factors are major contributors to RRT downtime, highlighting areas for practice improvement.