Dose Response Curve Flashcards
(8 cards)
Intro - Fundamental analytical tools
Dose-response curves are fundamental analytical tools in pharmacology, illustrating how a drug’s biological effect changes with increasing dosage. These curves are instrumental in determining both the efficacy and safety of pharmacological agents by characterising the relationship between drug concentration and therapeutic or toxic outcomes. Central to this analysis is the concept of the therapeutic index (TI), which quantifies the margin between beneficial and harmful effects.
2nd para - logarithmic scale, ec50
A typical dose-response curve plots drug concentration (often on a logarithmic scale) against the magnitude of the biological response. Two key parameters derived from these curves are EC₅₀—the dose at which 50% of the maximal effect is achieved, representing drug potency—and Emax, the maximum effect a drug can produce, reflecting its efficacy. Based on these properties, drugs are classified as full agonists (capable of achieving Emax), partial agonists (producing submaximal effects), or antagonists (inhibiting receptor activity without eliciting a direct response). Some antagonists, particularly inverse agonists, can suppress baseline receptor activity, while allosteric antagonists modulate receptor function without directly competing at the active site.
3rd para - Ti diagram
Dose-response data also inform the calculation of the therapeutic index (TI), commonly defined in preclinical settings as:
Ti = Td50/ ED50
4th para - TD50
Here, TD₅₀ is the dose that causes toxicity in 50% of a test population, and ED₅₀ is the dose that produces therapeutic benefit in 50%. A high TI implies a broad safety margin, whereas a narrow TI indicates that the effective and toxic doses are close together—posing a greater risk of adverse effects if dosing is not meticulously controlled. While TI is derived largely from animal models, in clinical contexts, the more practical concept of the therapeutic window—the plasma concentration range in which the drug is effective without being toxic—is used.
5th para - drug TI examples
Several clinically important drugs exhibit narrow therapeutic indices. Digoxin, used for heart failure, can induce life-threatening arrhythmias at only slightly elevated concentrations. Warfarin, an oral anticoagulant, has a narrow therapeutic window necessitating regular INR monitoring to prevent haemorrhage. Lithium, prescribed for bipolar disorder, can cause renal and neurological toxicity with minor increases in serum levels. Similarly, theophylline, a bronchodilator, can trigger seizures or arrhythmias at high concentrations.
6th para - drugs tdm
Drugs with narrow TIs require therapeutic drug monitoring (TDM) to ensure plasma concentrations remain within safe and effective limits. This adds complexity to treatment regimens and demands close patient supervision. Small variations in dose, drug interactions, or changes in patient physiology—such as altered hepatic or renal function—can significantly impact drug clearance and increase toxicity risk. Notably, impaired hepatic metabolism or renal excretion can lead to drug accumulation, even for drugs that undergo minimal first-pass metabolism.
7th para - drug binding to specific targets
At the molecular level, most drugs exert their effects by binding to specific targets—such as receptors, ion channels, enzymes, or transporters—via reversible, non-covalent interactions. However, as drug concentration increases, target specificity may decrease, leading to off-target effects and unwanted side reactions. This is particularly concerning for narrow-TI drugs, where such effects may emerge at or near therapeutic doses.
8th para - conc
The understanding of dose-response relationships is therefore crucial in both drug development and clinical application. During preclinical phases, these curves help define safe dosage limits and identify potential toxicity risks. In clinical settings, they inform prescribing practices, especially for drugs that require precision dosing.
