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Lecture 5

Lecture 5 Dose Response

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Lecture 5 PCL201 Dose ResponseMeasuring physiological response of drugreceptor interactionsResponsecan be anythingWhat happens when drug and receptor interactA responseacuteResponse varies with time and can be varied with doseThreshold minimum amount to elicit effectIncrease dose increase responseCharacterization o DR BindingDRDREffectDR interactionconformational changeresponseReaction is on and off similar to enzyme kineticsResponse is equivalent toconcentration of drug aintrinsic activityaAffinity measure the strength of the DR interactionResponse is relative to drug concentration and the number of receptors activatedIt is possible to saturate a signaling cascadeThe dose response curveCommon profile associated with specific drug interaction saturation leveling off with increased dosage Increased dose Increased response with saturation at high doses can lo longer elicit greater responseA fairly uncommon profile associated with nonspecific drug interaction is a linear relationship between response and dose indicating that increased response proportional to dose no maximal doseDose Response vs LogDose ResponseCompressionStraight midsegmentParallelism for drugs with similar mechanismsoYou can compare two drugs working on same systemParallelism for drugs of similar mechanism of actionSemilogarithmic transformationExpands concentration scale at low concentration binding changes rapidlyCompresses concentration scale at high concentration binding changes slowlyDoes not change the value of Kd affinityDoseResponse Curve Efficacy Emaxthe maximal response achieved by an agonistefficacy
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