Antagonism and Potentiation • Graded dose-response curves additionally supply information regarding antago­ nists-drugs that have interaction with receptors to intrude with their activa­ tion via agonists. keep watch over a hundred Q) (/) c zero Q. (/) Q) a: #Log dose of drug Compe titive j determine 1-2-4. D-R Curves of Antagonists and Potentiators • Bridge to Biochemistry Parallels among Receptor Antagonists and Enzyme Inhibitors Pharmacologic antagonism (same receptor) aggressive antagonists are analogous - aggressive antagonists: to aggressive inhibitors; they reduce ° reason a parallel shift to the perfect within the D-R curve for agonists ° may be reversed by way of zero seems to be to i the dose of the agonist drug . J, the efficiency of the agonist affinity (i Km) reaction yet no longer maximal (Vmax is still the same). Noncompetitive antagonists reduce V max yet don't switch the Km. � clinical 21 Section I • basic rules - Noncompetitive antagonists: • ° reason a nonparallel shift to the proper ° should be in basic terms in part reversed by way of zero seem to i the dose of the agonist J, the efficacy of the agonist Physiologic antagonism (different receptor) - agonists with opposing motion antagonize one another - instance: a vasoconstrictor with a vasodilator • Chemical antagonism: - Formation of a fancy among effector drug and one other compound - instance: protamine binds to heparin to opposite its activities • Potentiation - reasons a parallel shift to the left to the D-R curve - looks to i the efficiency of the agonist QUANTAL (CUMULATIVE) D-R CURVES • those curves plot the proportion of a inhabitants responding to a speci­ fied drug impression as opposed to dose or log dose. they allow estimations of the median powerful dose, or powerful dose in 50% of a population-EDSO. • Quantal curves can display the diversity of intersubject variability in drug reaction. Steep D-R curves mirror little variability; flat D-R curves indi­ cate nice variability in sufferer sensitivity to the consequences of a drug. Toxicity and the healing Index (Tl) • Comparisons among EDSO and TDSO values allow review of the relative protection of a drug (the healing index), as could comparability among EDSO and the deadly median dose (LDSO) if the latter is understood. TI TDSO = EDSO or LDSO EDSO healing a hundred poisonous OJ c "O c g_ (/) Q) 50 a: ct. 2 four 6 eight 10 mg/kg determine 1-2-5. Quantal 0-R Curves of healing and poisonous results of a Drug 22 � scientific Chapter 2 • • Pharmacodynamics As proven in determine 1-2-5, those D-R curves is additionally used to teach the connection among dose and poisonous results of a drug. The median poisonous dose of a drug (TD50) is the dose that explanations toxicity in 50% of a popu­ lation. • • From the knowledge proven, TI= 10/2 = five Such indices are of such a lot worth whilst toxicity represents an extension of the pharmacologic activities of a drug. they don't are expecting idiosyncratic reactions or drug allergic reaction. SIGNALING MECHANISMS: different types of DRUG­ RESPONSIVE SIGNALING MECHANISMS • Binding of an agonist drug to its receptor prompts an effector or sign­ • numerous types of drug-responsive signaling mechanisms are ing mechanism.