Uploaded byDr Pankaj Kumar Gupta
Dose Response Curve
The document discusses dose-response curves and their significance. It explains that dose-response curves show the relationship between the dose of a drug administered and the intensity of response produced. A log dose-response curve becomes sigmoid shaped and allows comparison of drug potency. The position, slope and maximum effect of the curve provide information about a drug's potency, efficacy, safety, therapeutic index and window. Quantal and graded dose-response curves are used to assess different types of drug responses.
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Introduction to Dose Response relationship and its significance in pharmacology.
Advantages of log dose response curves and their application in comparing drug efficacy.
Use of DRC to predict drug potency, safety, and effectiveness metrics like ED50 and LD50.
Example of potency comparison between Fentanyl and Morphine using their DRC.
Discussion on drug efficacy, showing that Morphine offers more analgesia than Aspirin.
Slope of DRC in assessing drug safety and implications of steep vs. shallow slopes.
Definition of ED50 and LD50, their calculation and relevance in drug safety.
The importance of therapeutic index as a safety margin and distinction from therapeutic window.
Assessment of risks versus expected therapeutic benefits in drug prescription.
Overview of graded vs. quantal dose response curves and their applications in pharmacology.
Closing remarks on dose response curves and their importance in clinical settings.
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Dose Response Curve
- 1. Dose Response Curve Dr.Pankaj Kumar Gupta Assistant Professor, Department of Pharmacology, ESIC Medical College & Hospital, Faridabad
- 2. Dose & Response Dose •Amount of drug to administered to produce a certain degree of response in a patient. Response • The change in activity of the cell or tissue produce by the selected dose of the drug is called the response.
- 3. • The doseand response is closely related to each other and this relationship is called as Dose response relationship. • There is direct relationship between dose & intensity of response of the curve- i.e. the intensity of response increases with the increase in dose. • A typical curve showing the dose response relationship is called dose response curve (DRC).
- 5. Dose Response Curve Doseresponse curve & log dose-response curve
- 6. Advantages of logdose response curve
- 7. Advantages of logdose response curve
- 8. Advantages of logdose response curve • Curvilinear (rectangular hyperbola) Vs Sigmoid curve. • If the dose is plotted on a logarithmic scale, the curve becomes sigmoid (S-shape) & a linear relationship between log of dose & the response is seen in the intermediate (30- 70% response) zone. • A wide range of drug doses can be easily displayed on a graph. • rectangular hyperbola) Vs Sigmoid curve. can be estimated easily with sigmoid curve as compared to curvilinear curve. • Comparison between agonists and study of antagonists becomes easier.
- 9. Significance of DRC •The DRC of drug is useful to predict: • Potency • Efficacy • Safety of drug • ED50 • LD50 • Therapeutic index • Therapeutic window
- 10. Potency • The positionof DRC on the X- axis is an index of drug potency. • A DRC positioned rightward indicates lower potency.
- 11. Log dose responsecurve for potency of two drug
- 12. •Drug Fentanyl ismore potent than drug Morphine, since it produces intensity of response as drug morphine as much smaller doses. •The relative potency is determined by comparing the dose of two agonists at which they produces half maximum response (EC50). •Eg: 0.1 mg of Fentanyl is equivalent to 10 mg of Morphine to produce analgesia, hence, Fentanyl is 10 times more potent than Morphine. Log dose response curve for potency of two drug
- 13. Efficacy • The upperlimit of DRC is the index of drug efficacy & refers to the maximal response that can be elicited by the drug. • Eg: Morphine produces a degree of analgesia not obtain with any dose of aspirin. Morphine is more efficacious than aspirin.
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- 15. •Drug A, B& C are equally potent but Drug A is more efficacious then drug B & C (Drug A>Drug B>Drug C) •Efficacy is a more decisive factor in the choice of the drug. Drug dose (Log)
- 17. •Hydromorphine, Morphine &Codeine are equally efficacious. (H=M=C>A) •Hydromorphine is more potent than Morphine & codeine. (H>M>C)
- 18. Safety • The slopof the upper part of the curve is useful in assessing the relative safety of drug. • Ex:- Most CNS depressants have steep slope which indicates a narrow margin of safety between the dose that produces sedation & the dose that produces coma. • The drug with more shallow slope of curve produces little increase in response over a wide dose range & has wider margin of safety.
- 19. Log dose responsecurve for safety of drug A & drug B
- 20. Log dose responsecurve for safety of drug A & drug B •Slope of Drug A is more steeper than Drug B (narrow margin of safety) •Slope of Drug B is more shallow than Drug A (wider margin of safety)
- 21. ED50 & LD50 •Median Effective Dose (ED50): is the dose of a drug necessary to produce a specific response in 50% of all population. • Median Lethal Dose (LD50): is dose of a drug which kills 50% of recipients.
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- 23. Therapeutic Index (TI) •The gap between the therapeutic effect DRC & the toxic effect DRC defines therapeutic index of a drug. • Therapeutic index = Median Lethal dose (LD50) Median Effective dose (ED50)
- 26. Clinical significance ofTherapeutic Index (TI) • The therapeutic index gives a measure of safety margin of a drug. • The closer that the ratio is to 1, the greater the danger of toxicity. • Drugs that have a low TI are said to have a narrow margin of safety. These drugs require that levels in the plasma be monitored and adjustments are made to the dosage in order to prevent a toxic effect from occurring.
- 27. Therapeutic range (TherapeuticWindow) • Optimal range of drug plasma concentrations at which most of the patients experience the desired effect. • It is between the minimum effective concentration (MEC) for obtaining the desired pharmaceutical response and the minimum toxic concentration (MTC) or maximal acceptable adverse effects.
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- 30. Difference between TherapeuticIndex & Therapeutic Window
- 32. Risk-benefit Ratio • Ajudgement on the estimated harm Vs expected advantages. – Estimated harm (adverse effects, cost, inconvenience) – Estimated advantages (relief of symptoms, cure, reduction of complications/mortality, improvement in quality of life) • A drug should be prescribed only when the benefits outweigh the risk.
- 33. TYPES OF DOSERESPONSE • GRADED DOSE RESPONSE – Continuous scale – Measured in a single biologic unit – Relates dose to intensity of effect • QUANTAL DOSE RESPONSE – All-or-none pharmacologic effect – Population studies – Relates dose to frequency of effect
- 34. GRADED DOSE RESPONSECURVES • Graded dose response curves are constructed for response that are measured on continuous scale Eg:- heart rate. • GRADED dose response curves relates the intensity of response to size of dose hence, used in characterizing actions of drug. • Graded dose response means slight increase of drug brings small increase in response • Eg:- increased dose of adrenaline causes gradual increase of heart rate & BP.
- 35. • Very lowdose of drug has no effect and response is obtained only beyond the threshold dose. • Very high dose has no additional effect and response remains constant at this maximal levels • Graded dose response means the pharmacological effect of drug expressed in quality or number such as heart rate by beat and blood pressure by mmHg
- 36. QUANTAL DOSE RESPONSECURVES • Quantal dose response curves are constructed for those drugs that elicit ‘all or none response’. • A Quantal dose-response relationship describes a drug effect which is binary (either present or absent). • A quantal response to a drug is observed in a population, and is either present or absent in any single individual. • Quantal dose-response graphs plot the rate of an outcome occurrence in a population against the drug dose • Eg: presence or absence of epileptic seizures after an experimental drug.
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