Dose response relationship

Dose response relationship

1. Dose Response Relationship Yousaf khan Lecturer Renal Dialysis IPMS- KMU

2. Dose Response Relationship The pharmacological effect of a drug depend on its concentration at the site of action, which in turn is determined by the dose of the drug administered. Such a relationship is called dose- response relationship.

3. Types of dose-response curves Graded dose response: As the concentration of a drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied ( the maximum effect) Quantal dose response curve: Certain pharmacological effects which can not be quantified but can only be said to be present or absent (all or none ).

4. Therapeutic index The relationship between the doses of a drug required to produce desired and undesired effect. Therapeutic index = LD50/ ED50 LD50: It is the dose of a drug, which is lethal for 50% of the population. ED50: It is the dose of drug, which produce the desired effect in 50% of the population.

5. Drug potency: The amount of a drug required to produce a desired response, the lower the dose required for a given response, The dose or concentration of a drug required to produce a given effect or the activity per unit weight of drug is called potency. Drug efficacy : it is the maximum effect of drug, it depend on the number of drug receptor complex formed and the efficiency with which the activated receptor produce a cellular function Therapeutic window : it is the range of concentration of the drug which produce desired response with minimal toxicity.

6. Combined effect of drugs Increased response: Summation or additive effect: The combined effect of two or more drugs is equal to the sum of their individual effect. Effect of drugs A+B = effect of drug A + effect of drug B Synergism : when combined the net effect is greater than the sum of their individual effect Potentiation: when one drugs has no apparent action by itself on one system but increase the effect of another drug is termed potentiation.

7. Combined effect of drugs Decreased response ( drug antagonism): the effect of one drug is decrease or abolished in the presence of another drug. Physical antagonism : the opposing action of two drugs is due to their physical property, e.g adsorption of alkaloids by activated charcoal – useful in alkaloid poisoning. Chemical antagonism : the opposing action of two drugs is due to their chemical property e.gantacids are weak bases, they neutralize gastric acid and useful in peptic ulcer Physiological antagonism : two drug act at different receptor or by different mechanism on the same physiological system and produce opposite effect e.g adrenaline and histamine on bronchial smooth muscle Histamine – bronchoconstriction and adrenalin -- bronchodialtion

8. Combined effect of drugs Receptor antagonism : the antagonist binds to the same receptor as the agonist and inhibits its effects. It can be competitive or non- competitive. Competitive antagonism : (equilibrium type) both agonist and the antagonist bind reversibly to the same site on the receptor e.g Acetylcholine → muscarinic receptor ← atropine Non – competitive antagonism : the antagonist bind to a different site on the receptor and prevent the agonist from interacting wit the receptor, in this type antagonistic effect can not be overcome by increasing the concentration of the agonist.

9. Factors modifying drug action Number of factor which can influence drug response Quantitative variation in drug response but rarely show qualitative variation. Drug factors Patient factors Route of administration age Presence other drug Body weight cumulation Sex, diet and environment Genetic factor Psychological factor Pathological state Tolerance

10. Drug factors Route of administration : drug is administered by different routes, its commonly exhibits quantitative variations, but some time qualitative variation in response Quantitative variation Qualitative variation Intravenous dose is less than oral dose Subcutaneous and intramuscular doses are also smaller than oral dose but larger than intravenous dose Presence of other drugs : addition, potentiation, synergism and antagonism Cumulation : if the elimination of a drug is slow, then repeated administration of the drug will result in its accumulation in the body causing toxiticty

11. Patient factors Age: In neonate: metabolizing function of the liver and excretory function of the kidney is not fully developed Children required smaller dose of drug than adult Weight : greater body weight the bigger the dose required Body surface area : greater body surface area larger the dose required. Sex : females usually required smaller dose than males

12. Patient factors Diet and environmental factors Genetic factor: genetically variation in drug response Psychological factor: personality of doctor as well as the patient can effect response to a drug. Placebo effect: dummy medicine having no pharmacological activity, the effect produce by placebo effect. Pathological states e.g drug metabolized in liver are not destroyed during liver disease.

13. Patient factors Tolerance: need for larger doses of a drug to produce a given response. Natural tolerance : genetically determined reduce/ lack of response to a drug Acquired tolerance: it develops on repeated exposure to a drug.

14. Drug interaction when two or more drug are given simultaneously the effect of one drug may be altered by another drug. Drug interaction can be occur in vitro or in vivo Result in either beneficial or harmful effects

15. Pharmaceutical interactions Can occur as a result of incompatibilty ( physical and chemical) of a drug with an intravenous solution When two or more drugs are mixed in the same syringe i.v infusion This may result in precipitation or inactivation of one or more drugs

16. Pharmacokinetic interaction These occur when one drug alters the absorption, distribution, metabolism or excretion of another drug. Absorption : antacids, iron etc interfere with the absorption of tetracycline by forming unabsorbable complexes with it Some drug affect absorption of other drugs by altering gastrointestinal motility. Distribution : plasma protein binding can cause displacement interaction, more than one drug can bind to the same site on plasma protein. E.g salicylate displace warfarin

17. Pharmacokinetic interaction Metabolism : this occur when metabolism of one drug is increased or decrease by other drug, Excretion : most of them occur in kidney e.g salicylates interfere with the excretion of methotrexate and potentiate its toxicity.

18. Pharmacodynamics interactions The interaction is due to action of drugs on receptor or physiological system. This may result either additive, synergistic or antagonistic effect. The interaction may result harmful effect

19. Thank you dear students