Therapeutic Index of drugs and Factors modifying drug action

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Therapeutic Index of drugs and Factors modifying drug action

  1. 1. • Ratio of median lethal dose to median effective dose. • This is the dose (mg/kg)which would kill one half of limited population of the same species & strain. • This is the dose (mg/kg) which produces desired response in 50% of test population
  2. 2. Margin of safety is the difference between therapeutic and lethal dose of the drug.
  3. 3. Larger the therapeutic index safer the drug. ex. Penicillin has high therapeutic index while digitalis has much less. Drugs with low TI • Digitalis • Gentamicin • Lithium • Quinine
  4. 4. TI not reliable guide for safety. Therapeutic index varies from species to species. Reliable only when LD50 & ED50 is determined in same strain of same species. ED50 is determined from DRC. No drug produces single effect but spectrum of effect aswellas differs in selectivity.
  5. 5. Individual differ in degree and character of drug response and therefore the optimum dose of drug that produces therapeutic effect varies from person to person.
  6. 6. Those related to the biological system 1. Body weight and size 2. Age and Sex 3. Species and race 4. Genetics – pharmacogenetics 5. Condition of health 6. Placebo effect
  7. 7. 7. Route of administration. 8. Drug interactions • Pharmacokinetic drug interactions • Pharmacodynamic Drug interactions 9. Resulting from repeated administration of drug: • Drug Tolerance-Tachyphylaxis; • Drug dependence
  8. 8. • Average dose is mentioned in mg/kg or as total single dose (50-100kg) • Do not apply for: Obese Edema Dehydrated Emaciation
  9. 9. Neonates, infants & children Pk factors- Gastric Emptying , Liver & Renal Functions Pd factors- Teratogenicity , Adverse Effects Old- Absorption , Metabolism , Excretion, Sensitivity, Half Lives Of Drugs.
  10. 10. FEMALES MALES • BODY SIZE SEXUAL FUNCTIONS • MENSTRUATION GYANACOMASTIA • PREGNANCY • LACTATION
  11. 11. • SPECIES – Some drugs resistant with some species •Rats- Digitalis •Rabbits-Atropine • RACE- •Blacks require higher and Mongols require lower conc. of Ephedrine and Atropine for pupilary dilatation. •Indians- chloramphenicol
  12. 12. Genetically mediated variations in drug responses Different rates of metabolism Ex. •Pseudocholinestrases •G6PD defeciency •Acetylation & hydroxylation
  13. 13. Gi diseases- Malabsorption syndrome, Achlorhydria,……. Liver diseases High first pass metabolism, Decrease -ppb, drug metabolism, Prodrug less effective Renal disease-Decrease clearence
  14. 14. •Inert substance •Psychological effect •Pts. Belief, attitude, expectations
  15. 15. 7. Route of administration. 8. Drug interactions • Pharmacokinetic drug interactions • Pharmacodynamic Drug interactions 9. Resulting from repeated administration of drug: • Drug dependence • Drug Tolerance-Tachyphylaxis;
  16. 16. • Those related to the conditions of administration 1. Route of administration. 2. Resulting from repeated administration of drug: drug tolerance-tachyphylaxis; drug dependence 3.Drug interactions GI absorption; protein binding/distribution; metabolism (stimulation/inhibition); excretion (ph/transport processes); receptor (potentiation/antagonism); changes in pH or electrolytes.
  17. 17. • Governs speed and intensity of drug response. drugs may have different uses with diff.routes • Iv doses •Smaller than oral •Quick onset of action •More chances of toxicity
  18. 18. • Repeated administration of drug may induce habit and dependence. Psychic dependence Physical dependence
  19. 19. • Requirement of large dose of a drug to elicit an effect ordinarily produced by normal therapeutic dose of the drug • Types- a. Pseudo tolerance b. True tolerance Natural Acquired (repeated) 1.Species 1.Tissue tolerance 2.Racial 2.Cross tolerance
  20. 20. • Decrease in pharmacological response of a drug after repeated administration at very short interval (occurs rapidly) Ephedrine Tyramine Amphetamine serotonin

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