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Therapeutic Index of drugs and Factors modifying drug action
1.
2.
3. • 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
4. Margin of safety is the difference between
therapeutic and lethal dose of the drug.
5. 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
6. 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.
7.
8. 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.
9. 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
10. 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
11. • Average dose is mentioned in mg/kg
or as total single dose (50-100kg)
• Do not apply for:
Obese
Edema
Dehydrated
Emaciation
13. FEMALES MALES
• BODY SIZE SEXUAL
FUNCTIONS
• MENSTRUATION
GYANACOMASTIA
• PREGNANCY
• LACTATION
14. • 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
15. Genetically mediated variations in drug
responses
Different rates of metabolism
Ex.
•Pseudocholinestrases
•G6PD defeciency
•Acetylation & hydroxylation
16. Gi diseases- Malabsorption syndrome,
Achlorhydria,…….
Liver diseases
High first pass metabolism,
Decrease -ppb, drug metabolism,
Prodrug less effective
Renal disease-Decrease clearence
18. 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;
19. • 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.
20. • 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
21. • Repeated administration of drug
may induce habit and
dependence.
Psychic dependence
Physical dependence
22. • 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
23. • Decrease in pharmacological response of
a drug after repeated administration at very
short interval (occurs rapidly)
Ephedrine
Tyramine
Amphetamine
serotonin