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Drug Receptor Interaction
Quantitative Aspects
By
Dr. Faraza Javaid
BACKGROUND
“All substances are poisons.”
- Paracelsus
DRUG EFFECT
Quantifying Drug Receptor Interaction
Concentration –
Binding Relationship
(Affinity)
Dose-Response
Relationship
(Efficacy, Potency)
Dose is the amount of a substance
administered at one time.
Dosage is the amount per unit weight of
the exposed individual.
Exposure is characterized by
 Number of doses
 Frequency of dosing
 The total period of time for the
exposure
5
The relationship between the
concentration of a drug at the receptor
side and magnitude of the response is
called dose response relationship .
It is of two types
1) Graded dose – response relationship
2) Quantal dose – response relationship
Dose Response Relationship
Two types of dose-response relationships…
Relates dose to gradual,
continuous increase in
Relates dose to frequency
response.
of “all or none response.”
Graded Dose Response Curve (DRC)
Response
(%)
0 1 2 3 4 5
Dose of Drug (mg/ml)
6 7
50%
100%
Maximal Response
Ceiling Dose
Why log DRC?
How to plot log DRC?
Normal DRC
• Inconvenient
• Hyperbola
• Very broad graph
• Difficult to analyze
• Difficulty in
comparison
Log DRC
• Convenient
• Sigmoid shaped
• Highly compressed graph
• Linear mid-portion easy
to analyze
• Mathematical advantages
on comparison of two
DRCs.
Information derived from a graded DRC
 Maximal effect : Emax
 Position of DRC: EC50 or ED50
 Comparison between curves.
Quantal Dose Response
Curve
 Pharmacodynamic variation is both
individual and at population level.
 Variability in pharmacodynamic
response in the population analyzed by
a quantal dose response curve.
Information from quantal DRC
Median Effective Dose (ED50)
Median Lethal Dose (LD50)
Evaluation of Drug Safety
Evaluation of Drug Safety
Therapeutic
index (LD50/ED50)
 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 Tolerance
Genetic factor
Psychological factor
Pathological state
 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
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.
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 metabolized during liver disease.
 When two or more drug are given
simultaneously the effect of one drug may
be altered by another drug.
 Result in either beneficial or harmful
effects
 Can occur as a result of incompatibility
(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
 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.
 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.
 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
25
Synergism
Correlated action or cooperation on the part
of two or more drugs
ADDITIVE EFFECT:
When effect of two drugs having the similar
action are additive i-e 2+2=4
eg. β-adrenocptor blocker plus a thiazide
diuretics have an additive antihypertensive
effect.
26
POTENCIATION( to make more powerful)
when one drug increases the action of
other drug, i.e 2+2=5
e.g trimethoprim plus sulphonamide
or when one drug have no effect as own
but increases the effect of other drug
i.e 2+0 =5
eg. levodopa and carbidopa
27
Dose:
It represents the amount of a drug to produce an effect
Therapeutic dose:
A dose which is required to produce a therapeutic effect
Toxic dose:
The dose which produces a toxic effect
Loading dose:
A large initial single or multiple doses are given for some
drugs to achieve a rapid steady state concentration
28
Maintenance dose:
The dose which is used to maintain the
steady – state concentration or to
maintain the therapeutic effect of a drug.
It is given at a fixed interval time
29
ED50 (Effective dose 50)
The dose or concentration which produces effect in
50% of the population in a group.
TD50 (Toxic dose 50)
The dose or concentration which produces toxic
effects in 50% of the population in a group.
LD50 (Lethal dose 50)
The dose or concentration which kills 50% of the
animals in a group
30
Pro-Drug
 It is a drug which is pharmacologically inactive
after administration, by the action of enzymes, it is
chemically altered
To active form in the body.
e.g Enalapril to Enalaprilat
Aspirin to Salicylates
Levodopa to Dopamine
Valciclovir to Acyclovir
“All substances are poisons;
There is none which is not a poison.
The right dose differentiates a poison
from a remedy.”
Paracelsus (1493-1541)
THANKYOU

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Drug Response.pptx

  • 1. Drug Receptor Interaction Quantitative Aspects By Dr. Faraza Javaid
  • 2. BACKGROUND “All substances are poisons.” - Paracelsus DRUG EFFECT
  • 3. Quantifying Drug Receptor Interaction Concentration – Binding Relationship (Affinity) Dose-Response Relationship (Efficacy, Potency)
  • 4. Dose is the amount of a substance administered at one time. Dosage is the amount per unit weight of the exposed individual. Exposure is characterized by  Number of doses  Frequency of dosing  The total period of time for the exposure 5
  • 5. The relationship between the concentration of a drug at the receptor side and magnitude of the response is called dose response relationship . It is of two types 1) Graded dose – response relationship 2) Quantal dose – response relationship Dose Response Relationship
  • 6. Two types of dose-response relationships… Relates dose to gradual, continuous increase in Relates dose to frequency response. of “all or none response.”
  • 7. Graded Dose Response Curve (DRC) Response (%) 0 1 2 3 4 5 Dose of Drug (mg/ml) 6 7 50% 100% Maximal Response Ceiling Dose
  • 9. How to plot log DRC?
  • 10. Normal DRC • Inconvenient • Hyperbola • Very broad graph • Difficult to analyze • Difficulty in comparison Log DRC • Convenient • Sigmoid shaped • Highly compressed graph • Linear mid-portion easy to analyze • Mathematical advantages on comparison of two DRCs.
  • 11. Information derived from a graded DRC  Maximal effect : Emax  Position of DRC: EC50 or ED50  Comparison between curves.
  • 12. Quantal Dose Response Curve  Pharmacodynamic variation is both individual and at population level.  Variability in pharmacodynamic response in the population analyzed by a quantal dose response curve.
  • 13. Information from quantal DRC Median Effective Dose (ED50) Median Lethal Dose (LD50) Evaluation of Drug Safety
  • 14. Evaluation of Drug Safety Therapeutic index (LD50/ED50)
  • 15.
  • 16.  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 Tolerance Genetic factor Psychological factor Pathological state
  • 17.  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
  • 18. 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.
  • 19. 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 metabolized during liver disease.
  • 20.  When two or more drug are given simultaneously the effect of one drug may be altered by another drug.  Result in either beneficial or harmful effects
  • 21.  Can occur as a result of incompatibility (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
  • 22.  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.
  • 23.  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.
  • 24.  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
  • 25. 25 Synergism Correlated action or cooperation on the part of two or more drugs ADDITIVE EFFECT: When effect of two drugs having the similar action are additive i-e 2+2=4 eg. β-adrenocptor blocker plus a thiazide diuretics have an additive antihypertensive effect.
  • 26. 26 POTENCIATION( to make more powerful) when one drug increases the action of other drug, i.e 2+2=5 e.g trimethoprim plus sulphonamide or when one drug have no effect as own but increases the effect of other drug i.e 2+0 =5 eg. levodopa and carbidopa
  • 27. 27 Dose: It represents the amount of a drug to produce an effect Therapeutic dose: A dose which is required to produce a therapeutic effect Toxic dose: The dose which produces a toxic effect Loading dose: A large initial single or multiple doses are given for some drugs to achieve a rapid steady state concentration
  • 28. 28 Maintenance dose: The dose which is used to maintain the steady – state concentration or to maintain the therapeutic effect of a drug. It is given at a fixed interval time
  • 29. 29 ED50 (Effective dose 50) The dose or concentration which produces effect in 50% of the population in a group. TD50 (Toxic dose 50) The dose or concentration which produces toxic effects in 50% of the population in a group. LD50 (Lethal dose 50) The dose or concentration which kills 50% of the animals in a group
  • 30. 30 Pro-Drug  It is a drug which is pharmacologically inactive after administration, by the action of enzymes, it is chemically altered To active form in the body. e.g Enalapril to Enalaprilat Aspirin to Salicylates Levodopa to Dopamine Valciclovir to Acyclovir
  • 31. “All substances are poisons; There is none which is not a poison. The right dose differentiates a poison from a remedy.” Paracelsus (1493-1541) THANKYOU