Pharmacology presentation on drug dose & response relationship.

1. Pharmacodynamics
DOSE – RESPONSE RELATIONSHIP
Sunil Kumar Singh
Roll No. 84
MBBS Batch 2021
RDASMC AYODHYA

2. Dose of Drug Administered
Plasma concentration of Drug
Drug bind to the Receptor
Response produced
Component of Dose-Response Relationship
1- Dose – Plasma Concentration Relationship
(determined by Pharmacokinetics consideration)
2- Plasma Concentration – Response Relationship
(describe dose – response relationship)
• Dose is the appropriate amount of a drug needed to produce a certain degree of response in a given patient.
• Response is desirable therapeutic effect or adverse effect of the drug.

3. E =
Emax X [D]
KD + [D]
E = observed effect of drug at dose [D]
Emax = maximal response (Efficacy)
KD = dissociation constant of drug – receptor
complex,
which is a measure of affinity between drug &
receptor
KD = [D] when E = Emax/2 or KD = EC50
• Drug Affinity is the extent to which a drug bind to the receptor at any given drug concentration.
• Drug receptor interaction obeys Law of Mass Action, that means intensity of response is proportional to
concentration of drug at site of action.
Which is described by given equation
[D]
Affinity

4. Dose Response Curve (DRC)
• When we plot a graph between Response and Dose
rectangular hyperbolic curve is obtained. (DRC)
• If we plot graph between Response & dose on a
logarithmic scale, the curve become sigmoid . (Log DRC)
A linear relationship is seen in the intermediate zone ( 30-
70%) of the curve.
Advantage of DRC
• A wide range of drug dose can be easily displayed on a
graph.
# very low dose – no enough response
# very high dose – toxicity can occur
• Comparison between agonist and study of antagonists
become easier.

5. Drug Potency is the amount of drug needed to
produce a certain response.
(lower the dose - higher the potency)
• Position of DRC on the dose axis is the index of
drug potency.
• A DRC positioned rightward indicates lower
potency.
Relative Potency is generally defined by comparing
the dose of two agonists at which they produce
half of maximal response.
Example - if 10mg morphine = 100 mg of pethidine
as analgesic, morphine is 10 times more potent
than pethidine.
Log dose
Drug Potency

6. •Drug Efficacy is the maximal response produced
by the drug.
•Usually measured under ideal conditions.
•Upper limit of DRC is index of Drug Efficacy.
Example –
morphine produces a degree of analgesia not
obtainable with any dose of aspirin. This shows
morphine is more efficacious than aspirin.
Log dose
Efficacy

7. Example :
Analgesic
• Aspirin is less potent as well as less efficacious
than morphine.
• Pethidine is less potent but equally efficacious as
morphine.
Diuretic
• Furosemide is less potent but more efficaceous
than metolazone.
CNS depressant
• Diazepam more potent but less efficacious than
pentobarbitone.
Depending on the type of drug , both high efficacy
or low efficacy could be clinically advantageous.

8. The slope of the DRC is also important.
A steep slope indicates that a moderate increase in dose will
markedly increase the response.
A flat slope implies that little increase in response will occur
over a wide dose range.
• Slope is related to safety of drug.
• Drug with steeper slope is less safe. (dose needs
individualisation)
•Drug with more flat slope is more safe. (standard doses can
be given to most patients)
Slope

9. • It is actual response of a drug in real time scenario
( not under ideal condition)
• Effectiveness is variable & it can be different in different patients.
• It depends on relative potency, efficacy, pharmacokinetics & pathophysiological variables.
Therapeutic Efficacy is expressed in term of
(a) Graded dose – response relationship
Effectiveness is measured by degree of benefit or relief afforded by drug.
Ex- levodopa – carbidopa combination is more effective than trihexyphenidyl in Parkinsonism.
(b) Quantal dose – response relationship
Effectiveness is measured by success rate in achieving a defined therapeutic end point in a population.
Response is either present or absent in an individual.
Therapeutic Efficacy / Clinical Effectiveness

10. Drug Selectivity
• One drug can produce different types of effects.
The extent of separation of DRCs of a drug for different
effects is a measure of its selectivity.
More the separation  more selective drug is
Example – Salbutamol is more selective bronchodilator
than Isoprenaline.
Chosen Response Aspirin Dose
Analgesic 0.3-0.6g
Antiplatelet 60-150 mg/day
Anti-inflammatory 3-5g/day

11. • A drug may have high efficacy but use of high
dose produces adverse effect.
Example– Prednisolone in bronchial asthma.
Therapeutic range/Therapeutic window is
bounded by dose with minimal therapeutic effect
& dose which produces maximal acceptable
adverse effect.
Defining therapeutic range for many drugs is
challenging task because effective dose for some
subjects may be toxic for others.
Therapeutic Window

12. Therapeutic Index =
LD50
ED50
LD50
ED50
Therapeutic Index / Safety Margin
Gap between therapeutic effect DRC & the adverse effect DRC
= Median Lethal Dose which
kills 50% of recipients.
= Median Effective Dose which
produce specific effect in 50%
individuals.
larger the therapeutic index
(TI), safer the drug is.
Example –
Benzodiazepines are more safer than
Barbiturates as CNS depressant.
Therapeutic Index

13. Risk - Benefit Ratio
• This term is frequently used , and conveys a judgement on the estimated harm &
expected advantages of a drug.
• Harm – adverse effect, cost, inconvenience.
• Advantages – relief of symptoms, cure, reduction of complications/mortality,
improvement in quality of life.
• A drug should be prescribed only when benefits outweigh the risk.

14. Drug Specificity
It is range of actions produced by a drug.
Certain drugs produce just one or a limited number of actions, while others have widespread effects on
many organs of the body.
Specificity is governed by:
(a) whether a drug acts on a single receptor target or on many targets, and
(b) how widely the target is distributed in the body.
Example -
• Omeprazole is a highly specific drug for inhibition of gastric acid secretion (proton pump inhibitor)
• Chlorpromazine is a drug acting on multiple targets (antagonistic action on dopamine D2, α adrenergic,
muscarinic cholinergic, histamine H1 and some 5-HT receptors .It also has Na channel blocking action)
• Dexamethasone which is an agonist only of glucocorticoid receptor, but produces effects involving many
organs and tissues, because the glucocorticoid receptor is expressed by practically every cell of the body.

15. Thank You !