Principles of pharmacodynamics

Principles of pharmacodynamics

1. PHARMACODYNAMICS
Mr. Jaineel Dharod
Dept. of Pharmacology

2. PHARMACODYNAMICS

3. INTRODUCTION
Pharmakon – Drug
Dynamics – Action / movement / power
It covers all the aspects relating to “What a drug
does to the body”
i.e. Mechanism of action

4. REVISION
Agonist
Antagonist
Inverse / Partial agonist
Efficacy
Intrinsic Activity
Ligand
Dose

5. PRINCIPLES OF DRUG ACTION
•Do NOT impart new functions on any system, organ or cell.
•Only alter the PACE of ongoing activity.
STIMULATION
DEPRESSION
IRRITATION
REPLACEMENT
CYTOTOXIC ACTION

6. WHERE CAN DRUG BIND?
MAJORITY OF DRUGS INTERACT WITH TARGET BIOMOLECULES:
Usually a Protein
1.ENZYMES
2.ION CHANNELS
3.TRANSPORTERS
4.RECEPTORS

7. TRANSDUCTION OF SIGNAL
•Most transmembrane signaling is accomplished by a small number
of different molecular mechanisms (transducer mechanisms)
•Large number of receptors share these handful of transducer
mechanisms to generate an integrated and amplified response

8. RECEPTOR FAMILIES
1. Ligand-gated ion channels (inotropic receptors)
2. G - Protein coupled receptor (Metabotropic receptors)
3. Enzymatic receptors (tyrosine kinase)
4. Receptor regulating gene expression (transcription factors/
Steroid)

9. Ligand
gated
G-protein
coupled
GPCR
Kinase
Linked
Nuclear
Location Membrane Membrane Membrane Intracellular
Effector Ion channel Ion Channel
or enzyme
Enzyme Gene
coupling Direct G-protein Direct Via DNA
Example Nicotinic Muscarinic Insulin Steroid ,
hormone

10. RECEPTOR UPREGULATION
–In topically active systems, prolonged deprivation
of agonist (by denervation or antagonist) results
in super sensitivity of the receptor as well as to
effector system to the agonist. Sudden
discontinuation of Propranolol, Clonidine etc.
–3 mechanisms - Unmasking of receptors
or proliferation or accentuation of signal
amplification

11. RECEPTOR DOWNREGULATION
–Continued exposure to an agonist or intense
receptor stimulation causes desensitization or
refractoriness: receptor become less sensitive to
the agonist
–Examples: Beta adrenergic agonist and levodopa
Causes:
–Masking or internalization of the receptors
–Decreased synthesis or increased destruction of
the receptors (down regulation) - Tyrosine
kinase receptors

12. FUNCTIONS OF RECEPTORS
1.To Regulate signals from outside the cell to inside the
effector cell – signals not permeable to cell
membrane
2.To amplify the signal
3.To integrate various intracellular and extracellular
signals
4.To adapt to short term and long term changes and
maintain homeostasis.

13. DRUG ACTION NON-RECEPTOR MEDIATED
•Physical and chemical means - Antacids, chelating
agents and cholestyramine etc.
•Alkylating agents: binding with nucleic acid and
render cytotoxic activity – Cyclophosphamide etc.
•Antimetabolites: purine and pyrimidine analogues – 6 MP
and 5 FU – antineoplastic and immunosuppressant activity
•False incorporation (PABA)
•Protoplasmic action (antiseptics)
•Formation of antibody (Vaccines)

14. TYPES OF AGONISM
1.Summation: Two drugs eliciting same response, but with
different mechanism and their combined effect is equal
to their summation. (1+1=2)
2.Additive: Two drugs eliciting same response, with same
mechanism and their combined effect is equal to their
summation. (1+1=2)
3.Synergistic: The combined effect of two drug effect is
higher than either individual effect. (1+1=3)

15. DOSE
•It is the required amount of drug in weight,
volumes, moles or IU to provide a desired effect.
•In clinical it is called as Therapeutic dose
•In experimental purpose it is called as effective
dose.
•The therapeutic dose varies from person to
person

16. Single dose:
Piperazine (4-5g) is sufficient to eradicate round worm.
Single IM dose of 250mg of ceftriaxone to treat
gonorrhoea.

Daily dose:
It is the quantity of a drug to be administered in 24hr, all at
once or equally divided dose.
Erythromycin is 1g per day to be given in 4 equally divided
dose (i.e., 250mg every 6 hr)

17. Total dose: It is the maximum quantity of the drug that is needed
the complete course of the therapy.
Ex:- procaine penicillin  early syphilis is 6 million unit 
given as 0.6 million units per day for 10days.

Loading dose: It is the large dose of drug to be given initially to
provide the effective plasma concentration rapidly. The drugs
having high Vd of distribution.
Chloroquine in Malaria:
600 mg Start
300mg after 8 hours
300 mg after 2 days

18. Maintenance dose:
Loading dose normally followed by maintenance dose.
Needed to maintain the steady state plasma concentration
attained after giving the loading dose.

19. THERAPEUTIC INDEX
•Depend upon factor of dose producing desirable effect 
dose eliciting toxic effect.
•Margin of safety



EC: Effective Concentration
LD: Lethal Dose
Therapeutic Index should be always more than one

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20. THERAPEUTIC WINDOW
Optimal therapeutic
range of plasma
concentrations at
which most of the
patients experience
the desired effect.

21. DRC
The dose–response relationship, or exposure–response
relationship, describes the magnitude of the response of
an organism, as a function of exposure (or doses) to
a stimulus or stressor (usually a chemical) after a certain
exposure time. Dose–response relationships can be described
by dose–response curves.

22. DOSE RESPONSE CURVE
Emax X [D]
E =
Kd + [D]
dose
%
response


100% -
50% -
Log dose
%
response

100% -
50% -
Saturation of Receptors

24. POTENCY AND EFFICACY
Potency: It is the amount of drug required to produce a certain response
Efficacy: Maximal response that can be elicited by the drug

Aspirin is less potent as well as less efficacious than Morphine
Pethidine is less potent analgesic than Morphine but equally efficacious
Diazepam is more potent but less efficacious than Phenobarbitone
Furosemide is less potent but more efficacious than Metalozone

25. POTENCY VS EFFICACY DRC
Hydralazine
Thiazide Fall
in
BP

26. DRUG TOLERANCE
Acquired Drug Tolerance in Monday Morning Disease.
•Nitro-glycerine – Monday, Tuesday workers get
headache, after they get tolerances.
•After holiday (Sunday) they get again headache .
Reverse tolerance:- Same amount drug produces increase
pharmacological response
Innate tolerance: Genetically lack of sensitivity to a drug.
Cross tolerances: Cross tolerance among drugs belonging to
same category

27. THANK
YOU