La farmacodinamia estudia los efectos bioquímicos y fisiológicos de los medicamentos y sus mecanismos de acción, interactuando de manera específica con los receptores proteicos del cuerpo. Las drogas pueden aumentar o disminuir la actividad celular, además de tener efectos de irritación, acción química o acción citotóxica, dependiendo del tipo de receptor y la interacción con otros medicamentos. Se destaca la importancia del índice terapéutico para medir la seguridad de un fármaco, diferenciando entre dosis efectivas y tóxicas.

2. Introduction
Pharmacodynamics is the
study of the biochemical
and physiological effects
of drugs and their
mechanisms of action.
Pharmacodynamics is
often referred to as
“what the drug does to
the body”.

3. In order to exert their effects, drugs usually
interact in a structurally specific way with a
protein receptor or act on physiological
processes within the body.
This activates a secondary messenger system
that produces a physiological effect.

4. Drugs do not create new action but they
can only modify (alter) the functions of
cells or tissues in body.
The drug–receptor complex initiates
alterations in biochemical and/or
molecular activity of a cell by a process
called signal transduction.

5. Principles of drug action

6. Stimulation
It refers to increase in
functional activity of
specialized cells.
Adrenaline stimulates
heart,
Caffeine stimulates
CNS.

7. Depression
It refers to
decrease in
functional
activity of
specialized
cells.
Barbiturates
depress
CNS,
quinidine
depresses
heart,
omeprazole
depresses
gastric acid
secretion.

8. Irritation
It is the effect of drugs on the
growth, nutrition and morphology
of living tissues which induce a
gross change in cellular function.
e.g., Irritant purgative Senna,
liniments to relieve muscular pain,
astringent

9. Replacement
This refers to the use of
natural metabolites, or
hormones in deficiency
conditions,
e.g., levodopa in Parkinsonism,
insulin in diabetes mellitus,
iron and vitamin B12 in
anaemia.

10. Chemical action
Some drugs act by
combining chemically
with substances
present in the body.
e.g., antacids
neutralise gastric
acid.

11. Cytotoxic action
Some drugs act by selective cytotoxic action on invading parasites or
cancer cells without affecting the host cells.
They are used for treatment of infectious diseases and cancer.
e.g., penicillin, chloroquine, remdesivir, cyclophosphamide.

12. MECHANISMS OF DRUG ACTION

13. Most drugs produce their effects by binding to specific
target proteins like receptors, enzymes and ion channels.
Drugs may act on the cell membrane, inside or outside
the cell to produce their effect.
Drugs may act by one or more complex mechanisms of
action.
Some of them are yet to be understood.

14. Through receptors:
• Drugs may act by interacting with specific receptors in the body.

15. Through enzymes and pumps:
Drugs may act by inhibition of various enzymes,
thus altering the enzyme-mediated reactions,
e.g. allopurinol inhibits the enzyme xanthine
oxidase;
acetazolamide inhibits carbonic anhydrase,
enalapril inhibits angiotensin converting enzyme,

16. Through ion channels:
Drugs may interfere with the
movement of ions across specific
channels,
e.g., calcium channel blockers, sodium
channel blockers, potassium channel
openers and GABA gated chloride
channel modulators.

17. By physical action:
The action of a drug
could result from its
physical properties
Adsorption – Activated
charcoal in poisoning,
Mass of the drug – Bulk
laxatives like psyllium,
Osmotic purgatives like
magnesium sulphate

18. By chemical interaction:
Drugs may act
by chemical
reaction.
Antacids –
neutralise
gastric acids,
Oxidising
agents – like
potassium
permanganate
is germicidal

19. By altering metabolic processes:
Drugs like antimicrobials alter the
metabolic pathway in the
microorganisms resulting in
destruction of the microorganism,
e.g., sulphonamides interfere with
bacterial folic acid synthesis.

20. Drug and receptor concepts

21. Receptor
Receptor: Receptors are protein
molecules present either on the
cell surface or within the cell with
which drug molecule interacts to
produce a response.
e.g., cholinergic receptors

22. Potency
Potency of a drug is the
concentration of a drug required to
produce a specified level of
response.
The potency of a drug is determined
by the affinity of a drug for its
receptor and the amount of
administered drug that reaches the
receptor site.

23. Affinity
Affinity : Ability of a drug to combine with the receptor.
Drug +
Receptor
D-R
complex
Effect

24. Efficacy
Efficacy (Intrinsic activity):
Ability of a drug to produce its
pharmacological action when
it interacts with its receptors.
The maximal response
produced by a drug (C max).

25. Agonist
Agonist: It is a drug that combines with receptor and
produces a response (has affinity and efficacy).
acetylcholine
cholinergic
receptors
Cholinergic
action

27. Agonist Receptor
Response

29. Antagonist
Antagonist: It is a drug that
combines with a receptor
without producing responses.
It blocks the action of the
agonist (has affinity but no or
zero efficacy).

30. Antagonist Receptor
No
Response
e.g., atropine is antagonist of cholinergic receptors
For example

32. Partial agonist
Partial agonist: It is a drug
that binds to the receptor
but has low intrinsic activity,
e.g. Pentazocine is a partial
agonist at μ opioid
receptors.

33. Drug Receptor Interaction

34. lock and key
Drug receptor interaction has been considered to be similar to ‘lock
and key’ relationship where the drug specifically fits into the
particular receptor (lock) like a key.

36. The rate theory proposes that the
magnitude of response depends
on the rate of agonist–receptor
association and dissociation.
The rate of receptors binding is
more initially but after it reaches
the peak there is a decrease.

38. Receptor types
The receptor types are:
•Ion channels receptor
•G-protein coupled receptors
•Enzymatic receptors (kinase linked receptor)
•Transcription factors (receptors that regulate
gene transcription or nuclear receptors)

39. Binding forces
•Ionic bond.
•Vander wal forces
•Hydrogen bond.
•Covalent bond.
The drug
receptor
interaction
involves
binding forces
between drugs
and receptors:

40. The effect of one drug blocked (or
inhibited) due to another drug is
said to be antagonism.
In other word, an interaction
between two or more drugs that
have opposite effects on the body.
Drug antagonism may block or
reduce effectiveness of one or more
of the drugs.
Drug Antagonism

41. Types of antagonism
Pharmacological
antagonism:
Competitive and
Non-Competitive
Physiological
antagonism
Chemical antagonism

43. Competitive Antagonism
If both the agonist and the antagonist compete for the same
receptor in a reversible manner, they are said to be
“competitive.”
The antagonist drug interacts with the receptor, and blocks it.
Therefore it does not produce pharmacological action.
The extent of antagonism depends on number of receptors
occupied by the both drugs (agonist and antagonist), their
affinity for receptors and their concentration.

44. Competitive Antagonism
The increase in concentration of either one of these drugs can
displace the other from receptor binding sites.
Drugs interact with their receptors by weak bonds
i.e. ionic bond or Hydrogen bond or Vander wal force.
Hence duration of action of drug is short. Both agonist and
antagonist have chemical resemblance (structural similarity).

46. Ex. Competitive antagonist and their receptors
Agonist
Competitive
Antagonist
Receptors
Acetylcholine
Adrenaline
Histamine
Morphine
Atropine
Phentolamine
Cetrizine
Naloxone
Cholinergic receptors
Adrenergic receptors
Histamine receptors
Opioid receptors

47. Non-Competitive Antagonism
In this situation, the
antagonist forms a more
stable bond (covalent bond)
with its receptors.
This drug-receptor
interaction is irreversible
and long lasting.
One drug bind to the
receptor in a manner which
makes it is impossible to
reverse the binding (e.g., a
strong covalent bond).

48. The antagonist may bind with different receptor in such a
way that agonist cannot able to produce its action.
The antagonist has no chemical resemblance with agonist.
A fundamental difference between competitive and non-
competitive antagonists is that competitive agonists reduce
agonist potency and non-competitive antagonists reduce
agonist efficacy.

50. Ex. Non-competitive antagonist and their receptors
Agonist
Non-competitive
Antagonist
Receptors
Nor-Adrenaline
Acetylcholine
Diazepam
Organophosphorous
compounds
Phenoxybenzamine
Bungarotoxin
Bicuculine
Atropine sulphate
alpha receptors
Cholinergic receptors
GABA receptors
Cholinergic receptors

51. Physiological Antagonism
In this situation, both an agonist and antagonist
interact with different receptors and have different site
of action, but still their actions are opposite to each
other.
Ex. glucocorticoids increase blood sugar level, and
insulin lowers it, but the two drugs act by completely
different pathways.

52. Chemical Antagonism
In this situation, a chemical
reaction take place
between two or more drugs
within the body and hence
biological activity become
blocked or diminished.
Ex. protamine acts as
antidote of heparin
molecules
• Antacids neutralize the gastric
acid
• Dimercaprol forms chelate with
mercury.

53. Therapeutic Index
Therapeutic index (TI)
used for measuring of
margin of safety of
the drug.
TI can also be expressed as the
ratio of the median toxic dose
(TD50) and the median
effective dose (ED50) of a drug.
This index is
commonly used
to measure a
drug's safety.

54. The therapeutic index formula
Therapeutic index (TI) = Median Toxic Dose (TD50)_
Median Effective Dose (ED50)
TD50 → drug dose that would produce a toxic effect in 50% of the
population,
ED50 → drug dose that will produce the desired therapeutic effect
in 50% of the population

55. Therapeutic window

56. Therapeutic Index

57. The larger value of TI indicates that there is a wide
margin between the toxic and effective dose,
whereas a smaller value indicates that there is a
narrow margin between the effective and toxic dose.
In case of drugs that have a low TI, even a small
increase in the dosage can produce toxic effects.
Additional care must be taken while prescribing a
drug with a narrow therapeutic index (NTI).

58. Therefore, the pharmaceutical industry has
been making efforts to replace NTI drugs
(drugs that could be toxic at relatively low
levels) with drugs with higher TIs.
Some drugs that have a narrow therapeutic
index are: warfarin, lithium, digoxin,
phenytoin, gentamicin, amphotericin-b, 5-
fluorouracil, zidovudine etc.

59. Prof. Amol Deore