Pharmacodynamics is the study of what drugs do to the body, including their mechanisms of action, pharmacological effects, and adverse effects. Drugs can act through various mechanisms including stimulation, depression, irritation, replacement, cytotoxicity, and interactions with receptors, enzymes, ion channels, antibodies, and transporters. Adverse drug reactions can be predictable based on a drug's pharmacological properties or unpredictable idiosyncratic reactions. Predictable reactions include side effects, secondary effects, toxicity, and iatrogenic disease, while unpredictable reactions include allergies and idiosyncrasies.

1. PHARMACODYNAMICS

2. PHARMACODYNAMICS
• Pharmacodynamics (Gr. Pharmacon: drug;
dynamis: power): In short, it covers all the
aspects relating to ‘what the drug does to the
body’. It is the study of drugs—their
mechanism of action, pharmacological actions
and adverse effects.

3. Types of Drug Action
1. Stimulation: e.g. adrenaline stimulates the
heart resulting in an increase in heart rate
and force of contraction.
2. Depression: e.g. general anaesthetics
depress the central nervous system.
3. Irritation- e.g. methyl salicylate.
4. Replacement - e.g. insulin in diabetes
mellitus, thyroxine in hypothyroidism.
5. Cytotoxic - e.g. antibiotics/ anticancer drugs.

4. Mechanism of Drug Action
• Nonreceptor-mediated Mechanisms
1. By physical action:
a. Osmosis - e.g. 20% mannitol in cerebral
oedema
b. Adsorption: Activated charcoal adsorbs
toxins.
c. Demulcent: Cough syrup by coating the
inflamed mucosa.

5. Mechanism of Drug Action
2. By chemical action:
a. Neutralize acid – eg : Antacids are weak
bases; hence they in the stomach in peptic
ulcer.
b.Chelating agents - desferrioxamine in iron
poisoning.

6. Mechanism of Drug Action
3. Through enzymes
– Some drugs act either by activating or inhibiting the enzyme activity.
4. Through ion channels
– Some drugs directly bind to ion channels and alter the flow of ions,
e.g. local anaesthetics block sodium channels in neuronal
membrane to produce local anaesthesia.
5. Through antibody production
– Vaccines produce their effect by stimulating the formation of
antibodies
6. Transporters
– Selective serotonin reuptake inhibitors (SSRIs) _ bind to 5-HT
transporter _ block 5-HT reuptake into neurons _ antidepressant
effect.
7. Others
– Anticancer drugs like produce their effect by binding to nucleic
acids.

7. Mechanism of Drug Action
Receptor-mediated Mechanisms
Receptors are macro-molecules present either
on the cell surface, cytoplasm or in the
nucleus which the drug binds with it and
interacts to produce cellular changes.

8. • Affinity: The ability of the drug to get bound to the
receptor.
• Intrinsic activity: The ability of the drug to produce
pharmacological action after combining with the
receptor.
• Agonist: A drug that is capable of producing
pharmacological action after binding to the receptor.
• Antagonist: has high affinity Without intrinsic activity.
It produces receptor blockade.

9. • Partial agonist: A drug that binds to the receptor
but produces an effect less than that of an
agonist.
– Partial agonist has affinity + less intrinsic activity.
• Inverse agonist: It has full affinity towards the
receptor but produces effect opposite to that of
an agonist.
– For example, benzodiazepines produce antianxiety
and anticonvulsant effects by interacting with its
receptors; but b-carbolines act as inverse agonist at
benzodiazepine receptor, and produce anxiety and
convulsions.

11. RECEPTOR TYPES

12. Regulation of Receptors

13. Dose–Response Relationship
• The pharmacological effect of a drug depends
on its concentration at the site of action which
is determined by the dose of the drug
administered.
• By increasing drug dose there will be an
increase in response.

15. Efficacy Vs. Potency
• Efficacy is the response
that can be produced by a
drug.
• Potency is the amount of
drug required to produce
an effect.

16. Therapeutic Index
TI = LD50 / ED50
LD50 ( Lethal Dose): It is the
dose of a drug that is
lethal for 50% of the
population.
ED50 ( Effective Dose ): It is
the dose of the drug
that produces desired
effect in 50% of the
population.

17. Combined Effects of Drugs
• A combination of two or more drugs can result in
an increase or a decrease in response.
Increased response:
1. Additive effect :
Effect of drugs A + B = Effect of drug A + Effect of drug B
2. Potentiation (supra-additive):
Effect of drugs A + B > Effect of drug A + Effect of drug B
3. Synergism:
When two drugs are given simultaneously, and the action of one
drug is increased by the other.

18. Combined Effects of Drugs
Decreased response (drug antagonism):
1. Physical antagonism: e.g. activated charcoal adsorbs toxic
substances in poisoning.
2. Chemical antagonism: e.g. chelating agents complex metals.
3. Physiological (functional) antagonism: e.g. insulin and glucagon on
blood sugar.
4. Receptor antagonism: The antagonist binds to the same receptor as
the agonist and inhibits its effects. It can be competitive or
noncompetitive.
a. Competitive antagonism: both agonist and the antagonist bind
reversibly to the same site on the receptor. Can be overcome
(reversible) by increasing the concentration of agonist.
b. Noncompetitive antagonism: The antagonist binds to a different
site on the receptor and prevents the agonist from interacting with
the receptor.

20. ADVERSE DRUG REACTIONS

21. Adverse Effect
• Adverse effect is defined as any undesirable or
unwanted effect due to drug administration.
Unpredictable reactions (Type B):
– These are nondose-related unpredictable
reactions to a drug.
– They are not related to the pharmacological
actions of the drug.
1. Idiosyncrasy
– It is usually a genetically determined abnormal
reaction to drugs.

22. Adverse Effect
2. Drug Allergy
It is an abnormal response
(local or systemic) to a
drug/foreign antigen
mediated by the immune
system.
• Type I hypersensitivity
(immediate type,
anaphylactic shock): It is
a rapidly occurring
reaction; anaphylactic
shock.

23. Adverse Effect
• Type I is a medical emergency and should be treated promptly
with:
1. Inj. adrenaline (1:1000) 0.3–0.5 mL intramuscularly.
2. Inj. hydrocortisone 100–200 mg intravenously.
3. Inj. pheniramine 45 mg intramuscularly/intravenously.
4. Intravenous fluids.
• Type II hypersensitivity (cytotoxic
reaction): The antibodies (IgG and
IgM) react with cell-bound antigen and
cause activation of complement,
which destroys the cells.
•Examples are blood transfusion reactions,
haemolytic anaemias produced by
cephalosporins, etc.

24. Adverse Effect
• Type III hypersensitivity (immune complex–mediated): In
this type of reaction, antibodies involved are mainly IgG.
AG:AB complexes are formed Fix complement Deposition of
complexes on vascular endothelium Destructive inflammatory
response.
– For example, serum sickness (fever, urticaria, joint pain) with penicillins;
acute interstitial nephritis with (NSAIDs).
• Type IV hypersensitivity (cell-mediated or delayed
hypersensitivity):
• It is mediated by sensitized T-lymphocytes. Re-exposure to the antigen
leads to a local inflammatory response.
• The manifestations usually occur 1–2 days after exposure to the
sensitizing antigen, e.g. contact dermatitis due to local anaesthetic
creams, topical antibiotics.

25. Adverse Effect
Predictable reactions (Type A):
– These are predictable reactions to a drug related to its
pharmacological actions.
• Side Effects
– These are the unwanted pharmacological effects of a drug that are
seen with therapeutic doses, e.g. atropine used in the treatment of
heart block also produces dryness of mouth, blurring of vision, urinary
retention, etc., which are the side effects.
• Secondary Effects
– The primary action of a drug may result in other effects, e.g.
immunosuppression by corticosteroids can lead to development of
opportunistic infections, e.g. oral candidiasis.
• Toxic Effects
– These are the effects of a drug that are either due to overdosage or
chronic use, e.g. bleeding due to chronic use/overdosage of
anticoagulants.

26. Adverse Effect
• Drug Dependence
1. Psychological dependence: There is an intense
desire to continue taking the drug as the patients
feel that their well-being depends upon the drug.
2. Physical dependence: Repeated drug use produces
physiological changes in the body that makes
continuous presence of the drug in the body
necessary to maintain normal function.
• The withdrawal signs and symptoms are generally opposite
to the effects produced by the drug.
• Iatrogenic Diseases
• It is physician-induced disease (‘Iatros’ is a Greek word,
means ‘physician’) due to drug therapy, e.g. acute gastritis
and peptic ulcer due to NSIDs.

27. Adverse Effect
• Teratogenicity
– Certain drugs when given during pregnancy may cross
the placenta and cause various dangerous effects in
the fetus
• Carcinogenicity and Mutagenicity
• Photosensitivity Reactions
• Hepatotoxicity
• Nephrotoxicity
• Ototoxicity
• Ocular Toxicity