Pharmacodynamics is the study of how drugs act on the body and their mechanisms of action. It involves drug-receptor interactions and explains the relation between drug effects. Pharmacodynamics provides a basis for rational drug use and design. Drugs can act through stimulation, depression, irritation, replacement or cytotoxic effects on cells. Their main targets are receptors, ion channels, enzymes, and transporter proteins. Understanding drug-receptor interactions is important for explaining drug effects and determining their potency and efficacy. Drug interactions can enhance or reduce the effects of drugs and should be considered when administering multiple medications.

1. PHARMACODYNAMICS
 Pharmcodynamics is the study of the mechanism of
action of drugs & explains what drug does to body & how
do they do it. It tries to explain the action-effect relation
as well as dose-relation effect. It involves the drug-
receptor interaction to elict the action of drug in the
body.
 Pharmacodynamics is the study of biochemical &
physiological effect of drugs & their mechanism of action.
 It provides basis for rational use of drugs & design of
better/effective drugs.

2. PRINCIPLES OF DRUG
ACTION
 Stimulation: It is the selective enhancement of the action of
specialized cells. e.g: adrenaline stimulates heart, pilocarpine
stimulates salivary gland
 Depression: It is the selective inhibition of the action of
specialized cells. e.g: barbiturates depresses CNS, quinidine
depresses heart, omeprazole depresses gastric acid secretion
 Irritation: It is the non-selective & noxious effect to the less
specialized cells. Irritation may result in inflammation,
corrosion or necrosis to cells.
 Replacement: It is the use of natural metabolites, hormonesor
their congeners in deficiency states. e.g: insulin in diabetes,
levodopa in Parkinsonism
 Cytotoxic action: It is the selective action on parasites or
cancer cells without affecting other cells of the body. e.g:
Penicillin, Zidovudine, Methotrexate

3. MECHANISM/TARGETS FOR DRUG
ACTION
1.Receptors
 Receptors are the integral membrane proteins embedded
in cell membranes that receives signals or binds with
ligands to initiate response or cell signalling. There are 4
types of receptors:
1. Ligand gated ion channels
2. G-protein coupled receptors
3. Kinase linked receptors
4. Nuclear receptors
2.Ion channels
 Ion channels are the channels in the cell membrane that
selectively allow the passage of particular ions. e.g: Na
channel, K channel, Ca Channel, Cl channel.
 Two important types are:
1. Ligand gated channels
2. Voltage gated channels

4. 3.Enzymes
 Enzymes are protein molecules that accelerates the
chemical reactions. Most of the biological reactions are
catalyzed by enzymes. Drug molecule may act as
enzyme inhibitor (sometime stimulates) to elict a
response.
 e.g: captopril inhibits ACE (Angiotensin Converting
Enzyme), Aspirin inhibits COX (Cycloxygenase)
4.Transporter Proteins/ Carrier proteins
 These are the protein molecules that allows the
movement of substrates by facilitated diffusion or
active transport.
 e.g: SLC (Solute carrier) proteins

5. Drug-Receptors
According to molecular structure and nature of
mechanism there are four types of drug receptors:
Type 1: Ligand-gated ion channels (ionotropic)
These are membrane proteins with a similar structure
to other ion channels and incorporate a ligand-binding
(receptor) site usually in the extracellular domain.
Typically, these are the receptors on which fast
neurotransmitters act. e.g:
 GABA receptor
 nACh receptor

6. Type 2: G-Protein coupled receptor (metabotropic)
These are also known as metabotropic receptors or
7-transmembrane-spanning (heptahelical)
receptors. They are membrane receptors that are
coupled to intracellular effector systems via a G-
protein. They constitute the largest family and
include receptors for many hormones and slow
transmitters.
e.g: Dopamine receptor, mACh receptor, etc
GPCR acts by:
1. Adenyl cyclase; cAMP Pathway
2. Phospholipase C; IP3-DAG Pathway
3. Ion channels
4. Rho A/Rho kinase

8. Type 3: Kinase Linked receptor
This is a large and heterogeneous group of membrane
receptors responding mainly to protein mediators. It
comprise an extracellular ligand-binding domain linked
to an intracellular domain by a single transmembrane
helix.
e.g: cytokine receptor, insulin receptors, etc

9. Type 4:Nuclear receptor
These are receptors that regulate gene transcription.
e.g: Steroid receptor, oestrogen receptor, etc

11. FUNCTIONS OF
RECEPTORS
 To propagate the regulatory signals.
 To amplify the signal.
 To integrate the intracellular & extracellular signal.
 To adapt short term & long term changes
 Drug potency: Potent drugs are those drugs which elict
a response by binding to receptor even at low
concentrations. It has high affinity and high intrinsic
activity.
 Drug efficacy: It is the maximal response that can be
elicted by a drug. It is the result of drug receptor
complex. It determines how effective is a drug.

12. DRUG RECEPTOR THEORY
 Clark’s Theory( receptor occupation theory)
 Response is a function of occupation of receptor
molecules by agonist. The response of a drug is directly
proportional to the number of receptors occupied.
D + R = DR
 Paton’s Theory ( rate theory)
 Response of a drug is proportional to the drug-receptor
complex formation. After complex formation no further
receptor occupancy can produce further effects. Effect is
produced by drug molecules based on the rate of
association & dissociation of drugs to & from the
receptors.

14. DRUG RECEPTOR INTERACTION
 Receptor is defined as protein molecule that receives
chemical signal from outside of the cell. When chemical
signals bind to receptor they show response or action.
 Ligand is defined as the molecules that binds with the
receptors to show response.
 Secondary messengers are the intracellular molecules
that are activated by receptors which produces action
inside the cell. e.g: cAMP, cGMP, Calcium ions, etc.
 Agonist: A drug which initiates a pharmacological
action after combining with the receptor is termed as an
agonist. An agonist is a drug or ligand that binds to the
same receptor. Agonist give maximum effect when bind to
the same receptor. It has high affinity & high intrinsic
activity. e.g: Salbutamol: β-adrenoceptor agonist.

15.  Partial Agonist: A drug with an affinity equal to or less
than that of agonist but with less intrinsic activity is
termed as partial agonist. e.g: Opioids: which acts on
several types of receptor as agonist or partial agonist.
 Inverse Agonist: A drug which activates a receptor to
produce an effect in opposite direction to that of agonist.
It has affinity but negative efficacy.
e.g: chlorpheniramine on H1 receptor
 Antagonist: Drugs which binds to the receptors but do
not produce response or causes receptor blockade is
termed as antagonist. It has affinity but no intrinsic
activity. e.g: Propanalol: β- antagonist, Atropine:
Muscarinic antagonist

16. DRUG INTERACTIONS
 Drug interaction can be defined as the modification of
the effect of one drug by prior or concomitant
administration of another drug. It may enhance or
diminish the effect of one or both drugs. It may modify
preventive, diagnostic or therapeutic activity of either
drugs.
 Causes of drug interaction:
 Drug explosion; administration of two or more drugs
 Patient refer to many doctors
 Irrational polypharmacy; concurrent use of prescribed &
non-prescribed drugs
 Patient non-compliance; do not follow instructions

17.  Drug Interaction (DI) may be:
 Pharmacokinetic interaction (ADME)
1. Multiple drug use may cause alteration of GI pH,
complexation, sequestration, alteration of mucosa,
alteration of GI contents which may effect absorbtion.
2. Drug interaction may cause decrease in distribution &
displaces protein binding due to competitive binding. It
may lead to decrease in effect & induce toxicity.
 Pharmacodynamic interaction
1. Drug interaction may affect drug-receptor binding,
modifies physiological action & efficacy of drugs. It may
cause synergistic or antagonistic effect on the body.
 DI also may be:
1. In vivo (inside the body)
2. In vitro (outside the body; may be physical or chemical
interaction)

18.  Combined effect of drugs:
 Synergism: It is the enhanced effect of the drugs when
combined together. One drug may enhance the activity
of another drug or both drugs can have better effects
together.
i.Additive effects: when two or more drugs are
combined together & their effects are increased.
Aspirin + Paracetamol (analgesic/antipyretic)
Amlodipine + Atenolol (Antihypertensive)
ii.Potentiation: when two or more drugs are combined
& their effects are more than additive action.
Levodopa + Carbidopa (inhibits peripheral metabolism)
Acetylcholine + Physostigmine (inhibits break down)

19.  Antagonism: It is the reduced or abolished effect of
drugs when combined together. One drug may inhibit
the activity of another or reduce the potency of another
drug.
 It may be:
 Physical antagonism
 Chemical antagonism
 Physiological antagonism
 Receptor antagonism
i.Competitive antagonism (reversible)
ii.Non-competitive antagonism (irreversible)

20. MEASURES TO AVOID DRUG
INTERACTION
 Read the prescription & follow the instructions.
 Communicate with doctor or pharmacist about dose of
drug , frequency, duration & method of use.
 Avoid poly-pharmacy.
 Tell doctor about your food, supplements, drug &
beverages uses.
 Tell your doctor about your disease or medical condition.
 Do not visit many doctors ( if necessary carry the
previous prescription ).
 Do not use drugs from someone else prescription.
 Discontinue drugs if any serious effect is found &
immediately contact doctor.

21. DOSE RESPONSE RELATIONSHIP
 It is the response given by the drug once administered
to the body. Dose response may vary between different
species & within same species under different
conditions. Therefore drug response studies help to
minimize errors & predict the efficacy of drugs.
 Each drug has a characteristic drug response curve for
specified set of conditions. In general drug response
curve confirms to S shape or sigmoid type.

23. Therapeutic window is a range of doses that produces therapeutic
response without causing any significant adverse effect in patients.
Generally therapeutic window is a ratio between minimum effective
concentrations (MEC) to the minimum toxic concentration (MTC). The
levels of drug should always be between MEC and MTC in order to
provide risk free therapeutic effects. If any drug crosses MTC then it will
surely elicit toxic effects and if drug is unable to surpass MEC then it will
cause therapeutic failure.

24. Therapeutic index (TI) describes a relationship between the doses of
a drug that causes lethal or toxic effects with the dose that causes
therapeutic effects. It is also called as therapeutic ratio.

25.  DESENSITISATION AND TACHYPHYLAXIS
 The effect of a drug gradually diminishes when it is given
continuously or repeatedly. Desensitisation and
tachyphylaxis are synonymous terms used to describe this
phenomenon, which often develops in the course of a few
minutes. The term tolerance is conventionally used to
describe a more gradual decrease in responsiveness to a
drug, taking days or weeks to develop. Drug resistance is
a term used to describe the loss of effectiveness of
antimicrobial or antitumour drugs. Many different
mechanisms can give rise to this type of phenomenon. They
include:
• change in receptors
• translocation of receptors
• exhaustion of mediators
• increased metabolic degradation of the drug
• physiological adaptation