Pharmacodynamic

1) Definitions
- It cover all aspects relating to “ what a drug does to a body”
- Pharmacodynamics refers to the relationship between drug concentration at the site of action and the
resulting effect.
2) Drug action
A/ Site of drug action:
- extracellular
- cellular
- intracellular
B/ Type of drug action:
- Stimulation
- Inhibition/Depression
- Replacement
- Irritation
- Cytotoxic
C/ Mechanism
- Drug act either by receptor or by non-receptor or by targeting specific genetics changes
F Receptor mediated action
Ÿ Receptors :
- are macromolecules which are protein, they present in the cell surface, cyctoplasm, or in nucleus.
- functions:
+ recognization of specific ligand molecule ( ligand binding domain)
+ transduction of signal into response ( effectors domain )
Ÿ Drug receptors interaction
- selectivity: degree of complementary corelation between drug and receptors
- affinity: ability of drug get bound to the receptors
- intrinsic activity or efficiacy: ability of drug to produce a pharmacological respone after making the
drug receptor complex
- agonist: which have both the high affinity as well as intrinsic activity and can trigger the maximal
biological response or mimic the effects of endogenous substances after combining with receptors
- antagonist: which have only the affinity but not instrinsic activity and can block or interfere qith the
binding of endogenous agonist
- partial agonist: these have full afinity to the receptors but with low instrinsic activity and these only
partly as effective as agonist
- inverse agonist: these have full affinity toward the receptors but instrinsic activity ranges between “0
to -1”

FNon-receptor mediated action

Ÿ some drugs may act through chemical action or physical action or other mode
- chemical action
- physical action
- false incorporation
- being protoplasmic action
- formation of antibody
- targeting specific genetic changes

3. Structural feature of drugs and their pharmacological activity

- Stereochemistry : space arrangement of the atom or 3-D structure of the molecule. It plays major role
in the pharmacological properties because:
+ Any change in stereospecificity of the drug will affect its pharmacological activity
+ The isomeric pairs have different physical properties (partition coefficient, pKa, etc.) and thus
differ in pharmacological activity.
- Factors influence pharmacological activity:
+ Optical and geometric isomerism
üOptical isomers:
- are compounds that contain at least one chiral carbon atom or are compounds that differ only in
their ability to rotate the pollarized light.
- Enantiomers (optical isomers) can have large differences in potency, receptor fit, biological
activity, transport and metabolism
- Geometric isomerism (cis-trans isomerisms): Occur as a result of restricted rotation about a
chemical bond, owing to double bonds or rigid ring system in the molecule. They are not mirror
images and have different physicochemical properties and pharmacological activity.They generally
do not fit to the same receptor equally well and if these functional groups are pharmacophores the
isomers will differ in biologic activity.
+ Conformational isomerism
- Conformational isomersim is the non-identical space arrangement of atoms in a molecule,
resulting from rotation about one or more single bonds.
- drug can exist in more than one conformation and thus the drug might bind to more than one
receptor but a specific receptor site may bind only to one of many conformations of a drug
molecule.
+ Isosterism and bioisosterism
Bioisostere is to enhance the desired biological or
physical properties of a compound without making
significant changes in chemical structure.
The utility of bioisosteres is extending to
 Improving potency
 Enhancing selectivity
 Altering physical properties
 Reducing or redirecting metabolism
 Eliminating or modifying toxicophores
 Acquiring novel intellectual property