Pharmacodynamics

Protein Drug Targets

Proteins or other biomolecules like DNA,RNA, heparin and peptides to which the drug binds and which are responsible for the therapeutic efficacy of  the drug.

Types of protein targets :-

  • enzymes
  • receptors
  • ion binding channels
  • Transporters

Receptors:-

 They are located on both the cell surface and within the cell where medicine produce their beneficial effects in various diseases states. Receptors are typically envisaged as cell surface recognition sites for endogenous hormones, neurotransmitters and neuromodulators.

There are 4 types:-

  • Ligand gated receptor
  • Enzyme linked receptor
  • G-protein coupled receptor
  • Intracellular receptor

Drug interacts with receptor by means of chemical forces or bonds:-

  • Covalent
  • Electrostatic
  • Lipophillic
  • Hydrogen

Agonist:-

An agent which activates a receptor to produce an effect similar to that of the physiological signal molecule

Antagonist:-

 An agent which prevents the action of an agonist on a receptor or the subsequent response but does not have any effect of it's own.

Protein binding;- 

Drugs cannot activate receptors if they are are stuck to protein which are there in our blood plasma these proteins acts like a sponge on different drugs not leaving the drug until these plasma protein binding sites are saturated with drug.

 

Agonist and Antagonist interaction

Binding of the drug with the protein binding sites does not ensures activation of receptor ,the tendency of the drug to bind to the receptors is said to be it's affinity while the tendency of the drug after binding to the sites to activate the receptor is known as it's efficacy.

Receptor binding curves

Receptor binding curves source:http://www.pdg.cnb.uam.es/cursos/Barcelona2002/pages/Farmac/Comput_Lab/Radioligandos/GraphPad/radiolig.htm    
Saturation binding experiments measure specific binding at equilibrium at various concentrations(often 6-12)of the radioligand to determine receptor number and affinity.

In addition to binding to the receptors of the physiological interest, radioligands binds to nonreceptor sites. When performing radioligand binding experiments it's important to measure both the total and non-specific binding and then calculate the specific receptor binding as the difference.
Non-specific binding is generally proportional to the concentration of radioligand within the range it is used).The left panel graph shows the total and nonspecific binding. The dotted curve shows the difference between total and non-specific binding which is the specific binding.
The right panel shows the specific binding on the graph with a logarithmic X axis. The saturation binding curve plotted on a log axis looks like dose-response curve.

Concentration effect curve


Dose-response curve for the effect of a drug on a target
source:https://doi.org/10.1016/B978-0-12-800883-6.00084-7

The dose-response curve has a sigmoid shape. The concentration of the drug at one -half maximal target cell activity is called ED50,for effective dose at 50% of maximal response. Generally, the intensity of response increase with increases with  increase in dose (or specifically concentration at the receptor),but at higher doses, the increase in response progressively become less and marked and the dose-response curve is a rectangular  hyperbola

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