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Wednesday, August 11, 2010

What is drug resistance, how a drug gets resistance and explanation of drug resistance mechanisms

What is drug resistance, how a drug gets resistance and explanation of drug resistance mechanisms:

We can define the term drug resistance as inability of a drug molecule to exhibit desired pharmacological action up on human body (eg .Insulin resistance)or microorganisms including bacteria’s , fungi and viruses (antimicrobial agents)

To understand a how a drug molecule gets resistance we should know in details, following aspects.

Mode of drug transport to active site and Drug Metabolism.

There are several and unique pathways ways for different drugs for getting resistance

1. Disturbance in mode of transport of drug to active site or drug receptor.

Drugs are absorbed from the dosage form in to body in following manner , if the drug is not in a paraentral dosage form , then it has to dissolve and get absorbed in to blood ,

This process of absorption of drug depends up on following transport mechanisms.

1.Active transport of a drug:

A drug is transported to the active site or from out side of the cell wall to inner cellular fluid , by carrier proteins and biopolymers , this transport involves binding of a drug to a carrier molecule and involves consumption of energy for formation of the complex or chemical bond , in the form of ATP , ATP molecule breakdown in to ADP and this energy is utilized to transport drug to active site.

In some drugs this transport system get affected over the time when the microorganisms or body develop a peptides and enzymes which do not facilitate active transport


2.Passive transport:

Drug is transported from one point to other by simple process of diffusion, and it is a concentration dependant process, where absorbed drug needs an environment which should support the binding of the transported drug to receptor site.


In some drugs it gets resistance when the surrounding environment is changed so that the drug molecule is hindered and receptor sites are blocked by other protein molecules.


2. Alteration of biochemical path way of microorganism, or an enzyme where the drug is supposed to act.

As discussed in earlier articles drugs are developed to mimic the biochemical system of human body or of microorganisms, hence many drugs are more or less similar to the bio-molecules of human body or of microorganisms excluding few. Genetic constitution of human body or of microorganisms is able to recognize these similarities , and which in tern up on regular input of a drug molecule in this system , triggers development of enzymes and proteins , or a alteration in the biochemical path way , which can bypass drug from biochemical path way or nullify the drugs activity.

3. Increased degradative metabolism of a drug.

This is a phenomenon responsible for drug resistance where a drug degradation is hastened making a drug ineffective or the dose required to get desired effect of a drug requires to be increased , many of drugs are metabolized by liver , there are many enzyme systems responsible for drug metabolism in liver (Cytochrome P40 enzyme system)

Up on regular intake of a drug molecule human body triggers synthesis of enzymes responsible for drug degradation , these enzymes may facilitate oxidative degradation or may cause degradation by various path ways like ,Oxydation , reduction, trans amination , acetylation , deamination, hydrolysis , or simple protein conjugation so as that drug molecule becomes pharmacologically ineffective.

4.Increased elimination of a drug of of cell or body :

This process enhance elimination of a drug out of microbial cell by tagging the drug with a protein which facilitate excretion of drug .This process develops up on time , after a repeated usage of a drug.


5.Enzymes responsible for drug resistance:

The classic example of drug resistance by an enzyme induction is betalactamase enzyme in betalactam antibiotics resistance.

Where betalactamase enzyme make betalactam antibiotics ineffective.

6.Cross resistance:

Drug resistance developed from one drug can develop drug resistance for the entire specific group of drug where the mode of acton of the drug is is more or less similar in the particular group of drug.

Example of this phenomenon is antibiotic resistance.

Each drug has its own metabolic degradation path way and mechanism of drug resistance , and to develop better drugs these path ways should be stuided which will lead to development of molecules which will protect drugs from getting drug resistance .Example Clavulanic acid , is combined with betalactam antibiotic to counteract betalactamase enzyme and to protect amoxicillin from betalactamase enzymatic degradation.

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