DRUG RESISTANCE

Drug resistance is the reduction in effective of a drug in curing a disease or improving a patient’s symptoms when the drug is not intended to kill or inhibit a pathogen then the term is equivalent to dosage failure or drug tolerance. More commonly the term is used in the context of diseases caused by pathogens.

Pathogens are said to be drug resistant when drug meant to neutralize then have reduced effect.

When an organism is resistant to mere than one drug it is said to be multidrug resistant.

Classification:

Drug resistance Occurs in several classes of pathogens:

Bacteria – antibiotic resistance

Endoparasites

Viruses – resistance to antiviral drug

Fungi

Cancer cells

The most prominent is antibiotic resistance.

Drug resistant also found in tumour cells.

When a drig is administered, those organisms which have a genetic resistance to the drug will survive and reproduce, and the new population will be drug resistant.

Antibiotic Resistance:

Antibiotic resistance is the ability of a microorganism to with stand the effects of antibiotics. It is a specific type of drug resistance.

Antibiotic resistance evolves naturally via natural selection acting upon random mutation.

One such a gene is generated, bacteria can then transfer the genetic information in horizontal fashion (between individuals) by plasmid exchange.

Antibiotic resistance can also be introduced into microorganism through transformation protocols. This can aid in implanting artificial genes into the microorganism.

If the resistance gene is linked with the gene to be implanted, the antibiotic can be used to kill effective organisms that lack the new gene.

Several studies have demonstrated that pattern of antibiotic usage greatly affect the number of resistant organisms which develop.

Ex: Over use of broad spectrum antibiotics such as 2^nd & 3^rd generation cephalosporind, greatly has tens the development of methicillin resistance.

Antifungal resistance:

Scedosporium prolificans infections are almost uniformly fatal because of their resistance to antifungal agents.

Mechanisms:

The 4 mechanisms by which microorganism exhibit resistance to antimicrobials are:

1.       Drug  inactivation or modification:

Ex: Enzymatic deactivation of pencillin G in some pencillin resistant bacteria through the production of β-Lactamases

2.       Alteration of target site:

Ex: Alteration of PBP, the binding target site of pencillins in MRSA and  other pencillin-resistant bacteria.

3.       Alternation of Metabolic pathway:

Ex: Sulfonamide-resistant bacteria donot require PABA, an important precursor for synthesis of folic acid & nucleic acids in bacteria inhibited by sulphonamides.

4.       Reduced drug accumulation:

By decreasing drig permeability and/or increasing active efflux (pumping out) of the drug across the cell surface.

Neoplastic resistance:

Cancer cell also have the ability to become resistant to multiple different drugs and shares many of same mechanisms.

Increased efflux of drug (as by p-glycoprotein, multidrug resistance – associated protein, lung resistance –

related protein and breast cancer resistance protein).

Enzymatic deactivation (i.e. glutathione conjugation).

Decreased permeability (drugs can’t enter the cell)

Altered binding sites.

Alternate metabolic pathways (the cancer compensate for effect of the drug)

In the presence of drugs, pathogens have evolved sophisticated mechanisms to inactivate these compounds, and they do so at a rate that far exceeds the pace of new development of drugs.

Ex: Include drug resistant strains of staphylococcus aureus, klebsiella pneumonia, and pseudomonas aeurginosa, Mycobacterium tuberculosis (TB) among bacterium and HIV-1 among viruses.

Many different bacteria now exhibit multidrug resistance, including staphylococci, enterococci, gonococci, streptococci, salmonella, and others.

In addition, some resistant bacteria are able to transfer copies of DNA that codes for a mechanism of resistance to other bacteria thereby conforming resistance to their neighbours, which then are also be pass on the resistant gene.

To limit the development of antibiotic resistance one should:

Use antibiotics only for bacterial infections.

Identify the causative organism of possible.

Use the right antibiotic; do not rely on broad range- antibiotics.

Nonstop antibiotics as soon as symptoms improve finish the full course.

Not use antibiotics for most colds, coughs, bronchitis, sinus infections, and eye infections, which are caused by viruses.