Drug Tolerance in pharmaceutical Industry and resistance


Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. Drug, toxin, or chemical resistance is a consequence of evolution and is a response to pressures imposed on any living organism. Individual organisms vary in their sensitivity to the drug used and some with greater fitness may be capable of surviving drug treatment. Drug-resistant traits are accordingly inherited by subsequent offspring, resulting in a population that is more drug-resistant. Unless the drug used makes sexual reproduction or cell-division or horizontal gene transfer impossible in the entire target population, resistance to the drug will inevitably follow. This can be seen in cancerous tumors where some cells may develop resistance to the drugs used in chemotherapy. Chemotherapy causes fibroblasts near tumors to produce large amounts of the protein WNT16B. This protein stimulates the growth of cancer cells which are drug-resistant. MicroRNAs have also been shown to affect acquired drug resistance in cancer cells and this can be used for therapeutic purposesThe development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules (almost always proteins). Because the drug is so specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Furthermore, there is mounting concern over the abuse of antibiotics in the farming of livestock, which in the European Union alone accounts for three times the volume dispensed to humans – leading to development of super-resistant bacteria. A person may develop tolerance to a drug when the drug is used repeatedly. For instance, when morphine or alcohol is used for a long time, larger and larger doses must be taken to produce the same effect. Usually, tolerance develops because metabolism of the drug speeds up (often because the liver enzymes involved in metabolizing drugs become more active) and because the number of sites (cell receptors) that the drug attaches to or the strength of the bond (affinity) between the receptor and drug decreases. Strains of microorganisms (bacteria or viruses) are said to develop resistance when they are no longer killed or inhibited by the antibiotics and antiviral drugs that are usually effective against them (or, in practice, when significantly higher than normal doses are required to have an effect). Similarly, cancer cells may develop resistance to chemotherapy drugs. Resistance appears because of the mutations that take place spontaneously in any group of growing microorganisms or cells, whether exposed to drugs or not. Most such mutations change the microorganism's or cell's structure or biochemical pathways in a way that is harmful to the microorganism or cell. But some mutations change the parts of the microorganism or cell that are affected by drugs, decreasing the drug's ability to work (that is, causing resistance). Because such mutations are very rare, there are normally only a few such resistant microorganisms or cells in any group.




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