In addition to their beneficial effects, most drugs have non-beneficial biological effects. Aspirin, which is commonly used to alleviate headaches, may also cause gastric irritation and bleeding. The non-beneficial effects of some drugs, such as cocaine and heroin, are so undesirable that the use of these drugs has to be strictly controlled by legislation. These unwanted effects are commonly referred to as side effects.
The over-usage of the same drugs, such as antibiotics, can result in the development of resistance to that drug by both the patients, microorganisms and virus the drug is intended to control.
Resistance occurs when a drug is no longer effective in controlling a medical condition. Drug resistance or tolerance, often referred to as tachyphylaxis, arises in people for a variety of reasons. For example, the effectiveness of barbiturates often decreases with repeated use because repeated dosing causes the body to increase its production in the liver of mixed function oxidases that metabolize the drug, thereby reducing the drug’s effectiveness.
An increase in the rate of production of an enzyme that metabolizes the drug is a relatively common reason for drug resistance. Another general reason for drug resistance is the down-regulation of receptors. Down-regulation occurs when repeated stimulation of a receptor results in the receptor being broken down. This results in the drug being less effective because there are fewer receptors available for it to act on.
Drug resistance may also be due to the appearance of a significantly high proportion of drug resistant strains of microorganisms. These strains arise naturally and can rapidly multiply and become the currently predominant strain of that microorganism. For example, antimalarial drugs
New drugs are constantly required to combat drug resistance, even though it can be minimized by the correct use of medicines by patients. They are also required for the improvement in the treatment of existing diseases, the treatment of newly identified diseases and the production of safer drugs by the reduction or removal of adverse side effects. The creation of hundreds, possibly thousands, of analogues, is aimed at, for example, improving the effectiveness, diminishing the toxicity or increasing the organism’s absorption of the drug.
This phase requires close collaboration between the biologists and chemists, who form a feedback loop. The biologists test the biological properties of compounds on biological systems while the chemists perfect the chemical structure of these compounds in the light of information obtained by the biologists.