Examples of drugs that result in tolerance include alcohol and opioids. One mechanism responsible for tolerance is accelerated metabolism, for example, by induction of hepatic enzymes such as the cytochrome P-450 system enzymes Drug Metabolism The liver is the principal site of drug metabolism (for review, see [ 1]). Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even... read more . Generally, tolerance leads to increasing doses of a drug being required to produce the same effect. Other possible mechanisms are a decrease in binding affinity between a drug and receptor and a decrease in the number of receptors. The mechanisms responsible for drug tolerance are not always known.
Examples of resistance include the following:
Strains of microorganisms are resistant when they are no longer killed or inhibited by previously effective antimicrobial drugs. The mechanism begins with a genetic change resulting from a mutation or gene acquisition. Because the previously effective antimicrobial drug preferentially eliminates nonresistant organisms, the resistant organisms become the predominant species (see Overview of Antibacterial Drugs/Antibiotic Resistance Antibiotic Resistance Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more ).
Tumors can become resistant if a mutation develops that confers resistance to an anticancer drug and that anticancer drug is used repeatedly, preferentially eliminating nonresistant tumor cells. For example, many patients with chronic myeloid leukemia have become resistant to the tyrosine kinase inhibitor imatinib because of the presence of the T315I mutation.
Corticosteroid resistance can affect the treatment of a number of disorders such as asthma or inflammatory bowel disease. The mechanism of this type of resistance is not fully understood but may involve a number of different factors (eg, infection, oxidative stress, allergen exposure, inflammation, deficient vitamin D3, genetic mutations or variations).