Chirality plays an important role in the development of many pharmaceuticals, being a general property of ‘handedness’; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases.

The purpose of this review is to examine in detail the new advances in the pathomechanisms and diagnosis of immediate and nonimmediate hypersensitivity reactions to quinolones, as well as analyze cross-reactivity among different quinolones. Hypersensitivity reactions to quinolones, especially anaphylactic reactions, have become more common in the past decade. This phenomenon could be related to their increased consumption. Although attempts have been made to standardize skin testing, the diagnosis of immediate hypersensitivity reactions to quinolones is mainly based on drug provocation. Some in-vitro, radioimmunoassay and basophil activation tests have also been used for diagnostic purposes, with results indicating that they could be complementary to in-vivo tests. Cross-reactivity seems to exist between first and second-generation quinolones, with lower levels with the third and fourth generations. However, no general rules exist for predicting cross-reactivity and it needs to be analyzed patient by patient. Nonimmediate hypersensitivity reactions also exist, especially maculopapular exanthema and fixed drug eruptions, and a T-cell mechanism has been demonstrated. Over the past decade the number of hypersensitivity reactions to quinolones has increased. These reactions can be severe and diagnosis difficult to confirm. Although new in-vitro tests hold promise, drug provocation testing remains the most frequently used and reliable diagnostic method.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity ofin vitrodiagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving thein vitrodiagnosis of allergic reactions to metamizole.

Heavy metals (HMs) are natural elements present in the Earth’s crust, characterised by a high atomic mass and a density more than five times higher than water. Despite their origin from natural sources, extensive usage and processing of raw materials and their presence as silent poisons in our daily products and diets have drastically altered their biochemical balance, making them a threat to the environment and human health. Particularly, the food chain polluted with toxic metals represents a crucial route of human exposure. Therefore, the impact of HMs on human health has become a matter of concern because of the severe chronic effects induced by their excessive levels in the human body. Chelation therapy is an approved valid treatment for HM poisoning; however, despite the efficacy demonstrated by chelating agents, various dramatic side effects may occur. Numerous data demonstrate that dietary components and phytoantioxidants play a significant role in preventing or reducing the damage induced by HMs. This review summarises the role of various phytochemicals, plant and herbal extracts or probiotics in promoting human health by mitigating the toxic effects of different HMs.