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Prolongation of QTinterval is apredictor offatal cardiac arrhythmias and sudden death. In clinical practice, medicines with possible and conditional risk of QTprolongation are combine. The danger of such interactions could be enhanced if medi- cines interact themselves at metabolic rate. The interaction of drugs with possible and conditional risk of QTprolongation and interaction of these drugs with drugs that can influence the metabolic activity of cytochrome P450 isoenzymes require specific attention from physicians. Predictability of QTprolongation by drug-drug interactions at metabolic rate in drug administration will increase the safety of pharmacotherapy of drugs with possible and conditional risk of QTprolongation.

Aim: To study effects of pharmaceutical products on the results of clinical and laboratory diagnostics., Materials and Methods: The list of vitally important pharmaceuticals, clinico-pharmacological articles of the National registry of medicinal products, formulary articles from the Federal guidelines on the use of pharmaceutical products. Formulary system, instructions for use of individual pharmaceutical products. Systemic and information-based approaches, logical and comparative analysis were used throughout the study., Results: Results of analysis enabled the authors to draw up separate lists of pharmaceuticals based on their influence on parameters of clinical laboratory diagnostics, such as the list of pharmaceuticals exerting marked effect on diagnostic characteristics (blood properties, primary and coagulative hemostasis, serum enzymes), the list of pharmaceuticals exerting marked effect on systematized laboratory characteristics; the list of pharmaceuticals exerting no effect on clinical and laboratory diagnostics; the list of pharmaceuticals whose effect on diagnostic characteristics awaits clarification., Conclusion: The results of the study can be used for the development of recommendations on pharmaceutical counseling and rational choice of pharmaceutical products being prescribed to concrete patients.

Analysis of current literature on morphology of wound processes in the cornea during up-to-date techniques effecting keratogenesis is performed.

Ability of drugs to cross blood-brain barrier (BBB) (BBB+ for BBB-penetrating and BBB- for non-penetrating compounds) is one of the most important properties of chemicals acting on the central nervous system (CNS). This work presents the results of modelling of the relationship between chemicals structure and BBB-crossing ability. The data set included 1513 compounds BBB+/- (1276 BBB+ and 237 BBB-). Computer modelling of structure-activity relationship was realized by two directions: using the "read-across" method and linear discriminant analysis (LDA) based on physico-chemical descriptors. It was found that a sum of donor-acceptor factors is the principal parameter, which define BBB penetration.

The authors report the results of a forensic medical investigation of 6 cases of death associated with the administration of pharmaceutical products documented by forensic medical experts of the Russian Centre of Forensic Medical Expertise. The results of the study are compared with the clinical data and summarized using the methods of tanatogenetic analysis. The following main clinical variants of iatrogenic anaphylactic shock (IAS) are distinguished: bronchospastic IAS (n = 1), asphyxic IAS (n = 1), hemodynamic IAS (n = 3), and combined (bronchospastic plus hemodynamic) IAS (n = 1). The signs of all these variants are described allowing for their diagnostics and differentiation diagnostics. These data can be used for the purpose of forensic medical diagnostics and elucidation of the mechanisms of tanatogenesis.

Biopharmaceutical classification system (BCS) is based on solubility tests; for various drugs they correlate with their bioavailability in human body. It is widely used in design and development of innovation drugs, new dosage forms (permeability amplifiers), in clinical pharmacology (drug-drug, drug-food interaction) and also by regulation agencies of several countries as the scientific approach, for testing of waiver on bioavailability. Review considers modern concepts and theoretical bases for prediction of bioavailability according to BCS. It gives characteristics of fundamental parameters of the system: absorption number, solubility number and the ratio of dose to the soluble part of the drug. Possible versions of BCS modification for its subsequent optimization are discussed.

Substrates of cytochrome P450 isoenzymes have been analyzed and systematized, and a database is created in which the substrates are classified in accordance with the chemical structure of drugs. Each substrate is characterized by the oxidation reaction and the resulting metabolites, with allowance for the Michaelis - Menten pharmacokinetic parameters. Each isoenzyme metabolises certain preferred substrates, depending on the presence of active structural groups or moieties susceptible to oxidation and on the stereoselectivity of drugs. The reaction direction also depends on the specific interactions between the active groups of a substrate and the given isoenzyme.

One of the approaches to the development of new medicines now is the exploration of the effects of low and ultra low doses (ULD) of biologically active substances and preparations traditionally used in rather high dosages. The purpose of our work was to investigate the influence of pharmacologically active substances of various classes at wide range of concentrations, including ultra low, on lipid peroxidation in cell membranes of mice brain and activity of acetylcholinesterase (AChE). The action of synthetic antioxidant (AO) from the group of hindered phenols (inhibitors of free-radical reactions) phenozan, neurotransmitter acetylcholine (ACh), hybrid compound "phenozan + ACh + alkyl radical C-10" (perspective for Alzheimer's disease therapy), tranquilizer from benzodiazepines phenazepam and hydrogen peroxide were investigated. The influence of the investigated substances at ULD (concentrations) on kinetic parameters of the reaction, catalysed with soluble and membrane AChE (Michaelis constant and maximal velocity), and also on lipid peroxidation (LPO) system (level of products and LPO velocity, contents of total lipids, phospholipids, cholesterol) in mice brain cell membranes in vitro and in vivo was revealed. Concentrational and dose curves were of compilated character with the presence of zero effect zones typical for the agents capable to work at ULD. The effects of super low and "usual" doses of investigated substances were commensurable.

Biochemical drugs classification is proposed. Drugs are divided into 6 classes, according to their action on: 1) signal-transduction systems, 2) other components of plasmatic membranes, 3) intracellularly, 4) gene therapy, 5) extracellularly, 6) invasive agents. Concrete biochemical mechanisms of action of every class drugs are considered and described.

The authors discuss a possibility of the design of the drug classification on the basis of their interaction with two systems of perception, conduction and realization of external signals by the cell. Review reciprocal interactions between the adenylate cyclase and polyphosphoinositide systems and the polytropic character of the action of biologically active substances within the limits of each system.

The author reviews his own and reported data on the action of toxic substances of varying chemical classes on the main stages of the process of oxidative phosphorylation. It has been shown that toxic substances can destroy oxidative phosphorylation by the following ways: by reducing the resistance of mitochondrial membranes (disconnectors of the protonophoric and ionophoric types); by inhibiting dehydrogenase activity; by disturbing electron transfer via the respiratory chain; by disordering transmembrane transport of cations or anions; by inhibiting ATPase activity. The characteristic classes of toxic substances and the most specific inhibitors are indicated for each of the points enumerated. It is pointed out that the most incident reasons for impairment of oxidative phosphorylation are inhibition of NAD X H-dehydrogenase and protonophoric dissociation of respiration and phosphorylation.

On the basis of analysis of a number of documents concerning the molecular mechanisms of actions of well-known drugs the first attempt has been made to subdivide their activities into traditional and nontraditional ones. The possibility of application of a number of well-known drugs to nontraditional fields of pharmacology has been demonstrated.

The paper discusses side effects of the drugs and presents their classification, based on the principles of a pathogenetic approach. The classification includes side effects related to absolute and relative overdosage; specific effects, apart from the underlying one, related to the chemical structure, pharmacokinetics and pharmacodynamics; nonspecific effects due to individual features of the body.