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II.3. Просмотрите текст и выпишите из него случаи употребления инфинитива. Переведите эти предложения письменно. Text a Drug absorption and distribution

In order to produce an effect, a drug must reach its target site in adequate concentration. This involves several processes, embraced by the general term pharmacokinetics. In general, the following processes are involved: (1) administration of the drug; (2) absorption from the site of administration into the bloodstream; (3) distribution to other parts of the body, including the target site; (4) metabolic alteration of the drug; and (5) excretion of the drug or its metabolites.

An important step in all of these processes is the movement of drug molecules through cellular barriers (e.g., the intestinal wall, the walls of blood vessels, the barrier between the bloodstream and the brain, and the walls of the kidney tubule), which constitute the main restriction to the free dissemination of drug molecules through the body. To cross most of these barriers, the drug must be able to move through the lipid layer of the cell membrane. Drugs that are highly lipid–soluble do this readily, hence they are rapidly metabolized and inactivated. They can also cross the renal tubule easily and thus tend to be reabsorbed into the bloodstream rather than being excreted in the urine.

Non–lipid–soluble drugs (e.g., neuromuscular blocking drugs) behave differently because they cannot easily enter the cells. Therefore, they are not absorbed from the intestine and they do not enter the brain. Because they may escape metabolic degradation in the liver, they are excreted unchanged in the urine. Certain of these drugs cross cell membranes, particularly in the liver and kidney, with the help of special transport systems, which can be important factors in determining the rate at which the drugs are metabolized and excreted.

The bloodstream carries drugs from the site of absorption to the target site and also to sites of metabolism and excretion, such as the liver, kidneys, and, in some cases, the lungs. Drugs distribute rapidly in tissues with high blood flow, and more slowly to tissues with low blood flow.

Drugs rapidly cross capillary membranes in the tissues due to passive diffusion and hydrostatic pressure. Permeability of capillary membranes for the drugs varies. Thus, drugs easily cross the capillaries of the glomerulus of the kidney and the sinusoids of the liver. The capillaries of the brain are surrounded by the glial cells that create a blood–brain barrier that act as a thick lipid membrane. Polar and ionic hydrophylic drugs cross this barrier slowly.

Drugs may accumulate in the tissues as a result of their physicochemical characteristics or special affinity of the tissues for the drug. Lipid–soluble drugs may accumulate in the adipose (fat) tissues because of partitioning of the drug. Tetracycline may accumulate in the bones because complexes with calcium are formed.

Plasma protein binding of drugs affects distribution. Many drugs are bound to plasma proteins, and in some cases more than 90% of the drug present in the plasma is bound in this way. This bound fraction is inert. A drug bound to a protein forms a complex that is too large to cross cell membranes. Protein binding reduces the overall potency of the drug and provides a reservoir to maintain the level of the active drug in the blood plasma. The effects of the drug, therefore, are reduced but prolonged by binding.

As the drug is infused intravenously, the plasma drug concentration increases to a steady–state concentration (Css). Under steady–state conditions, the fraction of the drug absorbed equals the fraction of drug eliminated from the body. A loading dose is given as an initial intravenous bolus dose to produce the Сss as rapidly as possible.

Intermittent intravenous infusions are those in which the drug is infused for short periods to prevent accumulation and toxicity. Intermittent intravenous infusions are used for a few drugs, such as the aminoglycosides. For example, gentamicin may be given as a 1–hour infusion every 12 hours. In this case, steady–state drug concentrations are not achieved.