Ticket 2.

1. Distribution of drugs in the body. Biotransformation of drugs in the body and ways of their extraction. The concept of bioavailability.

1. After absorption, many medicinal substances nonspecifically and reversibly bind to blood plasma proteins, mainly albumin. In this case, different drugs compete with each other for the same binding zones on the surface of the protein and displace each other. Protein-bound drug fractions do not penetrate into tissues and are virtually devoid of pharmacological action. Only the free fraction of the drug in plasma has the ability to penetrate tissues and act. The binding capacity of the blood decreases significantly with protein starvation, liver diseases, extensive burns, with age, and with the replacement of blood loss with protein-free fluids.

2. A dynamic equilibrium is maintained between the free fraction of the drug and the fraction bound by proteins: as the free substance is released into the tissue, its amount is replenished due to the previously bound proteins.

When administered intravenously, the following steps occur:

- the concentration of the drug in the blood reaches peak concentrations and enters primarily into well-vascularized tissues (heart, brain, kidneys, lungs), which take on the toxic effect - in the next minutes after administration, the drug is distributed throughout the water phase, including organs with slow blood flow (skeletal muscle, subcutaneous tissue)

3. drugs with high lipophilicity are absorbed by the adipose tissue, creating a depot that releases the drug as its concentration in the blood decreases

The significance of biotransformation lies in converting a dangerous substance into a less toxic and water-soluble substance, in order to subsequently remove them with the kidneys, bile, then (excretion routes). This goal is achieved by transferring drug molecules to more polar, more ionized, less lipophilic, less binding to plasma and tissue proteins, less penetrating through biological barriers that are not reabsorbed in the kidneys and intestines.

Biotransformation occurs in the cells of the liver, intestines, lungs, skin and blood plasma. A certain amount is excreted in the urine unchanged.

There are 2 phases of biotransformation: 1) the molecules undergo hydrolysis, oxidation or reduction.

2) When administered orally, the drug begins to undergo biotransformation already in the intestine and during the first passage through the liver, that is, before entering the systemic circulation. This stage of biotransformation is defined as first pass metabolism.

Bioavailability (bioavailability) characterized by the proportion of the drug from the administered dose, which enters the systemic circulation in an active form.

Depends on: presystemic metabolism, properties of the drug form, the rate of absorption, conditions affecting the adsorption of drugs.

2. Binding, engraving, adsorbating, irritating substances. Classification. Mechanism of action. Indications for use. Side effects. Contraindications. Comparative evaluation of preparations.

Astringents- substances that can interact with proteins, cause partial coagulation of proteins with the formation of insoluble albuminates. At the same time, the physicochemical properties of colloids of cells, extracellular fluid, mucus, exudate change.

Classification: Organic: Tannin, Oak Bark Decoction

Inorganic: lead acetate, bismuth basic nitrate, alum, zinc oxide, zinc sulfate, copper sulfate, silver nitrate.

Astringent properties: anti-inflammatory (the resulting film causes a thickening of the vascular wall and a decrease in permeability)

Analgesic (a film is formed including on the ends of sensitive nerve fibers)

Hemostatic (decreased capillary permeability)

Antimicrobial (mechanical protection with a film and coagulation of microbial proteins)

Antacid and gastroprotective (decrease in the secretion of hydrochloric acid due to the compacted surface of the wall of the gel, weakening of irritating actions, which promotes regeneration)

Indications for use: inflammation of the skin, mucous membranes, used in the form of lotions, text messages, rinses. Tannin and bismuth are used internally for colitis, enterocolitis.

Enveloping - substances that can swell in water with the formation of colloidal solutions-mucus.

Classification:

Organic compounds: Potato or rice starch mucus, flax seed mucus, marshmallow infusion, milk, egg white.

The mucus enveloping the surface of the tissues protects the mucous membranes from irritation, hence reducing inflammation and pain response. Large colloidal particles are able to adsorb toxins on their surface and reduce their absorption.

Inorganic compounds: Aluminum hydroxide, almagel, sucralfate

When taken orally, aluminum preparations neutralize acid, reduce the secretion of pepsin due to a film on the mucous membrane of the stomach, and at the same time have a cytoprotective effect.

Indications: inflammatory diseases of the gastrointestinal tract.

Absorbent agents are the finest, crushed, insoluble, indifferent powders with a large adsorption surface.

Talc, white clay, activated carbon, adsorbents. They are used externally as drying agents for diaper rash, eczema. Inside with diarrhea (absorb toxic substances), flatulence (absorb hydrogen sulfide).

Irritants -substances with the ability to easily penetrate the skin and mucous membranes due to their high lipophilicity and cause irritation of sensitive nerve endings, hyperemia at the site of application. Mustard plaster, turpentine, menthol, ammonia solution, pepper plaster.

Properties and mechanism of action: 1) improvement of tissue trophism due to increased blood supply in the damaged organ - reflexively according to the axon-reflex type, reflexively from the site of irritation according to the type of cutano-visceral reflex, formation in the subcutaneous tissue on the mesh; application of bav (histamine, pg) for this effect: neuralgia, myalgia, sciatica, rheumatoid arthritis, arthrosis, bronchitis, pneumonia

2) distracting - a decrease in pain: a) the imposition of impulses emanating from the diseased organ or parts of the body and from the place of application of the irritating agent, as a result, the irritation from the application drowns out the pain from the pathogen

B) the release of enkephalins indications at the same time: neuralgic, myalgic, joint pain, retrosternal with angina pectoris.

C) antianginal: reflex improvement of coronary blood flow. indications: angina pectoris

Contraindications : not recommended in the acute period of the disease due to possible exacerbation of the process, purulent skin lesions, psoriasis

D) analeptic (ammonia): reflex excitement of the vasomotor and respiratory center due to irritation of the sensitive receptors of the upper pathways. Indication: fainting. Contraindication: reflexive cessation of breathing in case of overdose