Interactions active ingredients when used oral drugs

In the process of absorption of drugs is influenced by various factors – as pharmacokinetic parameters, and route of administration of drugs into the body. Significant influence such factors, as physico-chemical properties of drugs (molecular size, solubility, stability, degree of ionization, ability to chelate- and complexes, etc.. d.) and formulations (eg, tablet disintegration, the presence of various nature and other auxiliaries.), time of passage through the digestive tract, content of the digestive tract, Numerous physiological factors of the patient (motor and secretory activity of the gastrointestinal tract, pH, osmolality, suction machine status and others.), metabolism (under the influence of bacterial intestinal microflora), the composition and viscosity of secrets, the permeability of the mucous membrane of the digestive tract and many other.

Medicinal substances may be absorbed in any part of the digestive tract. In a joint application of drugs is often observed interference in the absorption of substances in the digestive tract. The simplest interaction with oral medication occurs between drugs and fluids, which they wash down. Established, what if you drink a liquid medicine in an amount greater 200 ml, the absorption of substances is much faster, than the amount of water taken less 25 ml. This is because, Dissolved in a liquid hydrophilic drugs are distributed over a larger area of ​​epithelium and better absorbed.

Absorption also promotes a thin epithelial layer oral mucosa, which is well vascularized. This greatly simplifies the process of absorption. However, the substances in the oral cavity are briefly, which is reflected in the minor quantitative absorption process.

The surface area of ​​the gastric epithelium is significant, but it is covered with a thin layer of mucus, therefore the extent of absorption is limited by the residence time of the substance in the stomach. The acidic environment of the stomach favors the absorption of weak acids, that, usually, soluble in lipids, and are non-ionized form. Some substances, such as penicillins, destroyed, which reduces their therapeutic efficacy.

In general, the suction efficiency determined by the rate of gastric emptying and significantly decreases food intake, especially fat. To accelerate the absorption of drugs, They take them on an empty stomach.

The small intestine has the highest suction surface of all the digestive tract. However, inside it has different values ​​of pH, that affect the qualitative and quantitative characteristics of drug absorption, depending on their properties. In the duodenum pH 4-5; during the further digestive tract environment becomes more alkaline, and in the lower reaches pH 8.

The rate of absorption of medicinal substances is also dependent on the time of passage through the sections of the intestine. This is particularly true of substances, are transported across the cell membrane by facilitated diffusion (B vitamins), poorly soluble (griseofulvin) or carry an electric charge, hinders the penetration of the membrane, many antibiotics e.g..

In the intestine are absorbed even weak acids (eg, acetylsalicylic acid), are not ionized in the acidic environment of the stomach in the presence of hydrochloric acid. Some drugs are inactivated by the gut flora, which reduces the degree of their absorption and bioavailability. Besides, decrease in peripheral blood flow alters the rate of absorption, Distribution and metabolism of substances. In contrast, small intestine colon has no villi, However, the absorption of substances it is possible to, although not as effectively.

The main importance for the therapeutic effect using the combined drugs are those interactions, are associated with a change in velocity (slowing or decrease) and complete absorption, thereby changing the therapeutic effect of one or more active substances. In some cases, limit intake entails strengthening of the desired effect. For Example, in the treatment of enteritis and enterocolitis tansalom (It contains tanalbin and phenyl salicylate) binder fenilsalitsilata limits absorption, and thereby enhances its antimicrobial effect in the intestine.

Absorption of drugs in the stomach and intestine is generally proportional to the degree of lipophilicity. Absorption of non-ionized molecules is faster, since these substances are more lipophilic, than the ionized compounds.

Absorption of drugs from the gastrointestinal tract pH-dependent, significantly affect the process of ionization. Drug substances with properties of weak acids are well absorbed in the stomach, since in acidic medium (gastric pH around 2,0) They dissociate and less easily pass through the cell barrier, whereas drugs with properties of weak bases better absorbed in an alkaline environment of the intestine.

Of great practical importance is the change in the process of absorption of drugs under the influence antacids (aluminum hydroxide, Almagelum, precipitated calcium carbonate,, magnesium oxide, natriya carbonate). Their oral administration increases the pH of stomach contents, thereby increasing the degree of ionization of weak acids and a slowing the passage of ionized compounds through lipid layers biomembranes. This explains the decline in the overall operation of such substances, As antykoahulyantы indirect actions, barbiturates, phenylbutazone, Digoxin, acetylsalicylic acid, Indomethacin, Some sulfonamides, nitrofurans or combined with antacids. Such an effect is sufficient antacid, to completely prevent the sedative effect of derivatives of barbituric acid when given in usual therapeutic doses. Therefore, in medical practice, patients with peptic ulcer and gastritis giperatsidnyh prescribe these medications at intervals 3 o'clock. There is evidence, Concurrent use of tetracycline (250 mg) and sodium hydrogen carbonate (2,0 g) It reduces the absorption of the antibiotic on 50%. However, the use of antacids unstable in an acidic environment the drug substances, for example pancreatin, It protects them from inactivation. Antacids may increase the motility of the stomach and form complexes, therefore their influence on the absorption of many drugs almost unpredictable. Some medications, eg Almagelum, as well as liquid paraffin, to form a surface layer of mucosa, which impedes the absorption of drugs.

With prolonged use of chemotherapeutic agents (neomycin, polymyxin, kanamycin, tetracycline, sodium paraaminosalitsilata et al.) may occur "disorder" of the process of absorption of medicines and nutrients. The reason is a change in the composition of intestinal microflora (dysbiosis). As a result, the growth of Bacteroides, clostridia, anaerobic lactobacilli decreases the activity of enzymes of the mucous, involved in the absorption of drugs and nutrients (fat, carbohydrates, protein, vitamins). For Example, six-day oral administration of neomycin sulfate (3 g per day) lowers serum concentration of phenoxymethylpenicillin (0,25 g) in 2 times, digoksina (0,5 g) - In 3 times. Therefore, if necessary, the simultaneous use of these substances for a long time should be recommended parenteral administration and appropriate adjustment of benzylpenicillin dose glycoside.

It should also be taken into account, that changes in the intestinal microflora under the influence of broad spectrum antibiotics accompanied by increased effects acenocoumarol or other substances (neodikumarina (ethyl bïskwmacetata), fepromarona). The reason for this interaction is the reduction of intestinal microflora of synthesis of vitamin K2-antagonist anti proximity.

The change in the composition of the intestinal flora influenced by antibacterial broad-spectrum leads to accelerate the metabolism of estrogen. For this reason, when appointing an antibiotic against the backdrop of the admission of oral contraceptives, containing estrogen, possible pregnancy. Therefore, their combined use not recommended.

Not recommended simultaneous application colibacterin, bifidumbacterina, bifikola and antibacterial, that excludes the effects of bacterial substances. In the gut may be subjected to hydrolysis of salt benzylpenicillin, strofantina or other substances, Therefore they are used parenterally.

Some drugs (mefenamic acid, aminoglikozidy) toxic effect on the mucous membranes of the DIGESTIVE TRACT, that leads to disruption of other medical suction, as well as nutrients.

Because many drugs are absorbed in the proximal small intestine, It is very important to take into account the condition of the eye syndrome and bowel evacuation speed, What determines the time of the curative action of medicines and its effectiveness. Holinomimetikami increase peristalsis of the bowel, reduces the absorption of Digoxin, While m-holinoblokatora (atropine sulfate) and Narcotic analgesics (morphine hydrochloride, preparations of codeine, etc.) slow gastric emptying, that extends contact medicinal substances (digoksina, acetylsalicylic acid, etc.) with mucous, leads to her irritation, and sometimes to the izjazvleniju.

Some substances (drugs levodopa) the long delay in the stomach may partially be inactivated. These unwanted processes result in diminishing the effectiveness of drug therapy and its undesirable manifestations. However, the therapeutic efficacy of such substances, like digoxin, digitoxine, iron supplementation increases, because absorption is increased as a result of more prolonged contact with mucous membranes of the intestine.

Metoclopramide improves peristalsis of the DIGESTIVE TRACT, that increases the time and completeness in the gut of such substances, as diazepam, paracetamol, ethyl alcohol, tetracyclines and reduces the therapeutic efficacy of substances, that slowly absorbed (Digoxin, cimetidine, certain antibiotics).

The deceleration of gastric and intestinal motility, caused by drugs, leads to better absorption of the duodenal drugs slowly — tetracycline, digitoxin. When ulcers decrease motility promotes long finding in the stomach antacids and fuller expression of their therapeutic effect.

When you use laxatives eye syndrome there is an increasing and more rapid removal of both taken with them drugs. For Example, long-term use of laxatives contributes to an increased allocation of potassium from the body, What to consider when long-term use drugs digitalisa (Perhaps a manifestation of digitalisna arrhythmia) diuretic means (strengthening of hypokalemia).

Mutual influence on absorption of medicinal substances in their ingestion, a phenomenon occurring quite frequently. The same acetylsalicylic acid reduces absorption of indomethacin, diclofenac, digoksina. Paraaminosalicilovaya acid roughly halved reduces induction rifampitina. Use them separately, with an interval of 12 hours, as well as intravenous PASC does not affect their induction. The concentration of rifampicin decreases under the influence of isoniazid. While receiving Digoxin and neomycin (3 g) antibiotic concentration in the blood is reduced 3-5 time, and time to reach the maximum concentration in the blood increases its. When administered neomycin for 3 hours before taking digoxin area under the curve of concentration decreased in the blood to see 46-64%, and when taken with an interval of 6 the clock is on 25-31%. There is evidence of slowing vitamin intake₁₂ under the influence of different drugs — contraceptives, holestiramina etc. Suction zianokobalamina ingestion somewhat improves upon its joint admission with folic acid.

The drugs, containing Divalent metals, reduce the contents of tetracycline antibiotics in the blood when their joint application. So, under the influence of iron sulfate (40 mg) oxytetracycline concentration is reduced by 50-60%, metziklina-on 80- 85%, Doxycycline is on 80-90%. Absorption of tetracycline reduced not with the same power under the influence of different iron salts. For Example, ferric tartrat slows the absorption of the antibiotic on 50%, ferrous gluconate, succinate of iron-on 70-80%, and iron-on 85%. While receiving zinc sulfate 200 mg tetracycline concentration in blood last dropping 30-40%, While doxycycline concentration remains virtually unchanged. Other substances, containing magnesium ions, aluminum or calcium, also reduces the absorption of tetracycline.

Some drugs increase the absorption of other substances in a joint application. So, Caffeine increases concentration in the blood fenoximetilpenitsillina, mainly due to the increase of antibiotic intake process in gastrointestinal tract. Increases induction fenilbutazon fenoximetilpenitsillina; metoclopramide increases intake of pivampicillina and tetracycline.

When zimetidina and tetracycline or salicylic acid as a result of inhibition secreting hydrochloric acid in the stomach of a decrease in the intake of these substances. In turn, antibiotic does not affect the absorption of cimetidine. Other studies have found no effect of cimetidine on the pharmacokinetic parameters of ampicillin, trimethoprim and sulfamethoxazole.

Some drugs can have povrejdatee impact on membrane transport systems of the bowel. So, When neomitina sulfate, kanamycin, polymyxins, tetracyclines and iron, vitamin B12 or folic acid can significantly decrease absorption of the past. Damage to the intestinal epithelium, membrane transport systems is observed and fenitoina, that inhibits the absorption of folic acid.

Common cause reduction of intake is direct interaction of drugs in the gut lumen of inactive chelates formations, or chelating agents. The helatoobrazovateljam include oral preparations of input, that release calcium ions (glutaminat, pangamat, lactate and calcium gluconate, carbonate precipitated), Magnesium (potassium-magnesium aspartate, magnesium oxide, magnesium sulfate) and aluminum (Almagelum, Almagell and etc.). These medicinal substances easily form complexones with cardiac glycosides, nepryamыmy anticoagulants, sulьfanilamidami, fenilbutazonom and salicilatami. This casts doubt on the appropriateness of such combinations, as cardiac glycosides with pangamatom and calcium pananginom calcium pangamata and or sulfonamides to improve their endurance.

On the same principle of tetracycline antibiotics interact with iron ions, Calcium, Magnesium, aluminum, Zinc, manganese, cobalt. When combined with tetracycline, These cations, decreasing its concentration in the body. Since tetracycline has a bactericidal effect, reducing its therapeutic concentration in the blood below 0,6 µg/ml is invalid. Established, giperacidnogo in the treatment of gastritis or ulcers tetracycline combined with means may (almagelem, magnesium oxide, aluminum hydroxide) may reduce antibiotic concentrations in the blood to the patient 90%. When combined with the admission of tetracyclines and iron sulfate at a dose of zakisnogo 200 mg tetracycline level in the blood is reduced by 50%, metziklina hydrochloride (rondomicina) and doxycycline hydrochloride (vibramicina) - On 85%. Such interactions can be avoided, If applied separately with trehchasovym interval.

Tetracyclines form complexes with calcium ions growing teeth and bones in children, If during pregnancy, long take tetracycline. This manifests itself as hypoplastic teeth and their dark-yellow coloring due to deposition of calcium-tetracycline complex in tooth enamel and dentin. Therefore, it is not recommended to take tetracycline antibiotics to women during pregnancy and children under 8 years.

Chelation can form and other antibiotics — oleandomycin, oxacillin, dikloksacillin and lincomycin when interacting with calcium kazeinatom, present in dairy products. Insoluble complex with pectins food forms the paracetamol. The formation of complexes between drugs (phenylbutazone, rifampicin, gljukokortikoidami, fat soluble vitamins) and the bile acids when receiving holestiramina, white clay, Activated Carbon, because they bind bile acids in the gut, which can lead to absorption. Besides, cholestyramine can directly associate the digoxin, medicinal calcium and other substances and thereby reduce their intake. Sodium paraaminosalicilat, linking jelchne acid, reduces absorption of rifampicin, Therefore, these substances should be taken at intervals 10-12 hours.

However, it should be remembered, complexing compounds that are often used as antidotes for poisoning iron salts, heavy metals and salts, alkaloids of. For the same purposes use the phenomenon of adsorption, eg, Activated Carbon, poisoning by heavy metals, microbial toxins, medicinal substances, as well as with indigestion and flatulence.

Medications, taken orally, can interact with the components of food, that leads to a slow, accelerate or other violations of suction as medicinal, and nutrients.

Therapeutic effect of causes only the concentration of medicinal substances, that is in liquid state and in solution can penetrate cells and tissues. A related form of drugs with proteins, mainly albuminami, lipoproteins and other blood elements, represents the original Depot and serum only after reducing the concentration up to a certain level. When combination drug therapy or additional introduction in an organism of other substances can occur from a related displacement of earlier forms of substances, that leads to an increase in the concentration of their active form in the blood.