sublingual route. Sublingual - how is it? Let's figure it out together

Some medicines are placed under the tongue, absorbed, and as a result, they go directly into the small blood vessels located on the underside of the tongue. This route of administration (sublingual) is especially good for nitroglycerin used in angina pectoris, because the drug immediately enters the general circulation, bypassing the intestinal wall and liver. However, most drugs cannot be taken this way because their absorption will be incomplete.

Rectal administration

Many medicines taken by mouth can also be given in the form of a rectal suppository. In it, the drug is mixed with a low-melting substance, which dissolves after injection into the rectum. The thin mucous membrane of the rectum is well supplied with blood, so the drug is absorbed quickly. Suppositories are used in cases where the patient cannot take medicine by mouth due to nausea, inability to swallow, or if he cannot eat, for example, after surgery. Some drugs prescribed in the form of suppositories are irritating, so they have to use the parenteral route of administration (injections).

Advantages and disadvantages of routes of administration medicines

Intravenous administration

Advantages- rapid achievement of a therapeutic effect, the possibility of accurately calculating the dose of the drug in the blood, the possibility of administering drugs that are destroyed by other routes of administration.

Flaws- emotional stress for the patient, pain, the need for the participation of qualified medical personnel, the likelihood of infection of the patient, the possibility of developing some complications (thrombosis, embolism, etc.).

Intramuscular administration

Advantages- rapid achievement of a therapeutic effect, the possibility of introducing drugs that are destroyed by other routes of administration, the ability to create a "depot" of the drug at the injection site.

Flaws- emotional stress for the patient, pain, the need for the participation of qualified medical personnel, the likelihood of infection of the patient, the possibility of damage to blood vessels or nerves, the dependence of absorption on the speed of capillary blood flow.

Subcutaneous administration

Advantages- slow absorption, the possibility of introducing drugs that are destroyed by other routes of administration, the ability to create a "depot" of the drug at the injection site.

Flaws- emotional stress for the patient, soreness, the need for the participation of qualified medical personnel, the likelihood of infection of the patient, inefficiency in severe disorders of local circulation (shock, diabetes, low blood pressure).

Transdermal administration

Advantages- convenience for the patient, there is no need for the participation of qualified medical personnel, ensuring a constant concentration of the drug in the blood, the possibility of administering drugs that are destroyed by other routes of administration, reducing the frequency of taking the drug.

Flaws- increased cost of therapy, a limited range of drugs, the possibility of developing contact dermatitis.

Intranasal administration

Advantages- the rapid entry of the drug into the brain, the rapid development of the effect, there is no need for the participation of qualified medical personnel, the possibility of administering drugs that are destroyed by other routes of administration, convenience and ease of use.

Flaws- irritation of the nasal mucosa, allergic reactions on the nasal mucosa, a small part of the drug enters the blood, a limited range of drugs, the inability to ensure a constant concentration of the drug in the blood.

Oral administration

Advantages- comfort for the patient, there is no need for the participation of qualified medical personnel, the possibility of long-term therapy.

Flaws- absorption is unstable and incomplete: the drug may be poorly soluble, slowly absorbed, destroyed by gastrointestinal enzymes; affects food intake; can not be used when the patient is unconscious; should not be used for vomiting.

Sublingual administration

Advantages- rapid absorption through the oral mucosa; the concentration of the drug is higher, because it is not metabolized in the liver, is not destroyed by the secrets of the gastrointestinal tract, and is not bound by food

Flaws- you can not prescribe drugs of unpleasant taste; you can not prescribe drugs that irritate the mucous membrane.

1 Suction

At the stage of absorption, the medicinal substance from the intestinal lumen penetrates into the blood. The efficiency of this process may depend on the pH of the environment.

The degree of absorption of the drug also depends on intestinal motility. So, with increased motility of the gastrointestinal tract, the absorption of digoxin decreases, and with a weakening, it increases.

Inhibition of enzymes that promote absorption is another type of interaction.

2 Enteral routes of drug administration

enteral route includes: the introduction of the drug inside through the mouth (per os) or orally; under the tongue (sub lingua) or sublingually, into the rectum (per rectum) or rectally.

oral route

The oral route (also called oral administration) is the most convenient and simplest, therefore it is most often used for the administration of drugs. Absorption of drugs taken by mouth occurs mainly by simple diffusion of non-ionized molecules in the small intestine, less often in the stomach. The effect of the drug when taken orally develops after 20-40 minutes, so this route of administration is not suitable for emergency therapy.

At the same time, before entering the general circulation, the drugs pass through two biochemically active barriers - the intestines and the liver, where they are affected by hydrochloric acid, digestive (hydrolytic) and hepatic (microsomal) enzymes, and where most drugs are destroyed (biotransformed). A characteristic of the intensity of this process is bioavailability, which is equal to the percentage of the amount of the drug that has reached the bloodstream to the total amount of the drug introduced into the body. The greater the bioavailability of the drug, the more completely it enters the bloodstream and the greater the effect it has. Low bioavailability is the reason why some drugs are not effective when taken orally.

The rate and completeness of drug absorption from the gastrointestinal tract depends on the time of the meal, its composition and quantity. So, on an empty stomach, acidity is less, and this improves the absorption of alkaloids and weak bases, while weak acids are absorbed better after meals. Medications taken after meals can interact with food components, which affects their absorption. For example, calcium chloride taken after a meal can form with fatty acids insoluble calcium salts, limiting the possibility of its absorption into the blood.

sublingual way

The rapid absorption of drugs from the sublingual region (with sublingual administration) is provided by the rich vascularization of the oral mucosa. The action of drugs comes quickly (after 2-3 minutes). Sublingually, nitroglycerin is most often used for an attack of angina pectoris, and clonidine and nifedipine for the relief of a hypertensive crisis. With sublingual administration, drugs enter the systemic circulation, bypassing the gastrointestinal tract and liver, which avoids its biotransformation. The drug should be kept in the mouth until it is completely absorbed. Often sublingual use of drugs can cause irritation of the oral mucosa.

Sometimes, for quick absorption, drugs are used on the cheek (buccally) or on the gum in the form of films.

rectal route

The rectal route of administration is used less frequently (mucus, suppositories): in diseases of the gastrointestinal tract, in the unconscious state of the patient. The bioavailability of drugs with this route of administration is higher than with oral administration. About 1/3 of the drug enters the general circulation, bypassing the liver, since the inferior hemorrhoidal vein flows into the system of the inferior vena cava, and not into the portal.

3Parenteral routes of drug administration Intravenous administration

Medicinal substances are administered intravenously in the form of aqueous solutions, which provides:

rapid onset and precise dosing of the effect;

rapid cessation of the drug's entry into the blood in the event of adverse reactions;

the possibility of using substances that are collapsing, non-absorbable from the gastrointestinal tract or irritating its mucous membrane.

At intravenous administration the drug immediately enters the bloodstream (absorption as a component of pharmacokinetics is absent). In this case, the endothelium is in contact with a high concentration of the drug. The absorption of the drug when injected into a vein is very fast during the first minutes.

In order to avoid toxic manifestations, potent drugs are diluted with an isotonic solution or glucose solution and administered, as a rule, slowly. Intravenous injections are often used in emergency care. If it is not possible to administer drugs intravenously (for example, in burned patients), it can be injected into the thickness of the tongue or into the floor of the mouth to obtain a quick effect.

Sublingual is under the tongue. This is how this expression, which has become a pharmacological term, is translated from Latin. Sublingually, for example, I take validol when my heart aches ...

How does sublingual medication differ from oral (well, terms)?

The fact that when taking the drug under the tongue, it quickly penetrates into the blood. The medicinal substance instantly comes into contact with the mucous membrane of the sublingual oral cavity, where there are many blood vessels, and very close to the surface. Through them, the medicine enters the general circulation, passes through the heart, and then penetrates into the whole body. And the oral method involves the passage of the medicinal substance first through the intestines, where the medicine will lose a number of its best and most effective properties; and its entry into the metabolic process produced by the liver, which will quite noticeably decompose the medicine and also take away its healing effect. And only then this substance, that is, what is left of it, is absorbed throughout the body. Therefore, some drugs should only be taken sublingually in order to maintain their effectiveness and speed up the process.

And what are these medicines?

For the most part, drugs that help the heart and blood vessels are administered through the “under the tongue” method. Steroids and barbiturates, certain enzymes (proteins that speed up chemical reactions), vitamins and minerals are also administered sublingually.

The form of such preparations can be any. If only she would dissolve in saliva. These are tablets, powders, drops, even aerosols. True, such medicines do not affect the health of the teeth in the most positive way, well, for the sake of health, it’s not a pity to give up a tooth or two.

Moreover, some psychoactive substances are also taken sublingually. Rage, for example, some psycho in the Yellow House. He demands the consul of Venezuela to himself, the bastard, and declares that he is the son of Nikita Khrushchev and, in parallel, the Margrave of Brandenburg. Exhortations, of course, do not help. Then a doctor with sleeves rolled up to the elbow comes up to the psycho, takes this very aerosol with a known substance and, having waited for Margrave Khrushchev to open his mouth in another demand, deftly gives him a psychosoothing. The psycho rolls his eyes, slowly collapses on the bed, and the doctor with rolled up sleeves covers him affectionately, like a mother.

LSD, morphine, methamphetanim (it used to be called pervitin - remember?), alprazolam for anxiety and rebelliousness; clonazepam (for epilepsy) and other narcotic drugs, as well as psychedelic tryptamines, are also administered sublingually. They come in the form of a powder and are poured under the patient's tongue so that the necessary substance not only penetrates into the blood more quickly, but also “processes” the brain.

But that's not all! Allergens can also be used sublingually, in the general process of immunotherapy. However, let's hope that this cup will pass us all, filled with clonazepams, matemfetanim, enzymes and other alprazols. Amen.

Sublingual - how is it? This question is of particular interest to those who have been prescribed a medication that must be taken in this way. In this regard, we bring to your attention the definition of the presented term and a description of the principle of taking medicines.

Sublingual - how is it?

This pharmacological term was formed from two Latin words "sub" and "lingua", literally meaning "under" and "tongue", respectively. In other words, sublingual medical preparations carried out by placing them under the tongue. With this treatment, the drug enters the bloodstream through its direct absorption with the help of the sublingual region. It is worth noting that today there is a huge number of drugs that are produced for sublingual administration. These include barbiturates, steroids, of cardio-vascular system, as well as some enzymes and certain minerals, vitamins.

The principle of administration and action of the drug

Sublingual - how is it? Having clarified the definition of this pharmacological term, the following question arises of how exactly such a technique is carried out. medical supplies. It is worth noting that taking certain drugs by sublingual way is quite easy and simple. To do this, the tablet simply needs to be placed in the sublingual region and sucked until it dissolves. By the way, it is in the process of such administration that the medicine comes into contact with the oral mucosa, and Chemical substance penetrates into the epithelium, which is located at the bottom of the tongue. In this place oral cavity a large number of blood vessels are located, as a result of which the sublingual route of administration of medications quite quickly and effectively affects the diseased organ. This is explained by the fact that the chemical compounds of drugs are instantly introduced into the venous circulation, which, in turn, returns to the heart muscle, and then spreads throughout the body through the arteries.

The advantages of this approach

As medical practice shows, the sublingual method has a number of advantages over oral administration of drugs. After all, this path is much faster, and it also ensures that the medicinal substance enters the bloodstream, but before that it will inevitably come into contact with enzymes in saliva. As for the oral method, in this case, a high percentage of the drug will be destroyed by acids in the gastrointestinal tract, which significantly reduces its effectiveness.

Sublingual or buccal: which is better?

Along with the sublingual method, there is also such a method of taking medicines as transbuccal. The word is derived from the Latin "buccalis" meaning "cheek". In other words, this pill intake involves placing them between the gum and upper lip or just in the mouth. In this case, the chemical enters the bloodstream through the mucous membrane of the oral cavity.

It should be noted that the two presented methods practically do not differ from each other. But in the sublingual region there are more blood vessels. In this regard, doctors often recommend placing the medicine there.

Sublingual - how is it? Now you know the answer to this question, and you can safely take all the drugs that are intended for resorption.

Enteral routes

Oral (per os- through the mouth; inside) - the safest, most way. For complete safety, certain rules must be observed:

Solid dosage forms are best swallowed standing up and washed down with liquid up to 100 ml;

Enteric-coated tablets should not be crushed or given with milk or antacids (they destroy the coating of the tablets)

For children and elderly patients who find it difficult to swallow tablets, it is better to give drugs in a liquid state;

Take drugs at a certain time, in accordance with the meal.

Absorption of drugs by the oral route of administration occurs mainly in small intestine; through the hepatic circulation enters the liver, and then into the blood (after 30-60 minutes). Many factors influence the absorption rate: this is the time of taking the medicine, the state of the digestive system, and the composition of the food. The oral route of administration is not used if the drugs are acid-resistant, are destroyed in the digestive canal, exhibit an ulcerogenic effect (cause a stomach ulcer), and also because of the patient's condition (diseases of the digestive system, fainting, vomiting, violation of the act of swallowing).

sublingual (sub lingua- under the tongue) - this is a method of administration in which a tablet, capsule or a few drops of a drug solution applied to a piece of sugar is kept under the tongue until completely absorbed, while saliva is retained in the mouth. The effect occurs quickly (after 1-3 minutes), since drugs are well absorbed from the oral cavity through the capillaries and enter the big circle circulation, gastric enzymes do not affect the drug. This is how emergency aids are prescribed (nitroglycerin for an attack of angina pectoris, clonidine and nifedipine for a hypertensive crisis, etc.). In addition, there are still ways to take drugs on the cheek (subbucally) or on the gums in the form of a film.

Subbucal(subbuccalis) is one way to take medicines by mouth. Medicines are used in the form of polymer films (trinitrolong), which are pressed against the gum or buccal mucosa with the tongue. Under the action of saliva, pharmacologically active substances are gradually released and create a therapeutic concentration of the drug in the systemic circulation for a certain time.

rectal (per rectum- through the rectum) by introducing medicinal substances in the form of suppositories and microclysters (50-100 ml). Absorption occurs quickly (after 5-7 minutes), drugs enter the systemic circulation, bypassing the liver.

The strength of the drug with this method of administration is higher than when using it through the mouth, so the doses of drugs are reduced. Through the rectum, drugs are administered to young children, in case of fainting of the patient, with vomiting, in the presence of pathology of the stomach, intestines. But with this route of administration of drugs, it is impossible to predict the intensity of absorption.

parenteral routes

Inhalation(through Airways) introduce gaseous substances, liquids and aerosols. With this route of administration, rapid absorption occurs, since the adsorbent surface of the lungs is 100 m2. This method is used both for local action (bronchodilators, antibiotics) and for resorptive action (means for inhalation anesthesia).

For inhalation administration, special delivery systems are used:

Dosing aerosol inhaler containing propylene gas;

Inhaler for the introduction of a dry powder substance that is activated during breathing (turbuhaler and spacer)

Nebulizer.

When using most aerosol inhalers in respiratory system no more than 20-30% of the total dose of the drug enters, and the other part of the drug is retained in the oral cavity and pharynx.

The use of powder inhalers promotes the absorption of up to 30-50% of the drug. In addition, their advantage lies in the absence of propylene gas, which has a negative impact on the environment.

Inhalers that are activated during breathing (turbuhaler) facilitate the flow of drugs into the respiratory tract, since their use does not require a coordinated breath and pressure on the inhaler canister.

spacers used together with metered-dose inhalers. They contribute to an increase in the distance between the latter and the patient's oral cavity, as a result of which the risk of a reflex cough is reduced.

Nebulizers- These are devices that function by passing a powerful jet of air or oxygen under pressure through a solution of the drug or due to ultrasonic vibration of the latter. The dose of the drug is delivered within 10-15 minutes.

transdermally drugs are prescribed that are well absorbed through intact skin (for example, nitroglycerin in the form of an ointment to prevent an attack of angina pectoris). Some drugs (antibiotics, corticosteroids) when used in the form of ointments to treat skin diseases can be partially absorbed and have a side effect on the entire body. This should be especially taken into account when prescribing them to children.

To achieve an early resorptive effect of drugs, injection routes of administration are used.

They are characterized by:

Dosing accuracy;

Fast action;

Compliance with sterility;

Big costs;

The threat of overdose (especially with the introduction of drugs with a small spectrum of therapeutic action)

Risk of damage sciatic nerve when the drug is injected into the gluteal muscle.

Sterile aqueous and oil solutions(in this case, after the injection, you should warm or massage the injection site so that there are no infiltrates). The onset of action of the drug with this route of administration occurs after 5-15 minutes. Some depot preparations are sutured under the skin. Do not administer hypertonic solutions, irritating medicinal substances and drugs in the form of suspensions. It should be noted that in the event of a sharp decrease blood pressure(in shock, collaptoid states), the introduction of drugs under the skin is ineffective, since the absorption process slows down sharply.

Drug Administration intramuscularly ensures their rapid entry into the systemic circulation (after 10-15 minutes). Sterile aqueous, oily solutions, suspensions are administered intramuscularly. The volume of one injection is 10 ml. You can not intramuscularly inject drugs that can cause necrosis or tissue irritation (calcium chloride, norepinephrine), hypertonic solutions.

Intravenously drugs are administered in urgent cases. In this way, the route of administration of the drug immediately enters the bloodstream, so the speed of administration is very important. The introduction of drugs intravenously can be bolus (jet), slow or infusion (drip). Only sterile aqueous solutions are administered. It is impossible to inject oily solutions and suspensions intravenously, so that embolism of the vessels of vital organs does not occur.

When preparing a drug for intravenous administration, the nurse should know:

Can the drug be dissolved in a certain solvent;

To what concentration should the drug be diluted;

The intensity of drug administration;

How stable is the preparation after mixing;

Let's combine drug with other drugs and solvents.

Before parenteral administration, warm the oily solution to body temperature (36-37 ° C).

To enteral (from the Greek. ento- inside and enteron- intestine) routes of administration include:

Sublingual (under the tongue);

Transbuccal (for the cheek);

Oral (by mouth, per os)\

Rectal (through the rectum, per rectum).

Sublingual and buccal administration. With sublingual and transbuccal routes of administration through the oral mucosa, lipophilic non-polar substances are well absorbed (absorption occurs by passive diffusion) and hydrophilic polar substances are relatively poorly absorbed.

Sublingual and buccal routes of administration have a number of positive features:

They are simple and convenient for the patient;

Substances administered sublingually or buccally are not affected by hydrochloric acid;

Substances enter the general circulation bypassing the liver, which prevents their premature destruction and excretion with bile, i.e., the so-called effect of the first passage through the liver is eliminated (see p. 32);

Due to the good blood supply to the oral mucosa, the absorption of LB occurs quite quickly, which ensures the rapid development of the effect. This allows the use of such routes of administration in emergency conditions.

However, due to the small suction surface of the oral mucosa, only highly active substances used in small doses, such as nitroglycerin, some steroid hormones, can be administered sublingually or buccally. So, to eliminate an attack of angina pectoris, tablets containing 0.5 mg of nitroglycerin are used sublingually - the effect occurs after 1-2 minutes.

Oral administration. When drugs are administered orally, the main mechanism of drug absorption is passive diffusion - thus non-polar substances are easily absorbed. The absorption of hydrophilic polar substances is limited due to the small size of the intercellular spaces in the epithelium of the gastrointestinal tract. Few hydrophilic LB (levodopa, pyrimidine derivative - fluorouracil) are absorbed in the intestine by active transport.

The absorption of weakly acidic compounds (acetylsalicylic acid, barbiturates, etc.) begins already in the stomach, in the acidic environment of which most of the substance is non-ionized. But basically the absorption of all drugs, including weak acids, occurs in the intestine. This is facilitated by a large suction surface of the intestinal mucosa (200 m 2) and its intensive blood supply. Weak bases are better absorbed in the intestine than weak acids, since in the alkaline environment of the intestine, weak bases are mainly in a non-ionized form, which facilitates their penetration through the membranes of epithelial cells.

The absorption of medicinal substances is also influenced by their ability to dissolve in water (to reach the site of absorption, the substances must dissolve in the contents of the intestine), the particle size of the substance and the dosage form in which it is prescribed. When using solid dosage forms (tablets, capsules) great importance has the rate at which they break down in the intestine. The rapid disintegration of tablets (or capsules) helps to achieve a higher concentration of the substance at the site of absorption. To slow down absorption and create a more constant concentration of drugs, dosage forms with a delayed (controlled) release of drugs are used. In this way, drugs of the so-called prolonged action can be obtained, which, unlike conventional drugs, last much longer

(calcium channel blocker nifedipine in conventional dosage forms is prescribed 3 times a day, and its prolonged forms 1-2 times a day).

Ingested medicinal substances are exposed to hydrochloric acid and digestive enzymes of the gastrointestinal tract. So, for example, benzylpenicillin is destroyed by hydrochloric acid of gastric juice, and insulin and other substances of the polypeptide structure are destroyed by proteolytic enzymes. To avoid destruction of some substances under the action of hydrochloric acid of gastric juice, they are prescribed in special dosage forms, namely in the form of tablets or capsules with an acid-resistant coating. Such dosage forms pass through the stomach without change and disintegrate only in the small intestine (intestinal dosage forms).

Absorption of LB in the gastrointestinal tract can be influenced by other factors. In particular, it depends on the motility of the gastrointestinal tract. Thus, the absorption of many drugs, especially weak bases (propranolol, codeine, etc.), which are predominantly in a non-ionized form in the alkaline environment of the intestine, occurs more intensively when gastric emptying is accelerated (for example, when using the gastrokinetic metoclopramide). The opposite effect is observed with the introduction of substances that delay gastric emptying, such as M-cholinoblockers (for example, atropine). At the same time, an increase in intestinal motility and, consequently, an acceleration of the movement of contents through the intestines can disrupt the absorption of slowly absorbed substances.

The quantity and qualitative composition of the intestinal contents also affect the absorption of drugs in the gastrointestinal tract. The constituent components of food can interfere with the absorption of drugs. Thus, calcium, which is contained in large quantities in dairy products, forms poorly absorbed complexes with tetracycline antibiotics. Tannin contained in tea forms insoluble tannates with iron preparations. Some drugs significantly affect the absorption of other drugs administered at the same time. So, wheel-tyramine (used in atherosclerosis to reduce the level of atherogenic lipoproteins) binds bile acids in the intestine and thus prevents the absorption of fat-soluble compounds, in particular vitamins K, A, E, D. In addition, it prevents the absorption of thyroxine, warfarin and some other LVs.

From small intestine substances are absorbed into the portal (portal) vein and with the blood flow first enter the liver and only then into the systemic circulation (Fig. 1.4). In the liver, most drugs are partially biotransformed (and inactivated at the same time) and/or excreted in the bile, so only a part of the absorbed substance enters the systemic circulation. This process is called the liver first pass effect or liver first pass elimination (elimination includes biotransformation and excretion).

Due to the fact that medicinal substances have a resorptive effect only after they have reached the systemic circulation (and then distributed over organs and tissues), the concept bioavailability.

Bioavailability- part of the administered dose of the medicinal substance, which has reached the systemic circulation unchanged. Bioavailability is usually expressed as a percentage. The bioavailability of a substance when administered intravenously is assumed to be 100%. When administered orally, bioavailability is generally less. In the reference literature, bioavailability values ​​​​of drugs for oral administration are usually given.

When administered orally, the bioavailability of drugs can be reduced by different reasons. Some substances are partially destroyed by hydrochloric acid and / or digestive enzymes of the gastrointestinal tract. Some drugs are not well absorbed in the intestine (for example, hydrophilic polar compounds) or are not completely released from tablet dosage forms, which may also be the reason for their low bioavailability. Known substances that are metabolized in the intestinal wall.

In addition, many substances, before entering the systemic circulation, undergo very intensive elimination during the first passage through the liver and, for this reason, have low bioavailability. Accordingly, doses of such drugs when administered orally usually exceed the doses required to achieve the same effect when administered parenterally or sublingually. So, nitroglycerin, which is almost completely absorbed from the intestine, but is eliminated by more than 90% during the first passage through the liver, is prescribed sublingually at a dose of 0.5 mg, and orally at a dose of 6.4 mg.

For comparative characteristics preparations, in particular, preparations produced by different pharmaceutical companies and containing the same substance in the same dose, use the concept "bioequivalence". Two drugs are considered bioequivalent if they have the same

bioavailability and absorption rate constant (characterizes the rate of drug entry into the systemic circulation from the injection site). At the same time, bioequivalent drugs should provide the same rate of reaching the maximum concentration of a substance in the blood.

The oral route of administration, as well as the sublingual route, has some advantages over parenteral routes of administration, namely, it is the simplest and most convenient for the patient, does not require the sterility of drugs and specially trained personnel. However, only those substances that are not destroyed in the gastrointestinal tract can be administered orally, in addition, the degree of absorption is influenced by the relative lipophilicity of the drug. The disadvantages of this route of administration include the dependence of the absorption of medicinal substances on the state of the mucous membrane and intestinal motility on the pH of the medium and the composition of the intestinal contents, in particular, on interaction with food components and other drugs. A significant disadvantage is that many drugs are partially are destroyed during the first passage through the liver.

In addition, the drugs themselves can affect the process of digestion and absorption of nutrients, including the absorption of vitamins. So, for example, osmotic laxatives impede the absorption of nutrients from the intestines, and antacids, by neutralizing the hydrochloric acid of gastric juice, disrupt the process of protein digestion.

The use of the oral route of administration is sometimes simply not available in some patients (if the patient refuses to take medication, in violation of the act of swallowing, persistent vomiting, in an unconscious state, in early childhood). In these cases, drugs can be administered through a small gastric tube through the nasal passages or through the mouth into the stomach and/or duodenum.

Rectal administration. The introduction of drugs into rectum(rectal) is used in cases where the oral route of administration is not possible (for example, with vomiting) or the medicinal substance has an unpleasant taste and smell and is destroyed in the stomach and upper intestines. Very often, the rectal route of administration is used in pediatric practice.

Rectally, medicinal substances are prescribed in the form of suppositories or in medicinal enemas with a volume of 50 ml. When administered in this way, substances that irritate the rectal mucosa are pre-mixed with mucus and heated to body temperature for better absorption.

Medicinal substances are rapidly absorbed from the rectum and enter the general circulation, bypassing the liver by 50%. The rectal route is not used for the introduction of high-molecular drugs of protein, fat and polysaccharide structure, since these substances are not absorbed from the large intestine. Some substances are administered rectally for local action on the rectal mucosa, for example, suppositories with benzocaine (anesthesin).

The enteral route of drug administration is the most common. It is used for both local therapy organs of the digestive tract, and for the systemic administration of drugs. All regularities considered below refer to the latter case.
On the one hand, enteral administration usually does not require the participation of medical personnel and is most comfortable for the patient. As a rule, with the enteral route of administration, the likelihood of occurrence side effects drug therapy least. On the other hand, when drugs are administered enterally, their pharmacokinetics (and, consequently, their therapeutic effect) are subject to the greatest changes. This is due both to the peculiarities of the functioning of the gastrointestinal tract (the rate of evacuation of chyme and absorption processes from it, the intensity of local blood flow, concomitant diseases, etc.), and the possibility of destruction a large number medicinal substances. In the gastrointestinal tract, drugs can be destroyed or inactivated under the influence of:

• parietal enzymes and enzymes of gastrointestinal juices;
• liver enzymes (see Chapter 3);
• bile acids and pigments;
• mucus;
• normal microflora and products of its vital activity;
• chyme components.

degree of bioavailability and, accordingly, the rapid development therapeutic effects.
EXAMPLE. With sublingual administration of nitrates, their maximum concentration in the blood is reached within 1–2 min40. With sublingual administration of propranolol, its bioavailability is 3 times higher than with oral41. Sublingually administered nifedipine, clonidine to relieve hypertensive crisis, glycine - to normalize cerebral blood flow. Majority homeopathic medicines applied sublingually or subbucally.
The main drugs for sublingual and subbucal use are listed in Table. 1.11. As follows from the table, these drugs belong to different pharmacological groups and have different spectrums of therapeutic action.
With sublingual or subbucal administration of drugs, it is important to dissolve the corresponding dosage form evenly and completely, otherwise the flow of the drug into the blood decreases and the effectiveness of therapy decreases.

• So -

1. With sublingual and subbucal administration, drugs are not affected by gastric juice and first pass metabolism (see Chapter 3), they quickly enter the systemic circulation, bypassing the liver.
2. Sublingual and subbucal routes of administration are used for a limited number of drugs. The small suction surface of the oral mucosa makes it possible to prescribe only highly active drugs that are effective at low concentrations. In addition, this route of administration is unsuitable for the administration of irritants and substances with an unpleasant taste.

• Topical preparations are also used rectally, but their consideration is beyond the scope of this book.

• So -

1. Rectal administration ensures the rapid entry of medicinal substances into the systemic circulation and the development of a therapeutic effect.
2. With rectal administration, there is a large individual variability in pharmacokinetic parameters.

The advantages and disadvantages of oral administration of drugs are given in table. 1.14.
Table 1.14. Advantages and disadvantages of oral medications

Let's consider some of the factors that affect the bioavailability of drugs when administered orally, in more detail.
Gastric juice contains pepsin, which leads to the degradation of proteins, peptides and some other drugs, such as penicillins. It also contains hydrochloric acid, which lowers the pH in the stomach lumen.
On an empty stomach, the production of hydrochloric acid is insignificant, the pH of the stomach is slightly acidic. Eating leads to stimulation of the production of hydrochloric acid, and if a person eats regularly, then increased production of hydrochloric acid is observed some time (10-20 minutes) before a meal. Food components (especially milk, meat, eggs) gradually neutralize hydrochloric acid, however, with the gradual evacuation of chyme from the lumen of the stomach into the duodenum, the acidity of gastric juice increases, reaching a maximum value approximately 2 hours after eating. Only 3-4 hours after a meal, the pH of the stomach reaches the fasting value (Fig. 1.15)45. Therefore, food affects the bioavailability of drugs in various ways (Table 1.15).

food

Rice. 1.15. Scheme of changes in the pH of gastric juice depending on food intake -F-

Table 1.16. Ionization constants of some preparations 46

Rice. 1.16. Change in the number of ionized molecules for weak acids (a) and bases (b) pK: 1 - 2, 2 - 5, 3 - 9, 4 - 12
Therefore, unless otherwise specified, drugs are taken on an empty stomach. This technique minimizes the interaction of drugs and food components. Fasting is considered the use of drugs at least 30 minutes before meals (with regular meals) or 4 hours after a meal.
Stimulants of gastric secretion are prescribed 10-15 minutes before meals.
Acid-resistant drugs and digestive enzymes are taken with meals.
After eating, take medicinal substances that irritate the gastric mucosa.
It should be noted that the liquid used to drink them down can affect the bioavailability of drugs (Table 1.17).

Rice. 1.17. The effect of pH on drug absorption

• The distribution of drugs between the chyme and the intestinal lumen. Reception fatty foods increases the entry of lipophilic substances into the chyme.
• Interaction of drugs with small intestine juice, pancreatic juice and bile. These gastro-intestinal juices have an alkaline pH value, ie. may affect the bioavailability of drugs (see Fig. 1.14) or interact chemically with them.
• Intercellular transport flowing through the pores between endothelial cells. So along the gradient

concentration without energy expenditure, water and inorganic ions predominantly enter.
Intracellular transport55.


Intracellular Conjugated
Intercellular

Exocytosis

Endocytosis

Passive

Active

Rice. 1.18. Scheme of transport of drugs in the small intestine

It is important to note that, unlike passive transport, active transport is saturable; with an increase in the concentration of drugs in the intestinal lumen, its absorption can be increased only to certain values, and a further increase in the flow of drugs into the intestinal lumen does not lead to an increase in absorption processes (Fig. 1.19).
After drug absorption in the intestine epithelial cells metabolism may occur.
yaa
St.
from
gs
her
shsh
ve
§ about
8 ° he ve
With
R
a
to
e
l
The amount of drug received
Rice. 1.19. The dependence of the amount of absorbed medicinal substance on the incoming -O-

The main parameters that determine the amount of absorbed substance in the small intestine are its solubility in water and permeability through the wall of the small intestine (Fig. 1.20). Mathematical models have been developed to predict the amount of absorbed LV57. General form The relationship between the effective permeability and the proportion of the absorbed substance is shown in Fig. 1.21 (in this case, the solubility of the substance was assumed to be unlimited). From the above data, it can be concluded that if the effective permeability is less than 2, the absorption of drugs in the small intestine will be incomplete, and if this indicator is more than 2, complete absorption can be expected58.
Molecular weight, g/mol

Logarithm of the partition coefficient in the octanol/input system
Rice. 1.20. Permeability of the epithelial barrier by diffusion as a function of molecular weight and lipophilicity of drugs 56


With
e
more
e

Effective

Rice. 1.21. Relationship between drug absorption in the small intestine and its effective permeability59

Substances with low solubility are of particular interest, since for them the maximum absorption value is equal to the product of solubility and permeability60. Despite the fact that the process of receipt of any drug can be described by the scheme:
solid medicinal
dissolution w
medicinal > substance
into the body form in solution
for slowly soluble substances, the dissolution process is limiting (Fig. 1.22).

For poorly soluble drugs, the dissolution rate limits the intake of the drug into the body, an increase in the dose of the drug can lead to a decrease in its bioavailability. On fig. 1.23 shows the dependences of the blood concentration of a poorly soluble substance (griseofulvin) for two doses - 250 and 500 mg. When administered orally, 250 mg of the drug dissolves more than when taking 500 mg. Therefore, a lower dose of the drug corresponds to a greater systemic bioavailability.
Preliminary dissolution or chewing speeds up the dissolution process, which usually contributes to faster absorption of the drug. However, this increases the likelihood of drug interaction with food components, increases the area of ​​drug interaction with gastrointestinal juices. Therefore, some drugs are recommended to be chewed or dissolved before use, while others, in particular, capsules and enteric-coated tablets, which protect active substance from exposure to hydrochloric acid in the stomach, it is impossible to chew. -Q-

Rice. 1.23. The dependence of the concentration of griseofulvin