Students
The Department of Clinical Pharmacology is located in the clinic TashPMI and in the building of the student polyclinic on the 2 nd floor.
Assessment of students' knowledge is carried out by the rating system. Interim control is carried out by testing, and final examinations are conducted by oral interrogation and protection of the protocol on pharmacotherapy.
2018-2019
Lecture number 1
Topic: Clinical pharmacology. History. Subject. Goals, tasks. Problems of CF Pharmacodynamics of drugs
Foreword
Clinical pharmacology is an integrative science designed to connect basic pharmacology with clinical pharmacotherapy. Its appearance and development is due to the rapid growth of production and the introduction of new medicines into practice and an ever-increasing flow of information about the results of their use in the clinic. The use of drugs is the most universal method of treatment. Over the past decade, pharmacotherapy has achieved such successes that surpass its achievements in all previous centuries. However, this progress has given rise to problems associated with drug abuse. Therefore, the doctor must strictly observe the principles of deontology in the field of pharmacotherapy. In the end result, each drug, each combination of drugs, each method of drug therapy should be evaluated on three sides: harmlessness, effectiveness and advantage over other means. In connection with this, one of the most important tasks of the doctor is his temporary detection of the type and frequency of adverse effects of pharmacotherapy. The study of the effectiveness and safety of drugs is the basis their rational use. This requires the physician to take an individual approach to the patient, which is based on the fact that the risk of pharmacotherapy wives to be justified from a scientific, moral and legal point of view view. This is designed to teach the doctor clinical pharmacology.
In recent years, a number of capital guides have appeared on this discipline (Kukes VG, Kliniche Pharmaceutical Sciences, 1991; Lawrence DR, Benite PN, "Clinical Pharmacology", 1993; Belousov Yu.B "Moiseev VS, Lepakhnn VK, Clinical Pharmacology and Pharmacotherapy ", 1997 ; Gaevy MD, Galenko-Yaroshevsky PA, Petrov VI, "Pharmacotherapy with the basics of clinical pharmacology", 1996; Brukhausen F., Veldchenker X., Grobeker X., "Pharmacotherapy., Clinical pharmacology; Practice A manual for students and doctors, 1996; Kattsung B.G. "Basic and Clinical Pharmacology", 1998; and etc.). These guidelines serve as the basis for the study of clinical pharmacology and pharmacotherapy pi, but the opportunities for this in our country are limited for a number of reasons, including the complexity of mastering the material and financial problems.
The subject and tasks of clinical pharmacology (CF) and pharmacotherapy (FT)
KF is based on the achievements of experimental pharmacology and serves as the basis of FT. She studies the effect of drugs on the body of a sick person. The main goal of CF and FT is to achieve maxi a small therapeutic effect from the use of drugs with a minimum risk for the patient. This is done when the following conditions are true:
1) rational choice of medicines for a particular large ;
2) determination of the dosage form, optimal dosages, routes of administration and mode of application of the drugs;
3) monitoring of the effect of drugs and making adjustments to the FT conducted, depending on its effectiveness;
4) prevention and elimination of PE and negative consequences of FT.
CF should not be identified with FT, since their main tasks are different. KF conducts testing of new drugs, clinical testing and reassessment of old drugs, development of methods for effective and safe use of medicines, information and counseling, training dents and doctors. It solves the strategic problems of drug therapy, whereas FT is designed Cena for the solution of specific medical problems. Consequently, according to B.E. Votchala, the doctor must learn to think pharmacologically at the patient's bedside. Therefore, before starting the FT, he must answer the following questions:
1) What specific results does he want to obtain?
2) Which drugs can achieve the desired effect?
H) What drugs are most indicated for this patient?
4) How should they be assigned to get the best effect?
5) Which PE can cause the assigned prepa and how to warn them
or reduce?
Decision these issues depends on the knowledge of basic and clinical pharmacology and the ability to practice use this knowledge.
KF is divided into general and private. General KF studies the most common problems of FC and PD, private FC and PD of individual drug groups, their main and side effects, as well as the application at the end pathological pathology.
CF is a science that deals with the study of drugs as applied to humans (WHO definition). Its goal is the optimization of drug therapy, i.e. achieving maximum efficiency and safety .
KF consists of two main parts; pharmacology and therapeutic evaluation (determining the clinical value of drugs and the method of its optimal use).
• Pharmacology:
- FD - study of isolated and combined (with other drugs) the effects of drugs on the body of a young, elderly, healthy and sick person;
- FK - study of absorption, distribution, metabolism and excretion of drugs (ie, the effect of a healthy or sick person organism on drugs).
• Therapeutic evaluation of drugs:
- formal (formal) controlled therapeutic studies;
- monitoring of effectiveness and undesirable effects medicines.
Tasks of the KF
· Organization and conduct of clinical trials of new and old drugs.
· Development of methods for effective and safe FT.
· Organization of information and advisory work in les chebno care facilities, pharmacies and the public;
· Training of students, doctors and pharmacists.
The urgency of studying clinical pharmacology for the practical activities of a nurse .
The need to know the basics of CF by medical personnel is due to a steady increase in the number of new drugs, produced by the world pharmaceutical industry. It is known that at the present time the total number of preparations in different countries of the world exceeds more than 20 thousand titles. It is important to recognize that choosing a drug and its safe and effective The application depends on the information that can be obtained Only with a systematic study of the drug in clinical Unfortunately, at present, it is often unreasonable and uncontrolled to prescribe medicines, which leads to the development of unwanted side effects and complications that reduce effectiveness of treatment. That is why every medical The employee must have sufficient knowledge of the CF. Basic questions of general pharmacology
Practical aspects of pharmacokinetics
FK studies the processes of movement and transformation of LP in the body: the route of administration, absorption, races biotransformation and expression.
Ways of drug administration.
From They depend on the speed of the offensive and the maximum effect, its duration and intensity. Therefore, it is necessary to take into account the features and principles of the choice of ways of introducing drugs. They are divided into enteral (through the food channel) and parenteral (bypassing the food channel).
The simplest, most convenient and common way of introducing - through the mouth (enteral). However, the presence and nature of the pathological process in the digestive organs, the secretion of digestive glands, the solubility of LP in lipids, the ability to dissociate, possible the multiple release of substances into the intestinal lumen and re-absorption (cyclic processes), the state of the microbial flora of the intestine, interaction with various food and drug and so on. This is a serious disadvantage of the enteral route of administration, since all of these factors affect the absorption and bioavailability of the drug.
Bioavailability s - ratio-the number of LB, dissolved in the blood through defined The time taken after taking it, inside, expressed as a percentage. For example, if biodegradable the level of the drug is 50%, hence 50% of the dose was not received in the blood. When I / v vve bioavailability is 100%. In other ways of administration, it never reaches 100%, because LV must pass through the biological membranes of cells (the mucosa of the gastrointestinal tract, liver, muscles, etc.) and only a part of it gets into the systemic bloodstream. The effect of the drug depends on how large this part is. The bioavailability of LV is affected not only by the route of administration, but also by the individual characteristics of the patient, the condition Gastrointestinal tract, liver, cardiovascular system, kidneys, as well as pharmaceutical factors (dosage form, its composition, features of the drug production technology).
Enteral pathways also include administration through mucous of the mouth (eg, under the tongue), through the rectum. With these routes of administration, LVs immediately enter the total blood flow without primary passer through the liver.
Parenteral routes of administration include injection, inhalation and administration through the skin. With the help of injections, drugs are injected under the skin, into the muscles, into the veins, the arteries, into the cavity. When This effect occurs quickly, especially with intravenous administration, the accuracy of the dosage is ensured. Under the skin and in the muscles should not be administered drugs that have a strong irritant effect, and in the vessels-insoluble compounds and oily solutions because of the danger of embolism. The disadvantage of injections is tissue trauma, the need to observe sterility and the danger of unpredictable reactions (shock, collapse, convulsions).
With the help of inhalations, gaseous, vaporous substances and aerosols are introduced. In this case, LV enters the blood in an unchanged form, the effect occurs quickly. Disadvantage are the reactions times fights, accompanied by spasms of the larynx, bronchi, cough, reflex effects on the heart etc.
Fat-soluble substances (in the form of ointments and liniments) and electrolytes (by electrophoresis) are introduced through the skin ,
Absorption of LP. In the digestive tract, it depends on many factors. Ionized forms of LP poorly soluble in lipids and poorly absorbed. Therefore, the absorption of electrolytes the solubility in the lipids of the non-ionized form of the substance. Low acid compounds (e.g., salicylates) in acidic medium of the stomach (pH 1.0-1.5) are ionized poorly, therefore sucked advantageously in the stomach. Weak bases (eg, alkaloids ) are better absorbed in the intestine ( pH in the duodenum about 6.6), as poorly ionized in an alkaline environment. It is also necessary to consider Vat that the most acidic medium of the stomach happens during and immediately after a meal, and the least acidic - 1 hour before meals and after 1.5-2 hours after her. Therefore, acid connections should appoint during or immediately after a meal, and grounds for 1 hour before meals or 1.5-2 hours after eating.
A great influence on the absorption of drugs is provided by volume and nature of food that can change the pH of the environment. A significant role is also played by helatoobra mations (helaty- vnutrikompleks nye compound central element which is a metal atom). Chelation compounds are poorly tolerated are found in the intestines. They are formed by the interaction of PV with dairy products containing calcium caseinate, vegetables containing iron, and the like. Fats increase the absorption of fat soluble (vitamins AD K, E, antihelminthic drugs, etc.).
Since the absorption of most drugs occurs in the intestine, No the rate of gastric emptying , which depends on the gastric motility and the nature of the food.Suction It can be difficult to treat inflammation of the stomach and intestines, at simultaneous reception of several drugs. For example, the bases promote the ionization of acidic compounds and hinder their absorption, and vice versa. Substances that slow the peristalsis of the intestine (antispasmodics, holinoblokatory, etc.), contribute to absorption, and substances that accelerate peristalsis ticks (holinomimetiki, laxatives), worsen the absorption.
When appointing a medicine inside, it matters dosage form . The general rule is that "liquid forms are absorbed better than powders, the absorption of which depends on the degree of day-to-day transfer of particles, and the powders are absorbed better than tablets, pellets and granules. the dosage of drugs for internal administration depends on many factors, varies widely and is difficult to predict.
When you introduce drugs through the rectum, you should consider that they fall immediately into the general bloodstream, bypassing the liver. Lipophilic compounds (barbiturates, benzodiazepines, etc.) are absorbed well and quickly in the rectum, therefore, thiopental and sibazone can be administered rectally for rapid anesthesia and arrest of seizures if IV they can not be entered.
When parenteral administration of LV comes directly into the blood, or absorbed from the subcutaneous tissue, muscles and cavities (depending on the type of injection), from the alveoli (with inhal bypassing the liver. A doctor can more accurately provide for the concentration of LP in the blood and the effective dose.When LV is administered under the skin and in the muscles, it is necessary to take into account the state of the blood circulation, since with a slowing of the blood flow, the rate of absorption can significantly slow down.
When choosing the route of drug administration, it is necessary to consider the following main factors:
a) dosage form
b) resistance of the preparation in the digestive juices
c) the ability to be absorbed through the mucosa of the food canal and bioavailability
d) the purpose of therapy (for emergency assistance, preference is given to
parenteral route of administration, especially intravenous).
During the movement of PV in the body, they penetrate through biological membranes that have a lipoprotein structure, micropores and enzymes. Penetration through membranes is carried out through passive diffusion, filtration, active transport and pinocytosis.