Ministry of healthcare of the republic of uzbekistan

MINISTRY OF HEALTHCARE OF THE REPUBLIC OF UZBEKISTAN

TASHKENT MEDICAL ACADEMY

"CONFIRM"

The pro-rector on study

Prof........................ Teshaev O.R.

«__» _________________ 2012

Department: PHARMACOLOGY

Subject: PHARMACOLOGY

Technology of training on practical employment

On a theme:

CARDIAC GLYCOSIDES

(educational-methodical course book

for teachers and students of medical Universities)

Tashkent – 2012

Composers: the senior lecturer of department of pharmacology ТМА Makhsumov Sh. M.

the senior lecturer of department of pharmacology ТМА Zaytseva O. A.

Methodical working out is confirmed:

- At faculty meeting the report № from 20

Theme: CARDIAC GLYCOSIDES
1. Location and equipment of the lessons

• 
  department of pharmacology;
  
• 
  drugs, annotations to the drugs, slides, tables;
  
• 
  slide projector
  

2. The duration of the study of themes

Hours – 2

3. Purposes

- To form a general idea of ​​cardiac glycosides to their destination;

- To obtain knowledge about the sources of cardiac glycosides;

- To give an idea about the basic effects of cardiac glycosides;

- Give an idea of ​​the mechanisms of action of cardiac glycosides;

- To give knowledge of side effects of cardiac glycosides;

- Build knowledge of indications and contraindications to the use of cardiac glycosides;

- Ability to analyze the effect of shape, the appointment of the individual funds based on the total pharmacodynamic data of cardiac glycosides;

- To give an idea about the main and side effects, mechanisms of action of of non- glycoside cardiotonics;

- To give knowledge of the elements of pharmacotherapy with examples from the private formula.

Tasks

Student should know:

- Classification of cardiac glycosides;

- Influence of cardiac glycosides on cardiac function;

- The basic mechanisms of action of cardiac glycosides;

- Indications for the use of cardiac glycosides;

- Side effects and complications of cardiac glycosides;

- Main and side effects, mechanisms of action of of non- glycoside cardiotonics.
Student should be able to:

Perform practical skills - perform tasks for the recipe (prescription to: digitoxinum (tab, supp), strophanthinum K (amp)).

4. Motivation

Cardiotonic widely used in many fields of clinical medicine (cardiology, internal medicine, etc.), so knowledge of the main and side effects of cardiac as well as the characteristics of their destination, the ability to competently prescribe cardiac glycosides as necessary for students to further study of the private pharmacy, and general practitioners.

5. Intersubject and intrasubject connections

Teaching this topic is based on the knowledge bases of students of biochemistry, anatomy, histology, normal and pathological physiology of the cardiovascular system. Acquired during the course knowledge will be used during the passage of therapy, cardiology and other clinical disciplines, as well as for further study by a private pharmacy.

6. The content of lessons

6.1. Theoretical part

CARDIAC GLYCOSIDES
The agents that stimulate cardiac activity are often subdivided into cardiac glycosides and agents of «non-glycoside» structure.

Cardiac glycosides are agents of plant origin that are able to produce marked cardiotonic effect. They increase the myocardial activity providing both saving and effective work of the heart. Cardiac glycosides are used for the treatment of heart failure associated with coronary heart disease, myocardial disorders of different aetiology or cardiac arrhythmias.

Cardiac glycosides include non-saccharine part (aglycone or genin) and sugars (glycone).
Cardiotonic effect is the property of aglycone. The saccharine part determines the solubility of glycosides and their fixation in the tissues. Glycone can also affect the activity and toxicity of the compound.

The mechanism of cardiotonic action of cardiac glycosides is connected with their inhibitory effect on Na+, K+-ATPase in the cardiomyocyte membrane). This leads to a Na+ and K+ flow disturbance. As a result of this the K+ content inside the cardiomyocytes decreases, while the Na+ content increases. Meanwhile the difference between intra- and extracellular Na+ concentration decreases, and this limits trans­membrane Na+/Ca2+-exchange. The latter effect makes Ca2+ outflow less intensive thus helping to increase its content in the sarcoplasm and leading to its accumulation in the sarcoplasmic reticulum. In turn, this stimulates additional amounts of Ca2+ entering the cardiomyocytes from outside via the calcium L-channels. Action potential causes increased Ca2+ release also from the sarcoplasmic reticulum. During this process free

Ca2+ content in the sarcoplasm increases causing a cardiotonic effect. Ca2+ interact with the troponine complex and eliminate its suppressive effect on the proteins of the contractile myocardium. Actin interacts with myosin and this interaction manifests in rapid and intensive myocardial contraction.
OTHER CARDIOTONIC AGENTS

The stimulating influence on the heart is also characteristic of adrenomimetics, do­pamine, methylxanthines and glucagon. However, they can produce many unfavorable effects on the cardiovascular system (tachycardia, arrhythmia, other), which limit the administration of these agents as cardiotonics. There are also some new agents with different mechanisms of action (for example, agents that sensitize cardiomyocytes to the action of calcium ions). According to the mechanism of action, the first group of non- glycoside cardiotonics may be presented in the following way.

DRUGS INCREASING CAMP AND CA2+ CONTENT IN CARDIOMYOCYTES

- Drugs stimulating β1-adrenoceptors:

Dopamine

Dobutamine

- Phosphodiesterase inhibitors:

Amrinone

Milrinone
Used in this lesson, the new educational technology "brainstorming".

USE OF THE "BRAIN STORM"

To work on this technique to establish trust and overcome the psychological stress as an obstacle to open discussion. The method combines the ability to extend the stereotype of thinking to abstract from existing constraints and develop a dynamic mental activity, to intensify its training activities. The method taught to argue and defend their own point of view, to find the optimal solution, to build communication and persuading others to faithfulness advocated position.

The method includes:

- Greeting soaring thoughts, given that the unusual idea, the better;

- Receiving the largest number of proposals;

- A combination of ideas and their development;

- No comments and criticisms that interfere with the formation of ideas;

- Brief statement without arguments deployed;

- The division of those who generate ideas and those who work it.

Students are encouraged to discuss the problem of the influence of cardiac glycosides on cardiac function. Everyone expresses their proposals, which are written on the blackboard. Then in turn open position the template and compared with the responses of students. After being assessed the correctness of the assignment and tabulation.

Pattern of answers. The basic properties of cardiac glycosides:

- Selective effect on the heart;

- Strengthening of systole (positive inotropic effect);

- Slowing of heart rate (negative chronotropic effect);

- Reducing the rate of conduction (negative dromotropic effect);

- Increase the excitability of the myocardium (positive force bathmotropic).
6.2.Analitical part

Situational problem:

1. Patients with heart failure, accompanied by cirrhosis of the liver was performed in the hospital course of digitalization. Within 3 days he received the usual dose for such a course of digitoxinum, and therefore the stagnation became less pronounced. However, on day 4 he developed nausea, vomiting, bradycardia, against which developed arrythmia.

What is the cause of these complications?

What are the activities aimed at their elimination?

Response. The reason is the complications of digitoxinum intoxication as a result of slowing its inactivation due to liver cirrhosis. To deal with complications should appoint agents potassium, sodium citrate, disodium salt of ethylene diamintetrauksus acid or unitiol. The following methods of digitoxin dose should be reduced.

2. Patients with chronic heart failure and severe edema were treated with digitalis drugs. To speed up the elimination of edema was appointed diсhlotiazidum (saluretic), after which the patient showed signs of intoxication with cardiac glycosides.

The cause of intoxication and measures to prevent it?

Response. The reason for signs of cardiac glycoside intoxication after the appointment is to call the last diсhlotiazidum hypokaliemia, to prevent which should be administered with drugs diсhlotiazidum potassium.
3. In a patient with a history of chronic heart failure in the compensation stage, during an operation on an outpatient basis has developed shortness of breath, cyanosis of face and appeared a rapid pulse.

Which drugs should choose a doctor for relief of these symptoms on an outpatient basis?

What should be the follow-up drug therapy?

Response. For relief of acute heart failure, which developed in the outpatient physician should use the fast action of cardiac glycosides (strophanthinum, convallatoxinum, corgluconum). In the subsequent need to assign long-acting cardiac glycosides (digitalis preparations).

4. The patient on the background of an acute attack of myocardial infarction, ventricular fibrillation occurred, which must urgently cut short to save the life of the patient.

Which antiarrhythmic agent must be applied in this case and why?

Follow doctor's tactics.

Response. In this case, you need to apply lidocainum, because of its intravenous administration provides the maximum therapeutic effect after 1-2 minutes. However, the effect of lidocainum short (10-20 minutes), so to prevent a recurrence of arrhythmia should also appoint a long-acting antiarrhythmic agent, in this case, the appropriate use of anaprilinum.

5. An overdose of cardiac glycosides as a result of the accelerated digitalization provoked supraventricular arrhythmia.

Which drug is expedient to assign to a given situation to correct the arrhythmia and why?

Response. In this case it is advisable to appoint phenytoin, since the existence of the mechanism of its antiarrhythmic action of the central component will provide the greatest antiadrenergic therapeutic effect in this situation compared with other antiarrhythmic agents.
6.3. Practical part
To write prescriptions for: digitoxinum (tab, supp), strophanthin K (amp).
1. Prescribing FOR SOLID DOSAGE FORMS

Purpose: Prescribing FOR SOLID DOSAGE FORMS

Steps:

№	Action	Has not executed	Completely correctly executed
1.	The indicating to the pharmacist (Recipe)	0	10
2.	Transfer of the basic and auxiliary medical products which are a part of the written out medicine, with the dose indicating	0	30
3.	The indicating to the pharmacist about preparation of the medicinal form (M.f)	0	20
4.	The indicating to the pharmacist about amount of a given out drug	0	10
5.	The indicating to the patient about a way of drug intake, the indication to application	0	30
	In total	0	100

2. Prescribing FOR SOLUTION INJECTION

Purpose: Prescribing FOR SOLUTION INJECTION

Steps:

№	Action	Has not executed	Completely correctly executed
1.	The indicating to the pharmacist (Recipe)	0	10
2.	Transfer of the basic and auxiliary medical products which are a part of the written out medicine, with the dose indicating	0	30
3.	The indicating to the pharmacist about preparation of the medicinal form (M.f)	0	20
4.	The indicating to the pharmacist about amount of a given out drug	0	10
5.	The indicating to the patient about a way of drug intake, the indication to application	0	30
	In total	0	100

3. Prescribing FOR SOFT MEDICINAL FORMS

PURPOSE: PRESCRIBING FOR SOFT MEDICINAL FORMS

Steps:

№	Action	Has not executed	Completely correctly executed
1.	The indicating to the pharmacist (Recipe)	0	10
2.	Transfer of the basic and auxiliary medical products which are a part of the written out medicine, with the dose indicating	0	30
3.	The indicating to the pharmacist about preparation of the medicinal form (M.f)	0	20
4.	The indicating to the pharmacist about amount of a given out drug	0	10
5.	The indicating to the patient about a way of drug intake, the indication to application	0	30
	In total	0	100

7. Forms of control knowledge, skills and abilities

- oral;

- writing;

- experience the practical skills.
8. Criteria for evaluating the current control

№	Progress %	Ball	The level of student knowledge
1	96-100%	Excellent “5”	Complete the correct answer to the questions on classification, pharmacokinetics, pharmacodynamics, indications and contraindications to drugs, their side effects. Sums up the results and make decisions, think creatively, independently analyzed. Situational problem resolves correctly, with a creative approach, with full justification for the answer. Actively and creatively participate in interactive games, right to make informed decisions and summarize, analyze. Recipes are written in accordance with the dosage form and with the correct indication of the dose and indication for use. The correct spelling of all drugs of this pharmacological group with faithful indication of the form of release.
2	91-95%	Excellent “5”	Complete the correct answer to the questions on classification, pharmacokinetics, pharmacodynamics, indications and contraindications to drugs, their side effects. Creative thinking, self-analyzing. Situational problem resolves correctly, with a creative approach, the rationale for the answer. Actively and creatively participate in interactive games, correct decision maker. Recipes are written in accordance with the dosage form is a grammatical error. The correct spelling of all drugs of this pharmacological group with faithful indication of the form of release.
3	86- 90%	Excellent “5”	The questions on classification, pharmacokinetics, pharmacodynamics, indications and contraindications to drugs, their side effects are covered in full, but there are 2.1 errors in the response. Independently analyzed. Inaccuracies in the solution of case problems, but with the right approach. Actively involved in interactive games, make the right decisions. Recipes are written in accordance with the dosage form, with the proper indication of indication for use, but there are 3.2 grammatical errors. The correct spelling of all drugs of this pharmacological group, but there is a discrepancy in the forms of release.
4	81-85%	Good “4”	The questions on classification, pharmacokinetics, pharmacodynamics, indications and contraindications to drugs, their side effects are covered in full, but is 2-3 inaccuracies, errors. Into practice, understand the essence of the issue, says confidently, has fine performances. Situational problems solved correctly, but not adequately support the answer. Actively participating in interactive games, correctly makes the decisions. Recipes are written in accordance with the dosage form, with the proper indication of indication for use, but there are 3.2 grammatical mistakes, errors in dose. The correct spelling of all drugs of this pharmacological group, but is 2-3 errors in registration forms.
5	76-80%	Good “4”	Correct, but incomplete coverage of the issue. The student knows the classification, the indications for the use of drugs, their side effects, the basic properties, but do not fully understand the mechanism of action and the development of side effects. Understands the issue, says confidently, has fine views. Actively involved in interactive games. On case studies give incomplete solutions. Recipes are written in accordance with the dosage form, with the proper indication of the dose, but not all are testimony to the application. The correct spelling of all drugs of this pharmacological group, but there are 4.3 errors in the title and registration forms.
6	71-75%	Good “4”	Correct, but incomplete coverage of the issue. The student knows the classification, but not complete lists indications for the use of drugs, their side effects, the basic properties that do not fully understand the mechanism of action and the development of side effects. Understands the issue, says confidently, has fine views. On case studies give incomplete solutions. Recipes are written in accordance with the dosage form, with the proper indication of the dose, but not all are indications for use, is 2-3 grammatical errors. The correct spelling of all drugs of this pharmacological group, but there are 4.3 errors in the forms of release.
7	66-70%	Satisfactorily “3”	The correct answer to half of the questions posed. The student knows the classification is not complete lists the indications for the use of drugs, basic properties, but poorly versed in the mechanism of action, entangled in side effects. Understands the issue, says confidently, has fine performances only on selected topics. Situational problems solved correctly, but there is no justification response. Recipes are written with the correct indication of the dose, but not completely given testimony to the application and there is an error in specifying the form of release. Proper transfer of drugs of this pharmacological group, but there are grammatical errors in writing the names of drugs and mistakes in the registration forms.
8	61-65%	Satisfactorily “3”	The correct answer to half of the questions posed. Errors in classification errors in the testimony to the use of drugs, the properties are poorly versed in the mechanism of action, entangled in side effects. Says uncertainly, has fine performances only on selected topics. Mistakes in solving situational. Recipes are written in accordance with the dosage form, but without the indications for use and there are errors in the indication of the dose. The correct spelling of the drugs pharmacological symmetric group, but there are errors in the registration forms.
9	55-60%	Satisfactorily “3”	Reply with errors on half the issues raised. Student makes mistakes in classification, the indications for use, the properties are poorly versed in the mechanism of action, entangled in side effects. Says uncertainly, has a partial view on the subject. Situational problems solved incorrectly. Recipes are written with grammatical mistakes, without instructions for use and there are errors in the indication of the dose. Correct spelling of only half of the preparations of this pharmacological group, there are errors in the forms of release.
10	50-54%	Not satisfactorily “2”	The correct answer is 1 / 3 of the questions. The student does not know the classification, the indications for use, poorly versed in the mechanism of action, entangled in side effects. Situational problems solved incorrectly by the wrong approach. Recipes are written incorrectly, without instructions for use and there are errors in the indication of the dose. Correct spelling of less than half of drugs, there are errors in the forms of release.
11	46-49%	Not satisfactorily “2”	The correct answer is 1 / 4 of the questions posed. The student does not know the classification, the indications for use, poorly versed in the mechanism of action, entangled in side effects. Situational problems solved incorrectly by the wrong approach. Recipes are written incorrectly, without instructions for use and there are errors in the indication of the dose, grammatical errors. Correct spelling of less than half of drugs, there are errors in the registration forms and grammatical errors.
12	41-45%	Not satisfactorily “2”	Coverage of 1 / 5 of the questions correctly. The student does not know the classification does not fully transfer the products of this pharmacological group. Gives incomplete and partially incorrect answers to questions on the pharmacokinetics and pharmacodynamics of drugs. Half of the prescriptions written incorrectly, mistakes in dose formulations, and indications for use. Writing less than half the drugs without a release form.
13	36-40%	Not satisfactorily “2”	Lighting 1 / 10 of the questions in the wrong approach. Do not know the classification, the indications for use, confuses the basic properties of drugs. Practically does not understand the mechanism of action and side effects of drugs. All recipes are written incorrectly with blunders. The list of drugs of this pharmacological group is not given.
14	31-35%	Not satisfactorily “2”	Questions not answers. Do not know the mechanisms of action, adverse effects, the basic properties of drugs. . Can not write prescriptions for this section of pharmacology, since there is no logical link between the dosage form and by the introduction, does not know the indications for use.

9. Chronological map of lessons
№	Stages of training	Form of training	Duration (total 90)
1	Introduction to the session instructor (support themes)		5
2	Discussion topics practical training, assessment of baseline knowledge of students with new educational technologies (small groups, case studies, business games, slides, videos, etc.)	The survey, an explanation	25
3	Summing up the discussion		5
4	Providing students with visual aids (drugs, computer programs, diagrams, etc.) and giving explanations to them		10
5	Independent work of students in mastering skills	The study of drugs, prescriptions	15
6	Determine the degree of achievement on the basis of lessons mastered the theoretical knowledge and practical experience on the results and taking into account this assessment of the group	Oral questioning, written survey, tests, test results of practical work, discussion debate	25
7	Conclusion of the teacher on this lesson. Assessment of students' knowledge on a 100 point system and its announcement. Cottage set in the next class (a set of questions)	Information, questions for self-training	5

10. Control questions

1. From what plants are cardiac glycosides?

2. What effects are characteristic for the action of cardiac glycosides on the heart?

3. What effects observed in the application of cardiac glycosides in patients with heart failure?

4. What is the mechanism of action of cardiac glycosides?

5. What are cardiac glycosides used in acute heart failure?

6. Which is typical of cardiac glycosides pronounced latent period?

7. What are cardiac glycosides have a lasting effect?

8. What drugs are well absorbed cardiac glycosides in the digestive tract?

9. What are the main signs of toxic effects of digitalis drugs?

10. What drugs are used in cardiac glycoside intoxication?

11. Which means non-glycoside cardiotonics possess cardiotonic action?

12. What are the mechanisms of action of non-glycoside cardiotonics?

13. Give a description of dopamine and dobutamine.

14. What are the properties amrinone?

15. What are the side effects amrinone?

16. What is the difference of milrinone and amrinone?

17. To write prescriptions for: digitoxinum (tab, supp), strophanthin K (amp).

11. The recommended literature

Basic

1. Kharkevich D.A. Pharmacology. -M: Medicine, 2005, 2010.

2. Kharkevich D.A. The general recipe. - М: Medicine, 1982.

3. Kharkevich D.A.Management to a practical training on pharmacology. - М: Medicine,

1988.

4. Azizova S.S. Pharmacology. - Tashkent: Ibn-Sino, 2000, 2002, 2006.

Additional

5. Mashkovsky M.D.Drugs. Directory. - М: Medicine, 2001, 2005.

6. A directory of Vidal. - М, 2008, 2009.

7. Makhsumov M. N, Malikov M.M. Pharmakology. - Tashkent: Ibn-Sino, 1997.

8. Каcung B.G.Bazic and clinical pharmacology. - St.-Petersburg - Moscow. 1998.

9. Khakimov Z.Z., Azimov M.M., Zaytseva O.A., Radzhapova Sh.Z. The general recipe

Toshkent, 2005.
10. The general medical practice. Clinical references and a pharmacological directory. Under the editorship of I.P.Denisov. Yu.L. Shevchenko. F.G.Nazyrova. - М: GEOTAR-MEDIA, 2005.

11.://www.cibis.ru/catalogue/pharmacology_pharmacy_toxicology/a/sites/

52185.html;://medvedev-ma.narod.ru/farmakologia/0.htm;

12. http://max.1gb.ru/farm/;

13. //nmu-student.narod.ru/farmacology;

14. //shop.medicinform.net/showtov.asp?FND=&Cat_id=298696;

15. //www.ronl.ru/formakologiya/; ://www.evrocet.ru/cshop/book-18921;

16. //www.vsma.ac.ru/~pharm/; ://WWW.JEDI.RU/book-189216-115.html.