1. DRUGS FOR СONGESTIVE HEART FAILURE (CHF)

3. 2 MAIN TYPES of CHF SYSTOLIC CHF – insufficiency
of output (decrease of systolic contraction)
DIASTOLIC CHF - insufficiency of input (calcium overload of myocardium, decrease of dilatation during diastole)

4. Treatment of CHF Cardiac glycosides Nonglycoside cardiotonic drugs
Inhibitors of angiotensine transforming (converting) enzyme (IATE, IACE)
Antagonists of angiotensine II receptors (АRА II)
Diuretics
Peripheral vasodilators
Beta-adrenoblockers
Drugs of metabolic action

5. DRUGS FOR СONGESTIVE HEART FAILURE (CHF)

7. CARDIOTONIC DRUGS

8. NONGLYCOSIDE CARDIOTONIC DRUGS Beta-adrenergic agonists (Dobutamine)
CARDIAC GLYCOSIDES
NONGLYCOSIDE CARDIOTONIC DRUGS Beta-adrenergic agonists (Dobutamine)
Phosphodiesterase inhibitors
(Amrinone, Milrinone)

9. CARDIAC GLYCOSIDES

10. Purple Foxglove

11. Foxglove

12. Lily of the valley

13. Lychnis

14. Strophantus

15. Chemical structure of cardiac glycosides

17. Pharmacodynamics
Cardiac action
Extra cardiac action

18. Cardiac action Positive inotropic Positive bathmotropic
Negative chronotropic
Negative dromotropic

20. ECG changes under the influence of CG
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Changes which correlate to positive inotropic action
Narrowing QRS complex
Decreasing ST
T-blip – double-phased, negative
Changes which correlate to negative dromotropic action
Prolongation of PQ interval
Changes which correlate to negative chronotropic action
Increase of RR interval

21. MECHANISM OF CARDIOTONIC (POSITIVE INOTROPIC) ACTION Of CG
Promote increasing of Calcium ions concentration in myocardiocytes cytoplasm
- Transport of Са ++ inside the cell
- Stimulate exit of Са++ from sarcoplasmic reticulum
- Block К, Na-АTP-ase (braking repolarization)
Improve usage of macroergic substances by cells, decrease myocardium demand in oxygen
Increase tone of sympathetic nervous system

22. Ion Channels and Ionic Movements in the Myocardial Cell

26. Extracardiac action of CG
Diuretic
Sedative
(Inf. herbae Adonidis vernalis,
T-ra Convallariae)
Stimulating influence on smooth muscles (toxic doses)

27. Pharmacokinetics of CG
Absorption of CG in gastro-intestinal tract
Digitoxin – %
Digoxin – %
Celanid – %
Strophanthin – 3-5 %

28. ADMINISTRATION OF CARDIAC GLYCOSIDES
They are drugs of choice for patients with systolic CHF, accompanied by tachysystolic form of atria fibrillation
Patients with III and IV FC (according to NYHA) of CHF, in a case of transferring of II FC into III FC (functional class)
Supraventricular tachycardia and tachyarrhythmia
Improve disease currency, life quality, increase tolerance towards physical loads, but don’t affect level of mortality in patients with CHF

29. THERAPEUTICS TARGETS OF CG IN TACHYARRHITHMIAS OF SUPRAVENTRICULAR ORIGIN
Digoxin

30. MODE of ACTION of CG IN CASE OF CHF
Increasing of systolic and minute volumes of heart activity (enhancing cardiac muscle contractility, thus increasing output)
Improving of circulation in lungs and peripheral organs, decreasing volume of blood circulation, excretion of surplus liquid out of the organism
Elimination of hypoxia and metabolic acidosis in tissues

33. The following manifestations testify about therapeutic action of CG 1
The following manifestations testify about therapeutic action of CG Improving of general state of the patient (decreasing of weakness, short breath, sleep normalization, disappearing of edema, cyanosis, etc.) Tachycardia transforms into normo (brady)cardia Increasing of diuresis Typical changes in ECG

38. Schemes of digitalization
Fast (1-2 days)
Medium (3-4 days)
Slow (more than 5 days)
Nowadays rather often cardiac glycosides are administered from the beginning of treatment in supportive doses:
digoxin – 0,125-0,75 mg daily (digitalization lasts for 5-7 days),
digitoxin – 0,1-0,15 mg daily (digitalization lasts for days)

39. Contraindications for CG administration
1. Absolute contraindication – іntoxication with CG
2. Other contraindications
- diastolic CHF
- sinus tachycardia based on thyrotoxicosis, anemia, increased temperature, hypoxia
- insufficiency of aortal valves, isolated mitral stenosis, diffuse myocarditis

40. Intoxication with CG
Frequency -
6-23 %
Mortality -
over 40 %

41. Factors which promote INTOXICATION WITH CG
DECREASING OF TOLERANCE TOWARDS CG – in case of considerable damage of myocardium with pathological process (acute MI, myocarditis, chronic lung heart): “Patients which need CG the most are the most sensitive to them”
HYPOPOTASSIUMEMIA, HYPOMAGNESIUMEMIA
- administration of diuretics (furosemid, dichlothiazide), glucocorticoid hormones, glucose with insulin, amphoterricine B
- secondary hyperaldosteronism, vomiting, diarrhea
HYPERCALCIUMEMIA
KIDNEY and LIVER INSUFFICIENCY

44. Intoxication with CG

45. Treatment of intoxication with CG
Immediate abolition of CG introduction
Correction of hypopotassiumemia (KCl, panangin)
Introduction of unithiolum (1 ml of 5 % solution / kg of body weight i. m times per day)
Cleaning of GI tract (vaseline oil, cholestyramin, magnesium sulfate)
Treatment of arrhythmias (anaprilin, verapamil, difenin, lidokain, atropine)
Na ЕDTA (trilon B), Na citrate
Calcitrin
Antibodies towards digoxin (Digibind)
Oxygen therapy

46. NONGLYCOSIDE CARDITONIC DRUGS
Xantins, derivatives of isoquinoline (ethophiline)
Pyridines, and bipyridines (amrinon, milrinon)
Derivatives of imidazole (vardax)
Derivatives of piperidine (buquineran, carbazeran)
Polypeptides (glucagon)
Carboxyl antibiotics (lasolacid, calcimycin)
Derivatives of other chemical groups: L-carnitin, heptaminol, creatinol-o-phosphate, trapidil, etc.

47. POSITIVE INOTROPIC AGENTS
Beta Receptor Agonists
Phosphodiesterase inhibitors
Na+,K+-ATPase Inhibitors

48. NONGLYCOSIDE CARDIOTONIC DRUGS
Dobutamin – beta1-adrenomimetic - in case of acute and chronic CHF – intravenously dropply – 2, mcg/(kg.min); in case of constant infusion tolerance develops after 3-4 days; in case of increasing of dose – cardiac arrhythmias
Amrinon, milrinon – inhibitors of phosphodiesterase – for temporary improvement of patient’s condition in terminal stages of CHF

50. INHIBITORS OF ANGIOTENSINE CONVERTING ENZYME (IACE)
Captopril, enalapril, ramipril, lysinorpil
In case of CHF they brake pathological consequences of activation of renin-angiotensine system by inhibiting ACE:
production of angiotensine II decreases (vasoconstrictor, inductor of aldosterone, norepinephrine, endothelin secretion, myocardium hypertrophy)
Accumulation of bradikinin (inductor of prostacycline and nitrogen oxide synthesis)

51. captopril (capoten), ramipril, enalapril etc.

52. CAPTOPRIL (CAPOTEN)
Dose titration: from 6,25-12,5 mg per day to 12,5-50 mg 3 times a day until appearance of effect
Side effects: dry cough (can be decreased by NSAIDs), considerable decreasing of AP, worsening of kidneys’ function, hyperpotassiumemia, tachycardia, neutropenia, aphtose stomatitis
Contraindicated in case of bilateral stenosis of kidney arteries, should not be combined with potassium drugs

53. INHIBITORS OF ANGIOTESINE CONVERTING ENZYME (IACE) captopril (capoten), ramipril, enalapril etc.

54. ANTAGONISTS OF ANGIOTENSINE II RECEPTORS (АRА II)
LOSARTAN (COZAAR)
Blocks receptors of angiotensine II
Decreases mortality of patients with CHF
on 50 %
Breaks development of myocardium hypertrophy
It is approved to combine IACE with АRА II

55. Losartan (Cozaar), Irbesartan (Avapro) etc.

56. DIURETICS Dichlotiazide, hygrotone (oxodoline), clopamide (brinaldix)
Furosemid, etacrinic acid
Spironolacton
improve currency of the disease, increase tolerance of patients towards physical loads,
spironolacton decreases quantity of relapses and mortality

59. BETA-ADRENOBLOCKERS Carvedilol, methoprolol, bisoprolol, nebivolol
They decrease mortality, improve disease currency and quality of patients’ lives in case of stabile CHF
Mechanism of action in case of CHF
Renewing of quantity and sensitivity of beta-adrenoreceptors in heart, which leads to increasing of systolic volume after weeks of regular administration (paradox of beta-adrenoblockade)
Prevent calcium overload of myocardium, improve coronary blood circulation
Decrease production of renin
Prevent arrhythmias
Carvedilol – α1-adrenoblocking and antioxidant action

60. Scheme of administration of beta-adrenoblockers in a case of CHF
The treatment is started from a small dose
(3,175-6,25 mg carvedilol), every 2-4 weeks it is doubled until obtaining the effect (usually develops after 2-3 months).
Average effective doses:
carvedilol – 50 mg
metoprolol – 100 mg
bisoprolol – 5 mg
Administration of beta-blockers is possible only in a case of constant condition of the patient, before development of stabile improvement of condition temporary worsening may develop

61. DRUGS OF METABOLIC ACTION
Vitamins: Е, С, В group
Ryboxin
Mildronate
Phosphaden, ATP
Creatinphosphate
Potassium orotate, anabolic steroids
Trimetazidine
Drugs manifest cardiocytoprotective action, improve energetic metabolism in myocardium

62. Drugs of metabolic influence

63. PECULIARITIES OF TREATMENT OF DIASTOLIC DISFUNCTION OF MYOCARDIUM
Indicated:
IACE, АRА II,
Beta-adrenoblockers, calcium ions antagonists
Contraindicated:
Nitrates, diuretics, cardiac glycosides