Inhibitors of angiotensine transforming enzyme (IATE, IACE)
Antagonists of angiotesine II receptors (АRА II)
Diuretics
Peripheral vasodilators
Beta-adrenoblockers
Drugs of metabolic action
HEART GLYCOSIDES
HEART GLYCOSIDES
NONGLYCOSIDE CARDIOTONIC DRUGS (Dobutamin)
Purple Foxglove
Purple Foxglove
Foxglove
Foxglove
Lily of the valley
Lily of the valley
Lychnis
Lychnis
Chemical structure of heart glycosides
Chemical structure of heart glycosides
Pharmacodynamics
Cardiac action
Extracardiac action
Cardiac action
Cardiac action
Positive inotropic
Positive bathmotropic
Negative chronotropic
Negative dromotropic
ECG changes under the influence of HG
ECG changes under the influence of HG
Changes which correlate to positive innotropic 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
Increasing of RR interval
HG
HG
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 need in oxygen
Increase tone of sympatic nervous system
Extracardiac action of HG
Extracardiac action of HG
Diuretic
Sedative
Stimulating influence on smooth muscles
Absorption of HG in gastro-intestinal tract
Absorption of HG in gastro-intestinal tract
Digitoxin – 100 %
Digoxin – 60-80 %
Celanid – 15-40 %
Strophanthin – 3-5 %
HG of short action (strophanthin, corglycon)
HG of short action (strophanthin, corglycon)
- latent period – 5-10 min,
- action duration – 8-12 hours (corglycon), 1-3 days (strophanthin),
- slow intravenous introduction
HG of medium action duration (digpoxin, celanid)
latent period – 5-30 min. (i.v.), 30-60 min. (orally)
action duration – 3-6 days
slow intravenous, oral introduction
HG of long lasting action (digitoxin)
latent period – 4-12 hours
action duration – 2-3 weeks
oral introduction
They are drugs of choice for patients with systolic dysfunction of myocardium, accompanied by tachysystolic form of atria fibrilation
They are drugs of choice for patients with systolic dysfunction of myocardium, accompanied by tachysystolic form of atria fibrilation
Patients with III and IV FC (according to NYHA) of chronic heart insufficiency, in case of transferring of II FC into III FC
Supraventricular tachycardia and tachyarrhythmia
Improving of disease currency, life quality, increasing of tolerance towards physical loads, but absence of influence on mortality level in patients with CHI
Increasing of systolic and minute volumes of heart activity
Increasing of systolic and minute volumes of heart activity
Improving of circulation in lung and organic circulation circles, decreasing of CBV, excretion of surplus liquid from the organism
Elimination of hypoxia and metabolic acidosis in tissues
STARTING DIGITALIZATION (PERIOD OF SATURATION OF THE ORGANISM WITH THE DRUG)
STARTING DIGITALIZATION (PERIOD OF SATURATION OF THE ORGANISM WITH THE DRUG)
The aim is to reach full dose of action in the organism of the patient (effective therapeutic dose) of HG
SUPPORTIVE THERAPY
The aim is to support the full dose in the organism of the patient
Strophantin – 0,6-0,7 mg
Strophantin – 0,6-0,7 mg
Celanid – 2 мг (i.v.), 5 mg (orally)
Digoxin – 2 mg (i.v.), 3 mg (orally)
Digitoxin – 2 mg
Real full doses of action in certain patients can differ from the average full dose of action for 50-200 %
Fast (1-2 days)
Fast (1-2 days)
Medium (3-4 days)
Slow (more than 5 days)
Nowadays rather often heart glycosides are administered from the beginning of treatment in supportive doses:
digoxin – 0,125-0,75 mg/day (digitalization lasts for 5-7 days),
digitoxin – 0,1-0,15 mg/day (digitalization lasts for 25-30 days)
Contraindications for administration of HG
Contraindications for administration of HG
1. Absolute contraindication – іntoxication with HG
2. Other contraindications
- diastolic dysfunction of myocardium
- sinus tachycardia based on thyrotoxicosis, anemia, increased temperature, hypoxia
- insufficiency of aortal valves, isolated mitral stenosis, diffuse myocarditis
Intoxication with heart glycosides
Intoxication with heart glycosides
Cardiac symptoms
Worsening of contractive action of myocardium, increasing of circulation insufficiency
Disturbance of heart rhythm
Extracardiac symptoms
Extracardiac symptoms
Gastro-intestinal
Neurological and psychical
Eye symptoms
Disturbance of kidney function
Allergic reactions
Gynecomastia
Treatment of intoxication
Treatment of intoxication
Immediate quitting of HG introduction
Acceleration of HG excretion from GI tract
Correction of hypopotassiumemia
Introduction of unitiol
Treatment of arrhythmia
Oxygen therapy
Digitoxin is a choice drug when HI is combined with kidney insufficiency, but contraindicated if liver is damaged (it is metabolized by liver)
Digitoxin is a choice drug when HI is combined with kidney insufficiency, but contraindicated if liver is damaged (it is metabolized by liver)
Digoxin is not contraindicated even in case of liver cirrhosis (it is not metabolized in liver), but contraindicated in case of kidney insufficiency (it is excreted by kidneys)
Immediate quitting of HG introduction
Immediate quitting of HG introduction
Correction of hypopotassiumemia (KCl, panangin)
Introduction of unitiol (1 ml of 5 % solution / kg of weight i.m. 2-3-5 times per day)
Clearing 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
Xantins, derivatives of isoquinoline (ethophiline)
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.
Dobutamin – beta1-adrenomimetic - in case of acute and chronic heart insufficiency – intravenously dropping – 2,5-5-10 mcg/(kg.min); in case of constant infusion tolerance develops after 3-4 days; in case of increasing of dose – heart arrhythmias
Amrinon, milrinon – inhibitors of phosphodiesterase – for temporary improvement of patient’s condition in terminal stage of HI
Captopril, enalapril, ramipril, lysinorpil
Captopril, enalapril, ramipril, lysinorpil
In case of HI they brake pathological consequences of activation of renin-angiotesine system by inhibiting ATE:
production of angiotensine II decreases (vasoconstrictor, inductor of aldosterone, norepinephrine, endothelin secretion, myocardium hypertrophy)
Accumulation of bradikin (inductor of prostacycline and nitrogen oxide synthesis)
Increase duration and improve quality of life of patients with HI
Increase duration and improve quality of life of patients with HI
Increase tolerance towards physical loads
Decrease risk of recurring MI
Brake development of miocardium hypertrophy
Dose titration: from 6,25-12,5 mg per day to 12,5-50 mg 3 times a day until appearance of effect
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 nonsteroid antiinflammatory), 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
Of mixed action (influence on tone of arterioles and venules): sodium nitropruside, prasosine, inhibitors of ATE, ARA II
Isosorbide dinitrate (30-160 mg/day) +
hydralasin (50-300 mg/day) – for patients which have contraindications towards administration of IATE
Unfavorable action in case of HI:
They activate sympatic-adrenalsystem and intermediately renin-aldosterone system
Carvedili, methoprolol, bisoprolol
Carvedili, methoprolol, bisoprolol
They decrease mortality, improve disease currency and quality of patients’ lives in case of stagnant HI
Mechanism of treatment action in case of HI
Renewing of quantity and sensitivity of beta-adrenoreceptors in heart, which leads to increasing of systolic volume after 8-10 weeks of regular administration (paradox of beta-adrenoblockade)
Prevent calcium overload of myocardium, improve coronary blood circulation
Decrease production of renin
Prevent arrhythmias
Carvedilol – alpha1-adrenoblocking and antioxidant action
Scheme of administration of beta-adrenoblockers in case of HI
Scheme of administration of beta-adrenoblockers in case of HI
The treatment is started from a small dose
(3,175-6,25 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 case of constant condition of the patient, before development of stabile improvement of condition temporary worsening may develop
Vitamins: Е, С, В group
Vitamins: Е, С, В group
Ryboxin
Mildronate
Phosphaden, ATP
Creatinphosphate
Potassium orotate, anabolic steroids
Drugs manifest cardiocytoprotective action, improve energetic metabolism in myocardium
