Heart glycosides

Heart glycosides

• Heart glycosides

• Nonglycoside cardiotonic drugs

• 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

LOSARTAN (cosaar)

• LOSARTAN (cosaar)

• Blocks receptors of angiotensine II

• Decreases mortality of patients with HI

• on 50 %

• Breaks development of myocardium hypertrophy

• It is approved to combine IATE with АRА II

Dichlotiazide, hyhrotone (oxodoline), clopamide (brinaldix)

• Dichlotiazide, hyhrotone (oxodoline), clopamide (brinaldix)

• Furosemid, etacrine acid

• Spironolacton

• improve currency of the disease, increase tolerance of patients towards physical loads,

• spironolacton decreases quantity of relapses and mortality

Arterial: hydralasin, calcium ions antagonists, minoxydil

• Arterial: hydralasin, calcium ions antagonists, minoxydil

• Venous: nitrates, molsidomin

• 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

Indicated:

• Indicated:

• IATE, АRА II,

• Beta-adrenoblockers, calcium ions antagonists

• Contraindicated:

• Nitrates, diuretics, heart glycosides