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Post  counselor on Mon Oct 15, 2012 11:46 am


Consists of a pathological condition in which the heart does not ensure an adequate cardiac output to meet the metabolic needs, despite adequate filling pressure.

Underlying causes of heart failure are varied:
• Hypertension Hypertension,
• Pulmonary hypertension
• Severe valvular
• Severe coronary
• Cardiomyopathy
• Congenital heart disease

Others may be underlying causes, such as:
• Thyrotoxicosis
• Arteriovenous fistula
• Anemia
• Stress
• Obesity
• Infections of the myocardium
• Arrhythmias
• Taking medications that cause retention of salt and water

If the contractility of the myocardium is only modestly reduced, regulatory mechanisms can intervene to compensate for heart failure. Among these are:
1) sympathetic stimulation
2) Increased venous pressure and ventricular end-diastolic pressure then (which according to the law of Starling increases cardiac output)

Sympathetic stimulation is associated with activation of the renin-angiotensin-aldosterone system and increased release of vasopressin.

The activation of vasodilator mechanisms and sodium excretory tries to counterbalance the effect of vasoconstrictor mechanisms. In the chronic phase of heart prevail mechanisms vasoconstrictor and sodium-retentive.

In congestive heart failure, we have:
1) water-salt retention,
2) Increased venous pressure and arterial
3) Edema widespread, even pulmonary
4) Hypoxia
Five) Confusion

• The left ventricular failure, mild to moderate, may be treated with drugs that cause vascular changes that improve the hemodynamic situation (ACE inhibitors, angiotensin receptor blockers, organic nitrates, calcium channel blockers,   adrenergic blockers)
• For stronger forms of failure is necessary to make use of positive inotropic drugs belonging to the class of digitalis Digitalis and not

Digitalis glycosides

The glycosides are present in various plants:
• Digital (if known 20 species) belonging to the family Scrophulariaceae,
• strophanthus and oleander (apocinacee)
• scilla and lily (Liliaceae)

In their molecules are:
• A steroid aglycone with 23 or 24 carbon atoms.
• In position 17 there is a lactone unsaturated pentatomic (cardenolidi) or esatomico (bufadienolidi). The lactone ring in 17 is essential for the pharmacological activity
• The sugar is important for the solubility and pharmacokinetics, not for the pharmacodynamics.
• The part sugary linked to the nucleus is made up of various sugars. Glucose is never attached to position 3.

The fresh leaves contain glycosides of Digitalis Purpurea primary active:
-Purpurea glycoside A
Purpurea glycoside-B

By action of the enzyme digipurpidasi comes off a molecule of glucose and are formed glycosides secondary presenting aglycone and 3 molecules of digitossosio:

The Digitalis lanata has three primary glycosides:
A Lanatoside
Lanatoside B
Lanatoside C
The first two after detachment of a molecule of glucose damage acetildigitossina and acetilgitossina.
The Lanatoside C for separation of glucose generates acetyldigoxin.


Positive inotropic effect
• It is exercised on both atrial and ventricular muscle.
• The inotropic effect is much more pronounced when the contractile capacity is reduced.

The inotropic effect involves:
1) Increases intraventricular pressure stronger and faster,
2) Increased speed of ejection,
3) Increased cardiac output,
4) Minor diastolic volume.

1) The portion of extracitoplasmatica  subunit of Na +, K +-ATPase is the receptor pharmacology of cardiac glycosides
2) The glycosides diminish the activity of the Na +, K + membrane
3) This increases the intracellular concentration of Na +.
4) An increase of Na + increases the intra-cellular Ca + + is reduced because the activity of the exchanger Na +-Ca + + shows that the Ca + + to the outside of the cell.
5) An increase in the intracellular Ca + + is responsible for the positive inotropic.

The effects of cardiac glycosides are favored by low extracellular K + and high extracellular Ca + +.

Chronotropic effect and negative dromotropic effect
At therapeutic doses Digitalis glycosides have direct effects negligible, both the sinus node and on the atrio-ventricular node.

Both the negative dromotropic chronotropic effect which are indirect, ie mediated by cholinergic activation.

The negative chronotropic effect is due to reduced frequency of discharge of the sino-atrial node for:
• stimulation of vagal nuclei
• awareness of the SA node to acetylcholine
• sensitization of baroreceptors
• decrease in reflex sympathetic

The negative dromotropic effect is found in the ventricle and the atrioventricular junction. E 'due to:
• vagal effect at the level of the atrioventricular node
• reduction in sympathetic tone at the ventricular level

In the atria is not observed negative dromotropic effect, but positive, again for indirect and cholinergic nature. This is because:
• The fibers are very sensitive to the vagal atrial
• In the foyers cholinergic stimulation decreases the duration of the PA and the PRE
• The atria can respond to digitalis glycosides with higher frequencies in the case of atrial flutter or fibrillation.

Increased automaticity
This is a direct effect of Digitalis glycosides. It is observed in all the tissue specialized conduction infarction:

The increased automaticity depends on:
• increased slope of phase 4 of the action potential
• an increase in post-delayed depolarizations

Batmotropo negative effect in the ventricle
This is an indirect effect, due to reduction of the sympathetic tone, which controls the activity of the sympathetic ventricular much more

Effects on the cardiovascular system
Under normal conditions, digitalis glycosides evoke:
• vasoconstriction on arteries and veins (direct effect)
• increased blood pressure

In patients with heart failure cause
• vasodilatation (indirect effect) and
• reduction in blood pressure

Under stress has
• reduces stamina for the reduction of heart rate.


It 'absorbed in the amount of 40-90%.
Its absorption is influenced by:
• time of dissolution of the tablet,
• the presence of food in the stomach,
• gastric emptying time,
• presence of Eubacterium lentum intestine
• sequestering resins

Binds to the 25% bound to plasma proteins
In the heart tissue concentration is 15-30 times higher than other tissues.

The half-life is 1-2 days
Especially renal elimination

• E 'absorbed in the amount of 90-100%
• The absorption is influenced by the same factors listed for digoxin.
• Bonds to 95% bound to plasma proteins.
• The half-life of 7 days
• Elimination is primarily metabolic.

• It has poor oral absorption
• It has low protein binding drug for which
• Provides emergency and short effect.

1) Dose "digitalizzante" equal to the amount of drug that is present in the organism in conditions of therapeutic effect
2) Maintenance dose equal to the amount of drug eliminated daily (35% digoxin, digitoxin 10%)

Is used at a dose digitalizzante in case of an urgent need to ensure effective levels of drug.

Routes of Administration

-Oral administration (in effect 60-120 min)
-Intravenous administration (effect in 5-30 min)
NOT VIA intramuscular (produces necrosis)

-Oral administration


Monitoring blood levels
-The monitoring is required in the treatment of congestive heart failure where it is difficult to evaluate the therapeutic effect.
-The monitoring can be performed using immunological methods, comprerso RIA.
-If digitalis glycosides are used in case of atrial flutter or fibrillation simply measure your heart rate.

• Treatment of heart failure
For low-failure using diuretics, ACE inhibitors, angiotensin receptor blockers, organic nitrates, calcium channel blockers, -adrenergic blockers, before resorting to digitalis glycosides.
-I cardiac glycosides are used in more advanced stages of heart failure.
• Flutter and Atrial Fibrillation
The glycosidic-digitalics slow down the speed of AV conduction controlling therefore the ventricular rhythm.
-The frequency of the atria, however, may also increase.

-Toxicity in 25% of patients admitted

Increase the risk of poisoning:
1) Diuretics depauperatori of K
2) Overdose
3) Pharmaceutical product with different bioavailability
4) Reduced elimination
5) High blood concentrations of Ca
6) Hypothyroidism (reduced metabolism and increased sensitivity of the myocardium)
7) Interaction with other drugs:
rifampicin (increased metabolism)
quinidine (increases the bioavailability of digoxin)
verapamil and amiodarone ""
amphotericin B (causes hypokalemia)

Cardiac toxicity:
1) Sinus bradycardia up to block SA full (direct and indirect effect)
2) high-grade AV block (direct and indirect effect).
3) rhythm disturbances atrial depolarizations and premature supraventricular tachycardia (increased automaticity and delayed after-depolarizations)
4) rhythm disturbances ventricular premature depolarizations occurring as extrasystoles 2 or 3 pulses per time (rhythm bi-or tri-gemino)
5) Ventricular tachycardia and ventricular fibrillation (increased automaticity, after-depolarizations and sympathetic stimulation)

Gastrointestinal toxicity:
• Anorexia
• Nausea and vomiting (for stimulation of the CTZ)
• Diarrhea (rare)
• Abdominal pain

Neurological effects:
• headache and drowsiness
• Delirium and hallucinations
• Neuralgia
• Blurred vision and altered color perception

Other effects:
Gynecomastia in males for estrogenic activity

Poisoning Treatment
• Stop feeding of glycosides
• Discontinue diuretics that lower potassium levels
• Measure the plasma concentration of K
• Ventricular arrhythmias should be treated with lidocaine or phenytoin
• Atropine may improve sinus bradycardia and AV block.
• Antibodies antidigitale are available to treat cases of severe intoxication

Inotropic not Digitalis

Dopamine and dobutamine
Shock secondary to myocardial infarction
Heart failure surgery
Acute heart failure

The use of the two drugs should be carefully monitored because they can cause problems:
• arrhythmias
• hypertension
• vomiting

Acts as an agonist of dopamine D1 and D2 receptors.
Its use was limited to mild heart failure.
However, the mortality of patients treated with ibopamina is significantly higher.

Milrinone and amrinone
Act by inhibiting phosphodiesterase and therefore increasing intracellular levels of cyclic AMP.

Cause arrhythmias and long-term do not reduce but increase the mortality rate

It is recommended for use only for short periods

• Inhibits phosphodiesterase heart
• sensitizes the troponin C to calcium
• Summon vasodilation by interacting with K + channels

• Headache
• Hypotension hypokalemia
• Alteration of heart rate

Positive results, but it is necessary to further evaluate its therapeutic significance.

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