Congestive Heart Failure Medications Drugs Used For Treating Patients With Congestive Heart Failure

What Is Congestive Heart Failure (CHF) ?

Congestive heart failure (CHF) is a syndrome that occurs because the heart is failing as a pump. The left ventricle no longer functions as an adequate pump to maintain normal cardiac output (normal ejection fractions). This may be due to disease of the heart muscle (eg. - idiopathic cardiac myopathies), ischemic heart disease which leads to myocardial infarctions effecting left ventricular function (eg. - Obstructions to blood flow through the LAD, Circumflex, Obtuse or Marginal arteries of the left Coronary artery) chronic long term untreated hypertension (eg. - malignant hypertension), bacterial endocarditis, pulmonary hypertension (eg. - Eisenmenger’s Syndrome), chronic emphysema and bronchitis. Congestive failure may also occur if the patient has pulmonary hypertension that results in right ventricular failure (eg. - Cor Pulmonale).

Drug Classes Used To Treat CHF :

I. The Cardiac Glycosides (Cardenolides) - the Digitalis Preparations

Drug Members :

  1. Digitoxin (Crystodigin)
  2. Digoxin (Lanoxin)
  3. Deslanoside (Cedilanid-D)

Natural plant analogs of today’s modern glycoside preparations have been used for at least 3,000 years. Cardiac glycosides were used for heart conditions by the Egyptians, Romans and the early Europeans. The cardiac glycosides are commonly found in plants such as Milkweed, Lilly of the Valley, the Oleander plant, and in the Foxglove plant. This is a very good reason to preserve the earth’s rain forests because of the very real chance they hold plants that will one day cure diseases.

Mechanisms of Action :

The main action of the Cardiac Glycosides is to increase the force of cardiac contraction. They do this in the following ways :

1. A Rise In The Concentration Of Intracellular Sodium. An enzyme called Na+- K+ ATPase cleaves ATP to ADP and Pi. The energy released from the hydrolysis of ATP drives the Na+-K+ pump which normally pumps Na+ out of the cell and K+ into the cell. If, however, this pump is disabled by the inhibition of this enzyme, the net effect is the malfunction of the pump and an increase of sodium inside the cell with a loss of intracellular potassium to the extracellular space. The influx of Na+ is partly due to the passive re-entry of sodium inside the cell while the efflux of K+ is passive to the outside of the cell.

2. A Rise In The Concentration Of Intracellular Calcium . In the heart, there is a second pump called the Na+-Ca2+ pump. This pump normally takes 1 intracellular Ca2+ ion out of the myocyte in exchange for 4 extracellular Na+ ions brought into the myocyte. This pump is turned on by a diffusion gradient difference in extracellular to intracellular sodium when the extracellular sodium concentration is higher than the intracellular sodium concentration. When the [Na+]Outside drops because the [Na+]Inside rises, then the pump becomes deranged and stops pumping Ca2+ out of the cell. When the Na+ - K+ pump is disabled, there is a rise of [Na+]Inside the cell as well as a rise in the [Ca2+]Inside . The [Ca2+]Inside will rise because of passive diffusion back into the cell coupled with the fact that the cell is not pumping any Ca2+ ions out.

Summary : Since the cardiac cell experiences a rise in [Ca2+] inside the cell, the force and velocity of contraction in greatly increased. This is the prime mechanism of action of all cardiac glycoside drugs.

Additional Mechanisms Of Action :

1. The glycosides enhance vagal tone over the heart which :

The net effect of the glycosides on the heart is as follows :

    a. heart rate is slowed
    b. contraction is greater due to increased filling volumes - Starling’s Law
    c. ejection fraction is improved
    d. increased ejection velocity

Adverse Side Effects Of The Glycosides :

Fatigue, delirium, anorexia, headaches, hallucinations, visual disturbances, atrioventricular blocks, and EKG changes, nausea, vomiting, diarrhea, anorexia, blurred vision, color vision disturbances, and toxic psychosis.

EKG changes seen with administration of the glycosides :

  1. Prolonged P-R Interval
  2. Inverted T Wave
  3. S-T Segment Depression
  4. Shortened Q-T Interval

Medical Uses :

1. Used to treat congested heart failure
2. Used to treat/suppress supraventricular tachydysrhythmias such as :

    a. atrial flutter
    b. atrial fibrillation
    c. paroxysmal supraventricular tachycardia (PSVT)

II. Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)

Drug Members:

  1. Captopril (Capoten)
  2. Enalapril (Vasotec)
  3. Lisinopril (Prinivil)

Mechanism of the ACE Inhibitors - Blood Pressure Regulation - The Renin-Angiotensin Axis

Renin is released into the blood from the kidneys when blood pressure is low. Renin changes angiotensinogen in the blood to Angiotensin I which then, in the presence of angiotensin converting enzyme, is changed into Angiotensin II. Angiotensin II is a potent vasoconstrictor. An increased peripheral resistance (higher blood pressure due to vasoconstriction) creates a lot of afterload on the left ventrical. Untreated and sustained hypertension will eventually create so much work for the left ventricle that it will fail - eg. - congestive heart failure. Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) simply prevent or block the conversion of Angiotensin I to Angiotensin II. These medications do this by inhibiting the enzymatic activity of Converting Enzyme - the enzyme that converts Angiotensin I to Angiotensin II. Once Converting Enzyme is inhibited, the systemic blood pressure drops and with the lower blood pressure there is an improvement in cardiac function - i.e. - lower blood pressure, lower myocardial oxygen demand, reduced preload, decreased afterload and improved cardiac function.

Adverse Side Effects : GI distress, dizziness, skin rashes, hypotension

Medical Uses : To treat Hypertension and Congestive Heart Failure

III. Diuretics

Classes of Diuretics

  1. High Ceiling Loop Diuretics
  2. Benzothiadiazide Diuretics
  3. Potassium Sparing Diuretics
  4. Osmotic Diuretics

I. High Ceiling Loop Diuretics

Members

Mechanisms of Action

1. HCL diuretics block the reabsorption of sodium, potassium and chloride ions from the glomerular filtrate

2. HCL diuretics exert their action at the proximal tubule and the ascending loop of the Loop of Henle

The net effect of using these medications is the loss of water and electrolytes in the urine with the result that the plasma levels of these ions are also lowered (K+, Na+, Cl-, Mg2+, Ca2+ and H-.

Adverse Side Effects
1. Low plasma ion concentrations :

2. Increased loss of plasma ions in the urine :

3. Orthostatic hypotension
4. Dehydration

Note : The most serious side effects are : the loss of potassium and water.
Potassium rich foods that people can eat to help replace the lost potassium are :
Dates, bananas, raisins, apricots, tomatos, oranges, potatos, lima beans, carrots, peanuts, veal, chicken, turkey. liver, beef, milk, sardines and halibut to name but a few.

Medical Uses Of The High Ceiling Loop Diuretics :

  1. Congestive Heart Failure
  2. Control Of Hypertension
  3. Control Of General Edema
  4. Control Of Acute Pulmonary Edema
  5. Prevention Of Acute Renal Failure
  6. Severe Pneumonia
II. The Benzothiadiazide Diuretics
Members:
  1. Hydrochlorothiazide (Hydrodiuril)
  2. Chlorothiazide (Diuril)
  3. Clorthalidone (Hygroton)
  4. Benzthiazide (Aguapres)
  5. Bendroflumethiazide (Naturetin)
  6. Methyclothiazide (Aguatensen)
  7. Polythiazide (Renese)
  8. Indapamide (Lozol)
  9. Cyclothiazide (Anhydron)
  10. Hydroflumethiazide (Diucardin)
  11. Metolazone (Diulo)
  12. Quinethazone (Hydromox)
  13. Trichlormethiazide (Naqua)

Mechanisms of Action

These diuretics act on the early portion of the distal tubule of the nephron. They inhibit the reabsorption of sodium ions (Na+) and potassium ions (K+). Since there is a large amount of sodium and potassium in the glomerular filtrate, it exerts an osmotic effect and a great deal of water is drawn with these ions. It is excreted from the body as urine.

A nice feature of the Benzothiadiazides is that they stimulate the reabsorption of calcium from the glomerular filtrate. This is particularly good for postmenopausal women who are predisposed to osteoporosis. Therefore in the elderly and frail elderly populations, a physician should preferrably prescribe these diuretics rather than the high ceiling loop diuretics.

Adverse Side Effects :
1. Low plasma ion concentrations :

2. Increased loss of plasma ions in the urine :
3. Hyperuricemia (Gout)
4. Fatigue and Weakness
5. Hypercholesterolemia
6. Hypertriglyceridemia
7. Hyperglycemia Secondary To Insulin Suppression & Stimulation of Glycogenolysis

Medical Uses

  1. Congestive Heart Failure
  2. Control Of Hypertension
  3. Control Of Edema

    4. a. edema due to hepatic disease
    b. edema due to renal disease
    c. edema due to corticosteroid therapy
    d. edema due to estrogen therapy
III. Potassium Sparing Diuretics
Members :
I. Spironolactone (Aldactone) - Mechanism of Action

Spironolactone binds the receptor for aldosterone thus preventing the aldosterone directed protein synthesis in the cell’s nucleus. Aldosterone is a steroid hormone that binds to a cytosolic receptor which then, as a hormone-receptor complex, moves into the nucleus and directs DNA transcription - the making of protein compounds. Since the Aldosterone receptor is blocked, the transcription of the DNA is inhibited. While it is unclear at this time, aldosterone-induced protein synthesis might be responsible for the synthesis of Na+ - K+ ATPase - the enzyme that cleaves ATP to ADP and Pi which in turn produces the energy to run the Na+ - K+ pump.

Since the production of Na+ - K+ ATPase is inhibited, the net outcome is :

  1. excretion of Na+
  2. excretion of Cl-
  3. excretion of water
  4. retention of potassium
Note : Normally, the kidney excretes K+ in favor of retaining Na+. Potassium sparing diuretics derange this relationship and instead potassium is spared while sodium is lost.

Side Effects : diarrhea, drowsiness, headaches, impotence, mental confusion, gynecomastia, irregular menses, amenorrhea, hirsuitism, deepening of the voice, hyponatremia (low blood sodium) and hyperkalemia (high blood potassium). Many of these symptoms and signs occur because spironolactone acts like progesterone in the body.

Medical Uses :

  1. Used to treat congestive heart failure
  2. Used to treat hypertension
  3. Used to treat hypokalemia
  4. Primary Aldosteronism (Conn’s Disease)

Conn’s Disease is an adrenal cortex tumor that secretes aldosterone in high concentrations

2. & 3. Triamterene and Amiloride - Potassium Sparing Diuretics

Mechanism of Action :
1. Inhibition of sodium reabsorption in the distal tubule and collecting ducts by disrupting the Aldosterone-Dependent Na+ - K+ pump
2. Potassium is spared becuase sodium is wasted - a reciprocal relationship

Adverse Side Effects : Hyponatremia, Hyperkalemia, Hypotension, Nausea, Vomiting, Acidosis, Elevated BUN.

Medical Uses :

  1. To Treat Congestive Heart Failure
  2. To Treat Patients With Cirrhosis Of The Liver - i.e. - Reduction of Ascitis
  3. To Treat Hypertension
IV. Osmotic Diuretics

Member - Mannitol (Osmitrol)

Osmotic Diuretics should have these qualities :

  1. Freely filtered through the glomerulus
  2. It should undergo little or no reabsorption in the renal tubule
  3. It should be pharmacologically inert
  4. It should resist metabolic alteration

Mechanism Of Action :
It exerts an osmotic pressure in the glomerular filtrate that draws out water, sodium and potassium.

Adverse Side Effects : transient fluid overload, pulmonary edema, tachycardia, mental detachment, blurred vision, headache, confusion.

Medical Uses :

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