1. LASIX HISTORY
How was Lasix discovered?

Aventis introduced Lasix in 1956.

Aventis aims to make a difference by discovering, developing and marketing innovative prescription drugs and vaccines that protect and improve human health.

2. LASIX FACTS

Aventis is the world's third largest pharmaceutical company.

Aventis is developing leading positions in seven major therapeutic areas: cardiovascular disease, thrombosis, oncology, diabetes, central nervous system, internal medicine, and vaccines.

Around the world Aventis works to provide patients and healthcare professionals with therapeutic innovations that not only satisfy unmet medical needs, but also help lower the overall cost of healthcare.

3.ABOUT LASIX MEDICATION

Lasix contains furosemide, which belongs to a family of drugs called diuretics.

A diuretic helps reduce the amount of excess fluid in the body by increasing the amount of urine produced.

Diuretics prevent, treat or improve symptoms in a variety of conditions, such as:

• High blood pressure
• Congestive heart failure
• Edema
• Polycystic ovary syndrome
• Certain kidney disorders, such as kidney stones
• Diabetes insipidus
• Female hirsutism
• Osteoporosis

The potency of a diuretic is determined by its ability to result in sodium loss in the urine. This ability is measured as fractional sodium excretion. Fractional sodium excretion is the percentage of filtered sodium which is excreted in the urine. The more potent the diuretic, the greater the ability to interfere with the reabsorption of sodium from the renal tubules resulting in a larger amount of sodium remaining in the excreted urine. The greater the amount of sodium in the urine, the greater the volume of urine.

Potent diuretics include

Weak diuretics include

• osmotics
• inhibitors of urinary acidification
• thiazides
• loop diuretics
• xanthines
• aldosterone antagonists

STRUCTURE OF NEPHRON

(Each human kidney consists of about one million nephrons, together with a maze of blood vessels and some connective tissue.)

Osmotic Diuretics

Osmotic diuretics include any low molecular weight substance that is freely filtered by the glomeruli but poorly reabsorbed from tubular fluid. Examples include:

Osmotic diuretics cause expansion of the extracellular fluid volume by relocating intracellular fluid to the extracellular space, specifically to the plasma.

Inhibitors of Urinary Acidification

Carbon dioxide is produced in renal tubular epithelial cells or is brought to the kidneys in the blood. (1) Carbon dioxide reacts with water in the presence of carbonic anhydrase (CA) to form carbonic acid.(2) Carbonic acid spontaneously breaks down to hydrogen ion and bicarbonate.(3) This bicarbonate is reabsorbed. (3) Water in the cell ionizes to hydrogen and hydroxyl ions. Hydrogen ions from the above 2 sources exchange for sodium in the tubular fluid. The secreted hydrogen ion (4) combines with bicarbonate (5) in the tubular fluid to form carbonic acid (6) that disassociates into water and carbon dioxide (7). The carbon dioxide equilibrates across the renal tubular epithelium. The end result is that for each bicarbonate filtered into tubular fluid one bicarbonate is reabsorbed. The blue numbers on the diagram correlate with the blue numbers in the text above.

Diuretics which inhibit the enzyme carbonic anhydrase impair the reabsorption of bicarbonate from tubular fluid. Sodium and water are eliminated in urine in conjunction with the lost bicarbonate.

Acetazolamide is an example of this class of diuretics. The bicarbonate in the tubular fluid is negatively charged and will draw positively charged ions such as potassium into the urine, enhancing the loss of potassium. Some of the sodium which normally would have been reabsorbed from tubular fluid paired with bicarbonate will be reabsorbed with chloride instead. (for each negatively charged ion reabsorbed, one positively charged ion will be reabsorbed as well.) The increased reabsorption of chloride and increased loss of potassium coupled with impaired ability to reabsorb bicarbonate can lead to hyperchloremic acidosis and hypokalemia.

Carbonic anhydrase is also found in the eye where it is involved in the production of aqueous humour. Carbonic anhydrase inhibiting diuretics are most often used to reduce the production aqueous humour in patients with glaucoma. The diuretic effects occur in conjunction with the effects on fluid production in the eye. Therefore the side effects of acidosis, hyperchloridemia, hypokalemia and dehydration may occur in treated patients.

Thiazide Diuretics

Thiazides such as hydrochlorothiazide are moderately potent diuretics. They inhibit carbonic anhydrase to a minor degree and more importantly, impede the reabsorption of sodium and chloride in the distal convoluted tubule and loop of Henle. The end result is increased excretion of Na, Cl, K and water. Additionally thiazide diuretics decrease renal excretion of calcium and therefore should not be given to hypercalcemic patients. Potential side effects of thiazides include hypokalemia and metabolic alkalosis. Alkalosis occurs as the sodium that is reabsorbed is absorbed primarily with bicarbonate as the reabsorption of chloride is blocked. Thiazides are used in the treatment of arterial hypertension and may have some direct relaxing effect on vascular smooth muscle in addition to the diuretic effect. Thiaizide diuretics may decrease the severity of polyuria in patients with diabetes insipidus (decrease urine volume by 30-40%). It is not clear how a diuretic actually decreases urine volume in these patients

Loop Diuretics

Loop diuretics include Lasix (furosemide) and ethacrynic acid. They have a rapid oral absoprtion. There is a diuretic effect within minutes which persists for 1-3 hours. The action is to strongly inhibit Cl pump in ascending loop of Henle (and subsequently Na reabsorption). They can produce hypokalemia and metabolic alkalosis.

Aldosterone antagonists

Aldosterone antagonists like spironolactone compete with aldosterone for its physiologic binding site. Aldosterone antagonists are usually given with other, more potent, diuretics for their effect of potassium sparing. Hyperkalemia (increased levels of potassium) is a possible side effect

Xanthines

Xanthines include caffeine, theobromine, and theophylline which is a bronchodilator. Xanthines act to increase cardiac output which increases GFR (Glomerular filtration rate) resulting in a modest loss of Na, Cl, and water. Additionally a direct tubular action is suspected as their effect persists after GFR returns to normal.

4.LASIX EFFECTIVENESS
When is Lasix best taken?

Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.

The usual initial dose of Lasix is 40 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose of Lasix may be raised by 80 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. This individually determined single dose of Lasix should then be given once or twice daily (e.g., at 8 am and 2 pm). The dose of Lasix may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Edema may be most efficiently and safely mobilized by giving Lasix on 2 to 4 consecutive days each week.

Changes in blood pressure must be carefully monitored when Lasix is used with other antihypertensive drugs, especially during initial therapy. To prevent excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50 percent when Lasix is added to the regimen. As the blood pressure falls under the potentiating effect of Lasix, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

5.LASIX EFFECTS ON SPECIAL POPULATION
How do different people react to Lasix?

Pediatric - Although there is no specific information comparing the use of loop diuretics in children with use in any other age group, Lasix is not expected to cause different side effects in children than they do in adults.

Geriatric - Dizziness, lightheadedness, or signs of too much potassium loss may be more likely to occur in the elderly, who are more sensitive to the effects of Lasix. Elderly patients may also be more likely to develop blood clots

Pregnant woman - Studies have not been done in pregnant women. However, studies in animals have shown Lasix to cause harmful effects. In general, diuretics are not useful for normal swelling of feet and hands that occurs during pregnancy. Lasix should not be taken during pregnancy unless recommended by the doctor.

Nursing Mothers - Lasix has not been reported to cause problems in nursing babies. Lasix passes into breast milk. It is not known whether bumetanide or ethacrynic acid passes into breast milk. Lasix passes into breast milk and may affect a nursing infant. Lasix should not be taken without doctor's counsel if one is breast-feeding a baby.

6.LASIX EFFECTS ON MEDICAL CONDITIONS
(How does Lasix affect your existing condition/ailment?

The effect of Lasix on other medical conditions

7.OTHER/ALTERNATE USES OF LASIX
What else does Lasix treat?

Lasix is a "water pills" (diuretic) that increases the amount of urine you make, which causes your body to get rid of excess water. Lasix is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Lasix also reduces swelling/fluid retention (edema), which can result from conditions such as congestive heart failure, liver disease, or kidney disease. This can help to improve symptoms such as trouble breathing.

8.ADVERSE/SIDE EFFECTS of LASIX
What are the side effects of Lasix?

Lasix is a potent diuretic, which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required, and dose and dose schedule must be adjusted to the individual patient's needs.

Lasix adverse reactions are categorized below by organ system and listed by decreasing severity.

Gastrointestinal System Reactions Systemic Hypersensitivity Reactions Central Nervous System Reactions Hematologic Reactions Dermatologic-Hypersensitivity Reactions Cardiovascular Reaction Other Reactions

Whenever adverse reactions are moderate or severe, Lasix dosage should be reduced or therapy withdrawn.

9. USEFUL SITES

http://www.aventispharma-us.com
http://www.sigmaaldrich.com
http://www.courses.vetmed.wsu.edu/.../ diuretic.htm
http://www.pdrhealth.com