Furosemide

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[edit] BRAND NAMES

[edit] STRUCTURE

Furosemide.jpg

[edit] MECHANISM OF ACTION

Furosemide is a potent loop diuretic. it inhibits Na+/K+/2 Cl- co-transport in thick ascending limb, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium.

This co-transporter is responsible for 25% of the active sodium reabsorption.

By inhibiting the reabsorption of sodium and chloride, Furosemide increases the urinary excretion of sodium, chloride, and water. Furosemide also increases the excretion of potassium, hydrogen, calcium, magnesium, ammonium, and phosphate and, as it inhibits carbonic anhydrase, it increases bicarbonate excretion.

The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.

[edit] INDICATIONS

  • Edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome
  • Treatment of hypertension alone or in combination with other antihypertensive agents

[edit] DOSAGE

Tablets, Adults:

  • Edema: The usual initial dose is 20-80 mg/day orally.
  • Hypertension: The usual initial dose 20-40 mg twice a day.

[edit] CONTRAINDICATIONS

  • Contraindicated in patients with anuria and in patients with a history of hypersensitivity to sulfonylureas

[edit] WARNINGS AND PRECAUTIONS

  • Furosemide 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.
  • Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that Furosemide ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg Furosemide per minute has been used).

[edit] INTERACTIONS

  • Aminoglycosides: Furosemide increase the ototoxic potential.
  • Ethacrynic acid: Increased ototoxicity.
  • Cisplatin: : Increased ototoxicity.
  • Lithium carbonate: Lithium generally should not be given with diuretics because they reduced lithium’s renal clearance and add a high risk of lithium toxicity.
  • ACE inhibitors and angiotensin II receptor blockers: concomitant use may lead to severe hypotension and deterioration in renal function, including renal failure. An interruption or reduction in the dosage of Furosemide, ACE inhibitors, or angiotensin receptor blockers may be necessary.
  • Aspirin and other salicylates: Concomitant use may lead to salicylate toxicity because of competitive renal excretory sites

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Furosemide should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
  • Furosemide may inhibit lactation. Because it appears in breast milk, caution should be exercised when Furosemide is administered to a nursing mother.

[edit] SIDE EFFECTS

  • Hypersensitivity Reactions: Patients allergic to sulfonamides may also be allergic to Furosemide
  • Cardiovascular: Orthostatic hypotention
  • Endocrine/Metabolic: Hyperglycemia (use with caution in diabetic patients), hyperuricemia (gout may rarely be precipitated), hypovolemia (dehydration), hypokalemia, hypochloremia, metabolic alkalosis, hypomagnesemia, gout and hypercalciurea (Furosemide increases urinary excretion of calcium) which can rarely progress to renal stones.
  • Ototoxicity: Tinnitus and Hearing loss with IV/IM rapid injection or concomitant therapy with ototoxic drugs (e.g. aminoglycoside antibiotics, ethacrynic acid)
  • Dermatologic: photosensitivity, rash, pruritis, exfoliative dermatitis.
  • Hematology: Aplastic/ hemolytic anemia, thrombocytopenia, agranulocytosis, neutorpenia (all rare).

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antihypertensives
ACE inhibitors Benazepril (Lotensin)   Captopril (Capoten)   Cilazapril   Delapril   Enalapril (Renitec, Vasotec)   Fosinopril (Monopril)  Lisinopril (Prinivil, Zestril)   Moexipril (Univasc)  Perindopril (Aceon)  Quinapril (Accupril)  Ramipril (Altace, Triatec)   Trandolapril (Mavik)  Zofenopril (Bifril, Zopranol)
Angiotensin II receptor antagonist Azilsartan (Edarbi)   Candesartan (Atacand)   Eprosartan (Teveten)   Irbesartan (Aprovel, Avapro, Karvea)   Losartan (Cozaar)   Olmesartan (Benicar, Olmetec)   Telmisartan (Micadis)   Valsartan (Diovan, Tareg)
Renin inhibitors Aliskiren (Rasilez, Tekturna)
Alpha-1 blockers Doxazosin (Cardura)   Prazosin (Minipress)   Terazosin (Hytrin)
Alpha-2 agonists (centrally acting) Clonidine (Oral route)   Clonidine (Transdermal) (Catapresan)   Guanfacine (Tenex)   Methyldopa (Aldomet)
Calcium channel blockers Dihydropyridines‎ Amlodipine (Norvasc)   Barnidipine (Vasexten)   Felodipine (Plendil)   Isradipine (Dynacirc)   Lacidipine (Lacipil, Motens)   Lercanidipine (Zanidip)   Manidipine   Nicardipine   Nifedipine (Adalat)   Nisoldipine   Nitrendipine
Benzothiazepine‎ Diltiazem (Cardizem, Taztia XT, Tiazac, Tildiem)
Phenylalkylamine‎ Gallopamil   Verapamil (Calan)
Beta blockers Beta1 selective (cardioselective) Acebutolol (Sectral)   Atenolol (Tenormin)   Betaxolol (Kerlon)   Bisoprolol (Concor)   Celiprolol (Cordiax)   Metoprolol (Betaloc, Lopressor, Toprol-XL)   Nebivolol (Bystolic, Lobivon, Nebilox)
Nonselective (Beta1 and Beta2 blockers) Oxprenolol (Trasitensin)   Propranolol (Inderal)   Timolol (Blocadren)
Nonselective (Beta1, Beta2 and Alpha1 blockers) Carvedilol (Dilatrend)   Labetalol (Trandate)
Beta blocker with intrinsic sympathomimetic activity (ISA) Acebutolol (Sectral)   Celiprolol (Cordiax)
Lipophilic Beta blockers Propranolol (Inderal)   Metoprolol (Betaloc, Lopressor, Toprol-XL)   Oxprenolol (Trasitensin)
Diuretics Carbonic anhydrase inhibitors Acetazolamide (Diamox)
Loop diuretics Bumetanide   Etacrynic acid   Furosemide (Lasix)   Piretanide   Torasemide (Demadex)
Thiazide diuretics Chlorothiazide (Diuril)   Hydrochlorothiazide (Esidrex)
Thiazide-like diuretics Chlortalidone (Hygroton)   Indapamide (Lozol, Lozide)   Metolazone
Potassium-sparing diuretics Epithelial sodium channel blockers: Amiloride (Midamor)   Triamterene (Dyrenium)
Aldosterone receptor antagonists: Potassium canrenoate   Eplerenone (Inspra)   Spironolactone (Aldactone)
Osmotic diuretics Mannitol
Combination therapy Amiloride/Hydrochlorothiazide (Moduretic)   Spironolactone/Hydrochlorothiazide (Aldactazide)