Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
20-September-2008 09:55:49 - Metolazone Metolazone Systematic IUPAC name 7-chloro-2-methyl-3-2-methylphenyl- 4-oxo-1,2-dihydroquinazoline-6-sulfonamide Identifiers CAS number 17560-51-9 ATC code C03BA08 PubChem 4170 DrugBank APRD01109 Chemical data Formula C16H16ClN3O3S Mol. mass 365.835 g/mol Pharmacokinetic data Bioavailability ~65% Metabolism minimal Half life 14 hours Excretion primarily urine Therapeutic considerations Pregnancy cat. B Legal status Prescription only Routes Oral Not to be confused with Metaxalone, a muscle relaxant. Metolazone is a thiazide diuretic marketed under the brand names Zaroxolyn and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities. Contents 1 History 2 Structure 3 Mechanism of action 4 Pharmacodynamics 5 Use 6 Toxicity 7 References History Metolazone was developed in the 1970s. Its creator, Indian physician Dr. B. Vithal Shetty, has been active in helping the U.S. Food and Drug Administration review drug applications, and in the development of new medicines.1 Metolazone quickly gained popularity due to its lower renal toxicity compared to other diuretics especially thiazides in patients with renal insufficiency. Structure Metolazone is a quinazoline, a derivative of the similar diuretic quinethazone, as well as a sulfonamide. It is related to analogs of 1,2,4-benzothiadizine-1,1-dioxide benzothiadiazine. These drugs are called benzothiadiazides, or thiazides for short. Chemically, metolazone is not a substituted benzothiadiazine, and therefore is not technically a thiazide. However, since metolazone, as well other drugs like indapamide, act on the same target as thiazides and behave in a similar pharmacologic fashion, they are considered thiazide-like diuretics. Therefore, they are often included in the thiazide diuretics despite not being thiazides themselves.2 Mechanism of action Schematic of a nephron. The distal convoluted tubule is labelled 2nd convoluted tubule the proximal convoluted tubule is the first in this illustration. Schematic of a nephron. The distal convoluted tubule is labelled 2nd convoluted tubule the proximal convoluted tubule is the first in this illustration. The primary target of all thiazide diuretics, including metolazone, is the distal convoluted tubule, part of the nephron in the kidney, where they inhibit the sodium-chloride symporter. In the kidney, blood is filtered into the lumen, or open space, of the nephron tubule. Whatever remains in the tubule will travel to the bladder as urine and eventually be excreted. The cells lining the tubule modify the fluid inside, absorbing some material and excreting others. One side of the cell the apical side faces the lumen; the opposite side the basolateral side faces the interstitial space near blood vessels. The other sides are tightly joined to neighboring cells. As with other regions, tubule cells in the distal convoluted tubule possess the ATP-powered sodium-potassium antiporter Na+/K+-ATPase, which uses energy from ATP to transfer three sodium ions out from the basolateral surface toward blood vessels while simultaneously transferring two potassium ions in. The distal convoluted tubule cells also possess a sodium-chloride symporter on the apical side, which passively allows one sodium ion and one chloride ion to diffuse together in from the lumen where urine is forming into the cell interior. As sodium is pumped out of the cell by the ATPase, its intracellular concentration falls, and additional sodium begins to diffuse in from the tubule lumen as replacement. The symporter requires chloride to be transported in as well. Water passively follows to maintain isotonicity; excess chloride and potassium passively diffuse out the cell through basolateral channels into the interstitial space, and water accompanies them. The water and chloride, as well as the sodium pumped out by the ATPase, will be absorbed into the bloodstream. Metolazone and the other thiazide diuretics inhibit the function of the sodium-chloride symporter, preventing sodium and chloride, and therefore water too, from leaving the lumen to enter the tubule cell. As a result, water remains in the lumen and is excreted as urine, instead of being reabsorbed into the bloodstream. Since most of the sodium in the lumen has already been reabsorbed by the time the filtrate reaches the distal convoluted tubule, thiazide diuretics have limited effects on water balance and on electrolyte levels.2 Nevertheless, they can be associated with low sodium levels, volume depletion, and low blood pressure, among other adverse effects. Pharmacodynamics Metolazone is only available in oral preparations. Approximately 65% of the amount ingested becomes available in the bloodstream. Its half-life is approximately fourteen hours, similar to indapamide but considerably longer than hydrochlorothiazide. Metolazone is around ten times as potent as hydrochlorothiazide. The primary form of excretion is in the urine around 80%; the remaining fifth is evenly split between biliary excretion and metabolism into inactive forms.2 Use One of the primary uses of metolazone is for treating edema fluid retention associated with congestive heart failure CHF. In mild heart failure, metolazone or another diuretic may be used alone, or combined with other diuretics for moderate or severe heart failure. In addition to preventing fluid buildup, the use of metolazone may allow the patient to relax the amount of sodium restriction that is required. Although most thiazide diuretics lose their effectiveness in renal failure, metolazone retains active even when the glomerular filtration rate GFR is below 30-40 mL/min moderate renal failure. This gives it a considerable advantage over other thiazide diuretics, since renal and heart failure often coexist and contribute to fluid retention.3 Metolazone may also be used in renal kidney disease, such as chronic renal failure or the nephrotic syndrome. Chronic renal failure causes excess fluid retention that is often treated with diet adjustments and diuretics3 Metolazone may be combined with other diuretics typically loop diuretics to treat diuretic resistance in CHF, chronic renal failure, and nephrotic syndrome.4 Metolazone and a loop diuretic will synergistically enhance diuresis over the use of either agent alone. Using this combination, diuretic effects will occur at two different segments of the nephron; namely, the loop diuretic will act at the loop of Henle, and metolazone will act at the distal convoluted tubule. Metolazone is frequently prescribed in addition to the loop diuretic. Metolazone may be used for edema caused by liver cirrhosis as well. The other major use of metolazone is in treating hypertension high blood pressure. Thiazide diuretics, though usually not metolazone, are very often used alone as first-line treatment for mild hypertension. They are also used in combination with other drugs for difficult-to-treat or more severe hypertension. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNC 7 recommends thiazide diuretics as the initial medication for treatment of hypertension. Hydrochlorothiazide is by far the most commonly used, as it is both better-studied and cheaper about four times than metolazone, although as mentioned above metolazone is used in patients with moderate renal failure.2 Toxicity Since thiazide diuretics affect the transport of electrolytes and water in the kidney, they can be responsible for abnormalities of water balance and electrolyte levels. Removal of too much fluid can cause volume depletion and hypotension. Various electrolyte abnormalities may result, including hyponatremia low sodium, hypokalemia low potassium, hypochloremia low chloride, hypomagnesemia low magnesium, hypercalcemia high calcium, and hyperuricemia high uric acid. These may result in dizziness, headache, or heart arrhythmias palpitations.2 Serious, though rare, side effects include aplastic anemia, pancreatitis, agranulocytosis, and angioedema. Metolazone, like other thiazide diuretics, may unmask latent diabetes mellitus or exacerbate gout, especially by interacting with medicines used to treat gout. In addition, thiazide diuretics, including metalozone, are sulfonamides; those with hypersensitivity to sulfonamides sulfa allergy should not use them.2 References ^ Katague, David B. Chemistry Reviewer Still in Lab. News Along the Pike newsletter of the Food and Drug Administration' s Center for Drug Evaluation and Research. Volume 2, Issue 10. PDF. Accessed on January 25, 2006. ^ a b c d e f Jackson, Edwin K. Diuretics. In Goodman Gilman's The Pharmacological Basis of Therapeutics, 11th ed., ed by Laurence L. Brunton et al. New York: McGraw-Hill, 2006. ^ a b Braunwald, Eugene. Heart Failure and Cor Pulmonale. In Harrison's Principles of Internal Medicine, 15th ed., ed by Dennis L. Kasper et al. New York: McGraw-Hill, 2005. ^ Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR. Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Cardiovascular Drugs and Therapy. 2005 Aug;194:301-6. PMID 16189620. http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4170. Accessed on January 25, 2006. http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD01109.txt. Accessed on January 25, 2006. http://www.ijp-online.com/article.asp?issn=0253-7613;year=1974;volume=6;issue=1;spage=40;epage=53;aulast=Vithal;type=0. Accessed on January 25, 2006. http://www.centaurpharma.com/pdf/news/metolaz-scrip.pdf PDF. Accessed on January 25, 2006. v d e Antihypertensives C02 and diuretics C03 Sympatholytic agents Centrally acting/antiadrenergics α2 agonist Clonidine, Guanfacine, Methyldopa imidazoline receptor agonist Moxonidine, Rilmenidine adrenergic uptake inhibitor Rescinnamine, Reserpine Ganglion-blocking/nicotinic antagonist Mecamylamine, Trimethaphan Peripherally acting/antiadrenergics α1 blockers: Prazosin Indoramin Trimazosin Doxazosin Urapidil Guanidine derivatives: Betanidine Guanethidine Guanoxan Debrisoquine Guanoclor Guanazodine Guanoxabenz Vasodilators Diazoxide hydrazinophthalazine Hydralazine, Dihydralazine, Endralazine, Cadralazine Minoxidil Nitroprusside Phentolamine Other antihypertensives serotonin antagonist Ketanserin endothelin receptor antagonist Bosentan, Ambrisentan, Sitaxsentan MAOI Pargyline THI Metirosine Diuretics Low ceiling Thiazides at DCT Bendroflumethiazide Hydroflumethiazide Hydrochlorothiazide Chlorothiazide Polythiazide Trichlormethiazide Cyclopenthiazide Methyclothiazide Cyclothiazide Mebutizide Sulfonamides Quinethazone Clopamide Chlortalidone Mefruside Clofenamide Metolazone Meticrane Xipamide Indapamide Clorexolone Fenquizone Other Mersalyl Theobromine Cicletanine osmotic Mannitol, Urea carbonic anhydrase inhibitor at PT Acetazolamide High ceiling Loop diuretic at AL Bumetanide, Furosemide, Torasemide, Ethacrynic acid Potassium-sparing at CD ESC blockers Amiloride, Triamterene aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone Retrieved from http://en..org/wiki/Metolazone Categories: Thiazides Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Italiano This page was last modified on 1 July 2008, at 22:45
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie video
The Power of You video
Log into your Wholesale MonaVie Account
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.