Amiloride/Hydrochlorothiazide
Contents |
[edit] BRAND NAMES
[edit] STRUCTURE
[edit] MECHANISM OF ACTION
This is a combination of two diuretic agents with different but complementary mechanisms and sites of action, thereby providing additive diuretic and antihypertensive effects. Additionally, Amiloride helps to minimize the potassium loss characteristically induced by Hydrochlorothiazide.
Amiloride is potassium sparing diuretic that possesses weak (compared to the thiazide diuretics) natriuretic, diuretic and antihypertensive activity. Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the kidneys. This promotes the loss of sodium and water from the body, but without depleting potassium.
Hydrochlorothiazide is a thiazide diuretic, it acts on the distal convoluted tubule by inhibiting the sodium-chloride symporter. thus, it reduces NaCl reabsorption, leading to a retention of water in the urine. This symporter reabsorbs about 5% of filtered sodium. Hydrochlorothiazide enhance also Ca++ reabsorption in the distal convoluted tubule by inhibiting Na+ entry and thus enhancing the activity of Na+-Ca++ exchanger in the basolateral membrane of epithelial cells.
The onset of the diuretic action of Amiloride/Hydrochlorothiazide (Moduretic) is within 1 to 2 hours and this action appears to be sustained for approximately 24 hours.
[edit] INDICATIONS
Amiloride/Hydrochlorothiazide (Moduretic) is indicated alone or as an adjunct to other antihypertensive drugs in conditions such as:
- Edema of cardiac origin (heart failure);
- Hepatic cirrhosis with ascites and edema
- Hypertension
[edit] DOSAGE
Tablets containing 5 mg amiloride HCl and 50 mg hydrochlorothiazide.
Amiloride/Hydrochlorothiazide (Moduretic) should be administered with food.
HYPERTENSION
The usual dosage is one tablet given once a day or in divided doses. Some patients may require only half a tablet once a day.
EDEMA OF CARDIAC ORIGIN
Amiloride/Hydrochlorothiazide may be started at a dosage of one tablet a day. Dosage may be increased if necessary but must not exceed two tablets a day. The optimal dosage is determined by the diuretic response and the serum potassium level. Once an initial diuresis has been achieved, reduction in dosage should be attempted for maintenance therapy. Maintenance therapy may be on an intermittent basis.
HEPATIC CIRRHOSIS WITH ASCITES
Treatment should be initiated with a small dose (1 tablet once a day). If necessary, dosage may be increased gradually until there is effective diuresis. The dosage should not exceed two tablets per day.
Maintenance doses may be lower than those required to initiate diuresis; therefore, reduction in the daily dose should be attempted when the patient’s weight is stabilized. Gradual weight reduction in cirrhotic
patients is especially desirable to reduce the likelihood of untoward reactions associated with diuretic therapy
[edit] CONTRAINDICATIONS
- Hyperkalemia (defined as >5.5 mEq/l)
- Other concomitant antikaliuretic therapy or potassium supplementation
- Renal insufficiency (anuria, acute renal failure, severe progressive renal disease, and diabetic nephropathy)
- Hypersensitivity to any component of this product or other sulfonamide-derived drugs
[edit] PRECAUTIONS
[edit] INTERACTIONS
[edit] PREGNANCY AND LACTATION
[edit] SIDE EFFECTS
The most common side effects occuring in 3% to 8% of patients treated with Amiloride/Hydrochlorothiazide (Moduretic) are :
- Headache
- Weakness
- Nausea/anorexia
- Dizziness
- Rash
[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) |