Zator Plus
Zator Plus Uses, Dosage, Side Effects, Food Interaction and all others data.
Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule. Aldosterone interacts with a cytoplasmic mineralocorticoid receptor to enhance the expression of the Na+ K+ ATPase and the Na+ channel involved in a Na+ K+transport in the distal tubule . Spironolactone bind to this mineralcorticoid receptor, blocking the actions of aldosterone on gene expression. Aldosterone is a hormone; its primary function is to retain sodium and excrete potassium in the kidneys.
Originally spironolactone was only studied for its potassium sparing diuretic effect. Spironolactone competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.. Inhibition of this receptor leads to increased renin and aldosterone levels.
Spironolactone is structurally similar to progesterone and as a result is associated with progestogenic and antiandrogenic effects.
Torasemide inhibits the Na+/K+/2CI- carrier system (via interference of the chloride binding site) in the lumen of the thick ascending portion of the loop of Henle, resulting in a decrease in reabsorption of sodium and chloride. This results in an increase in the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases aldosterone production. The increased delivery and high aldosterone levels promote sodium reabsorption at the distal tubules, and By increasing the delivery of sodium to the distal renal tubule, torasemide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Torasemide's effects in other segments of the nephron have not been demonstrated. Thus torasemide increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance. Torasemide's effects as a antihypertensive are due to its diuretic actions. By reducing extracellular and plasma fluid volume, blood pressure is reduced temporarily, and cardiac output also decreases.
It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control. This effect is obtained by the increase in the excretion of urinary sodium and chloride.
Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with furosemide and spironolactone and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function.
Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action.
| Trade Name | Zator Plus |
| Generic | Spironolactone + Torasemide |
| Weight | 50mg |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Torrent Pharmaceuticals Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Spironolactone is used for Congestive heart failure, Hepatic cirrhosis with ascites and oedema, Nephrotic syndrome, Primary hyperaldosteronism, Essential hypertension, For the treatment of patients with hypokalemia
Spironolactone is a long-acting aldosterone antagonist. Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium and magnesium is retained.
Torasemide is used for the management of edema of cardiac, renal and hepatic origin.The management of hypertension, as a sole therapeutic agent or in combination with other classes of antihypertensive agents.
Zator Plus is also used to associated treatment for these conditions: Acne, Ascites, Congestive Heart Failure (CHF), Edema, High Blood Pressure (Hypertension), Hypokalemia, Idiopathic Hirsutism, Nephrotic Syndrome, Primary Hyperaldosteronism, Secondary hyperaldosteronism, Chronic heart failure with reduced ejection fraction (NYHA Class III), Chronic heart failure with reduced ejection fraction (NYHA Class IV), Idiopathic hyperaldosteronismEdema, High Blood Pressure (Hypertension)
How Zator Plus works
Spironolactone competitively inhibits aldosterone dependant sodium potassium exchange channels in the distal convoluted tubule. This action leads to increased sodium and water excretion, but more potassium retention. The increased excretion of water leads to diuretic and also antihypertensive effects.
As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface. This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule.
Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.
Dosage
Zator Plus dosage
Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome): An initial daily dosage of 100 mg of Spironolactone administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily. Combined therapy with other diuretics is indicated when more rapid diuresis is desired.
Primary hyperaldosteronism: After the diagnosis of hyperaldosteronism has been established, Spironolactone may be administered in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, Spironolactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.
Essential hypertension: For adults, an initial daily dosage of 50 to 100 mg of Spironolactone administered in either single or divided doses is recommended.
Hypokalemia: Spironolactone in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia.
Congestive heart failure: The usual initial oral dose is 10 mg or 20 mg once daily. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.
Chronic renal failure: The usual initial oral dose is 20 mg once daily. lf the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200mg have not been adequately studied.
Hepatic cirrhosis: The usual initial oral dose is 5 mg or 10 mg once daily, administered together with an aldosterone antagonist or a potassium sparing diuretic. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 40 mg have not been adequately studied. Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.
Hypertension: The usual initial oral dose is 2.5-5 mg once daily. If the 5 mg dose does not provide adequate reduction of blood pressure within 4 to 6 weeks, the dose may be increased to 10 mg once daily. If the response to 10 mg is insufficient, an additional antihypertensive should be added to the treatment regimen.
Side Effects
Gynaecomastia may develop in association with the use of Spironolactone. Other adverse reactions are: GI symptoms including cramping and diarrhoea, drowsiness, lethargy, headache, urticaria, mental confusion, impotence, irregular menses or amenorrhoea and post-menopausal bleeding.
Usually torasemide is well tolerated. However, a few side effects like dry mouth, dizziness, tiredness, skin rash, diarrhea, constipation, nausea, vomiting, orthostatic hypotention and muscle cramp may occur. All side effects usually are mild and transient.
Toxicity
Patients experiencing an overdose may present with drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Vomiting is generally induced or a gastric lavage is performed. Supportive treatment involves maintining hydration, electrolyte balance, and vital functions.
The oral LD50 in mice, rats, and rabbits is >1g/kg.
Spironolactone should be avoided in pregnancy due to reports of feminization of male fetuses in animal studies. Active metabolites of spironolactone are present in breast milk and levels that are likely inconsequential, though the long term effects have not been studied.
In animal studies, spironolactone slowed follicle development, ovulation, and implantation. Spironolactone increased the incidence of benign adenomas in the testes of male rats, benign uterine endometrial stromal polyps in female rats, and thyroid follicular cell adenomas in both sexes of rats. Spironolactone and canrenone are generally not considered to be mutagenic in tests but canrenone occasionally tests positive for mutagenicity with metabolic activation and spironolactone has occasionally tested inconclusive though slightly positive for mutagenicity.
The oral LD50 of torasemide in the rat is 5 g/kg. When overdose occurs, there is a marked diuresis with the danger of loss of fluid and electrolytes which has been seen to lead to somnolence, confusion, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, hemoconcentration dehydration and circulatory collapse. This effects can include some gastrointestinal disturbances.
There is no increase in tumor incidence with torasemide and it is proven to not be mutagenic, not fetotoxic or teratogenic.
Precaution
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal.
Precautions should be taken while torasemide is administered in the conditions like diabetes, gout, hypotension and liver failure.
Interaction
ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Lithium: Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Digoxin: Spironolactone has been shown to increase the half-life of digoxin.
Increased risk of severe hypokalaemia with amphotercin B, corticosteroids, carbenoxolone, hypokalaemia-causing medications. Increased risk of lithium toxicity. Increased potential for ototoxicity and nephrotoxicity with nephrotoxic or ototoxic medications e.g. aminoglycosides. High dose salicylates may increase the risk of salicylate toxicity. Increased risk of toxicity with digoxin. Reduced diuretic effect with NSAIDs. Increased risk of hypotension with antihypertensives.
Volume of Distribution
Volume of distribution data is not readily available.
The volume of distribution of torasemide is 0.2 L/kg.
Elimination Route
Spironolactone reaches a maximum concentration in 2.6 hours and an active metabolite (canrenone) reaches a maximum concentration in 4.3 hours. When taken with food, the bioavailability of spironolactone increases to 95.4%.
Giving spironolactone with food increases the maximum concentration from 209ng/mL to 301ng/mL. The time to maximum concentration also increases from 2.28 hours to 3.05 hours. The area under the curve varies from 2103ng/mL*hr to 4544ng/mL*hr.
Torasemide is the diuretic with the highest oral bioavailability even in advanced stages of chronic kidney disease. This bioavailability tends to be higher than 80% regardless of the patient condition. The maximal serum concentration is reported to be of 1 hour and the absorption parameters are not affected by its use concomitantly with food.
Half Life
1.4 hours.
Canrenone has a half life of 16.5 hours, 7-α-thiomethylspirolactone has a half life of 13.8 hours, and 6-ß-hydroxy-7-α-thiomethylspirolactone has a half life of 15 hours.
The average half-life of torasemide is 3.5 hours.
Clearance
Clearance data is not readily available.
The clearance rate of torasemide is considerably reduced by the presence of renal disorders.
Elimination Route
Metabolites of spironolactone are excreted 42-56% in urine, and 14.2-14.6% in the feces. No unmetabolized spironolactone is present in the urine.
Torasemide is mainly hepatically processed and excreted in the feces from which about 70-80% of the administered dose is excreted by this pathway. On the other hand, about 20-30% of the administered dose is found in the urine.
Pregnancy & Breastfeeding use
Pregnancy: Spironolactone should not be used during pregnancy
Lactation: Canrenone, an active metabolite of Spironolactone, appears in breast milk. If use of the drug is deemed essential an alternative method of infant feeding should be instituted.
Pregnancy: Adequate and well controlled studies of torasemide have not been carried out in pregnant woman. Because animal reproduction studies are not always predictive of human response, torasemide can be used during pregnancy only if clearly needed.
Nursing Mother: lt is not known whether torasemide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when torasemide is administered to a nursing mother.
Contraindication
Spironolactone is contraindicated in patients with acute renal insufficiency, significant impairment of renal function, anuria, hyperkalaemia or sensitivity to Spironolactone.
Torasemide is contraindicated in patients with known hypersensitivity to torasemide and other sulfonyl ureas. It is also contraindicated in patients who are anuric.
Special Warning
Use in children: Safety and efficacy of torasemide in children have not been established.
Acute Overdose
Symptoms of overdosage include drowsiness, mental confusion, dizziness, diarrhea and vomiting etc. Patients should induce vomiting or evacuate the stomach by lavage during Spironolactone overdoasge.
There is no human experience of overdoses of torasemide, but the signs and symptoms of overdosage can be anticipated to be those of excessive pharmacological effect: dehydration, hypovolemia, hypotension and hypokalemia. Treatment of overdose should consist of fluid and electrolyte supplement.
Storage Condition
Store in a cool and dry place protected from light. Keep out of reach of children.
Store Torasemide at room temperature less than 30° C and keep in cool and dry place, away from moisture and sunlight. Keep the medicine out of the reach of children.
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