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- Pharmacology For Metolazone + Spironolactone
Metolazone + Spironolactone Pharmacology
Metolazone + Spironolactone
About Metolazone + SpironolactoneN/AMechanism of Action of Metolazone + SpironolactoneN/APharmacokinets of Metolazone + SpironolactoneN/AOnset of Action for Metolazone + SpironolactoneN/ADuration of Action for Metolazone + SpironolactoneN/AHalf Life of Metolazone + SpironolactoneN/ASide Effects of Metolazone + SpironolactoneN/AContra-indications of Metolazone + SpironolactoneN/ASpecial Precautions while taking Metolazone + SpironolactoneN/APregnancy Related InformationContraindicatedOld Age Related InformationN/ABreast Feeding Related InformationContraindicatedChildren Related InformationN/AIndications for Metolazone + Spironolactone1.Hypertension
2.Oedema
Interactions for Metolazone + SpironolactoneN/ATypical Dosage for Metolazone + SpironolactoneN/ASchedule of Metolazone + SpironolactoneN/AStorage Requirements for Metolazone + SpironolactoneN/AEffects of Missed Dosage of Metolazone + SpironolactoneN/AEffects of Overdose of Metolazone + SpironolactoneN/AMetolazone
About MetolazoneA thiazide-like diuretic, Symporter inhibitor, Diuretic, Antihypertensive.Mechanism of Action of MetolazoneIt exerts thiazide like diuretic action by acting at site-3(central dilating segment of early distal tubule). It binds to Na+Cl- symporter and inhibits Na+Cl- symport at the luminal membrane. It increases natriuresis, kaliuresis and diuresis. It decreases Ca2+ excretion and increases Mg2+ excretion. It also inhibits PO4 reabsorption in proximal tubules. It also has minor carbonic anhydrase inhibitory action. The antihypertensive actions of the drug may be attributable to depletion of sodium and subsequent reduction in plasma volume and a decrease in peripheral resistance. Decrease in peripheral resistance is due to either the loss of sodium from the arteriolar wall or a direct action on the vascular bed. It is an effective drug in edema associated with congestive heart failure.
Pharmacokinets of MetolazoneAbsorption: It is absorbed orally up to 65%.Distribution: It is about 70% erythrocyte-bound and 30% protein bound. Metabolism: It is not significantly metabolized in the body. Excretion: Excreted mainly through urine as unchanged drugOnset of Action for Metolazone1 hourDuration of Action for Metolazone18 to 24 hoursHalf Life of Metolazone14 hoursSide Effects of Metolazone1.Gastrointestinal disturbances
2.Hypokalaemia
3.Hyponatraemia
4.Hypomagnesaemia
5.Dizziness
6.Headache
7.Muscle cramps
8.Fatigue
9.Arthralgia
10.Carbohydrate intolerance
11.Hypercalcaemia
12.Constipation
13.Nausea
14.Vomiting
15.Abdominal pain
16.Ototoxicity
Contra-indications of Metolazone1.Renal impairment
2.Hepatic impairment
3.Anuria
4.Hypersensitivity to the drug
5.Hyper sensitivity to sulfonamidesSpecial Precautions while taking Metolazone1.Renal impairment
2.Hepatic diseases
3.Avoid exposure to sun light as much as possible to prevent photosensitivity
4.Hyper urecaemia and Gout
5.Diabetes mellitus
6.Monitor and correct Fluid and electrolyte imbalance
7.Cirrhosis
8.Hypercalcaemia
9.Systemic lupus erythematosus
Pregnancy Related InformationUse with cautionOld Age Related InformationUse with cautionBreast Feeding Related InformationContraindicatedChildren Related InformationContraindicatedIndications for Metolazone1.Hypertension
2.Oedema
3.Congestive heart failure
Interactions for MetolazoneLoop diuretics like furosemide, bumetanide and digoxin : Metolazone can lower blood potassium and magnesium levels. This is especially true in patients who are also taking ?loop? diuretics such as furosemide, bumetanide, torsemide. Low potassium and magnesium levels can lead to heart rhythm abnormalities, especially in patients already taking digoxin.
Blood uric acid levels can increase during metolazone treatment, but precipitation of gout due to the increase is rare.
Lithium : Metolazone reduces excretion by the kidneys of lithium and can lead to lithium toxicity in patients being treated with lithium.
NSAIDs : Nsaids such as ibuprofen, naproxen and nabumetone can reduce the effectiveness of metolazone by interfering with the excretion of salt and water.
Alcohol: Alcohol may increase the side effects of metolazoneTypical Dosage for Metolazone2.5 to 10mg/day as a single or two divided doses. Increased if required to 20mg/day.
Rapid acting tablets: 0.5mg 0rally as once daily dosage
Maximum dose: 1gm/ day (for rapid acting tablets)
Schedule of MetolazoneGStorage Requirements for MetolazoneStore at a cool dry place away from light and at a temperature below 30 degree C. in a well closed container. Keep out of reach of children.Effects of Missed Dosage of MetolazoneTake the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the doseEffects of Overdose of MetolazoneTreatment is supportive and symptomatic. Remove drug from the body by induced emesis and gastric lavage. Monitor and assist respiratory, cardiovascular, and renal function as indicated. Monitor and support fluid and electrolyte balance. Spironolactone
About SpironolactoneSelective Aldosterone antagonist, antiandrogen, Potassium-sparing diuretic.Mechanism of Action of SpironolactoneSpironolactone is a steroid with structural similarity to aldosterone which exerts it`s pharmacological actions by acting as a competitive antagonist of aldosterone; in the distal part of nephron (late distal tubule and collecting duct). It prevents potassium secretion and decreases sodium reabsorption. It binds with minerelocorticoid receptor from the interstitial side and inhibits formation of aldosterone induced proteins competitively and thus increases sodium excretion and decreases potassium excretion. It increases Ca excretion also. It also blocks the effects of aldosterone on arteriolar smooth muscles and reduces peripheral resistance. It prevents aldosterone induced sodium and water retention and thus reduces blood volume and used as an effective diuretic in treatment of hypertension and also used to reduce potassium loss associated with the use of other diuretics. It is an effective diuretic in the management of congestive heart failure for mobilization of oedema fluid. It prevents aldosterone induced myocardial fibrosis and disease progression in patients with congestive heart failure.
Pharmacokinets of SpironolactoneSpironolactone is a steroid with structural similarity to aldosterone which exerts it`s pharmacological actions by acting as a competitive antagonist of aldosterone; in the distal part of nephron (late distal tubule and collecting duct). It prevents potassium secretion and decreases sodium reabsorption. It binds with minerelocorticoid receptor from the interstitial side and inhibits formation of aldosterone induced proteins competitively and thus increases sodium excretion and decreases potassium excretion. It increases Ca excretion also. It also blocks the effects of aldosterone on arteriolar smooth muscles and reduces peripheral resistance. It prevents aldosterone induced sodium and water retention and thus reduces blood volume and used as an effective diuretic in treatment of hypertension and also used to reduce potassium loss associated with the use of other diuretics. It is an effective diuretic in the management of congestive heart failure for mobilization of oedema fluid. It prevents aldosterone induced myocardial fibrosis and disease progression in patients with congestive heart failure.Onset of Action for Spironolactone1 to2 daysDuration of Action for Spironolactone2 to 3daysHalf Life of SpironolactoneN/ASide Effects of Spironolactone1.Headache
2.Drowsiness
3.Nausea
4.Duodenal and gastric bleeding
5.Ulceration
6.Gynecomastia
7.Menstrual irregularities
8.Testicular atrophy
9.Ataxia
10.Impotence
11.Diarrhoea
12.Vomiting
13.Hyper kalemia
14.Hyponatraemia
15.Agranulocytosis
16.Altered levels of blood urea nitrogen
17.Gastro intestinal disturbances
18.Rashes
19.Ototoxicity
Contra-indications of Spironolactone1.Hypersensitivity to the drug
2.Hyper kalaemia
3.Anuria
4.Acute and progressive renal insufficiency
Special Precautions while taking Spironolactone1.Renal impairment
2.Hepatic impairment
3.Fluid and electrolyte imbalance
Pregnancy Related InformationContraindicatedOld Age Related InformationUse with cautionBreast Feeding Related InformationContraindicatedChildren Related InformationUse with cautionIndications for Spironolactone1.Hypertension
2.Oedema
3.Diagnosis of primary hyperaldosteronism
4.Hirsutism
5.Premenstrual syndrome
6.Acne
7.Seborrhoeics
Interactions for SpironolactoneACE Inhibitors: Enhanced hypotensive effect; significant hyperkalaemia may occur.
Digitalis glycosides: Interaction is complex and may result in increased serum digoxin levels & subsequent digitalis toxicity.
Cyclosporin: Increased risk of hyperkalaemia.
Potassium Preparations: May result in hyperkalaemia, possibly with cardiac arrhythmias or cardiac arrest, especially in patients with impaired renal functions.
Salicylates: Diuretic effects reduced by salicylates.
Carbenoxolone: Ulcer healing effect antagonised by spironolactone.
Food: Increased absorption of spironolactone.
Lab tests: Interferes with radio-immuno assay for measuring digoxin, resulting in falsely elevated serum digoxin.
Typical Dosage for SpironolactoneHypertension: 50 to 100mg/day in divided doses.
Oedema: 25 to 200mg/day in divided doses.
Diagnosis of primary hyperaldosteronism: 400mg/day (short test) or up to four weeks (long test)
Hirsutism: 25 to 200mg/day in divided doses.
Premenstrual syndrome: 25mg four times on fourteenth day of menstrual cycle.
Acne: 100mg/day.
Schedule of SpironolactoneHStorage Requirements for SpironolactoneStore at room temperature in a well closed container and protects from light.Effects of Missed Dosage of SpironolactoneTake the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.Effects of Overdose of SpironolactoneTreatment is supportive and symptomatic. Remove drug from the body by induced emesis and gastric lavage. Monitor and support electrolyte balance. Reduce serum potassium with I.V. sodium bicarbonate or glucose with insulin. Potassium level is also reduced by a cation exchange resins like sodium polystyrene sulfonate given orally or as retention enema.
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