Frusemide + Spironolactone Pharmacology

Frusemide + Spironolactone

About Frusemide + Spironolactone
N/A
Mechanism of Action of Frusemide + Spironolactone
N/A
Pharmacokinets of Frusemide + Spironolactone
N/A
Onset of Action for Frusemide + Spironolactone
N/A
Duration of Action for Frusemide + Spironolactone
N/A
Half Life of Frusemide + Spironolactone
N/A
Side Effects of Frusemide + Spironolactone
N/A
Contra-indications of Frusemide + Spironolactone
N/A
Special Precautions while taking Frusemide + Spironolactone
N/A
Pregnancy Related Information
Contraindicated; since Spironolactone is contraindicated in pregnancy.
Old Age Related Information
N/A
Breast Feeding Related Information
Contraindicated; since Frusemide and Spironolactone are contraindicated in lactation
Children Related Information
N/A
Indications for Frusemide + Spironolactone
1.Hypertension associated with secondary hyper aldosteronism
2.Refractory Oedema
3.Chronic congestive heart failure
4.Hepatic cirrhosis with ascites
Interactions for Frusemide + Spironolactone
N/A
Typical Dosage for Frusemide + Spironolactone
Adult:
Oral:
Frusemide 20mg + Spironolactone 50mg; 1 to 4 tablets daily as single or divided doses
Frusemide 40mg + Spironolactone 50mg; 1 to 2 tablets daily
Schedule of Frusemide + Spironolactone
N/A
Storage Requirements for Frusemide + Spironolactone
N/A
Effects of Missed Dosage of Frusemide + Spironolactone
N/A
Effects of Overdose of Frusemide + Spironolactone
N/A

Frusemide

About Frusemide
A high ceiling loop diuretic, Symporter inhibitor,anthranilic acid derivative, Diuretic ,antiedema ,antihypertensive.
Mechanism of Action of Frusemide
Furosemide is a high ceiling loop diuretic which exerts it`s diuretic action by acting at site-2(thick ascending loop of Henle). It binds to Na+K+2Cl- co transporter and inhibits Na+K+2Cl- co transport in luminal membrane of thick ascending loop of Henle. It inhibits sodium and chloride re absorption and promotes excretion of sodium, water, chloride, potassium, calcium, and magnesium. It abolishes cortico-medullary osmotic gradient and blocks positive as well as negative free water clearance. It also has weak carbonic anhydrase inhibitory action.
It increase local prostaglandin synthesis and increases systemic venous capacitance and decreases left ventricular filling pressure. This causes relief in left ventricular failure and pulmonary edema. It causes renal and peripheral vasodilatation and decrease in peripheral resistance. It is preferred in the initial treatment of congestive heart failure for rapid mobilization of oedema fluid.
Vertigo: Diuretics are used in vertigo in assumption that vertigo is due to endolymphatic hydrops. They reduce labyrinthine fluid pressure.

Pharmacokinets of Frusemide
Absorption: Absorbed orally about 60%.
Distribution: It is widely distributed in a plasma protein bound form and crosses placenta. Metabolism: It is partly metabolized by glucuronide conjugation.
Excretion: Excreted as unchanged drug mainly through urine. Some drug is excreted through faeces
Onset of Action for Frusemide
Oral: 20 to 40 minutes
I.V.: 2 to 5 minutes
I.M.: 10 to 20 minutes
Duration of Action for Frusemide
Oral: 6 to 8hours
I.V.: 2 hours
Half Life of Frusemide
30 to 120 minutes
Side Effects of Frusemide
1. Dizziness
2. Headache
3. Diarrhoea
4. Anorexia
5. Nausea
6. Polyurea
7. Vomiting
8. Constipation
9. Frequent urination
10. Nocturea
11. Altered renal function tests
12. Weakness
13. Altered liver function tests
14. Dry mouth
15. Hypo calcaemia
16. Hypo kalaemia
17. Hypo natraemia
18. Transient deafness
19. Gastro intestinal disturbances
20. Visual impairment
21. Muscle cramps
22. Decreased tolerance to carbohydrates
23. Hyper uricaemia.
24. Electrolyte imbalance
25. Orthostatic hypotension
26. Aplastic anaemia
27. Agranulocytosis
28. Paraesthesia
29.Ototoxicity


Contra-indications of Frusemide
1. Hypo natraemia
2. Hypo kalaemia
3. Hypo volaemia
4. Hypotension
5. Hepatic coma
6. Hypersensitivity to the drug
7. Anuric renal failure

Special Precautions while taking Frusemide
1. Hepatic impairment
2. Renal impairment
3. Gout
4. Diabetes mellitus
5. Hypersensitivity to Sulfonamides
6. Fluid and electrolyte imbalance
7. Long term purgatives
8. Hepatic cirrhosis
9. Chronic Diarrhoea and dehydration.

Pregnancy Related Information
Use with caution
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Use with caution
Indications for Frusemide
1. Hypertension
2. Oedema associated with heart failure
3. Oedema due to renal and hepatic diseases
4. Acute pulmonary Oedema
5. Cerebral Oedema
6. Refractory Oedema
7. Hypercalcaemia
8. Oliguria
9. Forced diuresis in drug over dosage.
10. Vertigo

Interactions for Frusemide
Anticoagulants: Activity of anticoagulants may be enhanced.
Aminoglycoside antibiotics: Frusemide increases potential for ototoxicity.
Cisplatin: Frusemide increases potential for ototoxicity.
Digitalis glycosides: Diuretics induced potassium loss may precipitate digitalis toxicity, increased frequency of cardiac arrhythmias.
NSAIDs: Effect of frusemide reduced.
Lithium: Therapeutic and toxic effects of lithium increased.
Metolazone: Profound diuresis and greater than predicted electrolyte loss related to the ability of metolazone to block proximal tubular sodium reabsorption useful in patients refractory to frusemide.
Non-depolarizing muscle relaxants: Action of succinylcholine & tubocurarine potentiated by low doses reversed by high doses.
Food: Efficacy reduced when administered with food.
Propranolol: Plasma propranolol level may be increased.
Clofibrate: Increased diuretic responses.
Hydantoins: May decrease the diuretic effects.
Typical Dosage for Frusemide
Oral:
Oedema: 40mg in the morning. Increased if required; based on patient`s response up to 80mg.
Maintenance dosage: 20 to 40mg daily or on alternate days.
Maximum dose: 600mg/day.
Children: 3mg/kg/day.
I.V.:
Adult: 20 to 50mg as slow I.V. or I.M. injection. Increased by 20mg every 2hours. Higher I.V. doses must be infused
Children: 0.5 to 1.5mg/kg/day.
Maximum child dose: 20mg/day.
Oliguria: 250mg/day. Gradually increased; by 250mg at every 4 to 6 hours.
Maximum dose: 2gm
Hypertension: 40mg orally twice daily. Adjust the dosage according to patient`s response.
Hypercalcaemia: 120mg orally/day or 80 to 100mg I.V. every 1 to 2 hours
Acute pulmonary Oedema:
Adults: 40mg slow I.V. injection. Then 80mg within 1hour if required.
Children: 1mg/kg I.V.or I.M. Every 2 hours until desired response is gained.
Maximum dose: 6mg/kg/day.

Schedule of Frusemide
N/A
Storage Requirements for Frusemide
Store at controlled room temperature at a range of 15 to 30 degree C. in a well closed container and protects from light.
Effects of Missed Dosage of Frusemide
Take 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 Frusemide
Treatment is supportive and symptomatic. Monitor and support fluid and electrolyte balance by replacing fluids and electrolytes.

Spironolactone

About Spironolactone
Selective Aldosterone antagonist, antiandrogen, Potassium-sparing diuretic.
Mechanism of Action of Spironolactone
Spironolactone 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 Spironolactone
Spironolactone 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 Spironolactone
1 to2 days
Duration of Action for Spironolactone
2 to 3days
Half Life of Spironolactone
N/A
Side Effects of Spironolactone
1.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 Spironolactone
1.Hypersensitivity to the drug
2.Hyper kalaemia
3.Anuria
4.Acute and progressive renal insufficiency

Special Precautions while taking Spironolactone
1.Renal impairment
2.Hepatic impairment
3.Fluid and electrolyte imbalance



Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Use with caution
Indications for Spironolactone
1.Hypertension
2.Oedema
3.Diagnosis of primary hyperaldosteronism
4.Hirsutism
5.Premenstrual syndrome
6.Acne
7.Seborrhoeics

Interactions for Spironolactone
ACE 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 Spironolactone
Hypertension: 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 Spironolactone
H
Storage Requirements for Spironolactone
Store at room temperature in a well closed container and protects from light.
Effects of Missed Dosage of Spironolactone
Take 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 Spironolactone
Treatment 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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