General Information

Drug Code                              Preparation                             Strength

       106                                   Tab. Frusemide                        40 mg

       107                                   Tab. Frusemide                        10 mg/ml 2ml Amp.

Description of the Drug

            Frusemide is a potent loop diuretic.

Mode of Action

Frusemide inhibits the reabsorption of electrolytes primarily in the ascending limb of the loop of henle. It also increases renal blood flow and causes redistribution of blood flow within the renal cortex. Excretion of sodium, potassium, magnesium, calcium and chloride ions is increased and water excretion enhanced. It also decreases left ventricular filling pressure.

Pharmacokinetics :

Rapidly absorbed from the Git, is mainly excreted in the urine unchanged.  Frusemide crosses the placental barrier and is secreted in the milk. Duration of action for 2 – 3 hours, its effect starting rapidly after I.V. administration and within 1 hour of oral administration.

Clinical Information

Indications  

·    Treatment of edema associated with congestive cardiac failure, renal diseases (nephortic syndrome) and hepatic disorders.

·    Management of oliguria in acute or chronic renal failure.

·    Cerebral edema.

·    In hypertension or as an adjunct to other antihypertensive agents.

·    Forced alkaline diuresis in barbiturate poisoning.

Dosage

Adults:

            20 –80 mg – b.d.

Children:

            2 mg/kg – twice a day.

Route of Administration        Oral, I.M., I.V.

Contraindications  

·    States of electrolyte depletion.

·    Severe hepatic dysfunction.

·    Severe renal failure with complete anuria.

Precaution / Practice points

·    Excessive diuresis may cause dehydration, decreased blood volume and circulatatory collapse; correct hypovolemia before administration.

·    Electrolytes to be checked periodically.

·    Hypokalemia can occur especially in patients on salt restriction, cirrhosis and in the elderly. In digitalized patients this can precipitate cardio toxicity. Hence concurrent potassium supplements to be used.

·    It contains a sulphonamide moiety. So it is to be avoided in patients who are allergic to sulphonamides.

·    It causes hyperglycemia and aggravates or unmasks diabetes mellitus.

·    It is not effective in patients with a creatinine clearance of less than 30 ml.

·    Hyponatremia can occur in  patients with severe CCF when on salt restriction.

·    Can exacerbate or activate systemic lupus erythematosus in susceptible patients.

·    Administration Instructions:

-     Give I.V. injections very slowly – rate not more than 4 mg/minutes.

-       For infusion, diluents to be used is  normal saline or 5 % dextrose.

-     Administer tablets with food.

Drug Interactions

Potentially fatal:

·    Salicylate toxicity is increased due to decreased excretion.

·    Risk of major bleeding episodes due to increased effects of anticoagulants.

·    Lithium carbonate – by decreasing its excretion, may precipitate toxicity.

·    Increase toxicity of digoxin, amiodarone, disopyramide, astemizole, terfenadine, flecanamide and quinidine and antagonizes effects of lignocaine by causing hypokalemia.

Non fatal:

·    With amino glycosides – risk of ototoxicity is increased.

·    Indomethacin and ketorolac reduces effects of frusemide.

·    With  sulphonyl  ureas - loss of control of diabetes due to antagonism of its effects may occur.

·    Enhances hypotensive effects of antihypertensives agents.

·    Steroids antagonises diuretic effects of frusemide.

Adverse Effects

Common effects :

·    Orthostatic hypotension and dizziness.

·    Fluid and electrolyte imbalance including hypokalemia, hyponatraemia and hypochloraemic
alkalosis.

·    Hyperuricaemia can precipitate attacks of gout.

·    Otto–toxicity – tinnitus and hearing loss, especially if given along with amino glycosides.

Rare effects:

·    Hypersensitivity reaction – skin rashes, photosensitivity reaction, eosinophilia etc.,

·    Pancreaatitis and cholestatic jaundice.

·    Dizziness, headache and paraesthesias.

·    Hyperglycemia, increase inplasma cholesrol and TGL levels.

Drug Toxicity

At does of more than 700 mg/kg – dehydration, blood volume depletion, hypotension ,circulatory collapse, electrolyte imbalances – hypokalemia, metabolic alkalosis.

Treatment of Toxicity

Supportive and symptomatic treatment – management of electrolyte and fluid imbalance.

            I.V. fluids and trendelenburg’s position to combat hypotension.

Storage

            Protect  from light.

Shelf life                      3 years.

ACETAZOLAMIDE

General information

Drug Code                              Preparation                                Strength

       118                                   Tab. Acetazolamide                      250 mg.

Description of the Drug

            Acetazolamide, a sulphonamide derivative, is a carbonic anhydrase inhibitor.

Mode of Action

Blocks the action of carbonic anhydrase in the proximal convoluted tubule and hence prevents bicarbonate resorption, causing alkaline diuresis with potassium depletion. In the eye,  it decreased the formation of aqueous humour and so decreases intraocular pressure.

Pharmacokinetics :

Rapidly absorbed from the GIT.high concentrations are seen in RBCs, and the renal cortex. It is excreted unchanged in the urine. Action starts ½ hour after ingestion, maximum action at about 2 hours and action lasts for 12 hours.

Clinical Information

Indications  

·    Glaucoma – part of regimen used in treatment of wide-angle glaucoma and in acute management of an attack of closed angle glaucoma.

·    Urinary alkalinization – to accelerate removal of drugs like aspirin or treatment of urinary tract infection.

·    Rarely as an anticonvulsant for certain types of epilepsies refractory to other treatment regimes.

Dosage

            250 – 500 mg b.d.

Route of Administration    Oral:

Contraindications  

·    Hypersensitivity to sulphonamides or acetazolamide.

·    Hepatic disorders.

·    Adrenocortical insufficiency.

·    Hyperchloremic acidosis.

·    Severe renal failure.

·    Severe pulmonary obstruction.

·    States of sodium or potassium depletion.

Precaution / Practice Points

·    Use with caution inpatients with COPD, who are likely to develop acidosis.

·    Dosage to be adjusted in elderly persons and in renal dysfunction.

·    Plasma electrolytes and blood count to be monitored periodically while on long-term therapy.

·    Continuous administration of acetazolamide is associated with loss of diuretic activity.

·    Avoid in cirrhosis because encephalopathy  myay be precipitated by decreasing ammonium ion
excretion.

·    Use with caution in diabetics (loss of control may occur).

·    Instruct patient not drive or operate machinery and to Abstain from alcohol. Mental alertness may be impaired.

·    Administration instructions:

-     Take with food.

Drug Interactions

Potentially fatal:

·    Steroids increases the risk of hypokalemia.

·    May cause digitoxicity by causing hypokalemia , in patients stabilized on digoxin.

·    Reduced quinidine excretion and increase in toxicity.

·    Salicylates potentiate the toxicity of acetazolamide by interfering with its excretion.

Non fatal:

Antacids enhances the risk of calculus formation in patients taking acetazolamide.

            When combined with antiepileptics, can cause severe osteomalacia.

            Lithium excretion is increased by acetazolamide.

Adverse Effects

Common effects:

·    Metallic taste, anorexia.

·    Hypokalemia, hyperchloremic metabolic acidosis due to K + and bicarbonate loss.

·    Malaise, fatigue, depression , excitement, headache Weight loss , drowsiness.

Rare effects :

·    Crystallluria, tendency to form renal calculi, mainly due to phosphaturia and hypercalciuria.

·    Bone marrow depression.

·    Fever, rashes, and other hypersenstitivity reactions.

·    Parasthesias and myalgia.

Drug Toxicity

·    Electrolyte disturbances – hypokalemia and its consequences, hyperchloremic metabolic acidosis. Hypoglycemia may occur.      

·    CNS – drowsiness, stupor, parasthesias in large doses.

·    Nausea, confusion, agitation, sweating, convulsions may occur.

Treatment of Toxicity

            Gastric lavage , symptomatic and supportive line of management.

Storage

            Store in a cool place, protected from light.

Shelf life         31 months.

MANNITOL

General information

Drug Code                              Preparation                             Strength

       340                                   Inj. Mannitol                                         20 % w/v.

                                                                                                350 ml.

Description of the Drug

            Mannitol is a hexahydric alcohol related to mannose.

Mode of Action

Mannitol reaches the proximal tubule and loop of  henle by glomerular filtration. There it
exerts an osmotic force against reabsorption of water by the tubules, hence causing a diuresis.

Pharmacokinetics :

Mannitol is not absorbed orally and is given IV as 20 % solution. Distributed in the extra cellular space and extracts water form the intracellular compartment. It is rapidly excreted by the kidney and action starts 30 –60 minutes after administration. Duration of action is 1.5 – 3 hours.

Clinical Information

Indications  

·    To reduce raised intracranial pressure and raised interocular pressure.

·    Helps to preserve renal function and urinary output in acute renal failure when administered along with measures to maintain hydration.

·    Forced diuresis mainly in barbiturate poisoning.

·    To reduce cerebral edema before and after neurosurgery.

Dosage

            1 –2 gm / kg body weight, as 20% solution, infused over 30 min.

Route of Administration       I.V. infusion:

Contraindications  

·    Pulmonary edema, acute left ventricular failure.

·    Cerebral malaria.’

·    Intra cranial bleeding.

·    In patients with diminished cardiac reserve. Expansion of the extra cellular fluid by mannitol can precipitate congestive cardiac failure due to volume overload.

·    If urine flow is inadequate, expansion of the extra cellular fluid may lead to acute water intoxication.

Precaution / Practice Points

·    Should be carefully observed for signs of fluid and electrolyte imbalance.

·    Renal function to be monitored.

·    Administration instruction:

-     Infuse over 20 –30 minutes; caution avoid extravasations; monitor CVS status while administering.

-     Mannitol should not be administered along with whole blood.

Adverse Effects

Common effects:

·    Nausea, vomiting, headache, dizziness.

Rare effects:

·    Fluid and electrolyte imbalance, circulatory overload and precipitation of CCF.

·    Dehydration and hypovolemia if rapid diuresis occurs.

·    Hypersensitivity reactions, skin rahes.

·    Blurred vision.

Drug Toxicity

Polyuria, hypovolemia, hypotension, pulmonary edema, CVS collapse, electroylete imbalance, seizures.

Treatment of Toxicity

·    Symptomatic therapy. Maintenance of water and electrolyte balance.

·    Haemodialysis.

Storage :

            Store at temperature of 20o –30o C to avoid deposition of crystals.

Shelf    Life      3 years.

SPIRONOLACTONE

General information

Drug Code                              Preparation                             Strength

      385                                    Tab. Spironolactione                 25 mg

Description of the Drug :

Spironolactone is a potassium sparing diuretic which acts by antagonism of aldosteone.

Mode of Action :

Spironolactone is a steroid with a structure resembling that of aldosterone. Acts on the distal portion of the renal tuble as a competitive antagonist at the aldosterone receptor. Hence it decreases sodium reabsorption and potassium excretion at the distal tubule.

Pharmacokinetics :

Rapidly absorbed from the GIT. It crosses the placental barrier and is secreted in breast milk. It is excreted mainly in the urine and faeces in the form of metabolites. It has a slow onset of action in 3- 5 days.

Clinical Information

Indications  

·    Edematous conditions (especially effective where states of secondary hyperaldosteronism exists).

-     Congestive cardiac failure to treat the sodium and water retention caused by secondary hyperaldosteronism due to diminished intravascular volume.

-     cirrhosis of liver with as cites and edema – where aldosterone levels are exceptionally high.

-     Renal disorders like nephrotic syndrome.

·    Primary hyperaldosteronism – eg. Conn’s syndrome, ectopic ATCH production (tumours etc.,)

-     Useful for both diagnosis (by therapeutic trial ) as well as treatment.

·    Hypertension – as an adjunct to other drugs.

·    Hypokalemia – when other measures are inappropriate.

Dosage

Adult: 100 mg daily upto a maximum of 400 mg daily.

Children – 3-mg/kg body weight daily.

Route of Administration Oral:

Contraindications  

·    Severe renal impairment with anuris.

·    Patients with hyperkalemia, hyponatremia.

·    Nursing  mothers and pregnancy.

·    Hypersensitivity reactions.

·    Patients with active peptic ulcer.

·    Porphyria.

·    Addison’s Disease.

Precaution / Practice Points

·    Potassium supplements and other potassium sparing diuretics should not be given with spirinolactone . Warn patients against consuming potassium rich foods.

·    Adjust dose in patients with impaired hepatic or renal function.

·    Serum electrolytes, especially potassium should be estimated periodically.

·    Use with caution in patients likely into develop acidosis.

Drug Interactions

Potentially fatal:

·    Drugs blunting the renin – angiotension system like beta-blockers and ACE inhibitors when combined with spironolactone increases risk of hyperkalemia.

·    Risk of hyperkalemia enhanced by NSAIDs and cyclopsorin.

·    Lithium toxicity may occur due to decreased excretion.

Non fatal:

·    It enhances the effects of other antihypertensive agents and may diminish the vascular responses to adernaline.

·    Aspirin antagonizes diuretic effect of spirinolactone.

·    Enhances effects of digoxin.

Adverse Effects

Common effects :

·    As  a continuation of its effects – thirst dry mouth, lethargy and drowsiness occur due to
hyponatremia.

·    Gynaecomastia and other endocrine effects – deepening of voice, hirsutism, irregular menses, and impotence prostatic hypertrophy – on prolonged therapy.

Rare effects

·    Hypersensitive reactions – rashes, urticaria, fever.

·    Gastritis, bleeding from ulcers, abdominal pain, cramping and diarrhoea.

·    CNS – lethargy, ataxia, confusion, headache.

·    Hepatotoxicity.

·    Osleomalacia and blood disorders on prolonged therapy.

·    May be carcinogenic.

Drug Toxicity

Hyperkalemia, leading to complete heart block and death. Symptoms of dehydration, hypovolemia, drowsiness and confusion.

Treatment of Toxicity

·    Gastric lavage, continuous ECG monitoring.

·    I.V. glucose (20 – 50 % ) and insulin – 0.5 unit/gm of glucose infused.

·    Ion-exchange resin may be used.

·    Periodic electrolyte monitoring.

Storage                       Protect from light.

Shelf    Life                 3 years.