SPIRONOLACTONE
Chemistry - A synthetically produced aldosterone antagonist, spironolactone occurs as a cream-colored to light tan, crystalline powder with a faint mercaptan-like odor. It has a melting range of198°-207°, with decomposition. Spironolactone is practically insoluble in water and soluble inalcohol.
Spironolactone is not commonly used alone as most sodium is reabsorbed at the proximal tubules.
Combining it with a thiazide or loop diuretic will yield maximum diuretic effect.
Uses, Indications - The use of spironolactone in veterinary medicine is rather limited. It may beused in patients who develop hypokalemia on other diuretics and are unwilling or unable to supplement with exogenous potassium sources. It may also be effective in treating ascites as it has lesspotential to increase ammonia levels than other diuretics.
Spironolactone and its active metabolite canrenone, are both about 98% bound to plasma proteins.
Both spironolactone and its metabolites may cross the placenta. Canrenone has been detected inbreast milk. Spironolactone is rapidly metabolized (half-life of 1-2 hours) to several metabolites, including canrenone, which has diuretic activity. Canrenone is more slowly eliminated, with anaverage half-life of around 20 hours.
Contraindications/Precautions - Spironolactone is contraindicated in patients with hyperkalemia, anuria, acute renal failure or significant renal impairment. It should be used cautiously in patientswith any renal impairment or hepatic disease.
Use of spironolactone in patients with renal impairment may lead to hyperkalemia. Spironolactonereportedly inhibits the synthesis of testosterone and may increase the peripheral conversion oftestosterone to estradiol. Long-term toxicity studies in rats have demonstrated that spironolactone istumorigenic in that species. Safe use of this drug has not been established during pregnancy and, ascanrenone is distributed into milk, nursing should be discontinued if therapy with the drug isrequired.
Overdosage - Information on overdosage of spironolactone is apparently unavailable. Should anacute overdose occur, it is suggested to fol ow the guidelines outlined in the chlorothiazide andfurosemide monographs (preceeding this one).
Spironolactone may increase the half-life of digoxin and may either decrease or increase the half-life of digitoxin. Enhanced monitoring of digitalis serum levels and effects are warranted whenspironolactone is used with these agents. Spironolactone may mute the effects of mitotane if givenconcurrently, but very limited information is available on this potential interaction; monitorcarefully.
Spironolactone's diuretic effects may be decreased if aspirin (or other salicylates) are administered concomitantly.
Vascular responses to norepinephrine and regional or general anesthesia may be diminished inpatients also receiving spironolactone.
Additive or potentiated effects may occur if spironolactone is added to other diuretics or antihypertensive agents; dosage adjustments and increased monitoring may be necessary.
Food may enhance the absorption of spironolactone.
Drug/Lab Interactions - Spironolactone may give falsely elevated digoxin values, if using aradioimmune assay (RIA) method. Fluorometric methods of determining plasma and urinary 17-hydroxycorticosteroids (cortisol) may be interfered with by spironolactone.
Storage, Stability, Compatibility
Spironolactone tablets should be stored at room-temperaturein tight, light-resistant containers. An extemporaneously prepared oral suspension can be preparedby pulverizing commercially available tablets and adding cherry syrup. This preparation isreportedly stable for at least one month when refrigerated.Pharmacology - SPIRONOLACTONE
Aldosterone is competitively inhibited by spironolactone in the distal renal tubuleswith resultant increased excretion of sodium, chloride and water, and decreased excretion ofpotassium, ammonium, phosphate and titratable acid. Spironolactone has no effect on carbonicanhydrase or renal transport mechanisms and has its greatest effect in patients with hyperaldosteronism.Spironolactone is not commonly used alone as most sodium is reabsorbed at the proximal tubules.
Combining it with a thiazide or loop diuretic will yield maximum diuretic effect.
Uses, Indications - The use of spironolactone in veterinary medicine is rather limited. It may beused in patients who develop hypokalemia on other diuretics and are unwilling or unable to supplement with exogenous potassium sources. It may also be effective in treating ascites as it has lesspotential to increase ammonia levels than other diuretics.
Pharmacokinetics - SPIRONOLACTONE
No information was found regarding the pharmacokinetics of spironolactonein veterinary species. In humans, spironolactone is >90% bioavailable and peak levels are reachedwithin 1-2 hours. The diuretic action of spironolactone (when used alone) is gradually attained andgenerally reaches its maximal effect on the third day of therapy.Spironolactone and its active metabolite canrenone, are both about 98% bound to plasma proteins.
Both spironolactone and its metabolites may cross the placenta. Canrenone has been detected inbreast milk. Spironolactone is rapidly metabolized (half-life of 1-2 hours) to several metabolites, including canrenone, which has diuretic activity. Canrenone is more slowly eliminated, with anaverage half-life of around 20 hours.
Contraindications/Precautions - Spironolactone is contraindicated in patients with hyperkalemia, anuria, acute renal failure or significant renal impairment. It should be used cautiously in patientswith any renal impairment or hepatic disease.
Adverse Effects, Warnings
Adverse effects are usually considered mild and reversible upondiscontinuation of the drug. Electrolyte (hyperkalemia, hyponatremia) and water balance(dehydration) abnormalities are the most likely effects with spironolactone therapy. Transient increases in BUN and mild acidosis may occur in patients with renal impairment. GI distress(vomiting, anorexia, etc.), CNS effects (lethargy, ataxia, headache, etc.) and endocrine changes(gynecomastia in human males) are all possible.Use of spironolactone in patients with renal impairment may lead to hyperkalemia. Spironolactonereportedly inhibits the synthesis of testosterone and may increase the peripheral conversion oftestosterone to estradiol. Long-term toxicity studies in rats have demonstrated that spironolactone istumorigenic in that species. Safe use of this drug has not been established during pregnancy and, ascanrenone is distributed into milk, nursing should be discontinued if therapy with the drug isrequired.
Overdosage - Information on overdosage of spironolactone is apparently unavailable. Should anacute overdose occur, it is suggested to fol ow the guidelines outlined in the chlorothiazide andfurosemide monographs (preceeding this one).
Drug Interactions
Do not use spironolactone concurrently with other potassium-sparing diuretics (e.g., amiloride, triamterene) as hyperkalemia may result. Other drugs that may increase therisk of hyperkalemia if used concomitantly with spironolactone include indomethacin and ACEinhibitors (e.g., captopril, enalapril, etc.)Spironolactone may increase the half-life of digoxin and may either decrease or increase the half-life of digitoxin. Enhanced monitoring of digitalis serum levels and effects are warranted whenspironolactone is used with these agents. Spironolactone may mute the effects of mitotane if givenconcurrently, but very limited information is available on this potential interaction; monitorcarefully.
Spironolactone's diuretic effects may be decreased if aspirin (or other salicylates) are administered concomitantly.
Vascular responses to norepinephrine and regional or general anesthesia may be diminished inpatients also receiving spironolactone.
Additive or potentiated effects may occur if spironolactone is added to other diuretics or antihypertensive agents; dosage adjustments and increased monitoring may be necessary.
Food may enhance the absorption of spironolactone.
Drug/Lab Interactions - Spironolactone may give falsely elevated digoxin values, if using aradioimmune assay (RIA) method. Fluorometric methods of determining plasma and urinary 17-hydroxycorticosteroids (cortisol) may be interfered with by spironolactone.