Anesthesia Pharmacology: Renal Pharmacology
These diuretics inhibit the effects of aldosterone at the cortical collecting tubule and late distal tubule.
In the collecting tubule and duct, sodium reabsorption and potassium excretion is regulated by aldosterone.
Aldosterone increases potassium secretion by increasing Na/K ATPase activity and sodium and potassium channel activity.
Normally, sodium absorption in the collecting tubule results in a lumen-negative electrical force that drives potassium excretion.
Aldosterone antagonists interfere with this effect
Aldosterone antagonists act similarly with respect to proton movement, accounting for metabolic acidosis associated with aldosterone antagonists.
Pharmacologic antagonism at mineralocorticoid receptors ( spironolactone (Aldactone))
Inhibition of sodium transport through the luminal membrane (triamterene (Dyrenium), amiloride (Midamor))
Some Potassium-Sparing effects occur with nonsteroidal anti-inflammatory drugs, β-blockers, converting enzyme-inhibitors, and angiotensin receptor blockers.
Synthetic steroid: competitive aldosterone antagonist
Binds to cytoplasmic mineralocorticoid receptors, preventing receptor complex translocation to the nucleus.
Also inhibits formation of active metabolite of aldosterone, by inhibiting 5-alpha reductase activity.
Slow onset of action
Renal excretion; hepatic metabolism-- extensive metabolism (short half life)
Directly blocks Na entry through sodium-specific channels (apical collecting tubule membrane) -- note that since potassium secretion is coupled to sodium entry, potassium secretion (potassium-sparing) is reduced.
Excreted unchanged (urine)
Directly blocks Na+ entry through sodium-specific channels (apical collecting tubule membrane) -- note that since potassium secretion is coupled to sodium entry, potassium secretion (potassium-sparing) is reduced.
Conn's syndrome (primary hypersecretion).
Ectopic ACTH production (primary hypersecretion).
Secondary aldosteronism caused by:
Congestive heart failure.
Conditions that cause renal salt retention with reduced intravascular volume.
Other diuretics may further reduce intravascular volume thus worsening secondary aldosteronism.
Potassium-sparing diuretics can cause significant hyperkalemia
Factors that increase the likelihood of hyperkalemia include:
Presence of agents that reduce renin:
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Angiotensin receptor blockers
Hyperkalemia more likely when potassium-sparing diuretics are used as the only diuretic drug or in the presence of renal insufficiency.
Given in combination with thiazides, hypokalemia and metabolic alkalosis associated with thiazide use may be balanced by aldosterone antagonists
Since thiazide adverse effects may predominate (hyponatremia, metabolic alkalosis), due to variations in bioavailability, individual dose adjustment of the two drugs may be better.
Hyperchloremic Metabolic Acidosis:
Acidosis cause by inhibition of proton secretion along with potassium secretion (similar to type IV renal tubular acidosis
Endocrine abnormalities associated with synthetic steroids --Spironolactone (Aldactone)
Gynecomastia (breast enlargement)
Benign prostatic hyperplasia
Acute Renal Failure:
Triamterene (Dyrenium) plus indomethacin
Triamterene (Dyrenium) (poorly soluble) may precipitate in urine, causing renal stones:
May cause severe (potentially fatal) hyperkalemia
Potassium supplements should be discontinued prior to administration of aldosterone antagonists
Patients with chronic renal insufficiency are at particular risk
Hyperkalemia is also more likely to occur or it if β-blockers or ACE inhibitors are concurrently administered
Impairment of hepatic metabolism of triamterene spironolactone may require dose adjustment
Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp. 685- 713
Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732
This Web-based pharmacology and disease-based integrated teaching site is based on reference materials, that are believed reliable and consistent with standards accepted at the time of development. Possibility of human error and on-going research and development in medical sciences do not allow assurance that the information contained herein is in every respect accurate or complete. Users should confirm the information contained herein with other sources. This site should only be considered as a teaching aid for undergraduate and graduate biomedical education and is intended only as a teaching site. Information contained here should not be used for patient management and should not be used as a substitute for consultation with practicing medical professionals. Users of this website should check the product information sheet included in the package of any drug they plan to administer to be certain that the information contained in this site is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. Advertisements that appear on this site are not reviewed for content accuracy and it is the responsibility of users of this website to make individual assessments concerning this information. Medical or other information thus obtained should not be used as a substitute for consultation with practicing medical or scientific or other professionals.