Anesthesia Pharmacology: Renal Pharmacology
Adverse Diuretic effects and contraindications
Adverse Effects: Carbonic Anhydrase Inhibitors (Acetazolamide)
Hyperchloremic metabolic acidosis
Due to reduction in body bicarbonate stores
Bicarbonate loss is associated with:
Hypercalciuria (calcium salts, relatively insoluble at alkaline pH)
Renal potassium loss:
Increased sodium bicarbonate in the collecting tubule increases the lumen-negative and in inelectrical potential -- enhances potassium excretion
Counteracted by potassium chloride administration
Accumulation in renal failure (CNS toxicity)
Urinary alkalinization will decrease ammonium ion trapping, increasing the likelihood of hepatic encephalopathy.
Adverse Effects: Loop Diuretics
Increased delivery of NaCl and water to the collecting duct increases potassium and proton secretion-- causing a hypokalemic metabolic alkalosis
In managed by potassium replacement and by ensuring adequate fluid intake
Dose-related hearing loss (in usually reversible)
With decreased renal function
With concurrent administration of other ototoxic drugs such as aminoglycosides
May cause gout
Loop diuretics cause increased uric acid reabsorption in the proximal tubule, secondary to hypovolemic states.
Hypomagnesemia: loop diuretics cause:
Reduction in sodium chloride reabsorption
Decreases normal lumen-positive potential (secondary to potassium recycling)
Positive lumen potential: drives divalent cationic reabsorption (calcium magnesium)
Therefore, loop diuretics increase magnesium and calcium excretion.
Hypomagnesemia may occur in some patients.
Reversed by oral magnesium administration
Furosemide: skin rash, eosinophilia, interstitial nephritis(less often)
Dehydration (may be severe)
Hypercalcemia may occur in severe dehydration and if a hypercalcemia condition (e.g. oat cell long carcinoma) is also present.
Adverse Effects: Thiazides
Hypokalemic metabolic alkalosis and hyperuricemia
Impaired carbohydrate tolerance
May induce hyperglycemia
Impaired pancreatic insulin release
Decreased tissue glucose utilization
Hyperglycemia may be partially reversed by correcting a hypokalemic state
5% to 15% increase in serum cholesterol and an increase in low-density lipoproteins.
Significant adverse effect, occasionally life-threatening
Hypovolemia-induced increase in ADH
Reduced renal diluting capacity
Prevention: decreasing the drug dose or limiting fluid intake
Thiazides are sulfonamides: cross-reactivity within the group
Extremely rare reactions:
Acute necrotizing pancreatitis
Adverse Effects: Osmotic Diuretics
Volume expansion effects -- increased extra cellular fluid volume and hyponatremia may cause:
Pulmonary edema, complicating congestive heart failure
Headache, nausea, vomiting -- commonly observed
Dehydration and hypernatremia:
Leads to significant dehydration and in the absence of adequate fluid replacement leads to hypernatremia.
Adverse Effects: Potassium-Sparing Diuretics
Potassium-sparing diuretics can cause significant hyperkalemia
Factors that increase the likelihood of hyperkalemia:
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:
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 beta-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
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