Pseudohypoaldosteronism Medication
- Author: Alicia Diaz-Thomas, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD more...
Medication Summary
Drugs used in the management of pseudohypoaldosteronism (PHA) include alkalizing agents, potassium-binding resins, prostaglandin inhibitors, and diuretics.
Alkalinizing agents
Class Summary
These agents are used for correcting acidosis in children with early childhood hyperkalemia during the first few years of life. Correction of acidosis in pseudohypoaldosteronism type II (PHA-II) does not correct the hyperkalemia.
Sodium bicarbonate (Neut, Brioschi)
Sodium bicarbonate is preferred for alkali therapy because it is inexpensive and easy to prepare and does not have to be metabolized by the liver. Unfortunately, sodium bicarbonate is commercially available for oral use only in 325-mg (ie, 5-grain) and 650-mg (ie, 10-grain) tablets, which provide 4 mEq and 8 mEq per tablet, respectively. These tabs can be crushed and added to food or diluted in water to yield a bicarbonate concentration of 1 mEq/mL.
An alternative is to mix an 8-oz box of baking soda in 2.88 L of distilled water to produce a concentration of 1 mEq/mL. It is also feasible to administer an appropriate concentration of the intravenous (IV) product orally.
Citric acid and sodium citrate (Bicitra, Oracit)
Citric acid and sodium citrate are systemic alkalinizing agents that have been used to correct the acidosis in PHA; however, they are metabolized by the liver to bicarbonate. Bicitra is extensively used rather than Shohl solution because it does not require mixing by the pharmacist. It provides 1 mEq of sodium bicarbonate per milliliter. Potassium citrate solutions such as Polycitra and Polycitra-K have no use in PHA and should be avoided.
Antidotes, Other
Class Summary
Potassium-binding resins may be used to control hyperkalemia in patients with PHA.
Sodium polystyrene sulfonate (Kayexalate, Kalexate, Kionex, SPS)
Sodium polystyrene sulfonate may be required for control of hyperkalemia in patients with multiple target organ defects (MTOD) PHA type I (PHA-I). The resin partially releases the sodium ions in the large intestine, and these are replaced mole for mole by potassium ions.
NSAIDs
Class Summary
Prostaglandin inhibitors, like NSAIDs, inhibit the production of prostaglandin by blocking the action of cyclooxygenase (also called prostaglandin synthetase).
Indomethacin (Indocin)
Indomethacin has been used in selected cases of MTOD PHA-I and is thought to decrease urinary volume and sodium excretion. Response to indomethacin varies, and some patients may not benefit. Most patients with MTOD PHA-I continue to require sodium supplementation.
Diuretics, Loop
Class Summary
Diuretics are used to increase the rate of urine formation and output, thereby eradicating fluid overload and controlling hypertension.
Furosemide (Lasix)
Furosemide is a loop diuretic that has been effective in the treatment of PHA-II.
Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)
Thiazide diuretic that has been used occasionally to correct hyperkalemia and hypercalciuria in MTOD PHA-I; however, thiazides should be used with caution because they can exacerbate hypovolemia and salt wastage. Preferred treatment in patients with PHA-II because it can correct hyperkalemia, metabolic acidosis, hypertension, and plasma aldosterone and plasma renin levels. Unlike furosemide, it can also correct hypercalciuria. Does not result in catch-up growth in patients with PHA-II.
Diuretics, Thiazide
Class Summary
Diuretics are used to increase the rate of urine formation and output, thereby eradicating fluid overload and controlling hypertension.
In general, thiazides should be used with caution, because they can exacerbate hypovolemia and salt wastage.
Hydrochlorothiazide (Microzide)
Hydrochlorothiazide is a thiazide diuretic that has occasionally been used to correct hyperkalemia and hypercalciuria in patients with MTOD PHA-I.
Hydrochlorothiazide is the preferred treatment in patients with PHA-II because it can correct hyperkalemia, metabolic acidosis, hypertension, and plasma renin and aldosterone levels. Unlike furosemide, it can also correct hypercalciuria. It does not result in catch-up growth in patients with PHA-II.
Chlorothiazide (Diuril)
Chlorothiazide inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as of potassium and hydrogen ions.
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| Details | PHA Type I | PHA Type II | |||
| Renal PHA-I | MTOD PHA-I | Early Childhood Hyperkalemia | PHA-II | ||
| Synonyms | Classic PHA of infancy, Cheek and Perry syndrome, autosomal dominant PHA-I, subtype 4 RTA IV | Autosomal recessive PHA-I | Subtype 5 RTA IV | Adolescent hyperkalemic syndrome, Spitzer-Weinstein syndrome, subtype 3 RTA IV | Gordon syndrome, mineralocorticoid-resistant hyperkalemia, chloride shunt syndrome |
| Age | Newborn period, infancy | Newborn period, infancy | Infancy, childhood | Childhood | Adulthood |
| Organs | Kidney | Kidney, sweat glands, salivary glands, colon | Kidney | Kidney | Kidney |
| Genetics | Autosomal dominant, sporadic | Autosomal recessive, sporadic | Unknown | Unknown | Autosomal dominant, sporadic |
| Mechanism | Heterozygous MLR mutations (possible) | Defective Na transport in organs that contain ENaC | Maturation disorder in the number or function of aldosterone receptors | Chloride shunt | Chloride shunt |
| Serum potassium | High | High | High | High | High |
| Acidosis | Present | Present | Present | Present | Present |
| Serum sodium | Normal or low | Normal or low | Normal | Normal | Normal |
| PRA* | High | High | Normal or high | Normal or low | Low |
| Aldosterone | High | High | Normal or high | Normal or low | Low |
| Blood volume | Normovolemia, hypovolemia | Normovolemia, hypovolemia | Normovolemia | Hypervolemia | Hypervolemia |
| Blood pressure | Normal or low | Normal or low | Normal or low | Normal or low | Normal or low |
| GFR | Normal | Normal | Normal | Normal | Normal |
| Salt wasting | Renal | Renal, sweat or salivary glands, colon | Absent | Absent | Absent |
| Hypercalciuria | Present or absent | Absent | Absent | Present | Present |
| Therapy | Na supplementation, K-binding resins | High-Na, low-K diet, K-binding resins, hydrochlorothiazide | Na bicarbonate, K-binding resins | Dietary Na restriction, hydrochlorothiazide | Dietary Na restriction, hydrochlorothiazide |
| Prognosis | Outgrow by age 2 y | Lifelong therapy | Outgrow by age 5 y | Lifelong therapy | Lifelong therapy |
| *Plasma renin activity. ENaC = epithelial sodium channel; GFR = glomerular filtration rate; MLR = mineralocorticoid receptor gene; PHA = pseudohypoaldosteronism; RTA = renal tubular acidosis. | |||||
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