Acetazolamide (Diamox)

Indications

Central Sleep Apnea (CSA) (see Central Sleep Apnea)

  • Clinical Efficacy
    • Trial of Acetazolamide in Central Sleep Apnea Associated with Systolic CHF (Am J Respir Crit Care Med, 2006) [MEDLINE]: small trial (n = 12)
      • Acetazolamide Decreased Central Sleep Apneas and Nocturnal Oxygen Desaturation
      • Acetazolamide Improved Sleep Quality, Decreased Daytime Fatigue, and Decreased Daytime Somnolence
    • Short-Term Trial (4 Days) of Acetazolamide in Central Sleep Apnea in Cheyne-Stokes Respiration Due to CHF (Am J Cardiol, 2011) [MEDLINE]: small trial (n = 12)
      • Acetazolamide Decreased Central Sleep Apneas and Nocturnal Oxygen Desaturation
      • Acetazolamide Blunted the Chemosensitivity to Hypoxia and Increased the Chemosensitivity to Hypercapnia
      • In Exercise Testing, Acetazolamide Decreased Workload with No Difference in Peak Oxygen Consumption and an Increment in the Regression Slope Relating Minute Ventilation to Carbon Dioxide Output: suggesting a decrease in ventilatory efficiency

Chronic Mountain Sickness (see Chronic Mountain Sickness )

  • Clinical Efficacy
    • Trial of Acetazolamide in Chronic Mountain Sickness in Peru (Am J Respir Crit Care Med. 2005) [MEDLINE]
      • Acetazolamide Decreases Hypoventilation
        • Acetazolamide Increased Nocturnal SaO2 (by 5%), Decreased Nocturnal Heart Rate (by 11%), and Decreased Sleep Apnea-Hypopnea Episodes (by 74%)
      • Acetazolamide Decreased Erythropoietin and Decreased Hematocrit
    • Peruvian Trial of Chronic Acetazolamide in Chronic Mountain Sickness (Am J Respir Crit Care Med, 2008) [MEDLINE]
      • Chronic Acetazolamide (250 mg/day x 3 wks) Improved Erythrocytosis
      • Chronic Acetazolamide (250 mg/day x 3 wks) Improved Hypoxemia
      • Only Patients Treated for 6 mo Had a Decrease in Pulmonary Vascular Resistance (PVR)
      • Treatment Had No Adverse Effects

Metabolic Alkalosis (see Metabolic Alkalosis)

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Prophylaxis for Acute Mountain Sickness (see Acute Mountain Sickness)

  • For patients at moderate-high risk

Prophylaxis for High-Altitude Cerebral Edema (HACE) (see High-Altitude Cerebral Edema, [[High-Altitude Cerebral Edema]])

  • For patients at moderate-high risk

Pharmacology

Sulfonamide Diuretic with Carbonic Anhydrase Inhibitor Properties (see Sulfonamides, [[Sulfonamides]])

  • Acetazolamide Enhances Renal Bicarbonate Excretion

Organ-Specific Effects of Acetazolamide

  • Brain: acetazolamide inhibits the conversion of carbon dioxide to bicarbonate in the brain capillaries, increasing local tissue pCO2 (and decreasing the local pH), resulting in increased central ventilatory drive (in an attempt to decrease the pCO2)
    • Acetazolamide Has Been Demonstrated to Decrease Cerebrospinal Fluid Bicarbonate in Normal Subjects at Both 3,000 and 14,000 ft altitude (J Appl Physiol, 1968) [MEDLINE]
  • Kidney: acetazolamide increases renal hydrogen ion retention and increases renal bicarbonate excretion, causing a normal anion gap metabolic acidosis, resulting in increased ventilatory drive
  • Lung: acetazolamide inhibits the conversion of bicarbonate to carbon dioxide in the pulmonary capillaries, impairing the lung’s ability to excrete carbon dioxide -> in normal patients, minute ventilation will subsequently increase to maintain a normal pCO2

Overall Effects of Acetazolamide in Specific Subsets of Patients

  • Effect of Acetazolamide in Patients Who are Able to Increase Their Minute Ventilation (Normal Patient): minute ventilation will increase and pCO2 will decrease, since the increased ventilatory drive will exceed the impaired pulmonary excretion of carbon dioxide
  • Effect of Acetazolamide in Patients Who are Not Able to Increase Their Minute Ventilation (Severe COPD Patient): minute ventilation will not increase and pCO2 will increase due to the impaired pulmonary excretion of carbon dioxide, resulting in respiratory acidosis (Am Rev Respir Dis, 1983) [MEDLINE]

Metabolism

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Administration

  • PO (Prophylaxis for High-Altitude Illness): 125-250 mg PO BID started 1 day before ascent and discontinued after 2 days at final altitude
  • IV (Metabolic Alkalosis): 250 mg IV PRN

Dose Adjustment

  • Hepatic
  • Renal

Adverse Effects

Hematologic Adveese Effects

  • Aplastic Anemia (see Aplastic Anemia, [[Aplastic Anemia]]): moderate risk of aplastic anemia

Gastrointestinal Adverse Effects

Neurologic Adverse Effects

  • Acral Parasthesias (see Parasthesias, [[Parasthesias]]): occur in 35-90% of patients treated with acetazolamide for high-altitude illness prophylaxis
  • Fatigue (see Fatigue, [[Fatigue]])

Renal Adverse Effects

Other Adverse Effects

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References

  • Effect of acetazolamide on acute mountain sickness. N Engl J Med. 1968;279(16):839 [MEDLINE]
  • Effects of acetazolamide and hypoxia on cerebrospinal fluid bicarbonate. J Appl Physiol. 1968;24(1):17 [MEDLINE]
  • Relative effectiveness of acetazolamide versus medroxyprogesterone acetate in correction of chronic carbon dioxide retention. Am Rev Respir Dis. 1983;127(4):405 [MEDLINE]
  • Effects of acute and chronic acetazolamide on resting ventilation and ventilatory responses in men. J Appl Physiol (1985). 1993;74(1):230 [MEDLINE]
  • Acetazolamide in the treatment of acute mountain sickness: clinical efficacy and effect on gas exchange. Ann Intern Med. 1992;116(6):461 [MEDLINE]
  • Pathophysiology and epidemiology of chronic mountain sickness. Int J Sports Med. 1992 Oct;13 Suppl 1:S79-81 [MEDLINE]
  • Acetazolamide: a treatment for chronic mountain sickness. Am J Respir Crit Care Med. 2005;172(11):1427 [MEDLINE]
  • Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integr Comp Biol. 2006 Feb;46(1):18-24. doi: 10.1093/icb/icj004. Epub 2006 Jan 6 [MEDLINE]
  • Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173(2):234 [MEDLINE]
  • Acetazolamide for Monge’s disease: efficiency and tolerance of 6-month treatment. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1370-6. doi: 10.1164/rccm.200802-196OC. Epub 2008 Apr 3 [MEDLINE]
  • Effect of acetazolamide on chemosensitivity, Cheyne-Stokes respiration, and response to effort in patients with heart failure. Am J Cardiol. 2011 Jun;107(11):1675-80. Epub 2011 Mar 21 [MEDLINE]