Diddling with Diamox (acetazolamide): Mountains to Medicine

👁️ ➡️ 🧗‍♀️ ➡️ 🧠➡️ 🩸

Let’s talk about a drug you see prescribed for use in a few different scenarios: acetazolamide.

Definitely gained success in 1970s and reportedly in 1960s after successful Himalayan mountaineering expedition in preventing high altitude sickness. (Sorry, I had difficulty finding the reference on the 1960s one)

There was success in its use in 1982 (published in old JAMA article) in a jaunt up Mt Rainier when the treatment group received the drug and had less mountain sickness.

Physiology and Basic Chemistry

At the core of acetazolamide's action lies the fundamental carbonic anhydrase equation:

➡️ Catalyzed by carbonic anhydrase

➡️ Crucial for acid-base homeostasis, particularly in managing CO₂ levels and maintaining pH balance across various body tissues.

Mechanism of Action

Acetazolamide functions as a potent carbonic anhydrase inhibitor, particularly affecting isoenzymes CA II and CA IV. (All my nephrologists, click that link)

This inhibition leads to:

Reduced bicarbonate reabsorption in proximal tubules

Increased bicarbonate excretion

Development of metabolic acidosis

Enhanced ventilatory drive through peripheral and central chemoreceptor stimulation 🫁

The Chronic Hypercapnia Conundrum

Using acetazolamide in chronic hypercapnia presents a fascinating paradox in clinical medicine.

Look, it might seem logical to use a respiratory stimulant in patients with elevated CO₂ levels, but beware that there are several sophisticated physiological principles arguing against this overrated approach:

☝️ Metabolic Compensation Disruption:

Acetazolamide disrupts this delicate balance by inducing metabolic acidosis, potentially destabilizing long-standing compensatory mechanisms.

✌️Tissue Adaptation:

Chronic hypercapnia leads to cellular adaptations in CO₂ handling and pH regulation. Rapidly altering blood gases can alter these tightly adapted processes.

☝️ ✌️Energy Expenditure Impact:

This can potentially lead to fatigue in patients with already compromised respiratory function.

Your 3am Case 🕵️‍♂️

A 67-year-old male with severe COPD (FEV1 30% predicted) and chronic hypercapnia (baseline PaCO₂ 55 mmHg) was prescribed acetazolamide 250mg twice daily by his primary care physician in an attempt to improve his hypercapnia.

Within 48 hours, he developed worsening dyspnea and anxiety. Blood gases revealed:

• pH: 7.28 (decreased from baseline 7.36)
• PaCO₂: 58 mmHg
• HCO₃: 22 mEq/L (decreased from baseline 28)

Doctor’s Order

: Even 2 days of acetazolamide can cause metabolic acidosis in chronic hypercapnia

: 🚨Exercise caution in chronic hypercapnia

: 🚫🤰🚫 Avoid in pregnancy

: (Notice I did not include acetazolamide’s role as a diuretic in heart failure.)

Let me know below in comments if you want more posts like this!

References 📚

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24. https://jamanetwork.com/journals/jama/article-abstract/375750