Influence of methazolamide on the human control of breathing : a comparison to acetazolamide Teppema, Luc J.; Boulet, Lindsey M.; Hackett, Heather K.; Dominelli, Paolo Biagio; Cheyne, William Spencer; Dominelli, Giulio S.; Swenson, Erik R.; Foster, Glen E.
Acetazolamide is used to prevent/treat acute mountain sickness and both central and obstructive sleep apnoea. Methazolamide, like acetazolamide reduces hypoxic pulmonary vasoconstriction, but has fewer side effects including less skeletal muscle function impairment. Since methazolamide’s effects on respiratory control in humans are unknown, we (1) compared the effects of oral methazolamide and acetazolamide on ventilatory control, and (2) determined the ventilation-log PO₂ relationship in humans. In a double blind, placebo-controlled, randomized cross-over design, we studied the effects of acetazolamide (250 mg tid), methazolamide (100 mg bid) and placebo in fourteen young male subjects who were exposed to 7 minutes of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide, and acetazolamide, the CO₂ sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l/min/mmHg (NS) and estimated apnoeic thresholds were 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively (P < 0.001, placebo vs methazolamide and acetazolamide). The relationship between ventilation (V̇ I) and log PO₂ (using arterialized venous PO₂ in hypoxia) was linear, while neither agent influenced the relationship between hypoxic sensitivity (ΔV̇ I/Δlog PO₂) and arterial [H⁺]. Using ΔV̇ I/Δlog PO₂ rather than ΔV̇ I/ΔSaO₂ enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right- or left-ward shifts of the oxyhaemoglobin saturation curve occur. Since acetazolamide and methazolamide has similar effects on ventilatory control, methazolamide may be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side-effects of acetazolamide.
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