Influence of methazolamide on the human control of breathing: A comparison to acetazolamide

Abstract

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 impairment of skeletal muscle function. Given that the effects of methazolamide on respiratory control in humans are unknown, we compared the effects of oral methazolamide and acetazolamide on ventilatory control and determined the ventilationlog P O 2 relationship in humans. In a double-blind, placebo-controlled, randomized cross-over design, we studied the effects of acetazolamide (250 mg three times daily), methazolamide (100 mg twice daily) and placebo in 14 young male subjects who were exposed to 7 min of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide and acetazolamide, the CO 2 sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l min −1 mmHg −1 (n.s.) and estimated apnoeic thresholds 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively (P < 0.001, placebo versus methazolamide and acetazolamide).The relationship between ventilation (V I ) and log P O 2 (using arterialized venous P O 2 in hypoxia) was linear, and neither agent influenced the relationship between hypoxic sensitivity (ΔV I ∕Δ log P O 2 ) and arterial [H + ]. Using ΔV I ∕Δ log P O 2 rather than ΔV I /Δ arterial oxyhaemoglobin saturation enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right-or leftward shifts of the oxyhaemoglobin saturation curve occur. Given that acetazolamide and methazolamide have similar effects on ventilatory control, methazolamide might be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side-effects of acetazolamide. K E Y W O R D Saltitude sickness, carbonic anhydrase inhibitors, hypercapnia, hypoxia, respiration, ventilation

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

“…3B). A logarithmic function has been previously shown to be useful when comparing groups with different ODCs (33,35). The ventilatory response was also not different when expressed in absolute units; however, the response was nonlinear as expected (Fig.…”

Examination of novel diagnostic approaches and contemporary strategies for preventing acute mountain sickness

“…Its negative effect on the diaphragm and skeletal muscles, which occurs when using acetazolamide, has not been noticed. [26] Inhaled budesonide turns out to be ineffective in preventing severe altitude sickness, but it helps reduce blood pressure and increase blood saturation. It may be effective in preventing mild disease.…”

Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia

“…It is known to be more soluble in lipids than acetazolamide and thus can cross cellular membranes more easily (Maren, 1967). As with acetazolamide, it induces metabolic acidosis by causing renal bicarbonate excretion to effectively increase circulating [H + ], stimulate ventilation and improve arterial oxygenation in hypoxia (Teppema et al., 2020). It has been used for AMS prophylaxis since the 1980s, and in a limited number of studies has been shown to reduce symptoms (Forster, 1982), with at least one study reporting fewer side effects than acetazolamide (Wright et al., 1983).…”

“…xia (Teppema et al, 2020). It has been used for AMS prophylaxis since the 1980s, and in a limited number of studies has been shown to reduce symptoms (Forster, 1982), with at least one study reporting fewer side effects than acetazolamide (Wright et al, 1983).…”