Drug interactions

Many drugs used clinically affect oxygen tolerance, frequently enhancing oxygen toxicity. These fall into several broad categories: drugs that increase tissue oxygen consumption, drugs that undergo redox cycling or produce free radicals during metabolism, and drugs that affect endogenous antioxidant systems.

Epinephrine (adrenaline), norepinephrine (noradrenaline), thyroid hormone, and hyperthermia all increase sensitivity to pulmonary oxygen poisoning. Increased cellular metabolic rate is a common mechanism. There have been no studies investigating the effects of more commonly used adrenergic agents such as dopamine or dobutamine in adult patients receiving hyperoxic mechanical ventilation. As well as increasing cellular oxygen utilization, thyroxine lowers lung glutathione content. In contrast, dimethylthiourea, a sulfhydryl compound, protects rats from oxygen toxicity.

Corticosteroids are frequently administered to patients with acute respiratory failure. Mice pretreated with methylprednisolone (10 mg/kg/day for 7 days) suffer significantly greater mortality in hyperoxia. Steroid pretreatment inhibited phospholipid synthesis in lung slices, suggesting that methylprednisolone has an unfavorable effect on the surfactant system of mature lung. The timing of corticosteroid administration in acute lung injury appears to be critical. Methylprednisolone decreases the survival time of adult rats in hyperoxia and minimizes adaptive increases in lung superoxide dismutase. In contrast, when dexamethasone is administered to rats near the end of a 72-h exposure to hyperoxia (when lung inflammation is most pronounced) survival may be improved and lung damage minimized.

Bleomycin, a chemotherapeutic agent, causes acute and chronic lung damage attributed in part to the formation of hydroxyl radicals in the vicinity of cell nuclei. Lung damage due to bleomycin is synergistic with many other chemotherapeutic agents. Simultaneous administration of bleomycin and high FiO 2 produces accelerated lung injury and progressive pulmonary fibrosis. Despite isolated clinical reports to the contrary, in animal models administration of bleomycin well before oxygen exposure results in less rather than more lung injury. This discrepancy is due partially to differences in the acute and chronic effects of bleomycin on lung antioxidant defenses. Lung antioxidant enzymes initially decrease after intratracheal bleomycin administration but increase later.

Cyclophosphamide and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) similarly increase hyperoxic lung injury while decreasing antioxidant defenses. Nitrofurantoin increases hyperoxic lung injury because reduction of the nitro group of the antibiotic in the presence of oxygen leads to intracellular formation of both superoxide and hydrogen peroxide.

Many other agents used clinically have been investigated in experimental animal models of oxygen toxicity, which may not apply directly to human patients. It is unlikely that similar investigations will ever be performed in humans, and so the animal studies form the only available database.

Fat Burning Secrets

Fat Burning Secrets

Proven Fat Burning Tips Revealed. Tired of hiding your muffin top under layers of clothing? You are not alone. About one third of American adults are overweight. Now is the time to transform your soft, flabby body into the toned, sexy physique of your dreams. Forget yo-yo diets and easy weight  loss promises that leave you feeling like a fat failure.

Get My Free Ebook


Post a comment