Demeclocycline toxicity

Antidiuretic hormone antagonists are used to manage SIADH when water restriction has failed to correct the abnormality. This generally occurs in the outpatient setting, where water restriction cannot be enforced, or in the hospital when large quantities of intravenous fluid are needed for other purposes. Lithium carbonate has been used to treat this syndrome, but the response is unpredictable. Demeclocycline, in dosages of 600-1200 mg/d, yields a more predictable result and is less toxic. Appropriate plasma levels (2 mcg/mL) should be maintained by monitoring. Unlike demeclocycline, conivaptan is administered by IV injection, so it is not suitable for chronic use in outpatients. Lixivaptan and tolvaptan should soon be available for oral use. 

Phototoxicity Phototoxicity, for example, severe sunburn, occurs when the patient receiving a tetracycline is exposed to sun or ultraviolet rays. This toxicity is encountered most frequently with tetracycline, doxycydine, and demeclocycline [dem e kloe SYE kleen],... 

Tetracyclines Tetracyclines are broad spectrum antibiotics obtained from Streptomyces strains or prepared semisynthetically. Use of tetracyclines has resulted in three types of renal effects. First, the use of outdated tetracyclines results in direct proximal tubular toxicity characterized by the increased excretion of amino acids, glucose, and phosphate (Fan-coni syndrome). The mechanism of this response is unclear, but appears to be due to the formation of the degradation product anhydro-4-epi-tetracycline. Second, administration of some tetracyclines, particularly demeclocycline, can result in a dose-dependent, reversible nephrogenic diabetes insipidus, which appears to result from an inhibition of ADH effects on water reabsorption. Lastly, in patients with preexisting compromised renal function, tetracyclines can induce increased sodium excretion and azotemia. The mechanism of the naturesis may be due to an effect of tetracyclines on luminal membrane sodium conductance, while the azotemia appears to result from the antianabolic effects of the tetracyclines. 

ADH antagonists oppose the actions of ADH and other naturally occurring peptides that act on the same Vj receptor. Such peptides are produced by certain tumors (eg, small cell carcinoma of the lung) and can cause significant water retention and dangerous hyponatremia. This syndrome of inappropriate ADH secretion (SIADH) can be treated with demeclocycline. Lithium also works but has greater toxicity. 

In children under 8 years of age, demeclocycline (like other tetracyclines) causes bone and teeth abnormalities. Lithium causes nephrogenic diabetes insipidus as a toxic effect the drug is never used to treat SIADH because of its other toxicities. 

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