Letter Re: Veterinary Antibiotics

All this discussion of antibiotic nephrotoxicity on a “non-medical” forum reminds me of just why modern medical education is so onerous, including (in the U.S.) four hard years of school — two mostly classroom, two mostly clinical — followed by many more years of clinical residency training. During such training, one encounters lots of side effects of the various highly potent chemical agents known as pharmaceuticals. Watching out for the kidneys is one reason hospitalized patients have so much blood drawn over and over again (to monitor BUN [blood urea nitrogen] and creatinine, markers for renal function).

I guess the best TEOTWAWKI preparation would be to stockpile antibiotics and an experienced practitioner to administer them, preferably a board-certified infectious disease specialist. Unfortunately the latter are not available via mail order! Lacking such experienced members in your family or mutual assistance group, one is advised to be rather cautious in dosing — i.e. respect those meds — they can cure but they can also kill. In short, please “don’t try this at home” unless you absolutely have to.

On the specific subject of tetracyclines, the relevant paragraph in “the” standard textbook, Mandell’s Principles and Practice of Infectious Diseases (4th ed.) begins “The tetracyclines aggravate pre-existing renal failure by inhibiting protein synthesis, which increases the azotemia from amino acid metabolism…” The paragraph concludes with rather brief mention of toxicity in expired tetracyclines due to the outdated manufacturing issues [i.e. binders that are no longer used], but says “It is unlikely this complication will recur.”

The best reference to this issue I can readily find on-line (as opposed to textbooks) is as follows — pay attention to the years cited:

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INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY — ENVIRONMENTAL HEALTH CRITERIA 119 —
PRINCIPLES AMD METHODS FOR THE ASSESSMENT OF NEPHROTOXICITY ASSOCIATED WITH EXPOSURE TO CHEMICALS

Tetracyclines
The nephrotoxicity of tetracycline incited considerable interest in the early 1960s, shortly after its introduction. People, particularly children, developed a reversible proximal tubular dysfunction after receiving outdated drugs. The nephrotoxicity was found to be due to a degradation product, anhydro-4-epitetracycline. The problem has disappeared with the substitution of citric acid for lactose as a vehicle (Curtis, 1979).

Other rare effects of tetracycline that have been reported are impairment of renal-concentrating ability by demethyl-chlorotetracycline and occurrences of acute interstitial nephritis after minocycline treatment. More important to current usage is the awareness that the serum half-life of the two most commonly used drugs, tetracycline and oxytetracycline, is greatly prolonged in renal failure, and that the anti-anabolic effect of the tetracyclines, which inhibit the incorporation of amino acids into protein, may further contribute to negative nitrogen balance and uraemia by raising blood urea nitrogen (Curtis, 1979).
Reference cited : CURTIS, J.R. (1979) Drug-induced renal disease. Drugs, 18: 377-391.

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One last comment: A useful aphorism that I was taught in medical school is that “any drug can cause any side effect in any patient at any time (…but some are more likely than others).”
– A Public Health Physician