Tetracyclines toxicity

Tetracyclines are produced by various Streptomyces strains and are extensively applied in human and veterinary medicine. They display a broad spectrum of antimicrobial activity in combination with low toxicity and can be applied orally. The most commonly prescribed tetracycline drugs are tetracycline itself and oxytetracycline, an oxygenated derivative, which are directly isolated from fermentation liquors, and doxycycline whose partial synthesis from oxy-... 

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Tetracycline antibiotics have found wide application in animal industries for treatment, preventive maintenance and stimulation of growth of large horned livestock owing to what their residue amounts can be present at milk and meat of animals. Residue amounts of antibiotics are not toxic, however, capable to cause allergic reactions and to promote development of tolerance of the some people pathogenic bacterias. According with the legislative requirements of a number of the European countries it is forbidden to deliver to the population production polluted residual contents of tetracyclines. 

The tetracyclines are contraindicated if the patient is known to be hypersensitive to any of the tetracyclines. Tetracyclines also are contraindicated during pregnancy because of die possibility of toxic effects to the developing fetus. The tetracyclines are classified Pregnancy Category D drag. These drug also are contraindicated... 

It is important to use the tetracyclines cautiously in patients witii renal function impairment, hi addition, doses greater that 2 g d can be extremely damaging to die liver. The nurse should carefully check die expiration dates of die tetracyclines before administration because degradation of the tetracyclines can occur after degradation, the agents are highly toxic to the kidneys. 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

Thiatetracyclines contain a sulphur atom at position 6 in the molecule. One derivative, thiacycline, is more active than minocycline against tetracycline-resistant bacteria. Despite toxicity problems affecting its possible clinical use, thiacycline could be the starting point in the development of a new range of important tetracycline-type antibiotics. 

Prado N, Ochoa J, Amrane A (2009) Biodegradation by activated sludge and toxicity of tetracycline into a semi-industrial membrane bioreactor. Bioresour Technol 100 3769-3774... 

The answer is c. (Hardman, pp 1134-1135.) Hematologic toxicity is by far the most important adverse effect of chloramphenicol The toxicity consists of two types (1) bone marrow depression (common) and (2) aplastic anemia (rare) Chloramphenicol can produce a potentially fatal toxic reaction, the gray baby syndrome, caused by diminished ability of neonates to conjugate chloramphenicol with resultant high serum concentrations. Tetracyclines produce staining of the teeth and phototoxicity... 

Certain antibiotics such as the tetracyclines, streptomycin, neomycin and kanamycin can cripple the tubules if taken in excessive amounts. Toxic damage to the kidneys can affect not only their filtration functions, but can alter the organs control over blood levels of certain critical molecules. A complex biochemical-hormonal system controlling blood pressure and volume, for example, is regulated by the kidneys, so that chronic kidney damage can inflict damage on the... 

However, one should be aware of the fact that if a particular pharmaceutical is not detected in a WWTP effluent, this does not imply that it has been fully removed. On some occasions, it may have been degraded and give rise to unsuspecting or even more toxic compounds that will subsequently contaminate surface waters [30, 58-60]. As an example, anhydrotetracycline (ATC) and epianhydrote-tracycline (EATC) are tetracycline (TC) degradation products that cause Fanconi syndrome [61]. 

Renal function impairment If renal impairment exists, even usual doses may lead to excessive systemic accumulation of the tetracyclines (with the exception of doxycycline and minocycline) and possible liver toxicity. Use lower than usual doses and/or extend the dosing interval. 

Which of the following explains why tetracycline is selective for prokaryotes and minimally toxic to humans ... 

Bone. Although bone is a relatively inert tissue, it can accumulate such substances as tetracyclines, lead, strontium, and the antitumor agent cisplatin. These substances may accumulate in bone by absorption onto the bone crystal surface and eventually be incorporated into the crystal lattice. Tetracycline deposition during odontogenesis may lead to a permanent yellow-brown discoloration of teeth, dysplasia, and poor bone development. Lead can substitute for calcium in the bone crystal lattice, resulting in bone brittleness. Bone may become a reservoir for the slow release of toxic substances, such as lead and cisplatin. 

Although all tetracyclines have a similar mechanism of action, they have different chemical structures and are produced by different species of Streptomyces. In addition, structural analogues of these compounds have been synthesized to improve pharmacokinetic properties and antimicrobial activity. While several biological processes in the bacterial cells are modified by the tetracyclines, their primary mode of action is inhibition of protein synthesis. Tetracyclines bind to the SOS ribosome and thereby prevent the binding of aminoacyl transfer RNA (tRNA) to the A site (acceptor site) on the 50S ri-bosomal unit. The tetracyclines affect both eukaryotic and prokaryotic cells but are selectively toxic for bacteria, because they readily penetrate microbial membranes and accumulate in the cytoplasm through an energy-dependent tetracycline transport system that is absent from mammalian cells. 

Halling-Sprensen B., G. Sengelpv, and J. Tjpmelund (2002). Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria. Archives of Environmental Contamination and Toxicology 42 263-271. 

---