Phototoxicity tetracyclines

Bjellerup M, Kjellstrom T, Ljunggren B. Influence of tetracycline phototox icity on the growth of cultured human fibroblasts. J Invest Dermatol 1985 85(6) 573 4. 

Adverse effects with the tetracyclines include gastrointestinal upset drug interactions with dairy products, antacids, and iron and phototoxicity. Minocycline can also cause vestibular complications (headache and dizziness) and skin discoloration that is not typical with tetracycline and doxycycline.16... 

Tetracycline Tablets, capsules 250, 500 mg 500 mg twice daily before meals Maintenance dose 500 mg daily Gl upset, phototoxicity, tooth discoloration, drug and food interactions... 

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... 

Phototoxic reactions are most frequent with demeclocycline, and occur less frequently with the other tetracyclines minocycline is least likely to cause phototoxic reactions. 

No advantages over other tetracyclines as anti-infective higher incidence of phototoxicity active against water intoxication and SIADH... 

Phototoxicity occurs when skin exposed to sunlight, especially in the UVA region of 320 to 400 nm, reddens and develops blisters as a consequence of the presence of certain chemical species. The phototoxic chemical species that result in such reactions are ones to which an individual is exposed either directly on the skin or systemically. These compounds absorb ultraviolet radiation and, like the porphyrins discussed above, enter excited states interacting with 02 to generate destructive oxidant species and free radicals. Numerous chemical species, including furocoumarins, polycyclic aromatic hydrocarbons, tetracyclines, and sulfonamides, can be phototoxic. 

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],... 

Skin rashes are relatively common with flnoroqninolones. A retrospective cohort stndy in patients in general practice in the Netherlands focused on the nse of antibacterial agents and the occnrrence of adverse cntaneons events covered 469 505 consnltations with 87 475 patients, of whom 13 679 received prescriptions for antibiotics (57). After adjnstment for age, sex, and co-medications, the incidence density ratio (incidence density per 1000 exposed days) for varions gronps of antibacterial agents was as follows tetracyclines 1.0, macrohdes 1.1, flnoroqninolones 2.8, penicillins 2.9, and co-trimoxazole 4.4 (57). No details of the types of skin reactions were given, and it is therefore possible that phototoxic events were inclnded. Compared with other stndies, the reported rate of antibiotic-associated adverse cntaneons events in this ontpatient popnlation was rather low. 

Drugs that are likely to cause phototoxic reactions are amiodarone, nalidixic acid, various NSAIDs, phenothiazines (especially chlorpromazine), and tetracyclines (particularly demedocydine). 

A number of the tetracycline derivatives are phototoxic. In one study, chlortetracycline, doxycycline, and dimethylchlortetracycline treatment of normal human skin fibroblasts resulted in total cell death within 14 days when co-administered with UVA. A dimethylchlortetracycline and UVA cotreatment also showed a strong photosensitizing effect in a 7-day exposure study. These results, too, are consistent with clinically reported reactions in humans J15l... 

Bjellerup M, Ljunggren B. Double blind cross over studies on phototoxicity to three tetracycline derivatives in human volunteers. Photodermatology 1987 4(6) 281—7. 

Adverse effects of tetracyclines include resistant bacteria, folliculitis, candidiasis, gastrointestinal upset, and phototoxic effects. Tetracyclines must not be combined with systemic retinoids because of the increased probability for development of intracranial hypertension. Tetracycline is used in the treatment of moderate to severe acne vulgaris. It is the least expensive of the tetracyclines and therefore often prescribed for initial therapy. A common initial approach includes tetracycline 1 g daily (500 mg twice daily), 1 hour before meals after 1 or 2 months, when marked improvement of inflammatory lesions is observed, the dose may be decreased to 500 mg every day, for another 1 or 2 months. Drawbacks to the use of tetracycline include also a drug-food interaction with dairy prodncts. 

Doxycycline is commonly used in the treatment of moderate to severe acne vulgaris. It is more effective and produces less resistance than tetracycline. The initial dosage is usually 100 or 200 mg daily, followed after improvement by 50 mg/day as a maintenance dose it may be taken with food even thongh it is more effective when taken 30 minutes before meals. Subantimicrobial-dose doxycycline (20 mg) has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne. Positive ontcomes were achieved with no development of resistant organisms or change in normal skin flora. Adverse effects include resistant bacteria, folliculitis, candidiasis, gastrointestinal upset, and phototoxic effects such as photo-onycholysis. ... 

Rash, in areas of the body exposed to UV light, may be indicative of drug phototoxicity. Among the antibacterial agents, the tetracyclines and the sulfonamides are notably phototoxic. More recently, the fluoroquinolones have been implicated in phototoxic responses, and because these antibiotics are widely used, the incidence of this type of adverse effect is increasing. 

For example, tetracycline (506), a broad-spectrum antibiotic, and its derivatives are known to induce phototoxic or photoallergic reactions that involve photosensitization of biomolecules by the drug or the formation of one or more photoproducts and their subsequent photoreactions.1383 Singlet oxygen is probably involved. 

Gastrointestinal reactions that may occur during tetracycline administration include nausea, vomiting, diarrhea, epigastric distress, stomatitis, and sore throat. Skin rashes also may be seen. A photosensitivity (phototoxic) reaction may be seen witli tliis group of dni, manifested by an exa rated sunburn reaction when the skin is exposed to sunlight even for brief periods. Demeclocychne seems to cause the most serious photosensitivity reaction, whereas minocycline is least likely to cause this type of reaction. 

Demeclocycline lacks the C-6-methyl of tetracycline and is produced by a genetically altered strain of Streptomyces aureofaciens. Because it is a secondary alcohol, it is more chemically stable than tetracycline against dehydration. Food and milk co-consumption decrease absorption by half, although it is 60 to 80% absorbed by fasting adults. It is the tetracycline most highly associated with phototoxicity and has been shown to produce dose-dependent, reversible diabetes insipidus with extended use. 

The most important drugs with sensitizing effects are listed in Table 4. Tetracyclines, in particular demethylchlortetracycline, are commonly responsible for photodermatitis. However, this action does not have any immunological basis, but depends on a phototoxic effect (Harder et al. 1961 Maibach et al. 1967), similar to that produced by psoralens, certain dyes, cadmium sulphide, etc. 

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