快樂小藥師 Im pharmacist nichts glücklich

大家都知道四環素會讓牙齒永久變色，會影響骨骼，但是如果是用在小於兩歲以下的兒童，當他換牙後，新牙也會被染色嗎？

基本上，多數研究都顯示八歲以後就可以使用，Micromedex資料如下：

1) Tetracyclines are most noted for their effect on growing dentition and other bony tissues. The deposition of tetracycline in these tissues is a result of wide distribution of these drugs in the body. Their deposition in dental tissues, specifically enamel, leads to a yellow discoloration of the teeth, which eventually turns to gray or brown This effect can occur in deciduous teeth tetracycline is administered to pregnant females during last half of pregnancy, or with administration in children 8 years of age and younger. Tetracycline should be avoided in this population unless other drugs are unlikely to be effective or are contraindicated .
2) All of the tetracyclines are deposited in calcifying areas of bones and teeth and this may cause tooth discoloration. Although the exact mechanism of tetracycline incorporation into mineralizing tissue is not clearly understood, it is generally believed that chelation of calcium and tetracycline explains the presence of the drug in mineralized tissues . The severity of the tooth discoloration is directly related to the proximity of tetracycline incorporation to the dentinoenamel junction. Tetracycline appears to be incorporated into the dentin, not the enamel.
3) The type of discoloration varies somewhat according to the particular tetracycline used. Chlortetracycline tends to produce grey-brown teeth, but tetracycline, oxytetracycline and demethylchlortetracycline cause yellow discoloration. There is some evidence that oxytetracycline causes less discoloration than the other older tetracyclines. The severity of tooth discoloration depends on duration and total dosage of tetracycline therapy. Discoloration is usually only obvious in children who have received several courses of these drugs (Kucers & Bennett, 1979).
4) A case report describes a 29-year-old female, receiving 250 mg of tetracycline twice a day for the treatment of a skin abscess, who developed a heavy dark-brown extrinsic stain of the dentition on the lingual surfaces of the mandibular anterior teeth. The patient continued tetracycline therapy for 8 more months at which time coarse pumice treatments were necessary to restore the cosmetic appearances of the teeth. Following discontinuation of the tetracycline therapy, staining of the teeth did not recur. The circumstantial evidence of this case indicates that this may be the first report of extrinsic discoloration caused by tetracycline .
5) Enamel hypoplasia as well as tooth pigmentation may occur in the deciduous teeth following in utero or neonatal exposure to tetracycline .

另外牙醫學的資料是：

牙胚發育期服用了四環素類藥物，它能與多價陽離子的鈣起絡合作用，進而抑制鈣化的兩個相，晶核形成和晶體的生長，從而影響牙齒的發育和鈣化，導致釉質發育不全。

Micromedex的資料都有點歷史了，所以找一些比較近的

Product Information: Vibramycin(R) Calcium oral suspension syrup, doxycycline calcium oral suspension syrup. Pfizer Labs, New York, NY, 2007.

Permanent yellow-gray-brown discoloration of the teeth has been associated with tetracycline antibiotic use in children less than 8 years of age, and in children of mothers receiving tetracycline antibiotics during the last half of pregnancy. Tooth discoloration has occurred with short-term therapy, however, it is more common with long-term therapy.

Children are susceptible to tetracycline tooth stains from the time they are in utero until the age of 8. Since teeth start to develop before we're even born, pregnant women should not take tetracycline to prevent the possibility of the drug affecting the unborn baby's oral health.

而這篇的資料似乎又說如果是在出生前使用，可能對恆齒比較不會有影響：

International Journal of DermatologyVolume 43, Issue 10, Article first published online: 22 APR 2004

The calcification of deciduous teeth begins at approximately the end of the fourth month of gestation and ends at approximately 11–14 months of age. Permanent teeth begin calcifying after birth and are not affected by exposure to the TCN during the prenatal period. The calcification of permanent teeth is completed at 7–8 years of age with the exception of the third molar (“wisdom” teeth).

另外可以參考這一篇：

所以結論就是：八歲以前還是不要用比較好。

但是有人會問，如果是doxycycline呢？幾歲是安全的呢？

目前找到的文獻是顯示至少四歲都是安全的：

1. Dental staining after doxycycline use in children PMID: 29091225

2. The end of a dogma: the safety of doxycycline use in young children for malaria treatment PMID: 28407772

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