地美環素

地美環素
臨床資料
商品名（英語：Drug nomenclature）	脫甲氯四環黴素 (Declomycin)
其他名稱	RP-10192
AHFS/Drugs.com	Monograph
MedlinePlus	a682103
給藥途徑	口服
ATC碼	D06AA01 (WHO) J01AA01;
法律規範狀態
法律規範	處方藥（℞-only）;
藥物動力學數據
生物利用度	60 ~ 80%
血漿蛋白結合率	41 ~ 50%
藥物代謝	肝臟
生物半衰期	10 ~ 17 小時
排泄途徑	腎臟
識別資訊
	IUPAC命名法 (2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione; ;
CAS號	127-33-3 ; 64-73-3（鹽酸鹽）
PubChem CID	54680690;
DrugBank	DB00618 ;
ChemSpider	10482117 ;
UNII	5R5W9ICI6O;
KEGG	D03680 ;
ChEBI	CHEBI:4392 ;
ChEMBL	ChEMBL1591 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID1022893 ;
ECHA InfoCard	100.004.396
化學資訊
化學式	C21H21ClN2O8
摩爾質量	464.853 g/mol
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES NC(=O)C1C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)ccc(Cl)c4[C@@H](O)[C@H]3C[C@H]2C(C=1O)N(C)C;
	InChI InChI=1S/C21H21ClN2O8/c1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31/h3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31)/t6-,7-,14-,15-,21-/m0/s1 ; Key:FMTDIUIBLCQGJB-SEYHBJAFSA-N ;

地美環素（INN，USAN和BAN名稱：Demeclocycline），又名去甲基氯四環黴素或脫甲氯四環黴素，是衍變自金黃色鏈黴菌（英語：Streptomyces aureofaciens）突變菌株的四環素類抗生素。^[1]^[2]

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地美環素定位於治療各種類型的細菌感染^[3]，是用來治療萊姆病，痤瘡，和支氣管炎的抗生素^[4]^[5]^[6]，卻由於細菌對其逐漸普遍產生抗性，致使其現在越來越少被用來治療相關感染。^[7]^[8]^[9]

當抗利尿激素分泌異常綜合症（英語：syndrome of inappropriate antidiuretic hormone）發生且對病患的流質限制無效時，地美環素被美國等諸多國家在適應症外運用（英語：off-label use）於治療低鈉血症，即血內含鈉濃度低。^[10]從生物學角度上看，這是通過降低腎小管內細胞收集抗利尿激素的反應速度來奏效^[11]。其實，在上述病症中的作用主要是依賴於地美環素能夠致使人體無法集中尿液進而脫水，從而誘導腎原性尿崩症發生的副作用。^[10]^[12]^[13]

1975年，地美環素被首次報道用於抗利尿激素分泌異常綜合症的治療，隨後在1978年，一系列更大規模的研究發現是藥物在治療抗利尿激素分泌異常綜合症時，比當時唯一能夠使用的治療手段碳酸鋰更有效，藥物耐受性更好。^[14]^[15]地美環素曾是治療抗利尿激素分泌異常綜合症的首選藥物。但現時它可能會被現在能夠使用的加壓素受體拮抗劑（英語：vasopressin receptor antagonist）（如托伐普坦（英語：tolvaptan））取而代之。^[15]

禁忌

與其他四環素類抗生素相同，地美環素會干擾骨骼的發育，並可能使牙齒變色，故此禁止給藥於兒童、孕婦或是正處於哺乳期的婦女。^[9]

副作用與相互作用

這一部分與其餘四環素類抗生素類似。據報道，用藥中人士的皮膚可能會發生日光性反應^[15]，且與其他幾種已知的四環素類衍生物相同，地美環素會誘發腎源性尿崩症。^[16]此外，地美環素可能與鋰相同有着精神藥物類型的副作用。^[17]

四環素類抗生素可以和陽離子如鈣、鐵（口服）、鎂結合，使得他們不溶於腸道，也不被腸道吸收。同時，地美環素不應與食物（特別是牛奶等乳製品）或抗酸劑一同服用。^[9]

反應機理

和相關四環素類抗生素相同，地美環素通過與30S核糖體亞基結合來抑制氨酰基結合tRNA，從而阻止細菌合成蛋白質。因其只是阻止細菌的生長而非直接殺死細菌，故此只是具有抑菌作用，而沒有殺菌作用。^[1]^[7]

地美環素通過干擾腎臟中抗利尿激素與加壓素V2受體結合後的細胞內第二信使級聯反應（特別是抑制腺苷酸環化酶活化）來抑制腎對抗利尿激素的反應。^[18]^[19]^[20]然而，地美環素如何實現這一功能還有待闡明。^[20]

參考資料

[1]
Chopra, I.; Hawkey, P. M.; Hinton, M. Tetracyclines, molecular and clinical aspects. J. Antimicrob. Chemother. 1992, 29 (3): 245–277. doi:10.1093/jac/29.3.245.
[2]
J. Elks. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 2014-11-14: 356– [2019-07-23]. ISBN 978-1-4757-2085-3. （原始內容存檔於2020-08-01）.
[3]
DailyMed. Demeclocycline Hydrochloride - demeclocycline tablet. Drug label information. [2008-12-20]. （原始內容存檔於2018-10-12）.
[4]
Rosner, Bryan. The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine. 2007: 84, 86 [2019-07-23]. （原始內容存檔於2020-08-01）.
[5]
Ad Hoc Committee on the Use of Antibiotics in Dermatology. Systemic antibiotics for treatment of acne vulgaris: efficacy and safety. Arch. Dermatol. 1975, 111 (12): 1630–1636. PMID 128326. doi:10.1001/archderm.1975.01630240086015.
[6]
Beatson, J. M.; Marsh, B. T.; Talbot, D. J. A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice. J. Int. Med. Res. 1985, 13 (4): 197–202. doi:10.1177/030006058501300401.
[7]
Schnappinger, Dirk; Hillen, Wolfgang. Tetracyclines: Antibiotic action, uptake, and resistance mechanisms. Archives of Microbiology. July 1996, 165 (6): 359–369. doi:10.1007/s002030050339.
[8]
Klein, Natalie C.; Cunha, Burke A. Tetracyclines. Medical Clinics of North America. 1995, 79 (4): 789–801. doi:10.1016/S0025-7125(16)30039-6.
[9]
Lexi-Comp. Demeclocycline. The Merck Manual Professional. August 2008 [2019-07-23]. （原始內容存檔於2010-08-17）. Retrieved on October 27, 2008.
[10]
Goh KP. Management of hyponatremia. American Family Physician. May 2004, 69 (10): 2387–94 [2019-07-23]. PMID 15168958. （原始內容存檔於2008-10-16）.
[11]
Kortenoeven, M. L.; Sinke, A. P.; Hadrup, N.; Trimpert, C.; Wetzels, J. F.; Fenton, R. A.; Deen, P. M. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am. J. Physiol. Renal Physiol. 2013, 305 (12): F1705–F1718. doi:10.1152/ajprenal.00723.2012.
[12]
Hayek, Alberto; Ramirez, Jimeno. Demeclocycline-induced diabetes insipidus. JAMA. 1974, 229 (6): 676–677. doi:10.1001/jama.1974.03230440034026.
[13]
Miell, J.; Dhanjal, P.; Jamookeeah, C. Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review. Int. J. Clin. Pract. 2015, 69 (12): 1396–1417. PMC 5042094 . PMID 26289137. doi:10.1111/ijcp.12713.
[14]
Cherrill DA, Stote RM, Birge JR, Singer I. Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. Annals of Internal Medicine. November 1975, 83 (5): 654–6. PMID 173218. doi:10.7326/0003-4819-83-5-654.
[15]
Tolstoi LG. A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone. Medscape Pharmacotherapy. 2002, 4 (1) [2019-07-23]. （原始內容存檔於2013-06-06）.
[16]
Cox, Malcolm. Tetracycline Nephrotoxicity. Porter, George A. (編). Nephrotoxic Mechanisms of Drugs and Environmental Toxins. Boston, MA: Springer. 1982: 165–177 [2019-07-23]. ISBN 978-1-4684-4216-8. doi:10.1007/978-1-4684-4214-4_15. （原始內容存檔於2020-08-01）.
[17]
Mørk, A.; Geisler, A. A comparative study on the effects of tetracyclines and lithium on the cyclic AMP second messenger system. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1995, 19: 157–169. doi:10.1016/0278-5846(94)00112-U.
[18]
Eric Fliers; Marta Korbonits; J.A. Romijn. Clinical Neuroendocrinology. Elsevier Science. 2014-08-28: 43– [2019-07-23]. ISBN 978-0-444-62612-7. （原始內容存檔於2020-08-01）.
[19]
L. Kovács; B. Lichardus. Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. 2012-12-06: 180– [2019-07-23]. ISBN 978-94-009-0449-1. （原始內容存檔於2020-08-01）.
[20]
Ajay K. Singh; Gordon H. Williams. Textbook of Nephro-Endocrinology. Academic Press. 2009-01-12: 251– [2019-07-23]. ISBN 978-0-08-092046-7. （原始內容存檔於2020-08-01）.

[Chopra-1] [1]
Chopra, I.; Hawkey, P. M.; Hinton, M. Tetracyclines, molecular and clinical aspects. J. Antimicrob. Chemother. 1992, 29 (3): 245–277. doi:10.1093/jac/29.3.245.

[Elks2014-2] [2]
J. Elks. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 2014-11-14: 356– [2019-07-23]. ISBN 978-1-4757-2085-3. （原始內容存檔於2020-08-01）.

[DailyMed-3] [3]
DailyMed. Demeclocycline Hydrochloride - demeclocycline tablet. Drug label information. [2008-12-20]. （原始內容存檔於2018-10-12）.

[4] [4]
Rosner, Bryan. The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine. 2007: 84, 86 [2019-07-23]. （原始內容存檔於2020-08-01）.

[5] [5]
Ad Hoc Committee on the Use of Antibiotics in Dermatology. Systemic antibiotics for treatment of acne vulgaris: efficacy and safety. Arch. Dermatol. 1975, 111 (12): 1630–1636. PMID 128326. doi:10.1001/archderm.1975.01630240086015.

[6] [6]
Beatson, J. M.; Marsh, B. T.; Talbot, D. J. A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice. J. Int. Med. Res. 1985, 13 (4): 197–202. doi:10.1177/030006058501300401.

[Schnappinger-7] [7]
Schnappinger, Dirk; Hillen, Wolfgang. Tetracyclines: Antibiotic action, uptake, and resistance mechanisms. Archives of Microbiology. July 1996, 165 (6): 359–369. doi:10.1007/s002030050339.

[Klein-8] [8]
Klein, Natalie C.; Cunha, Burke A. Tetracyclines. Medical Clinics of North America. 1995, 79 (4): 789–801. doi:10.1016/S0025-7125(16)30039-6.

[Lexi-Comp-9] [9]
Lexi-Comp. Demeclocycline. The Merck Manual Professional. August 2008 [2019-07-23]. （原始內容存檔於2010-08-17）. Retrieved on October 27, 2008.

[Goh-10] [10]
Goh KP. Management of hyponatremia. American Family Physician. May 2004, 69 (10): 2387–94 [2019-07-23]. PMID 15168958. （原始內容存檔於2008-10-16）.

[11] [11]
Kortenoeven, M. L.; Sinke, A. P.; Hadrup, N.; Trimpert, C.; Wetzels, J. F.; Fenton, R. A.; Deen, P. M. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am. J. Physiol. Renal Physiol. 2013, 305 (12): F1705–F1718. doi:10.1152/ajprenal.00723.2012.

[12] [12]
Hayek, Alberto; Ramirez, Jimeno. Demeclocycline-induced diabetes insipidus. JAMA. 1974, 229 (6): 676–677. doi:10.1001/jama.1974.03230440034026.

[Miell-13] [13]
Miell, J.; Dhanjal, P.; Jamookeeah, C. Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review. Int. J. Clin. Pract. 2015, 69 (12): 1396–1417. PMC 5042094 . PMID 26289137. doi:10.1111/ijcp.12713.

[Cherrill-14] [14]
Cherrill DA, Stote RM, Birge JR, Singer I. Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. Annals of Internal Medicine. November 1975, 83 (5): 654–6. PMID 173218. doi:10.7326/0003-4819-83-5-654.

[Tolstoi-15] [15]
Tolstoi LG. A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone. Medscape Pharmacotherapy. 2002, 4 (1) [2019-07-23]. （原始內容存檔於2013-06-06）.

[Cox-16] [16]
Cox, Malcolm. Tetracycline Nephrotoxicity. Porter, George A. (編). Nephrotoxic Mechanisms of Drugs and Environmental Toxins. Boston, MA: Springer. 1982: 165–177 [2019-07-23]. ISBN 978-1-4684-4216-8. doi:10.1007/978-1-4684-4214-4_15. （原始內容存檔於2020-08-01）.

[17] [17]
Mørk, A.; Geisler, A. A comparative study on the effects of tetracyclines and lithium on the cyclic AMP second messenger system. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1995, 19: 157–169. doi:10.1016/0278-5846(94)00112-U.

[FliersKorbonits2014-18] [18]
Eric Fliers; Marta Korbonits; J.A. Romijn. Clinical Neuroendocrinology. Elsevier Science. 2014-08-28: 43– [2019-07-23]. ISBN 978-0-444-62612-7. （原始內容存檔於2020-08-01）.

[KovácsLichardus2012-19] [19]
L. Kovács; B. Lichardus. Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. 2012-12-06: 180– [2019-07-23]. ISBN 978-94-009-0449-1. （原始內容存檔於2020-08-01）.

[SinghWilliams2009-20] [20]
Ajay K. Singh; Gordon H. Williams. Textbook of Nephro-Endocrinology. Academic Press. 2009-01-12: 251– [2019-07-23]. ISBN 978-0-08-092046-7. （原始內容存檔於2020-08-01）.

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