|
楼主 |
发表于 2008-11-20 10:56:32
|
显示全部楼层
127-5-第五节 四环素类药物的副作用和毒性
严重影响生命的副作用不常见,低剂量或停药后,轻的副作用是可逆的。在二甲胺四环素控制RA的治疗中,副作用很少见,导致停药的只有7%。( I% g# l. [% ^3 Z& f
' q, p6 o1 X6 X 一、对骨、牙生长的影响 ; p A: r$ G4 O. W4 w. C! U
1 A# @6 r. `* m- ?. A 四环素可与新形成的骨、牙中所沉积的钙相结合。妊娠5个月以上的妇女服用这类抗生素时,出生的幼儿乳牙可出现荧光、变色、牙釉质发育不全,畸形和生长抑制。幼儿,尤其是出生后第1年,由于肾发育不全,药物不能充分排泄,即使短期用药,也极易引起乳牙的色素沉着和牙釉质发育不全,易于造成龋齿,牙染色由黄转为棕黄。剂量越大,黄染越深,牙釉质发育不全也更加显著。因此,年龄小于7-8岁儿童、怀孕5个月以上和哺乳的妇女等慎用或禁用。' |" R8 c- z' D" M& l
, I/ A3 q5 R0 _ T+ }* ?: w, z
二、胃肠道紊乱
& b; n! A7 A z0 U/ e8 b0 G4 U f
恶心、呕吐、上腹部不适、腹胀、腹泻、舌炎、口腔炎和肛门炎等。减少剂量至50mg,每天1次或2次,或与食物同服,可以减轻症状。在RA病人中,因为 RA本身有关节和全身的症状,同时又用其他有潜在肝脏毒性的药物,因此这些副作用不容易及时发现。为此,要求开始治疗 1个月后每 3个月检查全血细胞计数和肝、肾功能。: ?( ]' l' O5 N A; q
* T5 g0 g9 T5 q, {! d3 B 三、头晕或轻度头痛
- P. g: c( o# z& x# t) T+ s
4 W8 t ?% _( m/ ~4 W 妇女更加多见。减少开始剂量(50mg,每天1次或2次)可减轻其副作用,在2-4周逐渐增加剂量。9 U7 b2 @: x j4 y' I- W# A
9 t* W% w5 i1 @3 j% E$ V" } 四、其他
0 u1 t! T$ ? G2 @5 h9 `; g
4 c$ y6 b# s- g, G9 O% M. Q 有关于服用二甲胺四环素产生光敏反应的报道,服药1年或更长会产生灰黑色素沉着,在身体的任何部位都会有,特别在腿胫部。国外报道二甲胺四环素引起可逆性前庭副作用,包括恶心、呕吐、头晕、眩晕及运动失调。前庭反应妇女较男性多见,发生率与剂量高低无明显关系。脱氧土霉素的皮疹少见。因为四环素降低血浆抗凝活性,所以接受抗凝治疗的病人应该减少抗凝药物的剂量。 % S2 W. N$ b( o, f% E
9 m, \+ S; _& H 近年来,国外学者在用米诺环素治疗RA的研究过程中,还发现了该药可诱发类狼疮样症状,并称之为“米诺环素诱导自身免疫综合征(minocycline-induced autoimmune syndrome)”,其特点主要有可逆性的关节痛、关节炎、发热、晨僵、皮肤损害,偶有慢性活动性肝炎表现,同时出现抗核抗体阳性及p-ANCA抗体滴度增高。
5 v3 U/ B8 X E, i) p
" {- s, K% ~1 ^. K: z 五、菌群失调 , N2 N+ ?0 [6 J
$ ^4 I$ W2 |$ j4 h6 U& o
长期用四环素后,使正常菌群的分布发生改变,敏感菌受到抑制,耐药细菌、真菌(主要是白色念珠菌)等乘机在体内繁殖,发生消化道、呼吸道和泌尿道等感染。如果发生这种情况,应当马上停药,改用其他药物。脱氧土霉素的肠道二重感染少见。 W2 `- A Q: \& g
* d3 U0 N1 Z6 R2 D
综上所述,脱氧土霉素和二甲胺四环素对RA、反应性关节炎、骨关节炎和骨质疏松都有一定的疗效,且有副作用低的优点,尤其适用于肾功能不良的病人,这是一个有潜力的抗风湿药物。
. @* K& A, ^' T. Q+ A# | ( 叶益新 李小霞 张如峰 )9 T' i4 e* N E3 [
参考文献:
1 ~$ X3 g; [8 S' u, \. u4 q
0 |% A _2 ^ ~6 P2 u) y1 l* D 杨藻衰.医用药理学.北京:人民卫生出版社,1982.742-749 ) G6 N" ]$ z0 J1 l; v
1 N( s' u) l2 q4 v; s& X& g1 A/ L 季颖,张明发.米诺环素治疗类风湿关节炎.中国新药与临床杂志,2000.19(3):220一223
7 Z4 n$ g$ K+ E- p3 b, p
0 o- B( \! j0 E 李小霞,刘恕.美满霉素治疗类风湿关节炎 1例.中华风湿病学杂志,2001.5(4):269 ' \/ u3 p9 U3 k8 E' G; i+ z
/ A9 G0 Q7 a( U O# T1 r8 J 刘子荣,刘丽华,丁长海.米诺环素治疗类风湿关节炎.中国药理学通报,1999.15(6):500 , m" E. r/ M+ l) ~* R- h
- V9 ~8 T$ a6 T+ }# S 领玉胜.二甲胺四环素治疗与类风湿关节炎相关的白细胞碎裂性血管炎.国外医学皮肤性病学分册,1997.23(6):269一370
! M) o' T+ @/ J* h1 N" ?; }* Q, J% E! I; J( T8 y, I9 t
杨俊何.米诺环素治疗类风湿关节炎.国外医学抗生素分册,1996.17(3):233一234 ; k2 I) D' B# A% z" }" U
/ O/ d" I! z% `$ B! y Cooper SM. Tetracyclines. In: Shaun R, Edward D H. andClement B S, et al. eds,Kelley}s Textbook of Rheumatology. 6thed. Philadelphia: Saunders, 2001. 913一920
1 X+ a8 `% n' c/ n. E3 J: U/ x( u4 y" P# G9 Y
Alarcon GS. Minocycline for the treatment of rheumatoidarthritis. Rheum Dis Clin North Am,1998.24(3):489一499
$ J0 W5 Z7 K6 d* [# m; e H# F9 C& ^
Alarcon GS. Tetracyclines for the treatment of rheumatoidarthritis. Expert Opin Investig Drugs, 2000.9(7):1491一1498
8 @/ {% n M/ G5 G3 o$ Q2 a" r* g* g" h
Assad SA,Bernstein EF,Brod B, et al. Extensive pigments-tion secondary to minocycline treatment of rheumatoid arthritis. JRheumatol, 2001.28 (3) :679一682 $ l* ] j$ I) ^ T
4 t1 v' i) X. F ~6 |! f
Bluhm GB, Sharp JT, Tilley BC, et al. Radiographic results from the minocycline in rheumatoid arthritis(MIRA) trial. JRheum, 1997.24(7)1295一1302/ c8 f' e( q# E/ N# S/ n! @2 Y: J
# C$ x. k$ W4 v! W, X* J Case JP. Old and new drugs used in rheumatoid arthritis: ahistorical perspective. Part 2 : the newer drugs and drug strategies.Am J Therapy, 2001.8(3):163一179
' ]3 Z& v o. l/ e8 p7 w; [ R- b( e
3 n7 O2 k A7 @- V7 W+ s# b. s Dodd MA, Dole EJ,Troutman WG, et al. Minocycline-asso-ciated tooth staining. Ann Pharmacotherapy. 1998. 32(9) :887一889
, t0 z* l. G, X! H- i6 k4 s% o- ^, k, q8 |1 b+ ]
Elkayam O, Yaron M, Zhukovsky G, et al, Toxicity profileof dual methotrexate combinations with gold, hydroxy-chloroquine,sulphasalazine and minocycline in rheumatoid arthritispatients. Rheumatol Int,1997.17(2) :49一53
2 H4 j# u, D2 K" F6 T6 r, E a5 `. W9 [5 z3 C- d
Kawanaka N, Yamamura M, Hashimoto H, et al. An evalua-tion of efficacy of minocycline as an anti-rheumatic drug in pa-tients with active and refractory rheumatoid arthritis. Ryumachi.1998.38(6):801一809
1 z6 E) d) { V. V' S1 @9 }- u N- Y* ^1 ]3 G
Kloppenburg M,Mattie, H,Douwes N, et al. Minocycline inthe treatment of rheumatoid arthritis: relationship of serum con-centrations to efficacy. J Rheum.1995.22(4):611一616
" q* `& Z3 R$ b& I/ d) G) N) z3 I$ k* A. y+ ]# l7 P
Lai NS, Lan JL. Treatment of DMARDs-resistant rheuma-toid arthritis with minocycline: a local experience among the Chi-nese. Rheumatol Int,1998. 17(6) :245一247
/ x Q |6 R( l) d9 E' S- s8 \0 p5 U1 s! s: \5 Y
Langevitz P, Livneh A, Bank 1, et al. Benefits and risks ofminocycline in rheumatoid arthritis. Drug Saf,2000. 22(5) :405一414
' {( o3 P( d/ K$ F8 T2 T# k# J# e" }* B: D* \$ `- K( Y9 I
Marzo-Ortega H, Misbah S, Emery P. Minocycline inducedautoimmune disease in rheumatoid arthritis: a missed diagnosis? JRheumato1,2001.28(2):377一3787 f8 Q1 X" u6 i6 X# Q, h9 R$ ~6 t2 ]
* `3 @+ W$ Y8 } B7 l% d& A7 w Nordstrom D, Lindy O, Lauhio A, et al. Anti-collagenolyticmechanism of action of doxycycline treatment in rheumatoidarthritis. Rheumatol Int,1998. 17(5):175一180 6 l! Z5 @4 X" R' c F) E
+ Q2 W, f) [* g5 ?: }+ e: ~/ P
O"dell JR,Blakely KW,Mallek JA, et al. Treatment of earlyseropositive rheumatoid arthritis: a two-year, double-blind com-parison of minocycline and hydroxychloroquine. Arthritis Rheum.2001.44(10):2235一2241
) J- q8 U# T3 z4 a+ U
- I0 @7 U- J6 Y3 P, I2 J O'dell JR. How is it best to treat early rheumatoid arthritispatients? Best Pract Res Clin Rheumato1.2001.15(1):125一137 4 L; s& I- ? Q
0 H4 d" _+ `" \& H/ q2 `3 b O}dell JR. Is there a role for antibiotics in the treatment ofpatients with rheumatoid arthritis? Drugs. 1999. 57 ( 3 ):279-282
: E. h+ c2 w7 _, b0 l# `- v8 Q, ^! Q" k
O'dell JR, Haire CE, Palmer W, et al. Treatment of earlyrheumatoid arthritis with minocycline or placebo: results of a ran-domized, double-blind, placebo-controlled trial. Arthritis Rheum,1997.40(5):794一796.
' K, z0 F0 ?& Z! i9 y" g- x) G8 g
- k! b) K+ k% ^4 |2 K O}dell JR, Paulsen G, Haire CE, et al. Treatment of earlyseropositive rheumatoid arthritis with minocycline: four-year fol-low up of a double-blind, placebo- controlled. Drugs, 1999.57(3):279一282
7 l* w# [3 ?, O6 y$ [! u+ m) V: R c, I7 S# a) m
Pillemer SR, Fowler SE, Tilley BC, et al. Meaningful im-provement criteria sets in a rheumatoid arthritis clinkcal trial. MI-RA Trial Group. Minocycline in rheumatoid arthritis. ArthritisRheum.1997.40(3):419一4254 z/ Q' l. C# r8 R9 C' I' a
. t' k+ D' v& {) S/ T Pisetsky DS, Clair E W S. Progress in the treatment ofrheumatoid arthritis. JAMA,2001.286(22)2787一2790
x# s: `5 B4 a T- d6 u, J6 l0 g
3 ?/ N; R0 }2 H+ v Skinner M,Cathcart ES, Mills J A, et al. Tetracycline in thetreatment of rheumatoidarthritis a double blind controlled study.Arthritis Rheum. 1971.14(6) :727一732
) U5 X+ M3 o; J: p4 g) I
4 [( e& W% h7 N, L3 z2 }# L Sreekanth VR,Hands R, Wali JP, et al. Doxycycline in thetreatment of rheumatod arthritis--a pilot study. J Assoc PhysiciansIndia,2000.48(8):804一807
, U) V* e. F" ~$ Y' \, B$ S1 O
1 I0 T/ Z" e2 ?* e: \5 K Thomas L. Experimental mycoplasma infections as models ofrheumatoid arthritis. Federation Proc. 1973. 32:143一146
9 ]3 I1 a% i) L7 V+ C% C$ [; }5 E& a! ?+ p5 d
Tilley BC, Alarcon GS, Heyse SP, et al. Minocycline inrheumatoid arthritis. A 48-week, double-blind, placebo-controlledtrial. MIRA Trial Group. Ann Inter Med. 1995.122(2) :81一89, M- _2 n9 N- w& ^% ^
& Y8 P! K1 ]$ m Q! y$ ^ Tourtellotte CD. Tetracycline in RA. Arthritis Rheum.1971.14(6):788
) I- p2 a! I0 ], [) ?
" M& Z! A# |3 q Toussirot E, Despaux J, Wendling D. Do minocycline andother tetracyclines have a place in rheumatology? Rev Rhum EnglEd, 1997.64(7-9):474一480/ U. K5 X& u+ c) A ~* r7 ` U
! _/ C: l) k& H) w6 f4 K6 a; R" K
Wasel NR, Schloss EH, Lin AN. Minocycline-induced cuta-neous pigmentation. J Cutane Med Surg. 1998.3(2) :105一1088 N% g7 v# {& i) {" r2 l
' N. e4 ~# E7 \/ q. T
Westbury LW, Najera A. Minocycline-induced intraoralpharmacogenic pigmentation: case reports and review of the litera-ture. J Periodonto1,1997.68(1):84一91 |
|