Препараты Для Терапии Бронхообструкции

Download as
 PPT
Presentation Description 

No description available

authorSTREAM Premium Service
What's up on authorSTREAM?
Views: 93
Like it  ( Likes) Dislike it  ( Dislikes)
Added: June 15, 2009 This Presentation is Public 
Presentation Category : Entertainment All Rights Reserved
Presentation Statistics
Views on authorSTREAM: 3 | Views from Embeds: 90
- 36 views

Others - 54 views
Presentation Transcript

????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? 15 ???? 2009 ?.


????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? ????????????? ??? ?2-????????????????? ?-???????????? ????-IgE ????????? ?????? ????????


??? :??? Barnes and Adcock, 2003 GRE ??? ????? (????????, ?????????, ????????) GR ???? ????


??????? ??? ?? ???????? ???????????? :??????? ??? ?? ???????? ????????????


????????? ??????????????? ????????? ?????? ?????????????? ?????? ??? ???????? ??? :????????? ??????????????? ????????? ?????? ?????????????? ?????? ??? ???????? ??? Woolley KL Am. J. Respir. Crit. Care Med. 1996; 154:237-243. John M Am. J. Respir. Crit. Care Med. 1998; 157:256-262. Williams CM, J. Allergy Clin. Immunol. 2000; 105:847-859. Nelson DJ Am. J. Respir. Crit. Care Med. 1995; 151:475-481. Barnes PJ Am. J. Respir. Crit. Care Med. 1996; 154:S21-S27. Kai H Am. J. Physiol. 1996; 271:L484-L488.


?????? ??? :?????? ??? Laitinen LA, et al. J Allergy Clin Immunol. 1992;90:32-42.


????????????? ???????? :????????????? ???????? Busse et al., JACI 1998 ? PEF ???., ?/??? ?????? ??????? 800 ??? 400 ??? 200 ??? 100 ??? ??????? n=92-98 ? ?????? ??????


????????? ?????????? :????????? ?????????? Toogood et al: JACI 1982 -10 0 10 20 30 40 1600 -200 -150 -100 -50 0 50 100 150 ????????? ???, ?/??? ????????? ????? ???????????, ??-3 ???????? ????, ???


????????????? ?????????? ? ??????? :????????????? ?????????? ? ??????? ????????? ???? ???-???????? ????????? ????? ????????? ?? ????? ?????????????????? ? ?? ????????????? ??? ?????? ????????? ????? ??????????? 1 ??? ? ????? ??? ????????? ??.


????: ????-????? :????: ????-????? Holt S et al. BMJ 2001;323:1–8 Masoli M. et al. Eur Respir J 2004; 23: 552–558. ?????????? ?????????(8 ???????????? – 2324 ???????) (1435 ???????)


????? ?? ?????????? ???? ? ?????????? ???? ? 895 ??????? ?? ?????? 12 ???. ???????. :????? ?? ?????????? ???? ? ?????????? ???? ? 895 ??????? ?? ?????? 12 ???. ???????. Malmstrom, K et al. Ann Intern Med 1999;130,487-495


????????????? ???? ????????????? ??? :????????????? ???? ????????????? ??? * - ???????? ????? ????????? 1 ??? ? ???? ??? ????????? ??


?????????? ????????? ?? ?????? ????????, ??? ?????????? ?????????????? :?????????? ????????? ?? ?????? ????????, ??? ?????????? ?????????????? Pedersen S. et al. J. Allergy Clin. Immunol. 1995; 95:29–33. Alving, K., et al. Am. J. Respir. Crit. Care Med. 1995; 151:A129. 0 100 200 400 600 800 ???? ??????????, ??? 100 80 60 40 20 0 % ?? max


??????????: ???? - ????? :??????????: ???? - ????? Powell H and Gibson PG. MJA 2003; 178: 223–225


??????? ?????????????? ??? ? ????????????? ???? :??????? ?????????????? ??? ? ????????????? ???? ?????


?????? Foresi :?????? Foresi Foresi ?, Catena E. CHEST 2000; 117:440–446 ????????? 800 ???/??? ????????? 200 ???/??? ????????? 200 ???/??? + 800 ??? ????????? 800 -1 0 6 ??????


???? ??????? ??? ?????????? :???? ??????? ??? ?????????? Foresi ?, Catena E. CHEST 2000; 117:440–446


?????? ?????????????? ???????? ????, ???????? ??????? ?? ?????? ? 6 ???., ??????? ???? ?????? ?? ?? ?? 56% :?????? ?????????????? ???????? ????, ???????? ??????? ?? ?????? ? 6 ???., ??????? ???? ?????? ?? ?? ?? 56% ????? ???????? ??? ? ??? ????????????? ?????????? Suissa S et al. NEJM 2000;343:332-6 0 50 100 150 200 250 1 2 3 4 5 6 7 ????? ???????? SABA ? ???. ?????????? ?? ?? ?? 10 000 ??????? ? ??? Suissa S et al:AJRCCM 1994:159:604-10


??????????? ??????? ??? :??????????? ??????? ??? Horvath G Eur Respir J 2006; 27:172–187


??????????? ??????? ??? :??????????? ??????? ??? Kumar SD Am J Respir Crit Care Med 2000; 161:918–921 Mak JCW, Am J Physiol Lung Cell Mol Physiol  1995; 12:L41-L46. ?????????? ?????? ???? ß-???????????????? ? ??????? ?????????? ??? ?????? 1 ??? ????? ???????? ? ???.


???????? ???????? ??????? :???????? ???????? ??????? 1 - Rodrigo G. Chest 1999; 121:1977–1987 2 - Rowe BH. Cochrane Systematic Reviews 2001, DOI: 10.1002/14651858   3 - Ellul-Micallef R. Br J Clin Pharmacol 1983; 15: 419-422. 4 - Le Merre C et al. Am J Respir Crit Care Med 1997; 155:A352. 5 - Rodrigo G. Chest, 2006; Vol. 130, #5


?????????: ?????????? ? ???????? :?????????: ?????????? ? ???????? ? ????? ? ???????? ???? ????????? ?? ????? 1% ?? ???????? ????. ? ??????? ??????? ???????? ???????? ?? ????? 0,3% ?? ???? ???????? ???????. ???????????? ?????????? ? ????? ????????????? ? 300 ??? ??????, ??? ? ????? ?? ???????, ?????????? ????????. J Allergy Clin Immunol 2007;120:798-802.


?????????: ?????????? ? ?????????? :?????????: ?????????? ? ?????????? ???? ?????????? ? 5,5 ???. ?????????? ??????. ?????????? ?????? ? ???????????? ???, ???????? FDA ????????? ????????? ????? ??? ?????????? ?. ?????????? ???????????? ? ?????????? ? ?????????? American College of Allergy, Asthma and Immunology (ACAAI). FDA: www.fda.gov


????????????? ??????? ??? :????????????? ??????? ??? ???????: ????????? ?????? ???????? ??????? ??? ???????? ???????????? ?????? ??????????? ?????????: ????????? ??????? ????????????? ?-? ??????? ????????? ???????? ?????????? ????? (????) ?????????? ????? ?????? ??????????? (????) ?????????????, ?????????? ?????? ???????? ???????? ???????? ??????????? ????????? ??????. ??????????


????????????? ???: ????-?????? :????????????? ???: ????-?????? Powell H and Gibson PG. MJA 2003; 178: 223–225 ???? ?????? ???????- ?????????????? ???????? ????????????? ???????


Slide 27:Graeme P Currie and Brian J Lipworth. BMJ 2006;332;1439-1441


Slide 28:Graeme P Currie and Brian J Lipworth. BMJ 2006;332;1439-1441


Slide 29:Consensus Development Conference: Osteoporosis. Am J Med 1993


Slide 30:Laryngoscope, 114:1566–1569, 2004 ?????????? ????????? ??????????? ???????????? ?????????? ??????????? ?????????


????????? ???????? ??????? – ??????? ??? ????????? :????????? ???????? ??????? – ??????? ??? ????????? Miller-Larsson et al, 1999 Miller-Larsson et al, 1998 ???????? ?????


??????? ??? :??????? ??? AstraZeneca, data on file


?????????? :?????????? Bundschuh DS et al. Am J Resp Crit Care Med. 2001;16? O O H O O O O H C-21 O O H O O O OH H C-21 ?????????? ???????? ??????????-?? ???. ?????????? * 12 ???. ?????????? * 1212 * - ?????????? ????????????? = 100


?????????: ?????????? ? ????? :?????????: ?????????? ? ????? FDA: www.fda.gov 1 2 4 5 6 7 8 9 3 0 10 11 12 ??????? 13 14 15 16+ ?????????? ??? (HFA) ??? ??? ????????? ?? ?????????? ??? ???????????? ??? ??? (HFA) ????????? ????????? ?????????? ?? ??????????/?????????? ?? ????????? ?? 3 ???? ??????? ????????? ?????? ? 2-? ???


????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? ????????????? ??? ?2-????????????????? ?-???????????? ????-IgE ????????? ?????? ????????


?????????????? :??????????????


Slide 37:NOVITAS-MMDCCLX


Slide 38:??????? ???????, ?????????? ?? ????? ? ?????????


Slide 39:??????? ???????, ?????????? ?? ????? ? ?????????


Slide 40:ß ? as ??? ??????????????


Slide 41:ß ? ??? ?????????????? as ??? ???? PKA


1 ???. ?????? ß2-?????????????????? :1 ???. ?????? ß2-?????????????????? ?? ????????? ? ??????? ??? ??????? ? ??????? ???1 ????? ???????. ?????????: ???????????? ????? ?? ????????? SABA (?? FEV1) ?? 17.8% [95% CI, 27.2% - 8.5%]; ??????? ??? ?????? «????-?????» SABA ?? 34.8% [CI, 45.7% -24%]; PC20 ?? 26% [CI, 37% - 11%]; ß2-????????? ??????????: ???????????????? ????????? ?? 18.3% [CI, 31.6% -5.1%], ?????????? ?? 23.1% [CI, 39.4% - 6.8%], ????? ?? ????????????? in vitro ?? 32.7% [CI, 56.5% -9.0%]. Shelley R. Salpeter et al. Ann Intern Med.2004; 140: 802-813


Slide 43:as ?????????????? ß-??????? ßARK1=GRK2 ? ß Pi PKA PKG GRKs


Slide 44:Mark Boterman, 2006


????????? ß2-???????????????? :????????? ß2-???????????????? ???????? ???????????? ???? ???????; ????????? ?????? ????????????, ????????????? ? TNF-a ??????? ???????? ? ????????????; ???????????? ???????????? ?????? ?????? ? ???????????, ????????? ????????? ?????????; ??????? ????????????? ??????????? ???????; ???????? ???????? ????? ? ???????? ????????????? ???????; ????????? ???????? ???????; Barnes P. Effect of beta agonists on inflammatory cells. J. Allergy Clin. Immunol., 1999, 104 (2), 10-17.


Slide 46:Tamura G. New Engl J Med, 2005; 352:15 ?????? ??????????? ? ??????? 37 ???, ??? ???????????? ?????????? ? ?????????? ? 30 ???.


??????????????? :???????????????


???? - ?????? :???? - ?????? Kemp JP, et al. J Allergy Clin Immunol 1997;99(Suppl. 2):S329 0 10 20 30 40 50 NS * ** *** ??????? FORM 6 ???*2 FORM 12 ???*2 FORM 24 ???*2 ? ??? (L/min) 12 ????? ????? ??????????


?????????????? ? ß2-????????????????? ???????? ? ??????? :?????????????? ? ß2-????????????????? ???????? ? ??????? Lipworth BJ. Thorax 2001;56:506–507 Aziz I ?t al. Eur J Clin Pharmacol 1998;54:377–81. Lipworth BJ et al. Am J Med 1989;86:653–7.


Slide 50:X-C Lewell Berlin 1999 ?????????? ??????????


Slide 51:X-C Lewell Berlin 1999


Slide 56:Hanania NA et al. Am J Respir Crit Care Med Vol 165. pp 1353–1358, 2002


ß2-????????????????? ??????????? ????????: ?????? ? ????????? ???????? :ß2-????????????????? ??????????? ????????: ?????? ? ????????? ???????? Källström et al 1994 ?????????? (?????, ???????) ?????????? ?????????? (????????) 100 50 0 –10 –9 –8 –7 –6 –5 ???????????? ?? (%) Log (????/?) ??????- ???????


????????????? ?????????? ?????????? LABA :????????????? ?????????? ?????????? LABA Am J Respir Crit Care Med Vol 165. pp 1353–1358, 2002 M. Molimard, E. Naline, Y. Zhang. Eur Respir J 1998; 11: 583–588. In vitro - ? ?????? ?? ????????????? ???????, ?????????? (? ??????? ?? ?? ???????????) ????? ????????? ? ???????? ??????????? SABA.


«Down»-????????? ß2-?????????? :«Down»-????????? ß2-?????????? Giannini ? ?? al. Chest 2001;119;1671-1675


?????????? ? ???????, ???????????? ? ???????? ???????????? :?????????? ? ???????, ???????????? ? ???????? ???????????? Bateman ED et al. Respiratory Research 2006, 7:13


?????????? ?????????? ? ?????????????? ß2-AR :????? ??????????????? ?????? ??????? ????????? ??????? Pauwels RA 1997 Pearlman DS, 1992; D’Alonzo GE, 1994 ?????????? ????????: Ramage L, 1994; Nelson JA, 1998 ?????????: Giannini D, 1996 ?????????? ???????????: Cheung D, 1992 ?????????? ?????????? ? ?????????????? ß2-AR


?????????? ?? ?????????? ????????? ?? ?????????? ?????, ? ??????? «????» ? ?????????????????? ????????? , ?????? ?????? ? ?????? :?????????? ?? ?????????? ????????? ?? ?????????? ?????, ? ??????? «????» ? ?????????????????? ????????? , ?????? ?????? ? ?????? Borgström L, et al (1996), Palmqvist M, et al (1997), Tötterman KJ, et al (1998), Löfdahl C-G, Svedmyr N (1989) Rosenborg J, et al (2000) 0 6 12 ????????- ??????? ???????? ? ?????? ???????? ????????? ?????? ????? (????) ?????????? SABA ??????? ?? ??????????? ???????


??????? ????: :??????? ????: J. Malolepszy et al. Eur Respir J 2001; 18: 928–934 Ostrom NK (2003 ?) ?????????? ? ???? 228 ???/???. ?? ?????????? ?? ???????????? ?? ???????????? ? ??????? ???? Ankerst J (2003 ? ) ?????????? ? ???? 54 ??? ?? 4 ???? – ?? ???????? ????????? ????????????? ???????? ? ??????? ?? ?+ ?????/? ??? 20 ????????? ?? 3 ????: ?????????? 110 ?? ?????????? 90 ??


?????????????? ß-???????????????? :?????????????? ß-???????????????? ???????????????? ß-?????????? ????? ß-??????? 0 ~1-2 ???? ~5 ????? ?????? ? ?????? ?????? (Chong LK, 2003; Nishikawa DM, 1996; Nogami M, 1993) ??????? ? ?????? (Bengtsson B, 1982 ? 1984; Schafers MA, 2001)


?????????? vs ?????????? :?????????? vs ?????????? Kips JC Am J Respir Crit Care Med Vol 164. pp 923–932, 2001


????????? ???????????? :????????? ????????????


????????? 12 ?????? ? ???? – ??? ?????????? :????????? 12 ?????? ? ???? – ??? ?????????? Sears MR et al. Eur Respir J 2009; 33: 21-32 ??? ??????????? ???????????? ??????????? 68 000 ??????? 49906 ???????, ?????????? ?????????? 8 ????????? ??????? (0,34 ?? 1000 ??? ??????) 18098 ???????, ?????????? ??????? 2 ????????? ?????? (0,22 ?? 1000 ??? ??????) ???????? ????????????? ?? ???????


????????? ????????????? ??????? :????????? ????????????? ??????? Sears MR et al. Eur Respir J 2009; 33: 21-32


?????????? ???? ?????????? ?????? ??? ??????? ?????? ??? ?????? ???????????, ?????? ??? ????. :?????????? ???? ?????????? ?????? ??? ??????? ?????? ??? ?????? ???????????, ?????? ??? ????. Castle W et al. BMJ 1993; 306: 1034–1037. Nelson HS et al. Chest 2006;129;15-26 Salpeter SR et al. Ann Intern Med. 2006;144:904-912. Bateman, E. et. al. Ann Intern Med 2008;149:33-42


?????????? ???? ?????????? ?????? ??? ??????? ?????? ??? ?????? ???????????, ?????? ??? ????. :?????????? ???? ?????????? ?????? ??? ??????? ?????? ??? ?????? ???????????, ?????? ??? ????. Castle W et al. BMJ 1993; 306: 1034–1037. Nelson HS et al. Chest 2006;129;15-26 Salpeter SR et al. Ann Intern Med. 2006;144:904-912. Bateman, E. et. al. Ann Intern Med 2008;149:33-42 Novartis database (5 970 ???????): ?????????? ? ??????????? ?????????? ????????? ? 2 ???? ????, ??? ??? ?????? ???????. RELIEF study (18 124 ???????): ?????????? ?? ???????? ??????????, ?? ?? 14% ??????? ???? ?????????? ??. AstraZeneca databases (50 426 ? 68 004 ???????): ?????????? ?? ?????? ?? ?????????? ?? ??.


1960-?: ß2-?????????????????????????? ???????? ??????????? ?????????? ?? ?? :1960-?: ß2-?????????????????????????? ???????? ??????????? ?????????? ?? ?? ??????? ? ????????? ??????? ß2-?????????????????? ????????? ???????? ?????????? ? ??????? ??


1990-?: ß2-???????????????????????????? ???????? ??????? ?????????? ?? ?? :1990-?: ß2-???????????????????????????? ???????? ??????? ?????????? ?? ??


LABA + ???? :LABA + ???? P.J. Barnes. Eur Respir J 2002; 19: 182–191


LABA + ???? :LABA + ???? Barnes PJ Eur Respir J 2007; 29: 587–595


??????????????? ???????? ????? ??????????, ??? ??? ??????????, ??????????? ?? ??????????? :??????????????? ???????? ????? ??????????, ??? ??? ??????????, ??????????? ?? ???????????


????? ???????? :???? ß2-??????? ? ???????? ????? ???? ????????? ?????????: ??? ?????????? ????????? - 18%. ??? ??????? ????????? - 65%. ??? ????????? ????????? – ?? 74%. ????? ????????????????? ?????? ? ??????? ? ?????????????? ?? ?? ?????? ?????? ?? ????????? 150 ???? ? ????. ????? 60% ??????? ??????? ???????????? ???. ????? ???????? Cerveri I et al. Eur Respir J. 1997 Dec;10(12):2761-5.


????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? ????????????? ??? ?2-????????????????? ?-???????????? ????-IgE ????????? ?????? ????????


???????? ?????? ??????? :???????? ?????? ??????? ???????????? ??????? ??????? ?????????????: a-AR (???????????), ß-AR (?????????) ?????????????????: ?-??????????????? (???????????) ????????? ?????????? (????????, ???????????, ????????) ?????????????: NO


Slide 79:H-ACh R M1 a,ß-Adr R ???????????? ????? ????????????? ????? ???????????????? ?????, eg. n. vagus M2 M3 ????????? ?1 ? ?3 ?????????????????. ??? ?????? ??? ???????? ???????. ????????? M2 – ????????????????. ??? ???????? ???????? ???????.


?-???????????? :?-???????????? ??????????? ?????????? ???????? ??????? ????????


???????????????? ?????????? ? - ???????????????? :???????????????? ?????????? ? - ????????????????


??????? ????????????? :??????? ????????????? Disse B et al. Life Sci 1999; 64:457-464


???????????????? ???????? ???????????? ? ??????????? :???????????????? ???????? ???????????? ? ??????????? van Noord JA et al. Thorax 2000; 55: 289-94 ???1 (?) ???? ????? ????????? 1.5 1.6 1.1 1.3 1.2 1.4 ???? ????? ????????? 1.5 1.6 1.1 1.3 1.2 1.4 92-? ???? 1-? ???? 0 5 -1 1 2 3 4 6 0 5 -1 1 2 3 4 6 ?????????? ??????????? ???1 (?)


????????????? :?????????????


???????? ???????? ????? :???????? ???????? ????? ???????????? ??????? ??????? ?????????????: ß-AR (?) ?????????????????: ?-??????????????? (?) ????????? ?????????? (????????, ???????????, ????????)


????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? ????????????? ??? ?2-????????????????? ?-???????????? ????-IgE ????????? ?????? ????????


?????????? :??????????


?????????? (Xolair): ??????????? ????????????? 14 ???????????? 3143 ??????? :?????????? (Xolair): ??????????? ????????????? 14 ???????????? 3143 ??????? ???????? ????????? ??????? ??????? ????????????? IgE ? ??????? ?? 90%. ?????????? ?????????? ?????????? ???????????? ????? ?? 50%. ????????? 50% ???????, ?????????? ?????????? ???????? ??????????? ??????? ???? ??? ? ??????? ?? 119 ???/???. ?? ????????? ? ??????? ? ???????, ?????????? ?????????? ? 2,5 ???? ???? ????????? ???????? ??? ??? ?????? ??????. ??????? ????????????? ?????????? ??????? ???????????? ???????????? ??????. Boulet LP Am J Respir CritCare Med 1997;155(6):1835– 40. Busse W J Allergy Clin Immunol 2001;108(2):184– 90. Walker SThe Cochrane Library 2007, Issue 1


????????? ??? ??????? ???????????????? :????????? ??? ??????? ???????????????? ????????????? ??? ?2-????????????????? ?-???????????? ????-IgE ????????? ?????? ????????


?????????????????? ????????? :?????????????????? ????????? ??????????? ? ??????????? ???????? ????????????? ????????????? ?????????????? ?????????? I ???? (??T1-?????????), ? ???????? ?????????? ?????????? 5-??????????????


????????? :????????? ?? ????????????? ???????? LABA ????????? ????????????? ??????? (? ?.?. ????????? ?????) ????? ??????????????? ???????? ??????? ??????????? ????????????? ??????? ????, ??????? ??????????? ???????????? ????????? ? ????? ?????????????? ????????????????????? ?????????? ???????????? ???????? ??????????????? ? ??????????? ?? ????????, ??????????? ????, ?????? ????????????? ?????????? (???????????, ??????????????? ????????, ???? ? ?.?.), ????????????? ??????????? ? ???????


?????????? ? ??????????????? ????????? :?????????? ? ??????????????? ????????? ????????????? ??????? ?????? ?????? ?????????? (??? ?? ? ????) ß2-????????????????? ??? ?????? ?????? ????????????????


??????????? :??????????? GSK159802 ? ??????????? ?????????? / ??????????? ?????? (???+??????????) ?????????? ??????????????? 4 (??????????) ?????????? ????????? (CAT-213 ???????? ? ????????????? ?????????) ????????? ??????? TNF-a ?????????????? ???????? ? ????????????? IL-5 ? IL-4


??????????? ???????????? ?????? ????????? :??????????? ???????????? ?????? ????????? 14,9 ??? 80 ???????????? > 5 000 ????????? 897 ??? $ 20% ?????? ?? ????????? FDA


Slide 95:1981 1982 1983 1984 1985 2000


???????????? (????????????????) ????????? :???????????? (????????????????) ????????? ?????????? ?.?. ? ?????. ????????? ??????????? 2008; ?4: ?. 18-21