Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Hau het cac bo phan trong c the eu co the b lao : Lao xng, lao hach, lao
mang nao, lao phoi........... trong o lao phoi chiem ty le cao nhat (70%).
La mot trong t chng nan y thng gay t vog trc kia do khong co thuoc cha
Hien nay vi s tien bo cua hoa tr lieu cung vi s ho tr cua cac phng tien
chan oan va tr lieu hien ai benh lao co the ieu tr mot cach de dang benh
nhan co the khoi han sau thi gian ieu tr
Cac thuoc chong lao hien nay co t nhng rat hieu qua neu ieu tri ung cach
1 1 1 3
1 3
S lc ve benh lao.
S lc ve benh lao.
Theo thong ke cua to chc y te the gii OMS (1993)
a mot benh xa hoi gay ra bi Mycobacterium tuberculosis do Robert Koch
tm ra nam 1882 do o con goi la vi trung Koch hay BK
316trie
trie
1,9u ung
tng
ng
i iche
ima
nhie
tcvlao
mlao
lao
Viet nam theo thong ke cua hoi ngh chong lao 1994 th moi nam co them 45000-
50000 ca lao mi. Cac tnh thanh pha Nam tnh hnh benh lao rat nang:Ty le phat
trien lao mi hang nam la 100 ca/100.000 ngi dan, thanh pho Ho Ch Minh : 125
ca/100.000 ngi dan.
Robert Koch - Nobel 1905
1 2 1 4
1843 1910
2 4
Benh lao thng tap trung nhng nc ngheo la nhng nc cac ieu kien kinh HIV lam giam kha nang mien dch cua c the dan ti lam nang hn benh lao, cu
te thap, cac phng tien phong cha benh kem. Cac thuoc chong lao tuy re tien the tang so benh lao trong so ngi nhiem lao hay rut ngan thi gian chuyen t
nhng mot ca ieu tr lao thng dai (6-8 thang) do o oi hoi mot so lng thuoc nhiem lao sang benh lao
ln ma khong phai bat c mot quoc gia nao, mot gia nh hay ca nhan nao cung
co the cung de dang ap ng. Do o benh lao khong phai ch la mot hien tng y
hoc thuan tuy ma con la van e kinh te xa hoi.
Nhie
Macmlao
lao
NHiem lao Tran a chong lao
nc giau He mien dch
1 5 1 7
5 7
s e khang thuoc la van e ang bao ong. Th du : tai My trong nhng nam
1982-1986 ty le e khang Rifampicin la 0,5% en 1991 la 3%. e khang INH 1982-
1986 la 3% en 1991 la 7%.
1 6 1 8
6 8
Th mau
1 9 1 11
Acid mycolic
9 11
Cach li
10 12
Sau khi tiep xuc vi thuoc mot so BK b tieu diet so con lai trang thai ngu. luc
nay thuoc kem tac dung do o nen dung thuoc cach quang (2-3 lan tuan)
1 13 1 15
13 15
Hieu kh tuyet oi Ty le ot bien e khang thuoc kha cao. Trong 106 trc khuan co:
40 khang streptomycin
Trc khuan lao rat can oxy e phat trien. Khi thieu oxy BK se ngng 5 khang INH
phat trien va trang thai ngu. Dang nay khong nhay cam vi thuoc 0,1 khang Rifampicin
Luon luon phai phoi hp cac thuoc chong lao ( t nhat la 3 loai )
1 14 1 16
14 16
1 17 1 19
17 19
1 18 1 20
18 20
S S
thiosemicarbazon N
( Directly observer treatment) H2 N NH C NH 2 +
S
N N C HO
C 6 H 5 SO 2 Cl
N a2 C O 3
C NH N H2 C NH NH SO 2 C 6H5
O O
1 21 1 23
Isoniazid
21 23
ISONIAZID
ISONIAZID
ieu che
C O N HN H2
C H3 CO O H CO C 2 H5 C O N HN H2
N
1 22 1 24
22 24
1 25 1 27
25 27
ISONIAZID ISONIAZID
Phan ng vi PDAB
Phan ng the
CO N HN H2 CO O H
CO N HN H2 CO N HN H2 H2 O
+ N H2N H2
N N
Br2
CH 3
N Br N Br C H3 N CH N
NH 2 NH 2 + HOC N CH 3
Phan ng kieu alkaloid C H3
CH
Do trong nhan cha d vong co N bac ba nen INH mang tnh chat giong nh N CH N
alcaloid va cung cho nhng phan ng vi thuoc th chung cua alcaloid, th du : + CH3 CH 3
Vi thuoc th Dragendoc cho tua nau. N CH N
CH3
Tnh kiem
N trong nhan co tnh kiem nen co the tao tua vi nhieu kim loai nang (Fe, Cu, Zn,Al) CH3
N CH N
CH3
1 26 1 28
Kation quinoid
26 28
+ Isoniazid khuech tan ti tat ca cac mo va dch cua c the. tap trung mot cach
O CH 3 N O CH 3
N ang ke nao, phoi, khuech tan tot vao ba au. Isoniazid i qua nhau thai va
OH OH
sa.
Vanilin ftivazid
Isoniazid acetyl hoa gan va mat hoat tnh, S acetyl hoa tuy thuoc vao tng
ngi khong phu thuoc vao gii tnh tuoi tac va co tnh di truyen. Thi gian ban
huy la 14 gi phu thuoc vao toc o acetyl hoa
Ngi ta chia ra 2 nhom ngi:
Nhom ngi acetyl hoa cham : thi gian ban huy > 3gi
Nhom ngi acetyl hoa nhanh : thi gian ban huy < 70 phut
1 29 1 31
29 31
ISONIAZID ISONIAZID
Kiem nghiem
Th tinh khiet: Cl-, SO42- , tro sulfat, As INH la chuyen biet tr lao tuy rang no cung co tac dung tren mot so chung vi
khuan khac.
nh lng: Thuy phan INH bang acid hay kiem giai phong hydrazin. nh
lng hydrazin bang phng phap iod: INH la thuoc khang khuan hay diet khuan phu thuoc nong o thuoc, the lao, va
s tiep nhan cua c the.
CO N HN H2 CO O H INH la thuoc au tien dung cho ieu tr M. tuberculosis. nong o toi thieu co tac
dung: 0,025- 0,05 g/ml
H2 O INH co hieu qua va t oc hn cac thuoc khang lao khac nh aminosalicylic
+ N H2N H2
N acid, capreomycin, cycloserine, ethionamid.
N
N H2N H2 + I2 N2 + 4HI
2 N a2 S 2 O 3 + I2 2NaI + N a2S 4O 6
1 30 1 32
30 32
Isoniazid c che nhieu enzym.Trong te bao mycobacteria, isoniazid can tr gan: phat ban , vang da
tong hp acid mycolic, pha v s tong hp te bao vi khuan. Tuy nhien c che than kinh : viem day than kinh van ong va cam giac, co giat
cha ro rang O Co the oc tnh lien quan en s thieu hut vitamin B6 khi dung INH
C
CHO N H2 N HCO
HO CH2 O H
CO N HN H2 Chuyen hoa
Katalase c che hydratcarbon ><
Acid H3C N N
O mycolic
Peroxydase
C - Chuyen hoa Ch nh. Tr cac the lao trong s phoi hp vi cac thuoc chong lao khac.
N INH lam sang thng mau lien seo va kch thch an ngon cm
Acid beo
Dang dung . Vien :50mg,100mg, 300mg
Xiro: 10mg/ml
Dung dch tiem:100mg/ml
Lieu dung . 10mg/kg/ngay
1 33 1 35
33 35
PYRAZINAMID
ISONIAZID
N CO N H2
S e khang
1 34 N 1 N N 36
34 36
37 39
PYRAZINAMID PYRAZINAMID
bang phng phap moi trng khan cac phac o. Ch dung trong s phoi hp vi thuoc chong lao khac. B e
khang nhanh chong.
Thuy phan che pham vi NaOH giai phong NH3. Hng NH3 vao
H2SO4 0,05M va nh lng H2SO4 0,05M d bang NaOH 0,1M.
Dang dung. vien 500mg
1 38 1 40
38 40
ieu che
CH3CH2
2
CH NH2 + Cl C H2 C H2 Cl Ethambutol
HOCH2
1 41 1 43
41 43
ETHAMBUTOL
ETHAMBUTOL Tac ong dc lc
Ethambutol c dung ieu tr nhiem mycobacteria: M. tuberculosis; M. bovis;
Tnh chat. M. marinum; M. kansasii, M. avium, M. fortuitum, M. intracellulare. No thng
dung phoi hp vi isoniazid, pyrazinamid. No co tac dung ca tren chung a e
Bot ket tinh trang , hau nh khong mui. Tan trong cloroform, methylen khang INH
clorid; kem tan hn trong benzen; hi tan trong nc. Dang muoi HCl de tan
trong nc
C che tac ong
Nhiet o nong chay. 87.5-88.8oC .
Ethambutol c che Arabinosyl transferase, ket qua la c che tong hp
[] D 25 +13.7o (c = 2 trong nc). Lipoarabinomanan
Phan ng vi CuSO4 trong NaOH cho mau xanh H H O
HO O O P O
H OH
NH CH2 CH 2 NH CH 2 CH 3 H OH
CH3 CH2 OH H
Cu C
C H D arabinofurnosyl -1-monophosphoryldecaprenol
H CH 2 O H
CH 2 O H
Arabinosyl transferase ethambutol
Phan ng cua HCl
1 42
Arabiofuranose + galactose
1
Lipoarabinomanan
44
42 44
45 47
RIFAMPICIN
ieu che
ETHAMBUTOL OH OH
H3 C C H3 H3C C H3
O O
tac dung phu H3C CH
OH 3
OH O HN H H3C CH
OH 3
OH O HN H
C H C H3 C H C H3
co the gay au au, au khp, au bung. Phan ng phu quan trong nhat la tren C H3C O O
3
HN (C 2 H 5 )2 C H3 C O O
3
than kinh th giac dan en khong phan biet c mau xanh, o. Khong than C H3 O O C H3O O
C H 2 N (C 2 H
HCHO
trong ( ngng thuoc ) co the dan ti mu. Khong nen dung cho tre em. OH OH
O CH acid ascobic
3 O O CH
3 O
Dang dung. vien 100, 400mg Rifamycin
Lieu dung . 15mg/kg/ngay OH
H3C C H3
O
H3C CH OH O HN H
OH 3
H2 N N N CH3
C H 3 ( C H 2 )4 O N O C H C H3
3
C H3 C O O
C HO
Rifampicin
C H3O O
acid ascobic
OH
H2 O
O CH
3 O
1 46 1 48
46 48
1ml dung dch amonipersulfat 10% trong dung dch em photphat pH=7 Mau cua Chloramphenicol, corticosteroid, cyclosporin, diazepam cac chat nay. Rifampicin
dung dch chuyen t vang cam ti o tm. tang chuyen hoa AZT gan trong ieu tr HIV.
nh lng : bang phng phap o pho UV bc song 475nm
1 49 1 51
49 51
50 52