duoc ly hoc lam sang
If you can't read please download the document
TRANSCRIPT
-
DC L LM SNG TI LIU SU TM TNG HP DCH
Gii thiu Information Mc lc
Bin son ebook : L nh Sng
I HC Y KHOA H NI
Trang web : www.ykhoaviet.tk
Email : [email protected], [email protected]
in thoi : 0973.910.357
THNG TIN
THNG BO V VIC XUT BN BCH KHOA Y HC 2010 :
Theo yu cu v nguyn vng ca nhiu bn c, khc vi Bch Khoa Y Hc cc
phin bn trc, bn cnh vic cp nht cc bi vit mi v cc chuyn khoa
mi,cng nh thay i cch thc trnh by, Bch Khoa Y Hc 2010 c chia ra
lm nhiu cun nh, mi cun bao gm mt ch ca Y Hc, nh th s gip
bn c tit kim c thi gian tra cu thng tin khi cn. Tc gi xin chn thnh
cm n tt c nhng kin ng gp ph bnh ca qu{ c gi trong thi gian
-
qua. Tt c cc cun sch ca b sch Bch Khoa Y Hc 2010 bn c c th tm
thy v ti v t trang web www.ykhoaviet.tk c L nh Sng xy dng v
pht trin.
NG H :
Tc gi xin chn thnh cm n mi s ng h v mt ti chnh gip cho Bch
Khoa Y Hc c pht trin tt hn v ngy cng hu ch hn.
Mi tm lng ng h cho vic xy dng mt website dnh cho vic ph bin ti
liu hc tp v ging dy Y Khoa ca cc c nhn v Doanh nghip xin gi v :
Tn ngn hng : NGN HNG U T V PHT TRIN VIT NAM
Tn ti khon ngn hng : L nh Sng
S ti khon : 5111-00000-84877
CNH BO :
TI LIU NY CH MANG TNH CHT THAM KHO nhm mc ch nng cao hiu bit v Y
khoa. Tuyt i khng c t p dng cc thng tin trong ebook ny chn
on v t iu tr bnh, nht l vi nhng ngi khng thuc nghnh Y . Tc gi
ebook ny khng chu bt c trch nhim g lin quan n vic s dng thng tin
trong cun sch p dng vo thc tin ca bn c. y l ti liu su tm t
nhiu tc gi khc nhau, nhiu cun sch khc nhau, cha c kim chng , v
th mi thng tin trong cun sch ny u ch mang tnh cht tng i . Cun
sch ny c phn pht min ph vi mc ch s dng phi thng mi, bt c
hnh vi no lin quan n vic mua bn, trao i, chnh sa, in n cun sch ny
vo bt c thi im no u l bt hp l . Ni dung cun ebook ny c th
c thay i v b sung bt c lc no m khng cn thng bo trc.
GII THIU
-
B sch ny c L Sng su tm , bin dch v tng hp vi mc ch cung cp
mt ngun ti liu tham kho hu ch cho cc bn sinh vin y khoa, v tt c
nhng ai c nhu cu tm hiu, nghin cu, tra cu , tham kho thng tin y hc.
Vi tiu ch l b sch m , c xy dng da trn ngun ti liu ca cng ng ,
khng mang mc ch v li, khng gn vi mc ch thng mi ha di bt kz
hnh thc no , nn trc khi s dng b sch ny bn phi ng vi nhng
iu kin sau . Nu khng ng , bn khng nn tip tc s dng sch :
B sch ny c cung cp n tay bn , hon ton da trn tinh thn t nguyn
ca bn. Khng c bt kz s thng lng, mua chuc, mi gi hay lin kt no
gia bn v tc gi b sch ny.
Mc ch ca b sch phc v cng tc hc tp cho cc bn sinh vin Y khoa l
chnh, ngoi ra nu bn l nhng i tng ang lm vic trong nghnh Y cng c
th s dng b sch nh l ti liu tham kho thm .
Mi thng tin trong b sch u ch c tnh chnh xc tng i, thng tin cha
c kim chng bi bt c c quan Php lut, Nh xut bn hay bt c c quan
c trch nhim lin quan no . V vy, hy lun cn trng trc khi bn chp nhn
mt thng tin no c cung cp trong b sch ny.
Tt c cc thng tin trong b sch ny c su tm, tuyn chn, phin dch v
sp xp theo trnh t nht nh . Mi bi vit d ngn hay di, d hay d d cng
u l cng sc ca chnh tc gi bi vit . L nh Sng ch l ngi su tm v
phin dch, ni mt cch khc, ngi gip chuyn ti nhng thng tin m cc tc
gi bi vit cung cp, n tay cc bn .
B sch ny l ti liu su tm v dch bi mt sinh vin Y khoa ch khng phi l
mt gio s tin s hay mt chuyn gia Y hc dy dn kinh nghim,do c th
c rt nhiu li v khim khuyt khng lng trc , ch quan hay khch quan,
cc ti liu b tr c th cha hp l , nn bn cnh vic thn trng trc khi thu
nhn thng tin , bn cng cn c k phn mc lc b sch v phn hng dn s
dng b sch s dng b sch ny mt cch thun tin nht.
-
Tc gi b sch in t ny khng chu bt c trch nhim no lin quan n vic
s dng sai mc ch , gy hu qu khng tt v sc khe, vt cht, uy tn ca
bn v bnh nhn ca bn .
Khng c chuyn mn , khng phi l nhn vin y t , bn khng c ph p t s
dng nhng thng tin c trong b sch ny chn on v iu tr. T trc ti
ny, cc thy thuc IU TR BNH NHN ch khng phi l IU TR BNH. Mi
ngi bnh l mt thc th c lp hon ton khc nhau, do vic b nguyn xi
tt c mi thng tin trong b sch ny vo thc tin s l mt sai lm ln . Tc gi
s khng chu bt c trch nhim g do s bt cn ny gy ra.
V l b sch cng ng, to ra v mc ch cng ng, do cng ng , b sch ny
c pht trin c hay khng mt phn rt ln, khng ch da vo sc lc, s
kin tr ca ngi to ra b sch ny , th nhng ng gp, xy dng, gp , b
sung, hiu chnh ca ngi c chnh l ng lc to ln b sch ny c pht
trin. V mt mc tiu tr thnh mt b sch tham kho y khoa tng hp ph hp
vi nhu cu v tnh hnh thc tin trong lnh vc y t ni ring v trong cuc sng
ni chung . Tc gi b sch mong mi bn c nhng li ng gp chn thnh
mang tnh xy dng, nhng ti liu qu m bn mun san s cho cng ng , v
mt tng lai tt p hn. l tt c nim mong mi m khi bt u xy dng
b sch ny , ti vn kin tr theo ui .
Ni dung b sch ny, c th ch ng trong mt thi im nht nh trong qu
kh v hin ti hoc trong tng lai gn. Trong thi i cch mng khoa hc cng
ngh tin nhanh nh v bo nh hin nay, khng ai bit trc c liu nhng
kin thc m bn c c c th p dng vo tng lai hay khng . tr li cu
hi ny, ch c chnh bn thn bn , phi lun lun khng ngng-T MNH-cp
nht thng tin mi nht trong mi lnh vc ca i sng, trong c lnh vc y
khoa. Khng ai c th, tt nhin b sch ny khng th, lm iu thay bn.
Nghim cm s dng b sch ny di bt kz mc ch xu no, khng c
ph p thng mi ha sn phm ny di bt c danh ngha no. Tc gi b sch
ny khng phi l tc gi bi vit ca b sch , nhng mt rt nhiu cng sc,
thi gian, v tin bc to ra n, v li ch chung ca cng ng. Bn phi chu
-
hon ton trch nhim vi bt kz vic s dng sai mc ch v khng tun th ni
dung b sch ny nu ra.
Mi l thuyt u ch l mu xm, mt cun sch hay vn cun sch cng ch l l
thuyt, ch c thc t cuc sng mi l cun sch hon ho nht, bn khng
phi l c gi m l din vin chnh. V Bch Khoa Y Hc cng ch l mt ht thc
nh, vic s dng n xo nu hay nhn ging l hon ton ty thuc vo bn
c. V ngi to ra ht thc ny s vui mng v c truyn thm ng lc
tip tc c gng nu bit rng chnh nh bn m bit bao ngi khng cn phi
xp hng ch cu tr.
Mi ng gp lin quan n b sch xin gi v cho tc gi theo a ch trn. Rt
mong nhn c phn hi t cc bn c gi cc phin bn sau c tt hn.
Knh chc bn c, gia quyn v ton th ngi Vit Nam lun c sng trong
khe mnh, cuc sng ngy cng m no hnh phc.
Lng, Ngh An. Thng 8/2010
ABOUT
ebook editor: Le Dinh Sang
Hanoi Medical University
Website: www.ykhoaviet.tk
Email: [email protected], [email protected]
Tel: 0973.910.357
-
NOTICE OF MEDICAL ENCYCLOPEDIA PUBLICATION 2010:
As the request and desire of many readers, in addition to updating the new
articles and new specialties, as well as changes in presentation, Medical
Encyclopedia 2010 is divided into many small ebooks, each ebook includes a
subject of medicine, as this may help readers save time looking up informations as
needed. The author would like to thank all the critical comments of you all in the
recent past. All the books of the Medical Encyclopedia 2010 can be found and
downloaded from the site www.ykhoaviet.tk ,by Le Dinh Sang construction and
development.
DONATE
The author would like to thank all the financially support to help the Medical
Encyclopedia are developing better and more-and-more useful.
All broken hearted support for building a website for the dissemination of
learning materials and teaching Medicine of individuals and enterprises should be
sent to:
Bank name: BANK FOR INVESTMENT AND DEVELOPMENT OF VIETNAM
Bank Account Name: Le Dinh Sang
Account Number: 5111-00000-84877
DISCLAMER :
The information provided on My ebooks is intended for your general knowledge
only. It is not a substitute for professional medical advice or treatment for specific
medical conditions. You should not use this information to diagnose or treat a
health problem or disease without consulting with a qualified health professional.
Please contact your health care provider with any questions or concerns you may
have regarding your condition.
Medical Encyclopedia 2010 and any support from L nh Sng are provided 'AS
IS' and without warranty, express or implied. L Sng specifically disclaims any
implied warranties of merchantability and fitness for a particular purpose. In no
event will be liable for any damages, including but not limited to any lost or any
-
damages, whether resulting from impaired or lost money, health or honnour or
any other cause, or for any other claim by the reader. Use it at Your risks !
FOR NON-COMMERCIAL USER ONLY .
YOU ARE RESTRICTED TO adapt, reproduce, modify, translate, publish, create
derivative works from, distribute, and display such materials throughout the
world in any media now known or hereafter developed with or without
acknowledgment to you in Authors ebooks.
FOREWORD
These ebooks are Le Dinh Sangs collection, compilation and synthesis with the
aim of providing a useful source of reference-material to medical students, and all
who wish to learn, research, investigate to medical information.
Just a set of open-knowledge, based on community resources, non-profit
purposes, not associated with commercial purposes under any kind, so before you
use this books you must agree to the following conditions. If you disagree, you
should not continue to use the book:
This book is to provide to you, completely based on your volunteer spirit. Without
any negotiation, bribery, invite or link between you and the author of this book.
The main purpose of these books are support for studying for medical students, in
addition to others if you are working in health sector can also use the book as a
reference.
All information in the book are only relative accuracy, the information is not
verified by any law agency, publisher or any other agency concerned. So always
be careful before you accept a certain information be provided in these books.
All information in this book are collected, selected, translated and arranged in a
certain order. Each artical whether short or long, or whether or unfinished work
are also the author of that article. L nh Sng was only a collectors in other
words, a person to help convey the information that the authors have provided,
to your hand. Remember the author of the articles, if as in this book is clearly the
-
release of this information you must specify the author of articles or units that
publish articles.
This book is the material collected and translated by a medical student rather
than a professor Doctor experienced, so there may be many errors and defects
unpredictable, subjective or not offices, documents can be arranged not
reasonable, so besides carefull before reading information, you should also read
carefully the contents of the material and the policy, manual for use of this book .
The author of this e-book does not bear any responsibility regarding the use of
improper purposes, get bad results in health, wealth, prestige ... of you and your
patients.
7. Not a professional, not a health worker, you are not allowed to use the
information contained in this book for diagnosis and treatment. Ever, the
physician treating patients rather than treatment. Each person is an independent
entity and completely different, so applying all information in this book into
practice will be a big mistake. The author will not bear any responsibility to this
negligence caused.
8. As is the community material, these books could be developed or not are not
only based on their strength and perseverance of the author of this book , the
contribution, suggestions, additional adjustment of the reader is great motivation
for this book keep developed. Because a goal of becoming a medical reference
books in accordance with general requirements and the practical situation in the
health sector in particular and life.
9. The contents of this book, may only correct in a certain time in the past and the
present or in the near future. In this era of scientific and technological revolution
as sweeping as fast now, no one knew before is whether the knowledge that you
have obtained can be applied in future or not. To answer this question, only
yourself, have to always update-YOURSELF-for latest information in all areas of
life, including the medical field. No one can, of course this book can not, do it for
you.
-
10. Strictly forbidden to use this book in any bad purpose, not be allowed to
commercialize this product under any mean and any time by any media . The
author of this book is not the inventor of the book-articles, but has made a lot
of effort, time, and money to create it, for the advanced of the community. You
must take full responsibility for any misuse purposes and does not comply with
the contents of this book yet.
11. All theories are just gray, a thousand books or a book are only theory, the
only facts of life are the most perfect book, in which you are not an audience but
are the main actor. This Book just a small grain, using it to cook or fry breeding is
completely depend on you. And the person who created this grain will begin more
excited and motivated to keep trying if you know that thanks that so many people
no longer have to queue to wait for relief.
12. All comments related to the books should be sent to the me at the address
above. We hope to receive feedbacks from you to make the later version better.
13. We wish you, your family and Vietnamese people has always been healthy,
happy and have a prosperous life.
MC LC
-
KHI NIM V THUC BI 1.
CHUYN HA THUC BI 2.
I CNG V DC NG HC BI 3.
KHI NIM TNG TC THUC BI 4.
CC LOI TNG TC THUC BI 5.
IU TR NG C THUC CP TNH BI 6.
I CNG V DC LC HC BI 7.
THUC TC DNG TRN H ADRENERGIC BI 8.
THUC TC DNG TRN H H CHOLINERGIC BI 9.
I CNG H THN KINH THC VT BI 10.
THUC CHA PARKINSON BI 11.
THUC AN THN TH YU BI 12.
PHNG PHP K N
THUC NG V RU BI 13.
THUC T BI 14.
THUC AN THN KINH V THUC BNH THN BI 15.
THUC AN THN CH YU BI 16.
THUC CHA NG KINH BI 17.
THUC CHNG LAO - THUC IU TR PHONG BI 18.
THUC DIU TR NG C BI 19.
THUC KHNG VIRUS BI 20.
THUC KHNG SINH KHNG KHUN BI 21.
THUC ST KHUN - TY U BI 22.
THUC CHNG AMP TRICHOMONAS BI 23.
THUC CHNG GIUN SN BI 24.
THUC KHNG NM BI 25.
THUC IU TR ST RT BI 26.
THUC H ST - GIM AU - CHNG VIM BI 27.
THUC CHNG VIM STEROID BI 28.
THUC GIM AU GY NGHIN BI 29.
THUC GIM AU LOI MORPHIN BI 30.
THUC IU TR TNG HUYT P BI 31.
THUC H GLUCOSE MU BI 32.
THUC IU TR CN AU THT NGC BI 33.
THUC NG MU V TIU FIBRIN BI 34.
THUC TR TIM BI 35.
THUC IU TR TRU TIM MCH V CHONG BI 36.
THUC CHNG LON NHP TIM BI 37.
-
THUC CHNG TNG HUYT P BI 38.
THUC IU TR RI LON LIPOPROTEIN MU BI 39.
THUC IU TR THIU MU BI 40.
THUC IU CHNH RI LON H HP BI 41.
THUC IU CHNH RI LON TIU HO BI 42.
THUC LI NIU BI 43.
THUC CHA GOT BI 44.
THUC KHNG HISTAMIN H1 BI 45.
HORMON V THUC KHNG HORMON BI 46.
HISTAMIN V THUC KHNG HISTAMIN BI 47.
CC CHT IN GII CHNH V CC DCH TRUYN BI 48.
CC VITAMIN BI 49.
KHI NIM V THUC BI 1.
1.1. Khi nim v thuc :
Thuc l nhng sn phm c ngun gc t ng vt, thc vt, khong vt, ha
dc hay sinh hm :
-
+ Phng bnh, cha bnh.
+ Phc hi, iu chnh chc nng c th.
+ Lm gim triu chng bnh.
+ Chn on bnh.
+ Phc hi hoc nng cao sc khe.
+ Lm mt cm gic mt b phn c th hay ton thn.
+ Lm nh hng n qu trnh sinh sn.
+ Lm thay i hnh dng c th...
1.2. Tn thuc :
1.2.1. Tn ha hc : nu hot cht ca thuc l cht ha hc.
1.2.2. M s : c s dng trong qu trnh thuc cn ang c th nghim tin
lm sng v lm sng. V d dch chit t l Bch qu ( Ginkgo biloba L. ) trong qu
trnh th nghim mang m s EGb 761.
1.2.3. Tn chung ( nonproprietary name ), cn c gi l tn gc ( generic name ;
nom generique ). Tng ng vi mi thuc nht nh, mi nc c mt tn chung
c chp thun s dng trong nc . V d Php, tn chung cc thuc c ghi
trong Dc in quc gia. Cn M, tn chung ca thuc do mt hi ng xem xt
la chn.
1.2.4. Tn chung quc t ( INN = international nonproprietary name hay DCI =
Denomination commune internationale ). Nm 1953, WHO ngh nn chn cho
mi dc cht mt tn chung c quc t tha nhn da trn cc nguyn tc :
ngn gn, d c, d vit, kh nhm ln, tin s dng, phn nh nhm tc dng
dc l{ cng nh i din cu trc ha hc.
1.2.5. Tn bit dc hay tn c ch ( trade mark name; brand name; nom de
marque; sp cialit pharmaceutique; tn thng mi ). Sau tn bit dc c th c
du hiu chng t tn thuc c ng k{ ti Vn phng sng ch ( M )
hoc cu chng ti Ta n ( Php ). WHO khuyn co cc nc khng nn
dng tn chung quc t lm tn bit dc.
* V d cc tn thuc : paracetamol.
+ Tn chung quc t ( INN, DCI ) : paracetamol.
-
+ Tn chung M : acetaminophen. Tn chung Php : paracetamol.
+ Tn ha hc : N-acetyl p-aminophenol; P.acetamidophenol; 4-hydroxyacetanilid.
+ Tn bit dc : algotropin, cetamol, datril, efferalgan, panadol, paradon...
1.3. Hn dng :
+ Hn dng thuc l khong thi gian c n nh cho mt loi thuc m trong
thi gian ny thuc c bo qun trong iu kin quy nh phi m bo t
cht lng theo tiu chun ng k{.
+ Hn dng thuc thng c ghi bng s hoc bng ch trn nhn thuc nhm
ch r sau thi hn ny, thuc khng cn gi tr s dng.
+ Mt s k hiu v hn dng : HD ( Vit Nam ), expiry date, EXP. date, EXP., EXD.,
E.D.; Exp., use by, best before ( Anh )...
+ Cc k hiu tng t : validity, shelf-life ( tui th ca thuc ).1.4. Tiu chun cht
lng thuc:
1.4.1. Tiu chun GMP ( good pharmaceutical manufacturing practice ) : do WHO
quy nh.
K hiu : GMP
1.4.2. Tiu chun cc Dc in quc t hoc quc gia c uy tn
:
+ Dc in M ( USP = The United states pharmacopoeia ). c USP 24 ( USP
XXIV 2000 )
+ Dc in Anh
( BP = British pharmacopoeia ).
+ Dc in Chu u ( EP = European pharmacopoeia ).
+ Dc in Hn Quc ( KP = Korean pharmacopoeia )...
1.4.3. Tiu chun FDA
( Food and drug administration - C quan qun l thc phm v thuc ):
- KFDA = Korea food and drug administration.
- US-FDA = The United states food and drug administration.
-
1.4.4. Cc cp tiu chun Vit Nam v thuc :
a- Tiu chun Dc in Vit Nam ( DVN ): l tiu chun cp nh nc v thuc.
C DVN III ( 2002 ).b- Tiu chun c s :
+ L tiu chun do c s sn xut thuc bin son, p dng i vi cc sn phm
do c s sn xut ra. Vit tt : TCCS.
+ C 2 loi tiu chun c s :
- TCCS ca nhng sn phm lu hnh th trng : phi ng k{ vi c quan c
thm quyn. Cc mc tiu chun cht lng khng c thp hn cc mc quy nh
trong tiu chun DVN.
- TCCS ca cc thuc pha ch trong n v (khng lu hnh trn th trng): do th
trng n v xt duyt v ban hnh
1.4.5. Tiu chun ca cc nh sn xut nc ngoi
+ l tiu chun do nh sn xut t t ra cho cc sn phm ca mnh. Tiu
chun ny thng tng ng vi tiu chun ca cc Dc in quc gia hoc quc
t c uy tn cao ( BP, USP, EP, KP... ).
+ K hiu : home standard, in-house, munufacturer's ( standard, specification )
CHUYN HA THUC BI 2.
1. Hu qu ca chuyn ha thuc
2. Ni chuyn ha v cc enzym chnh xc tc
+ Nim mc rut : protease, lipase, decarboxylase.
+ Huyt thanh : esterase.
+ Phi : oxydase.
+ Vi khun rut : reductase, decarboxylase.
+ H TKT : MAO, decarboxylase.
+ Gan : l ni chuyn ha chnh, cha hu ht cc enzym tham gia chuyn ha
-
thuc.
3. Cc pha chuyn ha
Thng thng cc thuc c chuyn ha qua 2 pha.
3.1. Pha I:
bao gm cc phn ng: oxy ho, oxy kh v phn ng thu phn.
3.1.1. Phn ng oxy ho:
L phn ng ph bin nht, cxc tc bi cc enzym oxy ho (mixed function
oxydase enzym - mfO) c nhiu trong microsom gan - h enzym cytochrom P450
(Cyt P450).
Phn ng c thc hin theo nhiu bc:
a.C cht (thuc, RH) phn ng vi dng oxy ho ca Cyt - P450(Fe3+) to thnh
phc hp RH - P450 (Fe3+).
b.Phc hp RH - P450 (Fe3+) nhn 1 electron t NADPH, b kh thnh
RH - P450 (Fe2+).
c.Sau , phc hp RH - P450 (Fe2+) phn ng vi 1 phn t oxy v 1 electron
th 2 t NADPH to thnh phc hp oxy hot ho.
d.Cui cng, 1 nguyn t oxy c gii phng to H2O. Cn nguyn t oxy th 2
s oxy ho c cht (thuc): RH ROH, v Cyt - P450 c ti to.
Phn ng cho s oxy ha thuc c tm tt nh sau :R-H + 2e- + 2H+ + O2 R-OH
+ H2O*
Nhng phn ng oxy ho khc: MAO nm ti np th gan, thn, h thn kinh
trung ng, xc tc cho ging ho catecholamin v serotonin h thn kinh, lm
mt tc dng ca nhiu thuc c cha amin.
3.1.2. Phn ng kh: kh cc dn xut nitro, cc aldehyd, bi enzym nitro -
reductase, dehydrogenase.
RNO2 RNO RNHOH R-NH2
(Nitrobenzen, Cloramphenicol, Clorazepam)
3.1.3. Phn ng thu phn:
Cc ester (procain, aspirin, succinylcholin, clofibrat) :
R1COOR2 RCOOH + R2OH
Cc amid (procainamid, lidocain, indomethacin) :
RCONHR1 R- COOH + R1NH2
Mt s thuc v mt s cht l este hoc amid c thy phn nh esterase hoc
-
amidase gan, rut, huyt tng, no... Sau khi thy phn, cc cht ny l ra
cc nhm chc OH hoc NH2 v d dng lin hp vi acid glucuronic hoc acid
acetic hay acid sulfuric.
Amidase hot tnh yu hn esterase nn Procainamid kh chuyn ha hn
Procain. Do vy, Procainamid tc dng k o di hn Procain.
Acetylcholin l cht trung gian ha hc ca h thn kinh cng b thu phn thnh
acid acetic v cholin di s xc tc ca cholinesterase.
*a s cc thuc c chuyn ho pha I; Cc thuc sau khi c chuyn ho
s:
Gim tc dng hoc mt c tnh.
Hoc s to ra mt s nhm chc trong cu trc phn t:
- OH, - COOH, - NH2, - SHtham gia vo phn ng lin hp pha II
*Tuy nhin :
+ Mt s cht phi qua chuyn ha mi c tc dng :
- Levo dopa chuyn ha thnh Dopamin
- Aldomet chuyn ha thnh a- metyl noradrenalin
+ Mt s t cht qua chuyn ha c tc dng bng hoc mnh hn cht m
VD: - Phenacetin Paracetamol
- Diazepam Oxazepam
- Digitoxin Digoxin
- Prednisolon Prednison
(C th s dng cht con sn xut thuc).
+ Mt s t qua chuyn ha lm tng c tnh :
- Parathion Paraoxon (dit cn trng)
- Carbon tetraclorid CCl3-
(Cl - gy hoi t gan)
3.2. Pha II :
Sau khi ging ho pha I, cht chuyn ho va to thnh lin hp vi mt phn
t ni sinh: acid acetic, acid glucuronic, acid sulfuric, acid amin (glycin). . . cui
cng cho cht lin hp t tan trong lipid, d b ion ho, khng hp thu, khng cn
hot tnh, d tan trong nc v b thi tr - l qu trnh kh c:
iu kin: cc phn ng ny i hinng lng v c cht ni sinh
Cc phn ng lin hp chnh:
-
3.2.1. Vi acid glucuronic :
C nhiu cht lin hp vi acid glucuronic : cc acid mch thng hoc acid c nhn
thm (acid salicylic, acid nicotinic...) cho dn xut N-glucuronid.
Nhng cht c S khi glucuro - hp s to dn xut S - glucuronid.
Phn ng c th tm tt nh sau :
Dng glucuronid ca thuc va c to thnh s c tnh acid, ion ho c PH
sinh l, rt tan trong nc, cho nn s thi nhanh qua nc tiu hoc qua mt.
Nh vy phn ng glucuro lin hp r rng l mt qu trnh gii c ca thuc.
3.2.2. Lin hp vi acid sulfuric
Cc cht c nhm chc ru hoc phenol, v d Cloramphenicol, Estrol, Butanol ...
s lin hp vi acid sulfuric trong cytosol ca t bo di s xc tc ca enzym
sulfotransferase.
PAPS + R-OH R-SO4 + PAP H
C6H5OH + H2SO4 SO4
3.2.3. Vi acid acetic
Nhng thuc c cha amin bc nht (nh histamin), cc sulfamid, cc hydrazin
(nh isoniazid), u c th acetyl ho; sulfanilamid sau khi aceto hp s cho
nhng tinh th sc cnh kh tan, gy tn thng b my tit niu.
Trong c th cc phn ng chuyn ha thuc pha I, II xy ra ch yu gan,
ngoi ra cn xy ra mt s c quan nh thn, nim mc rut, phi, da... t
bo, phn ng chuyn ha xy ra li ni bo, cytosol, ty lp th, nhn v mng
bo tng.
4. c ch enzym v cm ng enzym chuyn ha thuc, hu qu
4.1. c ch enzym microsom
Vi thuc no mt tc dng sau khi b oxy ha microsom gan, sau khi enzym
chuyn ha b c ch, thuc s tng tc dng, tng c tnh. Mt vi v d ngi
:
4.2. Cm ng enzym microsom :
Hin tng lm tng tng hp cc protein - enzym gi l cm ng enzym.
(Induction); cht gy c hin tng cm ng enzym l cht gy cm ng.
(Inductor). n nay tm thy trn trn 200 cht gy c cm ng enzym oxy
ha thuc microsom gan, gip thuc chuyn ha nhanh hn bnh thng, mt
tc dng nhanh (hoc mt c tnh nhanh).
-
Sau y l danh mc mt vi cht gy cm ng enzym m ta thng gp :
Glutethimid, Barbiturat, Diphenylhydantoin, Meprobamat, Diazepam,
Chlorpromazin, Promazin, Iproniazid, Imipramin, Nikethamid, Phenylbutazon,
Tolbutamid, Carbutamid, Diphenhydramin, Rifampycin ...
Nhn xt :khi kt hp thuc cng mt lc
- Nu cht chuyn ho t tc dng hn cht m, th qua cm ng enzym, thuc s
gim nhanh tc dng v gim c tnh nh vi Meprobamat, Barbiturat,
Tolbutamid v.v..
- Nu phi qua chuyn ho th thuc mi c tc dng hoc tng tc dng, th cm
ng enzym, ngc li,
i k o theo tng mnh tc dng dc l{ (v c tnh) ca thuc , v d Parathion
CCl4, Primaquin, Imipramin v.v..
- Nu thuc khng chuyn ho qua miorosom gan, th bt c loi cht gy cm
ng no cng chng lm thay i dc ng hc v tc dng ca thuc , v d
vi Acetazolamid, Aspirin, Barbital, khng sinh loi Aminoglycosid, Lithium v.v....
- C thuc dng lin tc dn n gy cm ng enzym chuyn ho ca chnh thuc
: Rifampycin, Carbamazepin, mt s Barbiturat, Meprobamat,
Diphenylhydantoin, Phenylbutazon, Corticoid ...
5. ngha thc tin ca chuyn ho thuc qua gan
5.1. Qua chuyn ho nh hng n tc dng ca thuc :
5.1.1. Qua chuyn ho mt tc dng :
+ a s cc thuc qua chuyn ho to thnh cht t tan trong lipid, d lin hp, d
ion ho pH sinh l, mt tc dng v d thi tr ra ngoi.
V d : Clopromazin, cc Barbiturat, Phenytoin v.v..
+ Nhiu cht chuyn ho qu nhanh, nn mt tc dng nhanh. Do vy, ko di
tc dng ca thuc c th thay i cu trc bng cch thay i cc nhm chc d
b chuyn ho hoc bao vy cc nhm chc bng cch to ra cc lin kt khc.
V d : - Thay nhm methyl ca Tolbutamid bng Cl ta c Clopropamid c t/2
ko di 12 - 24 h, trong khi Tolbutamid c t/2 = 4 - 7 h.
- Procain b esterase thu phn mt tc dng nhanh. Khi thay i cu trc to
thnh Procainamid b chuyn ho chm hn nn tc dng k o di hn.
5.1.2. Qua chuyn ho mi c tc dng :
-
+ Mt s tin thuc (prodrugs bn thn cha c tc dng dc l{. Sau khi vo c
th, cc thuc ny b
chuyn ho to ra cht chuyn ho c tc dng dc l. V d :
Cyclophosphamid Aldophosphamid
+ Vi nhng thuc thng qua chuyn ho mi c tc dng, khi phi hp vi cc
cht gy cm ng enzym s lm tng tc dng ca thuc. Ngc li dng km vi
cc cht c ch s lm gim tc dng.
5.1.3. Qua chuyn ho vn gi nguyn tc dng :
Mt s cht sau khi chuyn ho sinh ra cht chuyn ho c tc dng nh cht m,
thm ch c cht t tc dng ph hn cht m.
VD: Phenacetin Paracetamol
5.2. Qua chuyn ho tng c tnh
* Carbontetraclorid sau khi chuyn ho qua gan to thnh gc t do CCl3. Chnh
gc t do triclomethyl gy c vi gan. Khi kt hp cc cht gy cm ng enzym
oxy ho cng lm tng c tnh ca CCl4 .
* Parathion l cht dit cn trng, bn thn n khng c ch cholinesterase ca
cn trng, vt ch, nhng trong c th cn trng v ngi parathion b chuyn
ho qua MFO to ra cht paraoxon c tc dng c ch cholinesterase ca cn
trng v ngi, gy c cho ngi v cn trng.
* Primaquin l thuc chng st r t khi vo c th b chuyn ho thnh
demethylprimaquin, 5 - OH - primaquin v 5 - OH - demethylprimaquin. Chnh 3
cht chuyn ho ny gy met-Hb hoc thiu mu tan mu.
Isoniasid (Rimifon) nh phn ng lin hp vi acid acetic to ra cc
acetylisoniasid. Acetylisoniasid b thy phn tip tc to ra acetylhydrazin v cht
chuyn ha ny b chuyn ha qua MFO to ra cht chuyn ha c vi t bo
gan. Trong iu tr lao, phi hp INH vi Rifampycin (mt cht gy cm ng
enzym microsom gam) s lm tng tn thng gan.
PHN PHI THUC
Gn thuc vo protein huyt tngSau khi thuc hp thu, thuc qua mu
chuyn n ni c tc dng, ti mu, thuc c chia lm 2 dng :
- Dng kt hp vi protein huyt tng
- Dng t do
-
* Kh nng gn vo protein huyt tng tuz theo tng loi thuc :
Gn mnh 75 - 98% : Sulfamid chm, Quinin, Rifampicin, Digoxin, Lincomycin,
indomethaxin, Dicumarol. . .
Gn yu : 1 - 8% : Sulfaguanidin, Barbital
Mt s t cht khng gn c vo protein huyt tng, l nhng phn t
nh, tan nhiu trong nc : Ure, ouabain, Glucocorticoid
ngha :
- Mt khi dng kt hp th thuc cha thm qua mng, cha c hot tnh ch
dng t do mi c tc dng v c tnh ( phc hp thuc - protein ).
Protein huyt tng l kho d tr thuc phc hp ( thuc- protein ) ko di s c
mt ca thuc mu, khng ging ho, khng khuych tn qua mng sinh vt,
khng thi. Phc hp l ngun cung cp thng xuyn dng t do, ko di
tc dng ca thuc.
- Do c gn vo protein huyt tng tnh ho tan ca thuc trong nc cng
tng theo ( Dicoumarol t tan trong nc s tr nn d tan trong huyt tng ).
- Nu hai thuc cng c i lc vi nhng ni ging nhau protein huyt tng,
chng s i khng cnh tranh, phn t do ca thuc tng, tc dng v c tnh
tng theo, do cn lu { phi hp thuc trong iu tr : ngi b bnh dng
Tolbutamid v Phenlbutazon ( y Tolbutamid b y, bnh nhn d b chong
do gim ng huyt t ngt).
- Tr em : kh nng gn thuc km, d nhy cm vi thuc.
* Trong qu trnh iu tr bnh nhng liu u tin ca thuc gn mnh vo
protein huyt tng bao gi cng phi cao ( liu tn cng ) bo ho v tr
gn, lm cho nhng liu tip tc ( liu duy tr ) c th t hiu lc.
* Nu thuc cng gn mnh vo protein huyt tng v vo t chc khc
( tc dng chn lc ) th iu trn khng cn ng.
V d : Digital gn vo protein, nhng cn gn mnh vo t chc tim ( Gp 5 ln
protein huyt tng ) tc dng r tim.
I CNG V DC NG HC BI 3.
-
1. CC CCH VN CHUYN THUC QUA MNG SINH HC
1.1. c tnh l ha ca thuc
- Thuc l cc phn t thng c trng lng phn t P M 600. Chng u l
cc acid hoc cc base yu.
- Kch thc phn t ca thuc c th thay i t rt nh (P M = 7 nh ion lithi)
cho ti rt ln (nh alteplase- tPA- l protein c P M = 59.050). Tuy nhin, a s
c P M t 100- 1000. gn "kht" vo 1 loi receptor, phn t thuc cn t
c mt kch c duy nht vi kch thc ca receptor c hiu thuc
khng gn c vo cc receptor khc (mang tnh chn lc). Kinh nghim cho
thy P M nh nht phi t khong 100 v khng qu 1000, v ln qu th khng
qua c cc mng sinh hc ti ni tc dng.
Mt s thuc l acid yu: l phn t trung tnh c th phn ly thun nghch thnh
mt anion (in tch (-)) v mt proton (H +).
C8H7O2COOH C8H7O2COO + H+
Apirin trung tnh Aspirin anion Proton
Mt s thuc l base yu : l mt phn t trung tnh c th to thnh mt cation
(in tch (+))
bng cch kt hp vi 1 proton:
C12H11ClN3NH3 C12H11ClN3NH2 + H +
Pyrimethamin cation Pyrimethamin Proton trung tnh
- Cc phn t thuc c sn xut di cc dng bo ch khc nhau :
Tan c trong nc (dch tiu ha, dch khe), do d c hp thu.
Tan c trong m thm qua c mng t bo gy ra c tc dng dc l
v mng t bo cha nhiu phospholipid .
V vy c hp thu vo t bo thun li nht, thuc cn c mt t l tan trong
nc/ tan trong m thch hp.
- Cc phn t thuc cn c c trng bi hng s phn ly pKa pKa c suy ra
t phng trnh Hend erson-HasselbACh:
K l hng s phn ly ca 1 acid; pKa = - logKa
pKa dng cho c acid v base. pKa +pKb=14
Mt acid hu c c pKa thp l 1 acid mnh v ngc li. Mt base c pKa thp l
1 base yu, v ngc li.
-
Ni mt cch khc, khi mt thuc c hng s pKa bng vi pH ca mi trng th
50% thuc c dng ion ha (khng khuch tn c qua mng) v 50% dng
khng ion ha (c th khuch tn c). V khi , nng phn t/ nng
ion= 1 v log 1 = 0. Ni chung, mt thuc phn tn tt, d c hp thu khi
C trng lng phn t thp
t b ion ha: ph thuc vo hng s phn ly (pKa) ca thuc v pH ca mi
trng.
D tan trong dch tiu ha (tan trong nc)
ho tan trong lipid cao d qua mng ca t bo
1.2. Vn chuyn thuc bng cch lc
Nhng thuc c trng lng phn t thp (1 00- 200), tan c trong nc
nhng khng tan c trong m s chui qua cc ng dn (d= 4 - 40 ) ca mng
sinh hc do s chnh lch p lc thu
tnh. ng dn ca mao mch c vn c ng knh l 30 , ca mao mch no l
7 - 9, v th nhiu thuc khng vo c thn kinh trung ng.
1.3. Vn chuyn bng khuch tn th ng (theo bc thang nng ).
Nhng phn t thuc tan c trong nc/ m s chuyn qua mng t ni c
nng cao sang ni c nng thp.
iu kin ca s khuch tn th ng l thuc t b ion ho v c nng cao b
mt mng . Cht ion ha s d tan trong nc, cn cht khng ion ha s tan
c trong m v d hp thu qua mng.
S khuch tn ca acid v base yu ph thuc vo hng s phn ly pKa ca thuc
v pH ca mi trng.
Th d: khi ung 1 thuc l acid yu, c pKa = 4, gian 1 d dy c pH= 1 v gian 2 l
huyt tng c pH = 7 (H.1)
-
p dng phng trnh Henderson - Hasselbach, ta c:
gian 1 (d dy):
[ R- COOH ]
log = --------------- 4 - 1 = 3; Log ca 3 = 1000
[ R - COO- ]
gian 2 (mu):
[ R- COOH ]
log = --------------- 4 - 7 = - 3; Log ca - 3 = 1/1000
[ R - COO- ]
V ch phn khng ion ha v c nng cao mi khuch tn c qua mng cho
nn acid ny s
chuyn t gian 1 (d dy) sang gian 2 (mu) v c hp thu.
Tr s pKa ca mt s thuc l acid yu v base yu c g hi bng1. Nn nh
rng base c pKa cao l base mnh v acid c pKa cao l acid yu.
cid yu pKa Base yu pKa
Salicylic acid
Acetylsalicylic acid
Sulfadiazin
Barbital
Boric acid
Reserpin
Codein
Quinin
Procain
Atropin
6.6
7.9
8.4
8.8
9.
Bng 1.1: Tr s pKa ca mt s thuc l acid v base yu ( nhit 250C)Nh
vy, salicylic acid (aspirin) uc hp thu nhiu d dy v phn trn ca ng tiu
ha. Quabng ny cho thy khi b ng c thuc, mun ngn cn hp thu hoc
thuc b hp thu ra ngoi, ta c th thay i pH ca mi t rng.
Th d phenobarbital (Luminal, Gardenal) l mt acid yu c pKa = 7,2; nc tiu
bnh thng c pH cng bng 7,2 nn phenobarbital b ion ha 50%. Khi nng pH
ca nc tiu ln 8, ion ha ca thuc s l 86%, do thuc khng thm
c vo t b o. iu ny c dng trong iu tr nhim c phenobarbital:
truyn dung dch NaHCO 3 1,4% base ha nc tiu, thuc s b tng thi tr.
-
i vi mt cht kh (th d thuc m bay hi), s khuch tn t khng kh ph
nang vo mu ph thuc vo p lc ring phn ca cht kh gy m c trong
khng kh th vo v ha tan ca kh m trong mu.
1.4. Vn chuyn tch cc
Vn chuyn tch cc l s ti thuc t bn ny sang bn kia mng sinh hc nh
mt "cht vn chuyn" (carrier) c hiu c sn trong mng sinh hc.
* c im ca s vn chuyn ny l:
- C tnh bo ha: do s lng carrier c hn
- C tnh c hiu: mi carrier ch to phc vi vi cht c cu trc c hiu vi
n.
- C tnh cnh tranh: cc thuc c cu trc gn ging nhau c th gn cnh tranh
vi 1 carrier, cht no c i lc mnh hn s gn c nhiu hn.
- C th b c ch: mt s thuc (nh actinomycin D) lm carrier gim kh nng
gn thuc
vn chuyn.
* Hnh thc vn chuyn: c hai cch
- Vn chuyn thun li (Vn chuyn tch cc th pht) : khi km theo carrier li c
c s chnh lch bc thang nng , v vy s vn chuyn ny khng cn nng
lng. Th d vn chuyn glucose, pyramidon theo bc thang nng ca Na +-
Vn chuyn tch cc thc th (Vn chuyn tch cc nguyn pht): l vn chuyn i
ngc bc thang nng , t ni c nng thp sang ni c nng cao hn. V
vy i hi phi c nng lng c cung cp do ATP thu phn, thng c
gi l cc "bm", th d s vn chuyn ca Na+, K+, Ca++,I-, acid amin.
-
Hnh 1.3. Cc cch vn chuyn thuc qua mng sinh hc
2. CC QU TRNH DC NG HC
2.1. S hp thu
Hp thu l s vn chuyn thuc t ni dng thuc (ung, tim) vo mu ri i
khp c th, ti ni tc dng. Nh vy s hp thu s ph thuc vo:
- ha tan ca t huc. Thuc dng di dng dung dch nc d hp thu hn
dng du, dch treo hoc dng cng
- pH ti ch hp thu v c nh hng n ion ha v tan ca thuc.
- Nng ca thuc. Nng cng cao cng hp thu nhanh.
- Tun hon ti vng hp thu: cn g nhiu mch, cng hp thu nhanh.
- Din tch vng hp thu. Phi, nim mc rut c din tch ln, hp thu nhanh.
T nhng yu t cho thy ng a thuc vo c th s c nh hng ln
n s hp thu. Ngoi tr ng tim tnh mch, trong qu trnh hp thu vo
vng tun hon, mt phn thuc s
b ph hu do cc enzym ca ng tiu ha, ca t bo rut v c bit l gan,
ni c i lc vi nhiu thuc. Phn thuc b ph hu trc khi vo vng tun hon
c gi l "first pass metabolism" (chuyn ha do hp thu hay chuyn ha qua
gan ln th nht v thng l ung thuc). Phn vo c tun hon mi pht
huy tc dng dc l{, c gi l sinh kh dng (bioavailability) ca thuc (xin
xem phn sau)
-
Sau y s im qua cc ng dng thuc thng thng v cc c im ca
chng.
2.1.1. Qua ng tiu ha
u im l d dng v l ng hp thu t nhin.
Nhc im l b cc enzym tiu ha ph hu hoc thuc to phc vi thc n
lm chm hp thu.
i khi thuc kch thch nim mc tiu ha, gy vim lot
2.1.1.1. Qua nim mc ming: thuc ngm di li
Do thuc vo thng vng tun hon nn khng b dch v ph hu, khng b
chuyn ha qua gan ln th nht
2.1.1.2. Thuc ung
Thuc s qua d dy v qua rut vi cc c im sau:
* d dy:
- C pH = 1- 3 nn ch hp thu cc acid yu, t b ion ha, nh aspirin,
phenylbutazon, barbiturat.
- Ni chung t hp thu v nim mc t mch mu, li cha nhiu cholesterol, thi
gian thuc d dy khng lu.
- Khi i hp thu nhanh hn, nhng d b kch thch
* rut non:
L ni hp thu ch yu v c din tch hp thu rt rng (> 40 m 2), li c ti
mu nhiu, pH
tng dn ti base (pH t 6 n 8).
- Thuc t b ion ha nhng nu t hoc khng tan trong lipid (sulfaguanidin,
streptomycin) th t c hp thu.
- Thuc mang amin bc 4 s b ion ha mnh kh hp thu, th d cc loi cura.
- Cc anion sulfat SO 4 khng c hp thu: MgSO 4, Na2SO4 ch c tc dng
ty.2.1.1.3. Thuc t trc trngKhi khng dng ng ung c (do nn, do
hn m, hoc tr em) th c d ng thuc t vo hu mn. Khng b enzym tiu
ha ph hu, khong 50% thuc hp thu qua trc trng s qua gan, chu chuyn
ha ban u.
Nhc im l hp thu khng hon ton v c th gy kch ng nim mc hu
mn.
2.1.2. Thuc tim
-
- Tim di da: do c n hiu si thn kinh cm gic nn au, t mch mu nn
thuc hp thu chm
- Tim bp: khc phc c hai nhc im trn ca tim di da - mt s thuc
c th gy hoi
t c nh ouabain, calci clorid th khng c tim bp.
- Tim tnh mch: thuc hp thu n hanh, hon ton, c th iu chnh liu c
nhanh. Dng tim cc dung dch nc hoc cc cht kch ng khng tim bp
c v lng mch t nhy cm v mu pha long thuc nhanh nu tim
chm.Thuc tan trong du, thuc lm kt ta cc thnh phn ca mu h ay thuc
lm tan hng cu u khng c tim mch mu.
2.1.3. Thuc dng ngoi
- Thm qua nim mc: thuc c th bi, nh git vo nim mc mi, hng, m
o, bng quang
iu tr ti ch. i khi, do thuc thm nhanh, li trc tip vo mu, khng b c
c enzym ph hu trong qu trnh hp thu nn vn c tc dng ton thn: ADH
dng bt xng mi; thuc t (lidocain, cocain) bi ti ch, c th hp thu, gy c
ton thn.
- Qua da: t thuc c th thm qua c da lnh. Cc thuc dng ngoi (thuc
m, thu c xoa bp, cao dn) c tc dng nng ti ch st khun, chng nm,
gim au.
Tuy nhin, khi da b tn thng, vim nhim, bng... thuc c th c hp thu.
Mt s cht c d tan trong m c th thm qua da gy c ton thn (thuc
tr su ln hu c, cht c cng nghip anilin)
Gi m ni bi thuc (bng p), xoa bp, dng thuc gin mch ti ch, dng
phng php ion -di (iontophoresis) u lm tng ngm thuc qua da.
Hin c dng thuc cao dn mi, lm gii phng thuc chm v u qua da, duy
tr c lng thuc n nh trong mu: cao dn scopolamin, estrogen, nitrit
Da tr s sinh v tr nh, c lp sng mng manh, tnh thm mnh, d b kch
ng cho nn cn thn trng khi s dng, hn ch din tch bi thuc.
- Thuc nh mt: ch yu l tc dng t i ch. Khi thuc chy qua ng mi - l
xung nim mc mi, thuc c th c hp thu trc tip vo mu, gy tc dng
khng mong mun.
2.1.4. Cc ng khc
-
- Qua phi: cc cht kh v cc thuc bay hi c th c hp thu qua cc t bo
biu m ph nang, nim mc ng h hp. V din tch rng (80 - 100 m2) nn
hp thu nhanh. y l ng hp thu v thi tr chnh ca thuc m hi. S hp
thu ph thuc vo nng thuc m trong khng kh th vo, s thng kh h
hp, ha tan ca thuc m trong mu ( hay h s phn ly
mu: kh )
Mt s thuc c th dng di dng phun sng iu tr ti ch (hen ph
qun).
- Tim tu sng: thng tim vo khoang di nhn hoc ngoi mng cng
gy t vng thp (chi di, khung chu) bng dung dch c t trng cao
(hyperbaric solution) hn dch no tu.
2.1.5. Thng s dc ng hc ca s hp thu: sinh kh dng (F)
2.1.5.1. nh ngha:
Sinh kh dng F (bioavailability) l t l phn trm lng thuc vo c vng
tun hon dng
cn hot tnh v vn tc hp thu t huc (biu hin qua C max v Tmax) so vi liu
dng . Sinh kh
dng phn nh s hp thu thuc.
2.1.5.2. ngha
-
KHI NIM TNG TC THUC BI 4.
1. Mt s khi nim c bn
Tng tc thuc l hin tng xy ra khi hai thuc tr ln c s dng ng
thi. S phi hp lm thay i tc dng hoc c tnh ca mt trong nhng th
thuc .
Khi phi hp thuc nhm li dng tng tc thuc theo hng c li tng hiu
qu iu tr, gim tc dng ph hoc gii c thuc. Th nhng, trong thc t
iu tr c nhng tnh hung hon ton bt ng: cng mt thuc mc liu iu
tr m khi phi hp vi thuc ny li gim hoc mt tc dng, ngc li, dng vi
thuc kia th li xy ra ng c.
T l tng tc thuc tng theo cp s nhn vi s loi thuc phi hp, c ngha
l nguy c ri ro, tht bi cng tng theo.
Do vic cho thuc v phi hp thuc trong iu tr l 1 vn phc tp, lun
t ra cho ngi thy thuc phi cn nhc v lun phi quan tm n hin tng
tng tc thuc c th xy ra.
Nhn nh v tng tc thuc hng dn cho bnh nhn khi s dng thuc v
c nhng li khuyn vi bc s khi gp nhng n thuc phi hp khng ng.
Cc tnh hung c th xy ra khi phi hp thuc c tm tt nh sau:
2. S phi hp thuc dn ti tng tc dng - tng tc c tnh hip ng
S phi hp thuc lm tng hiu qu tc dng l mc tiu trong iu tr. l s
tng tc mang tnh hip ng thuc, n xy ra ti cc receptor khc nhau, nhng
c cng ch tc dng l: lm tng hiu qu iu tr.
Cc kh nng c th xy ra vi loi tng tc ny l:
2.1.Hip ng cng (Additive)
* Khi phi hp hai hay nhiu thuc vi nhau m tc dng thu c bng tng tc
dng ca cc cht thnh phn, ta c hp ng cng. Th d:
Nh c s phi hp ny m Olcandomycin ni rng c ph tc dng, cn
Tetraxyclin th gim c liu, do gim c c tnh.
* Nhng tng tc c th xy ra ti cc receptor khc nhau nhng c cng ch
-
tc dng rt ph bin trong iu tr. V d:
Phi hp thuc li tiu - an thn vi cc thuc chng tng huyt p iu tr
bnh huyt p cao.
Phi hp khng sinh vi cc thuc gim tit HCL iu tr vin lo t ng tiu
ho.
Phi hp khng sinh c c ch tc dng khc nhau trong iu tr lao
* Cc phi hp ny thng c p dng ph bin trong iu tr, tuy nhin cng
hay gp nhng tng tc bt li do bc s v tnh phi hp cc thuc c tn bit
dc khc nhau, nhng thc t li l cng mt hot cht .
V d: Phi hp cc khng sinh nhm Aminoglycozid: Gentamycin + Streptomycin -
> lm tng suy thn v ic khng hi phc.
2.2. Hip ng tng cng (Potencial)
* Khi tc dng phi hp vt tng tc dng ca cc cht thnh phn, ta c hip
ng tng cng. Loi hip ng ny thng xy ra khi cc cht thnh phn tc
dng ln nhng khu khc nhau trn cng mt chui phn ng:
V d:
P.A.BA FH2 FH4
(-) (-)
Sulffamid Trimethoprim
Pyrimetamin
Acid Folic l Coenzym gip vi khun to nn cc base purin, thymin v cc acid
amin cn tng hp ADN, ARN vi khun pht trin.
Sunfamid do cnh tranh vi P.A.B lm gim lng FH2, cn cc dn cht Pirimidin
(trimethoprim, pirimethamin) li c ch enzym DHFR xc tc cho qu trnh
chuyn FH2 thnh FH4, lm gim lng FH4.
Kt qu cui cng l thiu acid Folic, v vy c ch s pht trin vi khun. Hai loi
thuc dng chung s c tc dng hip ng vt mc (ch khng phi mt
php cng thng thng), mnh hn hn khi dng n c tng loi, l
nguyn tc to nn cng thc thuc khng khun hoc thuc chng st rt c
hiu lc cao.
* Khi phi hp li hai thuc tc dng km khun nh trong ch phm : Co -
trimoxazol (Bactrim) gm: Sulfamethoxazol + Trimethoprim) , ta li thu c tc
-
dng dit khun. Ch phm ny c tc dng rt tt vi nhng vi khun khng
cc khng sinh khc.
Ch phm Fansidar: (Sulfadoxin + Pyrimethamin).
Hip ng vt mc cn c to nn khi cht chnh - cht ch vn, c tng
tim lc nh cht phi hp c th khng tc dng ln mt c quan ch vi cht
chnh.
V d: Clofibrat dng chung vi thuc khng Vitamin K lm tng tc dng chng
ng mu, mc d Clofibrat khng c tc dng chng ng.
Thuc co mch adrenalin s lm tng tc dng gy t tng vng ca novocain khi
dng phi hp .
Khi iu tr cao huyt p thng phi hp thuc li tiu vi thuc gin mch,
thuc li tiu lm gim lu lng tun hon v thuc gin mch c tc dng h
huyt p tt hn.
Tt c nhng tng tc hip ng k trn, u thuc loi tng tc v mt dc
lc, ngha l hip ng v mt tc dng.
3. S phi hp thuc dn ti gim tc dng - tng tc c tnh i khng.
* Khi phi hp thuc ngi ta c gng trnh nhng phi hp lm gim tc dng
ca nhau. Tuy nhin, nhiu lc tng tc ny li c s dng nh mt v kh li
hi gii c thuc hoc lm gim nhng tc dng ph ca cht ch vn.
C nhng kh nng i khng sau
i khng
Ho hc Dc l Vt l
Dc ng hc Dc lc hc
Hp thu Phn b Chuyn ho Thi tr Cnh tranh Khng cnh
3.1. i khng ho hc
* Tng tc ho hc c th gp vi tt c cc loi phn ng ho hc m ta
bit. Khi trn chung cc thuc ngoi c th nu xy ra hin tng ta, c khi
chuyn thnh dng kh bay ln, hoc dung dch i mu ta c th d dng nhn
bit v trnh c.
V d: Cc mui ca kim hu c v acid hu c, khi trn chung s xy ra phn
-
ng trao i, dn n gim tan: Streptomycin sulfat trn vi natri benzyl
penicilin, dimedrol clohydrat vi barbital natri (ta dimedrrol v barbital).
iu ng ch { l c nhng phn ng ta khng nhn thy c nhng n li to
ra cc sn phm khng c hot tnh hoc c vi c th.
V d:
- Khng nn trn vitamin B12 vi bt kz mt vitamin no trong syrine v coban s
ph hu cc vitamin. Khi trn B12 vi B1, sn phm to thnh s gy d ng do tc
ng ca B12 n B1.
- Glucose l mt cht c tnh kh, v vy vic pha mt thuc nh morphin,
noradrenalin, glycozid tr tim vo dung dch ny truyn nh git hoc tht
trc trng l khng nn.
Nhng tng tc xy ra ngoi c th gi l tng k (incompatility), cn tnh n
c kh nng phn ng khi thuc vo c th. Cc alcaloit b ta bi thuc cha
tanin, tetraxyclin to chelate vi cc ion kim loi ho tr II.III lc thuc s khng
c hp thu. Hin tng gi l tng tc thuc (interaction).
- Nhng tng tc i lp rt cn trnh v lm gim tc dng ca thuc
V d:
Khng ung vitamin B1 cng mt lc vi cc penicilin hoc streptomycin v
vitamin B1 ph hu cc khng sinh ny.
Nu ng thi dng vitamin B1 vi vitamin B6 th pyridoxin s ngn cn qu trnh
photphorin ho ca vitamin B1, tc l cn tr vitamin B1 chuyn thnh dng c
hot tnh sinh hc.
Khng ung acid nicotinic (vitamin PP) vi vitamin B6 v vitamin PP s ph hu
vitamin B6 (vitamin PP l cofactor ca enzym NADP).
- Nn nh rng vitamin B6 l ng yu t hot ho ca enzym vn chuyn nhm -
NH2 v kh carboxyl ca cc acid amin; Do khi iu tr bnh Parkinson khng
nn phi hp Levodopa vi vitamin B6 liu cao.
3.2. i khng vt l
Cc thuc bc : albumin (lng trng trng), tinh bt s gim tc dng ca mt s
thuc kch ng (corticoid).
Than hot l cht hp ph tt nhiu thuc khi ng c.
3.3. i khng dc l:
bao gm i khng dc lc hc v i khng dc ng hc.
-
3.3.i khng dc lc hc
L i khng do i lp v tc dng v c ch tc dng. C 2 loi i khng:
3.3.1. i khng cnh tranh:
2 thuc tc dng ln cng mt receptor (Rp), thuc no c i lc mnh hn vi Rp
s pht huy c tc dng.
Ni mt cch khc: cht ch vn (agonist) v cht i khng (antagonist) cnh
tranh vi nhau cng mt ni ca receptor, thuc no c i lc mnh hn vi
receptor s pht huy tc dng.
V d:
Nalorxon - morphin
Atropin - Pilocarpin (Rp M)
Histamin - phenergan (Rp H1)
Histamin - cimetidin (Rp H2)
Acetylcholin - piperazin (Rp N ca c giun)
Isoproterenol - propranolon (Rp b)
3.3.2. i khng khng cnh tranh
Cht i khng c th tc ng ln Rp v tr khc vi cht ch vn; cht i
khng lm cho Rp bin dng, qua Rp s gim i lc vi cht ch vn v nu c
tng liu cht ch vn cng khng t c hiu lc ti a.
V d: mt s cht khng histamin Rp H1 : terfenadin ,astemizol
Cc thuc lm mt tc dng ca nhau do tc dng i lp nhau:
+ Strychnin hng phn tu sng, lm tng cng kin c, cn thuc t hoc cura
i khng khng cnh tranh vi tc dng ny ca strychnin.
+ Acetylcholin - cura
+ Atropin lm mt tc dng co c vng ca Morphin do thng c phi hp
vi Morphin gim au do co tht ng mt, ng niu
+ Ephedrin c tc dng cng ph giao cm s b cn tr nu dng cng
Pilocacpin - cht cng giao cm.
+ Cc khng sinh nhm Beta - lactam s b gim tc dng nu dng cng vi
Tetraxtyclin v tc dng gim tng hp protein trong t bo vi khun ca
Tetraxyclin s lm chm s phn bo v do lm Penicilin kh ph v v vi
khun hn.
3.4. i khng dc ng hc
-
* Loi tng tc ny xy ra trong sut qu trnh tun hon ca thuc trong c th,
k t khi bt u thm nhp n lc o thi.
3.4.1. Tng tc lc hp thu (Absorption = A)
* Do thay i ion ho ca thuc
S vn chuyn thuc qua mng sinh hc ch yu theo c ch khuch tn th ng
v do ph thuc vo h s phn b m / nc ca thuc. Ch nhng cht
khng ion ho mi phn tn tt trong m v d qua mng theo c ch ny.
Theo phng trnh trn ta nhn thy:
Cc cht c bn cht acid yu s hp thu tt trong mi trng acid:
Phenylbutazon, cc Barbiturat, Aspirin hp thu tt d dy.
Cc cht c bn cht base yu s hp thu tt trong mi trng kim: Quinin,
Ephedrin, Atropin, Morphin hp thu tt rut.
Vic thay i mi trng ca mt thuc c th do cc thuc dng km gy nn,
cng c th do thc n v cc cht lng dng ung thuc to ra.
+ Khi iu tr bng Levodopa, nn trnh dng nhng ch phm m thu phn v
Levodopa s b gim hp thu, cc cht m khi vo c th s phn hu thnh acid
amin v cnh tranh carrier vi levodopa khi hp thu.
+ Thuc chng toan d dy lm tng pH ng tiu ho, ngn cn hp thu thuc l
acid yu ( aspirin, barbiturat, sulfamid, cumarin) .
+ Hydroxyd AL cn tr hp thu INH, Doxycyclin.
+ Khi ung Tetraxyclin nn trnh dng nhng ch phm cha kim loi nng nh
Fe, Al, Mg v Tetraxyclin r to chelate vi kim loi nng do khng hp thu
c.
+ Cholestyramin - mt cht lm ta mui mt, dng ngn cn qu trnh hp
thu cc cht bo, gy h mc cholesterol/ mu, cng c th to phc vi mt s
thuc v cn tr hp thu.
+ Cholestyramin lm gim hp thu cc vitamin tan trontg du (A.D.E.K) acid folic,
vitamin B12. Nu dng cholestyramin ko di, cn b cung cc vitamin trn.
+ INH iu tr lao, nn b xung vitamin B6 (20 mg - 25 mg/ ngy) v INH to
phc vi B6 c th gy ri lon chc phn thn kinh do thiu B6 (Pyridoxin).
3.4.2. Tng tc trong qu trnh phn b: (Ditribution = D)
* Khi tun hon trong mu, thuc thng dng lin kt vi Protein ca huyt
tng. Dng ny khng c tc dng dc l{ v cng khng b chuyn ho. Tuy
-
nhin lun tn ti mt cn bng ng gia dng thuc lin kt v thuc t do.
Dng t do l dng c tc dng dc l. Nu s dng hai thuc c cng mt im
gn trn phn t protein, thuc no c i lc mnh s y thuc kia ra khi v tr
v chim ly protein. V d: Tolbutamid + Phenylbutazon ( y tolbutamid b
y), d b chong do gim ng huyt t ngt.
y l loi tng tc bt li gp nhiu trong k n bi v thng xy ra bt ng
trong sut qu trnh tun hon ca thuc trong c th.
3.4.3. Tng tc giai on chuyn ho: (Metabolism = M)
Gan l c quan chuyn ho thuc quan trng nht ca c th. S suy gim chc
nng gan k o theo nhng thay i cc thng s dc ng hc ca thuc:
* Nhng thuc c tc dng tng cm ng enzym s lm tng tc chuyn ho
ca cc thuc dng phi hp hoc ngay c chnh n khi dng lp li, do lm
gim tc dng. Cc thuc thng gp l: Phenobarbital, Rifampicin, Doxycyclin,
Spironolacton
* Nhng thuc c tc dng c ch enzym microsom gan: Cloramphenicol,
Cimetidin. Quercetin, Levodopa, INH lm cho nhiu thuc khc ko di tc dng
v tng c tnh. V d: Cimetidin lm chm chuyn ho qua gan ca Diazepam,
DPH, Theophilin, Carbamazepin, Lidocain, Metromidazol
Cc thuc cn lu { khi phi hp vi cc cht trong bng trn l cc hormon
(thyroid, corticoid, estrogen), theophylin, thuc chng ng kinh, thuc chng
ng mu dng ung, thuc h ng huyt, thuc tim mch chuyn ho qua
gan
3.4.4.Tng tc thuc giai on thi tr: (Elimination = E)
Cc cht kim s lm tng tc o thi cc thuc c tnh acid nh Barbiturat,
Aspirin do vy lm gim tc dng ca cc cht ny. Ngc li cc cht c tnh acid
nh vitamin c, dch p hoa qu s tng o thi cc alcaloid.
Vic gim tc dng do nhng tng tc dc ng hc gy ra thng rt kh
trnh v n bt ng; hu qu rt phc tp.
Trc y nhiu trng hp xy ra khi phi hp thuc khng gii thch c . Ti
sao cng mt thuc liu iu tr nhng lc th khng hiu lc, lc th c nguy
c ng c. Ngy nay nh s pht trin ca dc ng hc, nhiu vn c
sng t. Chnh v vy trong bn hng dn s dng thuc by gi thng c thm
mc dc ng hc (pharmacokinetics) v tng tc thuc (interactions). iu
-
gip cho ngi s dng nh hng tt hn, trnh c nhng tai bin v nng
cao hiu qu iu tr.
Cc thuc b nh hng nhiu l thuc bi xut ch yu qua thn dng cn hot
tnh. Thuc phi hp c th lm qu trnh bi xut ca thuc dng km theo c
ch:
Thay i pH ca nc tiu:
* Cc antacid nh NaHCO3, Maalox, Kavet gy kim ho nc tiu, do lm
tng thi tr cc thuc c bn cht acid yu nh barbiturat, salicylat; Ngc li,
vi cc thuc l alcaloid (th d: quinidin, theophylin) th tc bi xut li c
nguy c b gim, dn n tng tc dng.
* Vitamin C liu cao (>2 g) gy acid ho nc tiu, lm tng thi tr cc thuc c
bn cht alcaloid dn n gim tc dng, nhng li ko di thi gian tn ti ca
cc salicylat gy tng nguy c chy mu.
nh hng n c ch trao i cht ng thn:
V d:
Probenecid s cnh tranh carrier bi xut ca nhiu loi thuc (cc penicilin,
cephalosporin) v lm chm qu trnh bi xut ca cc thuc ny.
Corticoid cn tr tc dng ca cc thuc li tiu do i lp v c ch bi xut
mui - nc.
{ ngha ca tng tc thuc:
Li dng
- Ci thin tc dng dc l
- Ci thin dc ng hc ca thuc
- Gii c
Trnh
- Phi hp lm tng c tnh v tc dng ph
- Phi hp lm gim tc dng dc l v hiu qu iu tr.
CC LOI TNG TC THUC BI 5.
-
1.TNG TC THUC - THUC
Nhiu thuc khi cho dng cng mt lc s c tc dng qua li ln nhau, c gi l
tng tcthuc. Trong lm sng, thy thuc mun phi hp thuc lm tng t
c dng iu tr, gim cctc dng khng mong mun. Song trong thc t, nhiu k
hi khng t c nh th. V vy, khi k n
c t 2 thuc tr ln, thy thuc rt cn hiu r s tng tc gia chng.
1.1. Tng tc dc lc hc
L tng tc ti cc receptor, mang tnh c hiu
1.1.1. Tng tc trn cng receptor: tng tc cnh tranh
Thng lm gim hoc mt tc dng ca cht ng vn (a gonist), do cht i kh
ng (antagonist) c i lc vi receptor hn nn ngn cn cht ng vn gn vo
receptor: atropin khng acetylcholin v pilocarpin ti receptor M; nalorphin khng
morphin ti receptor ca morphin;
cimetidin khng histamin ti receptor H2.
Thuc cng nhm c cng c ch tc dng, khi dng chung tc dng khng tng b
ng tng liu ca mt thuc m c tnh li tng hn: CVKS, aminosid vi dy VIII.
1.1.2. Tng tc trn cc receptor khc nhau: tng tc chc phn.
- C cng ch tc dng: do lm tng hiu qu iu tr.
Th d: trong iu tr bnh cao huyt p, phi hp thuc gin mch, an thn v li
tiu; trong iu
tr lao, phi hp nhiu khng sinh (DOTS) tiu dit vi khun cc v tr v cc gi
ai on pht
trin khc nhau.
-
C ch tc dng i lp, gy ra c chc phn i lp, dng iu tr nhim
c: strychnin liu cao, kch thch ty sng gy co cng c, cura do c ch dn
truyn tm vn ng, lm mm
c; histamin tc ng trn receptor H 1 gy gin mch, tt huyt p, trong
khi noradrenalin tc ng ln receptor 1 gy co mch, tng huyt p.
1.2. Tng tc dc ng hc
L cc tng tc nh hng ln nhau thng qua cc qu trnh hp thu, phn phi,
chuyn ha v thi tr v th n khng mang tnh c hiu.
-
1.2.1. Thay i s hp thu c a thuc
- Do thay i ion ha ca thuc:
Nh ta bit, ch nhng phn khng ion ha ca thuc mi d dng qua c m
ng sinh hc v
d phn tn hn trong lipid. phn ly ca thuc ph thuc vo hng s pKa ca
thuc v pH ca
mi trng. Cc thuc c bn cht acid yu (nh aspirin) s hp thu tt
trong mi trng acid (d dy), nu ta trung ha acid ca dch v th s hp thu
aspirin d dy s gim i.
-
Vi cc thuc dng theo ng ung: khi dng vi thuc lm thay i nhu ng r
ut s lm
thay i thi gian lu gi thuc trong rut, thay i s hp thu ca thuc qua ru
t. Mt khc cc thuc d tan trong lipid, khi dng cng vi parafin (hoc thc n
c m) s lm tng hp thu.
-
Vi cc thuc dng theo ng tim bp, di da: procain l thuc t , khi trn v
i adrenalin l
thuc co mch th procain s chm b hp thu vo mu do thi gian gy t s
c ko di. Insulin trn vi protamin v km (protemin - zinc- insulin-
PZI) s lm ko di thi gian hp thu insulin vo mu, ko di tc dng h ng
huyt ca insulin.
- Do to phc, thuc s kh c hp thu:
Tetracyclin to phc vi Ca ++ hoc cc cation kim loi khc rut, b gim hp
thu. Cholestyramin lm ta mui mt, ngn cn hp thu lipid, dng lm thuc h
cholesterol mu.
- Do cn tr c hc:
Sucralfat, smecta, maaloc (Al 3+) to mng bao nim mc ng tiu ha, lm
kh hp thu cc thuc khc.
trnh s to phc hoc cn tr hp thu, 2 thuc nn ung cch nhau t nht 2
gi.
1.2.2. Thay i s phn b thuc
l tng tc trong qu trnh g n thuc vo protein huyt tng. Nhiu thuc,
-
nht l thuc
loi acid yu, gn thun nghch vi protein (albumin, globulin) s c s tranh chp
, ph thuc
vo i lc v nng ca thuc trong huyt tng. Ch c thuc dng t do mi
c tc dng
dc l. V vy, tng tc ny c bit c ngha vi thuc c t l gn vo protei
n huyt tng
cao (trn 90%) v c phm vi iu tr hp nh:
. Thuc chng ng mu loi khng vitamin K: dicumarol, warfarin
. Sulfamid h ng huyt: tolbutamid, clopropamil
. Thuc chng ung th, c bit l methotrexat
Tt c u b cc thuc chng vim phi steroid d dng y khi protein huyt
tng, c th gy nhim c.
1.2.3. Thay i chuyn ha
Nhiu thuc b chuyn ha gan do cc enzym chuyn ha thuc ca microsom g
a n (xin xem
phn dc ng hc). Nhng enzym ny li c th c tng hot tnh (gy cm
ng) hoc b c
ch bi cc thuc khc. Do s lm gim t/2, gim hiu lc (nu l thuc gy c
m ng enzym) hoc lm tng t/2, tng hiu lc (nu l thuc c ch enzy m)
ca thucdng cng.
- Cc thuc gy cm ng (inductor) enzym gan: phenobarbital, phenytoin,
carbamazepin, griseofulvin, rifampicin...
- Cc thuc c ch (inhibitor) enzym gan: allopurinol, cloramphenicol, cimetidin,
MAOI, erythromycin, isoniazid, dicuma rol.
Cc thuc hay phi hp vi cc loi trn thng gp l cc hormon (thyroid, cortic
oid, estrogen), thuc chng ng kinh, thuc h ng huyt, thuc tim mch.
Ph n ang dng thuc trnh thai ung, nu b lao dng thm rifampicin, hoc b
ng kinh
dng phenytoin, c th s b "v k hoch" do estrogen trong thuc trnh thai b
gim hiu qu v
-
b chuyn ha nhanh, hm lng tr nn thp.
1.2.4. Thay i thi tr thuc
Thi tr (elimination) thuc gm 2 qu trnh l chuyn ha thuc gan ( ni
phn trn ) v
bi xut (excretion) thuc qua thn. Nu thuc bi xut qua thn dng cn hot
tnh th s tng/ gim bi xut s c nh hng n tc dng ca thuc.
- Thay i pH ca nc tiu: khi mt thuc lm thay i pH ca nc tiu, s lm
thay i ion
ha ca thuc dng km, lm thay i bi xut ca thuc. Th d barbital c pK
a = 7,5; pH
= 7,5 th 50% thuc b ion ha; pH = 6,5 th ch c 9% b ion ha pH = 9,5 th
91% barbital b ion ha. V vy, khi ng c cc thuc barbiturat, truyn dch
NaHCO3 base ha nc tiu s
tng bi xut barbiturat.
Cc thuc l acid yu (vitamin C, amoni clorid) dng liu cao, lm acid
ha nc tiu s lm tng thi tr thuc loi alcaloid (quinin, morphin).
- Bi xut tranh chp ti ng thn: do 2 cht cng
c c ch bi xut chung ti ng thn nn tranh chp nhau, cht ny lm gim bi
xut cht khc. Dng probenecid s lm chm thi tr penicilin, thiazid lm gim
thi tr acid uric nn c th gy bnh gut.
1.3. Kt qu v ngha ca tng tc thuc
1.3.1. Tc dng hip ng
Thuc A c tc dng l a, thuc B c tc dng l b. Khi kt hp thuc A vi thuc B
c tc dng
c. Nu
c = a + b, ta c hip ng cng (additive effect)
c > a + b, ta c hip ng tng mc (synergysm)
Hip ng cng thng khng c dng lm s ng v nu cn th tng liu thu
c ch khng phi hp thuc.
Hip ng tng mc thng dng trong iu tr lm tng tc dng iu tr v l
m gim tc
dng ph, tc dng c hi. Hai thuc c hip ng tng mc c th qua tng t
c dc ng hc (tng hp thu, gim thi tr) hoc tng tc dc lc hc (trc
-
tip hoc gin tip qua receptor)
1.3.2. Tc dng i khng
Nh trong nh ngha trn, nhng khi tc dng c ca thuc A + B li nh hn tc d
ng cng ca tng thuc (c < a + b) ta gi l tc dng i khng. i khng c th
ch mt phn (partial
antagonism) khi c < a + b, nhng cng c th i khng hon ton khi a lm mt h
on ton tc dng ca b.
Trong lm sng, thng dng tc dng i khng gii c.
-
i khng c th xy ra ngoi c th, gi l t ng k (incompatibility), mt loi
tng tc thun ty l ha:
+ Acid gp base: to mui khng tan. Khng tim khng sinh loi acid (nhm
lactam) vo ng dn dch truyn c tnh base.
+ Thuc oxy ha (vitamin C, B 1, penicilin) khng trn vi thuc oxy kh (vitamin
B2)
+ Thuc c bn cht l protein (insulin, heparin) khi gp mui kim loi s d kt
ta.
+ Than hot, tanin hp ph hoc lm
kt ta nhiu alcaloid (quinin, atropin) v cc mui kim loi
(Zn, Pb, Hg...)
- i khng xy ra trong c th:
Khi thuc A lm gim nng ca thuc B trong mu (qua dc ng hc) hoc l
m gim tc dng ca nhau (qua dc lc hc), ta gi l i khng (antagonism)
V dc lc hc, c ch ca tc dng i khng c th l:
+ Tranh chp trc tip ti receptor: ph thuc
vo i lc v nng ca thuc ti receptor. Th
d: acetylcholin v atropin ti receptor M -
cholinergic; histamin v cimetidin trn receptor H 2
d dy.
+ i khng chc phn: hai cht ng vn (agonist) tc dng trn 2 receptor khc
nhau nhng
chc phn li i khng trn cng mt c quan. Strychnin kch thch tu sng, gy
co git; cura
-
c ch dn truyn tm vn ng, gy mm c, chng c co git. Histamin kc
h thch receptor H1
lm co c trn kh qun, gy hen; albuterol (Ventolin), kch thch rec eptor 2
adrenergic lm gin c trn kh qun, dng iu tr cn hen.
1.3.3. o ngc tc dng
Adrenalin va c tc dng kch tch receptor
adrenergic (co mch, tng huyt p), va c tc dng kch thch receptor
adrenergic (gin mch, h huyt p). Khi dng mt mnh, do tc dng
mnh hn
nn adrenelin gy tng huyt p. Khi dng phentolamin (Regitin) l thuc c ch
chn lc receptor ri mi tim adrenalin th do ch kch thch c receptor
nn adrenelin gy h huyt p, tc dng b o ngc.
ngha ca tng tc thuc
Trong lm sng, thy thuc dng thuc phi hp vi mc ch:
- Lm tng tc dng ca thuc chnh (hip ng tng mc)
- Lm gim tc dng khng mong mun ca thuc iu tr
- Gii c (thuc i khng, thuc lm tng thi tr, gim hp thu, trung ha...)
- Lm gim s quen thuc v khng thuc
Tuy nhin, nu khng hiu r tc dng phi hp, thy thuc c th lm gim tc d
ng iu trhoc tng tc dng c ca thuc. Trong cc sch hng dn dng thu
c, thng c mc tngtc ca tng thuc.
2. TNG TC THUC - THC N- UNG
2.1. Tng tc thuc - thc n:
Thng hay gp l thc n lm thay i dc ng hc ca thuc.
2.1.1. Thc n lm thay i hp thu thuc:
- S hp thu ph thuc
vo thi gian rng ca d dy. D dy khng phi l ni c ch c nng hp
thu ca b my tiu ha. Tuy nhin, do pH rt acid (khi i, pH
1; khi no pH 3) cho nn cn
lu :
+ Ung thuc lc i, thuc ch gi li trong d dy khong 10 - 30 pht.
-
+ Ung thuc vo lc no, thuc b gi li trong d dy khong 1 - 4 gi, do :
. Nhng thuc t tan s c thi gian tan, khi xung rut s c hp thu nhanh
hn (penicilin
V). Tuy nhin, nhng thuc d to phc vi nhng thnh phn ca thc n s b gi
m hp thu (tetracyclin to phc vi Ca ++ v mt s cation ho tr 2 khc).
. Cc thuc km bn trong mi trng acid (ampicilin, erythromycin) nu b gi l
u d dy s b ph hu nhiu.
. Vin bao tan trong rut s b v (cn ung trc ba n 0,5 - 1h hoc sau ba n
1 - 2 gi)
. Nhng thuc d kch ng ng tiu ha, n n ung vo lc no.
-
S hp thu cn ph thuc vo dng bo ch: aspirin vin nn ung sau khi n s g
im hp thu 50%, trong khi vin si bt li c hp thu hon ton.
2.1.2. Thc n lm thay i chuyn ha v thi tr thuc
Thc n c th nh hng n enzym c huyn ha thuc ca gan, nh hng n
pH ca nc tiu, v qua nh hng n chuyn ha v bi xut thuc. Tuy
nhin, nh hng khng ln.
Ngc li, thuc c th nh hng n chuyn ha mt s cht trong thc n.
Thuc c ch enzym mono- amin- oxydase (MAOI) nh iproniazid - l enzym kh
amin - oxy ha ca nhiu amin ni, ngoi sinh -
c th gy cn tng huyt p kch pht khi n cc thc n c nhiu tyramin
(nh khng c chuyn ha kp, lm gii phng nhiu noradrenalin ca h giao c
m trong thi gian ngn.
2.2. Tng tc thc n ung
2.2.1. Nc
-
Nc l ung (dung mi) thch hp nht cho mi loi thuc v khng xy ra t
ng k khi ha tan thuc.
- Nc l phng tin dn thuc (dng vin) vo d dy -
rut, lm tng tan r v ha tan hot
cht, gip hp thu d dng. V vy cn ung nc (100 -
200 mL cho mi ln ung thuc) trnh ng vin thuc ti thc qun, c
th gy kch ng, lot.
-
- c bit cn ch :
+ Ung nhiu nc trong qu trnh dng thuc (1,5 -
2 l/ ngy) lm tng tc dng ca thu c
(cc loi thuc ty), lm tng thi tr
v lm tan cc dn xut chuyn ha ca thuc (sulfamid, cyclophosphamid).
+ Ung t nc hn bnh thng duy tr nng thuc cao trong rut khi ung
thuc ty sn, ty giun (niclosamid, mebendazol).
+ Trnh dng nc qu, nc khong base hoc cc loi nc ngt ng hp c g
as v cc loi nc ny c th lm hng thuc hoc gy hp thu qu nhanh.
2.2.2. Sa
Sa cha calci caseinat. Nhiu thuc to phc vi calci ca sa s khng c
hp thu (tetracyclin, lincomyc in, mui Fe...)
Nhng thuc d tan trong lipid s tan trong lipid ca sa chm c hp thu.
Protein ca sa cng gn thuc, lm cn tr hp thu.
Sa c pH kh cao nn lm gim s kch ng d dy ca cc thuc acid.
2.2.3. C ph, ch
-
Hot cht cafein tr ong c ph, nc ch lm tng tc dng ca thuc h st gim
au aspirin, paracetamol; nhng li lm tng tc dng ph nh nhc u, tng
nhp tim, tng huyt p nhng bnh nhn ang dng thuc loi MAOI.
- Tanin trong ch gy ta cc thuc c Fe hoc al caloid
- Cafein cng gy ta aminazin, haloperidol, lm gim hp thu; nhng li lm tng
ha tan ergotamin, lm d hp thu.
2.2.4. Ru ethylic
Ru c rt nhiu nh hng n thn kinh trung ng, h tim mch, s hp thu
ca ng tiu ha. Ngi nghin ru cn
b gim protein huyt tng, suy gim chc nng gan, nhng li gy
cm ng enzym chuyn ha thuc ca gan (xin xem bo "ru"), v th ru c t
ng tc vi rt
nhiu thuc v cc tng tc ny u l bt li. Do khi dng thuc th khn
g ung ru.
Vi ngi nghin ru cn phi dng thuc, thy thuc cn kim tra chc nng g
an, tnh trng
-
tm thn... chn thuc v dng liu lng thch hp, trong thi gian dng thu
c cng phi ngng ung ru.
3. THI IM UNG THUC
Sau khi nhn r c tng tc g ia thuc- thc n- ung, vic chn thi
im ung thuc hp
l t c nng cao trong mu, t c hiu qu mong mun cao v gi
m c tc dng ph l rt cn thit.
Nn nh rng: ung thuc vo lc i, thuc ch b gi li d dy 10 -
30 pht, vi pH 1; ung lc no (sau n), thuc b gi li 1 - 4 gi vi pH 3,5.
Nh vy, tuz theo tnh cht ca thuc, mc ch ca iu tr, c mt s gi
chn thi im ung thuc nh sau:
3.1.Thuc nn ung vo lc i (trc ba n 1/2 - 1 gi)
- Thuc "bc" d dy cha lo t trc khi thc n c mt, nh sucralfat.
-
Cc thuc khng nn gi li lu trong d dy nh: cc thuc km bn vng trong
mi trng acid (ampicilin, erythromycin), cc loi vin bao tan trong rut
hoc cc thuc gii phng ch m.
3.2. Thuc nn ung vo lc no (trong hoc ngay sau ba n)
-
Thuc kch thch bi tit dch v (ru khai v), cc enzym tiu ha (pancreatin) ch
ng i tho
ng loi c ch gluconidase nn ung trc ba n 10 - 15 pht.
- Thuc kch thch d dy, d gy
vim lot ng tiu ha: cc thuc chng vim phi steroid, mui kali, quinin
-
Nhng thuc c thc n lm tng hp thu, hoc do thc n lm chm di chuy
n thuc nn ko di thi gian hp thu: cc vitamin, cc vin nang amoxicilin,
cephalexin, cc vin nn
digoxin, sulfamid.
- Nhng thuc c hp thu qu nhanh lc i, d gy tc dng ph: levodopa,
thuc khng histamin H1.
3.3. Thuc t b nh hng bi thc n, ung lc no cng c: prednisolon,
-
theophylin, augmentin, digoxin.
3.4. Thuc nn ung v o bui sng, ban ngy
- Cc thuc kch thch thn kinh trung ng, cc thuc li niu trnh nh
hng n gic ng.
- Cc corticoid: thng ung 1 liu vo 8 gi sng duy tr c nng n
nh trong mu.
3.5. Thuc nn ung vo bui ti, trc khi i ng.
- Cc thuc an thn, thuc ng
Cc thuc khng acid, chng lot d dy. Dch v acid thng tit nhiu vo ban
m, cho nn
ngoi vic dng thuc theo ba n, cc thuc khng acid dng cha lot d dy n
n c ung mt liu vo trc khi i ng .
Cn nh rng khng nn nm ngay sau khi ung thuc, m cn ngi 15 - 20
pht v ung nc
(100- 200 mL nc) thuc xung c d dy.
Dc l thi khc
(chronopharmacology) cho thy c nhiu thuc c hiu lc hoc c tnh
thay i theo nhp ng y m. Tuy nhin, trong iu tr, vic cho thuc cn tuz th
uc vo thi gian xut hin triu chng.
IU TR NG C THUC CP TNH BI 6.
1. I CNG
1.1. Nguyn nhn ng c thuc cp tnh :
+ Do nhm ln : ca thy thuc hoc ca bnh nhn
+ Do nhm ln :
- Loi thuc,
- Liu lng
- ng dng
-
- Thi gian dng
+ Do c :
- Ca bnh nhn :
t t
- Ca ngi khc : uc
1.2. Triu chng ng c thuc cp tnh :
Khng c hiu :
+ Ri lon thn kinh : ng li b, hn m hoc kch ng, co git
+ Ri lon tim mch : ri lon nhp tim, gim hoc tng huyt p
+ Ri lon h hp : kh th, tng tit m ri, ri lon h hp chu kz
+ Ri lon tiu ha : au bng d di, nn ma, xut huyt tiu ha
+ Ri lon thn - tit niu : b i, thiu niu, v niu ( suy thn cp ).
1.3. Nguyn tc iu tr :
+ Nhanh chng loi tr cht c ra khi c th.
+ Trung ha cht c c hp thu vo c th.
+ iu tr triu chng v hi sc cho bnh nhn.
2. CC BIN PHP IU TR :
2.1. Loi tr cht c ra khi c th :
2.1.1. Qua ng tiu ha :
a- Gy nn :
+ Siro ipeca 15 - 20 ml, pha long trong 250 ml nccho bnh nhn ung. Nu sau
15 ph bnh nhn khng nn c th dng nhc li.
+ Trng hp khng c thuc, bnh nhn cn tnh, c th ngoy hng, cho ung
mn tht, hoc ung 250 ml dung dch natri clorid ( NaCl ) u trng.
+ CC : bnh nhn hn m, ng c cc acid, base mnh.
b- Ra d dy :bng dung dch thuc tm ( KMnO4 ) 0,1 %, tanin ( acid tanic ) 5%
hoc nc m cho ti khi nc ra tr thnh trong.
+ Vi cc thuc hp thu nhanh nh aspirin, cloroquin, meprobamat, thuc ng
barbiturat, colchicin th ra d dy v gy nn ch c tc dng trong vng 6 h
-
u, khi cht c cn d dy.
+ i vi nhim c cc loi thuc ng BZD, cc thuc c chu kz gan-rut?, nhim
c hn hp hoc nhim c cc cht khng r th nn ra d dy trong vng 24
h ( nu khng c chng ch nh )
+ BZD : benzodiazepin,
+ Cc thuc c chu kz gan-rut : morphin, strychnin, cloramphenicol,
chlorpromazin,tetracyclin, quinin, sulfamid chm, cc hormon sinh dc, digitoxin,
imipramin
+ CC : bnh nhn hn m ( v d a nhm ng cao su vo kh qun hoc cht
nn quay ngc ng vo phi, gy t vong ), ng c cc cht n mn ( nh
acid, base mnh v ng cao su c th lm rch thc qun ).
c- Dng cc cht hp ph :
Sau khi ra d dy, cho ung than hot 30 - 40 g/ln, cch 4 h/ln ( u im ? ).
+ C nhiu u im :
- Hon ton khng c,
- R tin,
- S dng n gin, thun tin
- Ngn cn c chu kz gan - rut ca cc thuc thi theo ng mt.
+ Cht thay th ?
Cht thay th :kaolin hoc bt than ci, bt go, bt ng rang chy tn nh.
2.1.2. Qua ng h hp :
+ Ch nh :ng c cc thuc thi qua ng h hp nh cc thuc m th kh (
ether, halothan), ru, kh t, xng, carbon monoxyd ( CO ), aceton
+ Cc thuc hay dng :
- Pentetrazol ( BD : cardiazol, corazol, tetracor.. ), ng 1 - 5 - 10 ml dd 10 %. Tim
SIV, IM 0,5 -1,0 g tuz BN.
L 10 - 30 ml dd 10 % : ung 20 git/ln
x 2 - 3 ln/24 h.
Vin nn 0,10 :
ung 1 - 2 vin/ln x 2 - 3 ln/24 h.
- Lobelin : ng 3 - 10 mg/1 ml. Tim IM, SC 10 mg hoc tim IV chm 3 mg
+ H hp nhn to.
2.1.3. Qua ng tit niu :
-
a- Thuc li niu thm thu : + Mannitol ( BD : mannidex, osmitrol, osmosal ).
L 100 - 250 - 500 - 1.000 ml dd 10 - 20 %. Truyn IV 1 - 2 g/kg, tc 10 - 20 ml/1
ph ( tuz bnh nhn ).
+ Glucose u trng
10 - 20 - 30 %
+ Ringer lactat ( 1 l dd cha 3,1 g natri lactat;
6 g NaCl; 0,4 g KCl; 0,4 g CaCl2 ). t dng.
* Chng ch nh chung: suy thn nng, suy tim nng, ph phi cp,
tng huyt p, try tim mch nng
* Ch : ch nn dng cc thuc li niu thm thu khi chc chn chc nng thn
cn tt. Khi dng cc thuc ny s lm tng thi tr cc khng sinh nn cn phi
tng liu khng sinh.
b- Kim ha nc tiu :p dng khi iu tr ng c cp cc thuc c bn cht l
acid yu ( thuc ng barbiturat, NSAID ( aspirin, diclofenac, indomethacin,
phenylbutazon )). Thng dng 2 loi sau :
+ Natri hydrocarbonat
( NaHCO3 ). L 500 ml dd ng trng 1,4 %. Truyn nh git IV 2 - 3 l/24 h.
- Nhc im : a thm Na+ vo c th, do d gy tai bin ph no khi chc
nng thn khng tt ( 1 g NaHCO3 c 0,273 g Na ).
+ Trometamol ( THAM, trihydroxymetylaminmetan ).
- Bit dc : alcaphor, talatrol, thamac tat, tham E
- L 250 ml dd tim truyn 9,15 g km 1,5 g acid acetic kt tinh v pH 8,6. Ngi
ln truyn IV 1 g/3 kg/24 h ( 250 - 500 ml ).
c- Acid ha nc tiu : p dng khi iu tr ng c cc thuc c bn cht base
hu c : quinin, cloroquin, dn xut quinolein, imipramin, mecamylamin,
quinacrin, nicotin, procain, phenothiazin Hay dng :
+ Amoni clorid
( TK : amchlor, acid-amon ). Dng bt, ung 3,0 - 6,0 g/24 h ( c th 10,0 - 12,0
g/24 h ), chia lm 2 - 3 ln.
+ Acid phosphoric : ung 15 - 100 git/24 h ( pha vi nc ).
Vic acid ha kh thc hin hn vic kim ha nc tiu, ng thi c th chu
ng tnh trng nhim toan k m hn tnh trng nhim kim nn cng d gy nguy
him cho c th.
-
2.2. Trung ho cht c :
Trong lm sng thng hay dng cc cht tng k ha hc ngn cn hp thu
cc cht c, lm mt hot tnh hoc i khng vi tc dng ca cht c.
2.2.1. Cc cht tng k ha hc ti d dy :
ngn cn hp thu cht c vo c th, sau khi ra d dy c th cho bnh
nhn ung cc thuc :
+ Tanin 1 - 2 %, 100 - 200 ml
( tanin 5 % ra d dy )
+ C th thay bng nc ch xanh, l i, sim, b gic Tanin c tc dng lm kt
ta nhiu alcaloid nh strychnin, quinin, quinidin, apomorphin, morphin, cocain,
cc kim loi nng ( mui km, coban, ng, ch, thy ngn ).
+ Sa, lng trng trng ( 6 qu trng/1 l nc ) : ngn cn hp thu cc mui thy
ngn, phenol.
+ Than hot ( BD : carbolenum, ostacol, medicoal ). C dng bt, vin nn 0,25 -
0,50 g , nh dch 2 %. Ung 30 - 40 g bt/ln, ngy 3 - 4 ln, cch nhau 4 h.
C th thay bng bt go, bt ng rang chy, kaolin. Than hot c tc dng hp
ph mnh trong cc trng hp nhim c cc alcaloid ( morphin, strychnin ),
cc mui kim loi nng ( sublime - HgCl2 ), cc cht mang in tch (+) v (-) cho
nn c th p dng c trong hu ht cc trng hp nhim c qua ng
tiu ha.
2.2.2. Cc cht tng k ha hc dng ng ton thn :
To Met-Hb : khi iu tr ng c acid cyanhydric - HCN ( Sn ).
+ Natri nitrit 3 % ( l 0,3 g/10 ml ) Tim IV 1 l trong 3, sau 5 tim IV 50 ml dd
natri thiosulfat 50 % ( cn c ng natri thiosulfat 0,5 g/5 ml, 2 g/10 ml ).
+ Dimercaprol ( BAL = British anti Lewisit ).
( BD : antoxol, dicaptol, dithioglycerin ), ng 100 mg/1 ml v 200 mg/2 ml.
- iu tr ng c cc kim loi nng ( arsen, vng, thu ngn ).
Lewisit = yperit :
cht c gy ngt
Tim IM 2 - 3 mg/kg/ln :
- Ngy N1, 2 : cch 4 h tim 1 ln,
- Ngy N3 : cch 6 h tim 1 ln.
-
- Cc ngy sau :
2 ln/24h.
+ EDTA ( ethylen diamino tetraacetic acid ) hoc cc mui Na v Ca ca acid ny (
EDTA calci dinatri v EDTA dinatri ( Na2EDTA ) iu tr ng c cc ion ha tr 2
nh Pb2+, Fe2+, Cr2+, Cu2+ v digitalis ( thi tr Ca2+ ).
- EDTA dinatri ng 0,5 g/10 ml. Pha vo dung dch glucose hoc NaCl ng trng,
truyn IV rt chm 1 - 2 ng/24h ( trong 2h ) ( trnh cn tetani ). t iu tr 5
ngy, ngh 7 ngy mi c iu tr t tip theo.
- EDTA calci dinatri ng 0,5 g/10 ml. Cch dng :
ng IV : pha 1 ng trong 250 - 500 ml dd glucose 5 %, truyn IV chm trong 2
h, chia lm 2 ln/ngy. Liu trung bnh : 15 - 25 mg/kg/24 h, ti a 50 mg/kg/24 h.
t iu tr 5 ngy, ngh 2 ngy gia 2 t iu tr.
ng tim IM : dd 20 %. Liu lng : 12,5 mg/kg/ln, cch 4 - 6 h tim 1 ln, ti
a 50 mg/kg/24 h. Ha thm dd procain 1 % tim IM.
2.2.3. S dng cc thuc i khng dc l c hiu :
+ V d : naloxon ( BD : nalon, narcan ), ng 0,4 mg/1 ml; tim IV, tim IM iu
tr ng c morphin v cc thuc gim au gy nghin.
Tuy phng php ny iu tr c hiu qu nhanh v tt, nhng do c rt t thuc
c tc dng i khng c l{ c hiu, cho nn phn ln phi iu tr theo triu
chng.
2.3. iu tr triu chng v iu tr hi sc cho bnh nhn :
2.3.1. S dng cc thuc i khng sinh l :
+ Dng cc thuc kch thch TKTW iu tr ng c cc thuc c ch TKTW v
ngc li.
- Thuc kch thch TKTW: bemegrid, cafein, amphetamin, long no, pentetrazol
- Thuc c ch TKTW : thuc ng barbiturat, thuc an thn, thuc m..
+ Dng thuc gin c cura iu tr ng c cc thuc gy co git
( pentetrazol, strychnin ).
* Nhc im : phi dng thuc i khng vi liu cao, thng l liu c cho
nn c hi cho bnh nhn.
2.3.2. Hi sc tng hp :
a- Hi sc tim mch : dng cc thuc tr tim gi n nh huyt p, chng try
-
tim mch.
+ VD : dng nordrenalin ng 1 mg/1 ml. Pha 1-4 ng trong 500 - 1000 ml dd
glucose 5 %, truyn SIV ( tc 2 - 4 mg/1 ph ).
+ DOCA
( desoxycorticosteron acetat ), ng 5 - 10 mg, vin t di li 5 mg. Tim IM 1 -
2 ng/24 h. Nu nh cho ngm di li 1 - 2 vin/24 h.
b- Hi sc h hp : dng cc thuc kch thch h hp :
+ Pentetrazol ( BD : cardiazol, corazol ) ng 0,10 g/1 ml. Tim IM, SC, IV ti 6 - 8
ng/24 h.
+ Cafein ng 0,07 - 0,25 - 0,40 g/1 ml.
Tim SC 0,07 - 1,5 g/24 h.
+ H hp nhn to, th oxy.
c- Thm phn phc mc hoc chy thn nhn to:
+ Ch nh :
- Cc trng hp nhim c nng ( ng c cc kim loi nng, sulfamid, barbiturat
liu cao )
- Khi thn suy, cc phng php iu tr thng thng khng mang li kt qu.
- Khi c chng ch nh dng cc thuc li niu thm thu.
d- Thay mu :ch nh :
+ Ng c phospho trng : phi lm sm trc 8 h k t khi ng c mi c kh
nng cu c nn nhn.
+ Ng c cc thuc vi liu cht : cc thuc chng st rt, cht c t bo ( cc
thuc chng ung th ), isoniazid, dn xut salicylat
( nht l tr em )
+ Cc cht lm tan mu : saponin, sulfon
+ Cc cht gy Met-Hb : anilin, thuc gim au h st dn xut anilin
( phenacetin, paracetamol ), nitrit, cloroquin
Giai on u c th iu tr bng xanh methylen ng 0,10 g/
5 ml. Pha 10 ml vo 500 ml dd glucose 5%, truyn IV.
Hoc tim IV vitamin C 4,0 - 6,0g/24h. Nu khng c kt qu th phi thay mu.
* Ch : bin php thay mu cn phi lm sm v khi lng mu thay th phi
ln ( 7 l ) th mi c kt qu. Nu ngy hm sau mu cn cha nhiu Met-Hb
th c th phi truyn li.
-
2.3.3. Cng tc chm sc ngi bnh :
a- Ch dinh dng :cho n cc thc n nh ( cho, sp, ph ), d tiu, ca-lo.
Nu bnh nhn khng n c phi t sonde d dy hoc truyn hu mn khi c
tn thng thc qun ( ng c acid, base mnh )
Cn b sung thm nhiu vitamin, nht l vitamin nhm B, C. B sung thm insulin
khi truyn nhiu glucose.
b- Chng bi nhim ( ph qun, phi, ng tit niu ) : khng sinh.
c- Cng tc h l : gi v sinh thn th sch s, chng lo t, ht m ri
I CNG V DC LC HC BI 7.
Dc lc hc nghin cu tc dng ca thuc ln c th sng, gii thch c ch ca
cc tc dng
sinh ha v sinh l ca thuc. Phn tch cng y c cc tc dng, cng cung
cp c
nhng c s cho vic dng thuc hp l trong iu tr. y l nhim v c bn nh
t v cng l kh khn ln nht ca dc lc hc.
1. C CH TC DNG CA THUC
1.1. Receptor
-
Tc dng ca phn ln cc thuc l kt qu ca s tng tc gia thuc vi recep
tor (th th
cm). Receptor l mt thnh phn i phn t (macromolcular) tn ti vi mt l
ng gii hn
trong mt s t bo ch, c th nhn bit mt cch c hiu ch mt phn t "th
ng tin" t nhin
(hormon, cht dn truyn thn kinh), hoc mt tc nhn ngoi lai (cht ha hc, t
huc) gy
ra mt tc dng sinh hc c hiu, l kt qu ca tc dng tng h .
Thnh phn i phn t
-
ca receptor thng l protein v ch c protein mi c cu trc phc tp
nhn bit c hiu ca mt phn t c cu trc 3 chiu.
Receptor c 2 chc phn:
1) Nhn bit cc phn t thng tin (hay cn gi l
ligand) bng s gn c hiu cc phn t ny vo receptor theo cc lin kt
ha hc:
-
Lin kt ion: cc cht ha hc mang in tch (nh nhm amoni bc 4 cu acetylc
holin c in
tch dng), s gn vo vng mang in tch tri du ca receptor theo lin
kt ny, vi lc lin
kt khong 5- 10 kcal/ mol.
-
Lin kt hydro: do s phn b khng ng u electron trong phn t nn c mi
lin kt gia nguyn t hydro vi cc nguyn t c in tch m cao nh oxy, nit
v fluor. Lc lin kt khong 2- 5 kcal/ mol
- Lin kt Van- der-
Waals: l lc lin kt ca mi tng h gia cc electron vi cc nhn ca
cc phn t st bn. Lc lin kt ph thuc vo khong cch gia cc phn t, lc
ny tng i yu, khong 0,5 kcal/ mol. Cc thuc c vng benzen, c mt
electron phn b ng u thng c mi lin kt ny.
Cc lc lin kt trn u l thun nghch.
-
Lin kt cng ha tr: l lc lin kt gia cc nguyn t bng nhng cp in t c
hung. V l lc lin kt ln 50- 150 kcal/ mol nn l lin kt khng thun nghch
nhit c th, khng c cht
xc tc. Loi lin kt ny t gp. Th d lin kt gia cht alkyl ha vi t bo ung t
h, cc thuc c ch enzym mono - amin oxydase (MAOI), thuc tr su ln hu
c vi cholinesterase.
Mt phn t thuc c th gn vo receptor theo nhiu kiu lin kt.
Th d: acetylcholin gn vo receptor M- cholinergic:
-
Hnh 2.1. Phc hp acetylcholin - receptor M
Acetylcholin gn vo receptor M theo ng ni sau:
- Hai O ca chc ester to lin kt hydro vi receptor
- Nhm CH2- CH2 gn vi receptor bng lin kt phn t (lc Van - der- Waals)
- Hai gc CH3 ca amin bc 4 gn vo cc khoang ca v tr anion cng bng lc
Van- der- Waals
2) Chuyn tc dng tng h gia ligand v receptor thnh mt tn hiu gy ra
c p ng t bo. Cc receptor nm nhn t bo
c hot ha bi cc ligand gn trn cc v tr c hiu
ca ADN nm trong cc vng iu ha gen, gy ra s sao chp cc gen c hiu (r
eceptor ca hormon steroid, vitamin D 3...). Cc receptor nm mng t bo v
xa nhn nn khng tham gia
trc tip vo cc chng trnh biu hin ca gen. Khi cc ligand tc ng ln rece
ptor s lm sn 2+xut ra cc phn t trung gian - "ngi truyn tin th 2" (AMPv,
GMPv, IP 3, Ca, diacetyl glycerol...)- Nhng cht ny s gy ra mt lot phn ng
trong t bo, dn ti mt thay i chuyn ha trong t bo, cng vi hoc khng
c s thay i v biu hin gen (receptor ca adrenalin, ca benzodiazepin...).
Nh vy, khi thuc gn vo receptor ca t bo th gy ra c tc dng sinh l.
Nhng c khi thuc gn vo t bo m khng gy ra tc dng g, ni gn thuc
c gi l ni tip nhn
(acceptor) hoc receptor cm, (silent receptor) nh thuc m gn vo t bo m,
digitalis gn vo gan, phi, thn...
Thuc gn vo receptor ph thuc vo
i lc (affinity) ca thuc vi receptor. Hai thuc c cng
receptor, thuc no c i lc cao hn s y c thuc khc ra. Cn tc dng c
a thuc l do hiu lc (efficacy) ca thuc trn receptor . i lc
v hiu lc khng phi lc no cng i cng
-
nhau: acetylcholin l cht dn truyn thn kinh ca h ph giao cm, khi gn vo r
eceptor M, gy
hiu lc lm tng tit nc bt, co ng t, chm nhp tim...; atropin c i lc tr
n receptor M
mnh hn acetylcholin rt nhiu nn y c acetylcholin ra kh i receptor M, n
hng bn thn
n li khng c hiu lc g. lm sng, tc dng
ca atropin quan st c chnh l tc dng ca
s thiu vng acetylcholin trn receptor M: kh ming (gim tit nc bt), gin
ng t, nhp tim nhanh...
1.2. Cc c ch tc dng c a thuc
1.2.1. Tc dng ca thuc thng qua receptor
Thuc tc dng trc tip trn cc receptor ca cc cht ni sinh (hormon, cht d
n truyn thn
kinh): nhiu thuc tc dng trn cc receptor sinh l v thng mang tnh
c hiu. Nu tc dng ca thuc ln rec eptor ging vi cht ni sinh, gi l cht
ng vn hay cht ch vn (agonists), nh pilocarpin trn receptor M -
cholinergic. Nu thuc gn vo receptor, khng gy tc dng
ging cht ni sinh, tri li, ngn cn cht ni sinh gn vo receptor, gy tc dn g
c ch cht ng vn, c gi l cht i khng (antagonists), nh d -
tubocurarin tranh chp vi acetylcholin ti receptor N ca c vn.
- Mt s thuc thng qua vic gii phng cc cht ni sinh trong c th gy tc
dng:
amphetamin gii phng adren alin trn thn kinh trung ng, nitrit lm gii phng
NO gy gin mch...
Xt trn nhiu mt, protein l mt nhm quan trng ca receptor -
thuc. Do , ngoi receptor t bo, cc receptor ca thuc cn l:
-
Cc enzym chuyn ha hoc iu ha cc qu trn h sinh ha c th b thuc c c
h hoc hot ha:
. Thuc c ch enzym: captopril c ch enzym chuyn angiotensin I khng hot
tnh thnh angiotensin II c hot tnh dng cha cao huyt p; cc thuc chng
vim phi steroid c ch
-
cyclooxygenase, lm gim t ng hp prostaglandin nn c tc dng h st, chng
vim; thuc tr tim digitalis c ch Na +- K+ ATPase...
. Thuc hot ha enzym: cc yu t vi lng nh Mg 2+, Cu2+, Zn2+
hot ha nhiu enzym protein kinase, phosphokinase tc dng ln nhiu qu trnh
chuy n ha ca t bo.
- Cc ion: thuc gn vo cc knh ion, lm thay i s vn chuyn ion qua mng t
bo. Novocain cn tr Na + nhp vo t bo thn kinh, ngn cn kh cc nn c
tc dng gy t; benzodiazepin lm tng nhp Cl - vo t bo, gy an thn.
1.2.2. Tc dng ca thuc khng qua receptor
Mt s thuc c tc dng khng phi do kt hp vi receptor.
- Thuc c tc dng do tnh cht l ha, khng c hiu:
Cc mui cha cc ion kh hp thu qua mng sinh hc nh MgSO 4, khi ung s "
gi nc"
thnh rut vo lng rut v gi nc trong lng rut nn c tc dng ty; khi tim
vo tnh mch
s ko nc t gian bo vo mu nn c dng cha ph no.
Isosorbid, mannitol dng liu tng i cao, lm tng p lc thm thu trong huy
t tng. Khi
lc qua cu thn, kh ng b ti hp thu ng thn, lm tng p lc thm thu tron
g ng thn, c
tc dng li niu.
Nhng cht to chelat hay cn gi l cht "cng cua" do c cc nhm c cc nh -
OH, -SH, -
NH2, d to phc vi cc ion ha tr 2, y chng ra khi c th. Cc c ht "cng c
ua" nh EDTA (ethyl diamin tetra acetic acid), BAL (British anti lewisit -
dimercaprol), d- penicilamin thng
c dng cha ng c kim loi nng nh Cu 2+, Pb2+, Hg2+
hoc thi tr Ca 2+ trong ng c digital.
Than hot hp ph c cc hi, cc c t nn