- Lieu dung: 1 4mg/ 24h pha trong dung dich glucose dling truong, truyen tinh mach Lieu toi da 10mg/ 24h.
2.4. Thuoc kich thich gian tiep h~ adrenergic
2.4.1. Ephedriri
Ngu6ngoc
1\1nhien: ephedrin la alcaloid cua cay Ma hoang, dang d5ng phan ta tuyen. T6ng hop: thuoc duoc t6ng hop l~n d~u tien vao nam 1927, Ia dong phan
hiru tuyen.
Ca hai dang dgu duoc dung trong lam sang.
Duoc d{Jnghoc
Thuoc hap thu duoc qua moi duong: duong uong, duong tiem va dung ngoai. Sau khi uong' 2- 4 gio, thuoc dat n5ng dQ toi da trong mau, duy tri tac dung 4- 6 gio. Ephedrin khong hi phan huy hdi COMT va MAO, nguoc lai no con co tac d\mg phong toa MAO. Trong cd th~, hi chuy~n hoa ch~m va it hdi cac ph an (tng oxy hoa va khi't amino Thai tru chu yeu qua nuoc ti~u. Thdi gian han thai 3- 6 gid.
Tac df:lng
- Tren h~ giao cam: tac d\mg cua ephedrin yeu hdn adrenalin, it dQCva keo dai hdn. Tuy nhien, neu dung lien t1,lC,keo dai thi tac d1,lngcua ephedrin se hi giam hoi[l.cmat do chat d~n truygn th~n kinh d synap hi c~n ki~t.
- Tren tu~n hoan: kich thich tim, co m~ch, tang huyet ap (so voi
noradrenalin thi tac d1,lngtang huyet ap yeu hdn nhung keo dai hdn). - Tren ho hap: kich thich ho hap, gian cd trdn phe quan nen duqc dung digu
tri hen phe quan.
- Tren th~n kinh trung udng: ephedrin gay kich thich th~n kinh trung udng m~nh hdn cac catecholamin. Tac d1,lngkich thich m~nh nhat d vo nao va hanh nao.
- 'I'ren vo nao: lieu thap thu6c gay tang hung phan, sang khoai, tinh tao,giam met moi. Lieu cao gay h6i hop, mat ngu, run tay, tang van d(_)ng. giam met moi. Lieu cao gay h6i hop, mat ngu, run tay, tang van d(_)ng.
- 'I'ren hanh nao: kich thich trung tam ho hap va van mach, lam tang ho
hap, twin hoan, giup tang cuong va h6i phuc cac trung tam nay khi bi uc
che. Vi vay, hien nay no duocxep vao nhorn chat dopping cam dung trong
th~ thao.
Co che: ephedrin co tac dung phong be MAO lam tang luong catecholamin n(_)isinh (Cica trung uong va ngoai vi) nen gian tiep cuong giao cam. Ngoai ra, thuoc con kich thich ngon sci giao cam lam tang tiet catecholamin.
Chidinh.
Hen phe' quan.
Ho hap bi uc che (nhu khi gay te tuy song, ng(_)d(_)cruou, thuoc ngu ...). Ha huyet ap do truy tim mach, h(_)ichung Adam - Stockes.
Viem va sung huyet mfii, hong
Ttic dung khong mong muon
Thu6c gay kich thich: h6i hop, mat ngu, Ioan nhip tim, tang huyet ap.
ensphdm va lilu dung
- Che ph~m: vien nen 10mg,thu6c nho mill, 1- 3%(sulfarin);6ng tiem 25mg/ mL. Ngoai ra con co cac dlilngkhi dung, siro ph6i hqp vOicac thu6c khac.
- Lieu dung: Tiem dUdida, blip 10mg/ llln, 20mg/ 24h. U6ng 10mg/ llln, 60mg/ 24h.
Lieu t6i da 150mg/ 24h.
2.4.2. Amphetamin
Amphetamin co cac tac dl,lngva co che tac dl,lngtuong tl.;iephedrin, nhung co m(_)tso'di~m khac
Tren thlln kinh thl.;icV?t: co tac dl,lngcUdnggiao cam gian tiep yeu.
Tren thlln kinh trung uong: kich thich thlln kinh trung uong mlilnh hon, gay sang khoai, hung phan, giam m~t moi, tang kha nang lao d(_)ngtri oc va chan tay. Tuy nhien, khi dung lau se gay suy nhuqc, m~t moi, trllm cam va gay nghi~n. Hi~n nay, amphetamin dl.;iOCxep vao nhom thuOc gay nghi~n, chat rna tuy nen khong duqc dung trong lam sang.
Ngoai ra, amphetamin con gay tinh trlilng chi'm an nen co tac dl,lng vdi b~nh beo phi, tuy nhien khong nen dung dieu tri beo phi vi co nhieu tac dl,lng khong mong mu6n tren thlln kinh.
3. THUOC DC CHE H~ ADRENERGIC (Thuoc huy giao cam)
Thuo'Cuc che' he adrenergic (thuoc huy giao cam) la cac thuoc co tac dung ngan can mot So'tac dung khi kich thich h~ giao cam hoac han che tac dung cua cac thuoc cuong giao cam. Thuo'Cuc che true tiep receptor adrenergic hoac gian tiep lam giam IU<;Ingcatecholamin dsynap than kinh cua h~ adrenergic.
3.1.Thuoc uc che h~ 13-adrenergic (/3- blockers) 3.1.1. Dij,cdilmcluing
Duoc dl)ng hoc
Hftu het cac thuoc dgu hap thu duoc qua dudng tieu hoa. Sau khi uong khoang 1- 2 gid thuoc dat n6ng d(>to'i da trong mau, Chuyen hoa qua gan lftn dau va sinh kha dung cua phan IOncac thuoc phu thuoc vao tinh hoa tan trong lipid. Propranolol, alprenolol, oxprenolol co chuyen hoa qua gan lftn dftu len, sinh kha dung thap. Betaxolol, pindolol, penbutolol d~ hoa tan trong nude, it tan trong lipid co chuyen hoa qua gan lftn dftu thap, sinh kha dl,lng cao. Thuo'C phan bo' Wi cac t6 chuc trong cd th~, qua dU<;Ichang rao mau nao. Phftn IOncac thuo'Cchuy~n hoa dgan va thai tru chu yeu qua nudc ti~u. Thdi gian ban thai cua cac thuo'Ckhac nhau, tu 10 philt den 24 gid. Thdi gian ban thai keo dai d
b~nh nhan suy gan, th~n (bang 4.3).
Bang 4.3. M¢t so d~c tfnh dl1<;1cd¢ng h9C eua thuoc (lcche 13-adrenergic
Ten thuoc Tan trong lipid Sinh kha dl,mg Thai gian ban thai
Acebutolol Thap 50% 3- 4h
Atenolol Thap 40% 6- 9h
Betaxolol Thap 90% 14- 22h
Carvedilol Khong ra 25-35% 6- 8h
Esmolol Thap Khong ra 10 phut
Labetalol Trung binh 30% 5h
Metoprolol Trung binh 50% 3- 4h
Nadolol Thap 33% 14- 24h
Pindolol Trung binh 90% 3- 4h
Propranolol Cao 30%* 3,5- 6h
Sotalol Thap 90% 12h
Timolol Trung binh 50% 4- 5h
Tac dung
Cac thuoc dgu co cac d~c di~m tac dung giong nhau tren tim, mach, huyet
ap, co tron va chuyen hoa, chi khac nhau vg cuong d9 tac dung.
- Tren tim mach: thuoc trc che' receptor 131- adrenergic lam giam hoat dong cua tim: giam sire co bop co tim, giarn nhip tim, giam d~n truyen, giam tieu thu oxy cua co tim nen co tac dung chong 10<;1nnhip tim. othoi gian dl1u dung thu6c, sue can ngoai bien co th~ tang nhe nhung dung lau dai sue can ngoai bien se tra vg binh thuong hoac giam nhe. Thu6c lam giarn tiet renin va lam giam huyet ap a ngtroi bi tang huyet ap, it anh huang tdi nguoi binh thuong. Tac dung tren h~ tim mach cua cac thu6c nay cang r6 khi h~ giao cam a trang thai kich thich.
- Tren co tron: lam tang co co trcn khi phe' quan, co tron tieu hoa (do d6i khang vCii(32).
- Tren ngo<;1itiet: lam tang tiet dich khi phe quan, dich tieu hoa ...
- Tren chuy~n hoa: lam giam chuy~n hoa, uc che ph an hllY glycogen va lipid, uc che tac d\lng gay tang dudng huyet clla cac catecholamin.
- Cac tac d\lng khac:
Tac d\lng cUdng giao cam n9i t<;1i:ngoai cac tac d\lng uc che receptor 13nhu da trinh bay a tren, m9t s6thu6c trong nhom (nhu pindolol, acebutolol...) con co tac d\lng kich thich tung phl1n tren receptor 131va 132.Cac thu6c nay duqc gQila co hO<;1ttinh giao cam n9i t<;1i.Ket qua clla cac tac d\lng trai ngllqc nhau nay lam giam bCittac d\lng tren tim va tren phe quan clla thu6c uc che 13.Vi v~y, cac thu6c uc che 13co hO<;1ttinh cudng giao cam n9i t<;1iit gay tac d\lng kh6ng mong mu6n (nhu ch~m nhip tim, hen phe quan) hon cac thu6c chi uc che receptor 13
don thul1n.
Thu6c con co tac d\lng 6n dinh mang te bao thl1n kinh, te bao co tim va co van nen ciing co tac d\lng ch6ng 10<;1nnhip, gay te va an thl1n nh~.
Chi djnh
Tang huyet ap. Con dau thiit ng\ic.
LO<;1nnhip tim do cudng giao cam, sau nh6i mau co tim. Tang nhan ap.
M9t sO'b~nh thl1n kinh: dau ni'ia dl1u,run co, cang th£ng ... Giai dQcthu6c cudng13-adrenergic.
Tac d,!-ng khong mong muon
Ch~m nhip tim.
Co thiit khi phe quan gay con hen.
Gay con dau va loet da day, ta trang,
Khi ngung thuoc d9t nget c6 th~ lam nang them con dau that nguc, tham
chi gay d9t tli. Vivay, truce khi ngung thu6c, phai giam li~u dan dan.
Chong chi dinh
Suy tim, cham nhip xoang, bloc nhi that d9 2, 3. Hen phe' quan.
Loet da day - ta trang tien tri~n. Nhuoc co.
NgUdimang thai.
Tuangtcicthuoc
'I'ac dung uc che' tim, ha huyet ap cua thuoc uc che P- adrenergic tang len khi dung cung vdi cac thu6c cung uc che tim ha huyet ap nhu: thu6c chen kenh Ca" (verapamin, tildiazem), thu6c gian mach true tiep (diazoxid), reserpin, thuoc gay me (halothan, enfluran) ...Vivay, khi phdi hop cAndi~u chinh lieu.
Cimetidin va thu6c uc che enzym gan, lam tang nong d9 trong huyet tuong cua cac thu6c uc cheP- adrenergic.
Thu6c uc che P- adrenergic c6 th~ che If':ptac d\lng h~ dUdnghuyet do qua li~u insulin va sulfonylure.
Thu6c eh6ng viem kh6ng steroid lam giam tac d\lng h~ huyet ap cua cac thu6c lic che P- adrenergic.
Ccicthuoc va bi~tdUf}C
Dlja vao vi tri va cd che, thu6c lic che P- adrenergic duqc chia lam 2 nh6m: - Kh6ng chQnIQc(lic che ca PI va P2): propranolol, labetalol, sotalol, timolol,
pindolol, alprenolol, oxprenolol...
- ChQnIQctren tren PI: atenolol, acebutolol, metoprolol, practolol, betaxolol, esmolol...
Cac thu6c n6i chung gi6ng nhau v~ tac d\lng, cd che tac d\lng, chi khac nhau ve eudng d(>Uled\mg va m(>t86 d~e di~m rieng. Cae d~c di~m tac d\mg va li~u dung cua cac thu6c di~n hinh duqc tom tiit trong bang 4.4.
Bang 4.4. M¢t so d~c di§m tac dl,mg va lieu dung cua thuoc Ltcche p-adrenergic
Ten thuoc- bi~t dllQc ChQnlQc ClIdng giao 6n djnh Lieu dungl 24h
tren~1 cam nQi t~i mimg
Acebutolol (Sectral) + + + 200- 600mg Atenolol (Ternomin) + - - 50- 100mg Betaxolol + - - 20- 40mg Esmolol + - - 50-2OOll9/kg/phUt Metoprolol (Lopressor) + - + 50- 300mg Carvedilol* - - + 12,5- 25mg Labetalol* - - 200- 400mg Nadolol - - - 20- 160mg Pindolol (Visken) - + - 5- 15 mg Propranolol (Avlocardyl, - - + 40- 120mg Inderal) Sotalol (Sotalex) - - - 80- 240mg Timolol 10- 30mg - - - (Timaco, Blocadren) (+): C6 (-): KhOng (*): Dc che caa,
3.2. Thuoc uc che tr\ic tiep h~0.-adrenergic
3.2.1. Thu{)c z£cche' a- adrenergic khong chon 19c 3.2.1.1. Phentolamin
Duac d9ng h9C
Hap thu nhanh qua duong tiem, duy tri tac dung ngan. Sau khi tiern tinh mach tac dung xuat hien ngay tire thi va keo dai 15- 30 phut, tiem b:1p 15- 20 phut co tac dung, duy tri 30- 45 phut. Thu6c chuyen hoa dgan va thai tru qua nude ti~u chu yeu dang da chuyen hoa.
Tacdlfng
Phentolamin uc che'ca receptor 0.1 va 0.2 lam gian mach va ha huyet ap, Thuoc gay tang nhip tim do phan x~.
Tac d\lng khac: phong be ca receptor serotoninergic va tang giai phong histamin, phong be kenh K+,kich thich cd trdn d~ day - ru¢t va tang tiet dich.
Chi dinh
Dl,iphong va dieu tri tang huyet ap.
Ttic dung khongmong muon
Thuong g~p Ia ha huyet ap, nhip tim nhanh do phan xa hoac loan nhip, thieu mau C\lCbq cd tim va cac roi loan tieu hoa nhu dau bung, buon non, viem loet da day ta trang cap.
Chong chi dinh.
Nh6i mau co tim hoac ti€n si'inhci mau co tim.
Dau that nguc, thieu nang mach vanh, xo cirng manh vanh. Suy than.
cu«ph6m va lieu dung
Thuong dung 5mg/ l~n, tiem blip hoac tinh mach, L<;>thuOc tiem 5mg.
3.2.1.2. cs« thuoc hluic
Tolazolin va phenoxybenzamin co d~c di~m tac dung, tac dung khong mong muon, chi dinh, chong chi dinh tuong tu phentolamin. Tuy nhien, phenoxybenzamin co th~ dung duong uong va tac dung keo dai 24 gid.
3.2.2.Thuoc ric che'chon 19ca1-adrenergic
3.2.2.1. Prazosin
Duac d9ng hoc
Thuoc hap thu qua duong tieu hoa, sinh kha d\lng til 43- 82%. Thuc an lam ch~m hap thu thuOc. Sau khi uong 1- 3 gid thuoc dl:\tn6ng dq toi da trong mau, duy tri tac d\lng 24 gid nhung phai di€u tri 4- 6 tu~n moi d~t hi~u qua d~y duo Thuoc ph an bo khlip cac t6 chuc, cao nhat la d ph6i, dqng ml:\chvanh, dqng ml:\chchu, tim, thap nhat d nao. Lien ket voi protein huyet tudng 97%, qua du<;lC sua m~. Thuoc chuy~n hoa d gan b:1ngphan ung khi'i methyl. Thai tril chu yeu qua nuoc ti~u dl:\ngchuy~n hoa.
Tac dlfng
- Tren tim ml:\ch:prazosin UCche ch<;>nl<;>ctren receptor U1 gay gian m~ch, giam suc can ngol:\ivi va hl:\huyet ap. Khac phentolamin, prazosin it lam tang nhip tim do phan Xl:\.Khong anh hUdng Wi luu lU<;lngmau qua th~n va chuc nang th~n.
- Tac d\lng khac: gian cd trdn tuyen ti€n li~t do do lam tang luu lu<;lngnuoc ti~u d ngudi b~nh phi dl:\ituyen tien li~t lanh tinh, giam cholesterol toan ph~n va LDL- cholesterol.
Chi dinh
Tang huyet ap. Suy tim sung huyet. Phi dl:\ituyen ti€n li~t.
Ttic dung khcmgmongmucin
Thuong g~p la chong mat, nhuc dau, met moi, ngu ga, danh tro'ng nguc, ha
huyetap the dung, kho mieng, tao bon, sung huyetmiii va ro'i loan tinh d\1C.
Chong chi dinh
Suy tim do tAcnghen nhu hep van hai la, hep dQng mach chu,
cn«phdm va lieu dung
Che pham: vien nang 1, 2 va 5mg.
Lieu dung: khoi dau O,5mg/Illn, 2-3 Illnl24h, duy tri 1-2mg/llln, 2 Illnl 24h.
3.2.2.2. Cdc thuoc hluic
Terazosin va doxazosin co d~c di~m t~c dung, chi dinh, tac dung khong
mong muon, chong chi dinh tuong tlj prazosin, nhung doxazosin co thoi gian tac
dung keo dai hen.
3.2.3.Alcaloid ntim cua ga
Cac alcaloid cua nam cua ga duoc Iftytit Claviceps purpurea, mot loai nam ky sinh tren cac loai ngii ccc, dac biet la hia mach den.
Dua vao cftu truc hoa hQcchia alcaloid cua nam clja ga thanh 2 nhom: - Nhom co cftu truc polypeptid: ergotamin, dihydroergotamin, ergotoxin. - Nhom co cftu truc amin (d~n xuftt cua acid lysergic): ergometrin,
metylergometrin.
DUlJcd()ng h(}c
Cac thuoc hftp thu qua dUdng tieu hoa kern va khong 6n dinh. Tuy nhien, toc dQhftp thu cua thuoc Umg len khi uong cung cafein. Chuy~n hoa m~nh d
gan va thai trit phlln Ion qua m~t. Thdi gian ban thai 2- 3 gid.
Tcicdung va co che'
Cac alcaloid clja ga dgu co d~c di~m tac d\1ng va cd che giong nhau, chi khac nhau vg cUdngdQtac d\1ngva muc dQchQnIQctren cac cd quan (ergotamin va dihydroergotamin tac d\1ng uu tien tren m~ch ngo~i vi con ergometrin tac d\1ng uu tien tren tl:icung).
- Tren cd trdn m~ch mau: tac d\1ng cua thuOc phuc t~p va ph\1 thuQCvao nhigu yeu to' (lo~i m~ch mau, ligu dung ...). d ligu digu tri, ergotamin va d~n xuftt gay co m~ch ngo~i vi nhftt la khi m~ch d tr~ng thai gian (tuy nhien, thuo'c gay gian m~chdnhung m~ch bi co thAt). Ligu cao, thuOc gay co m~ch m~nh va keo dai c6 th~ dAn Wi thieu mau C\lCh('>cd tim va ho~i tli chi. Thuoc gian m~ch trljc tiep (natri nitroprussiat) doi khang, lam mftt tac d\lng co m~ch cua cac alcaloid clja loa m~ch.