Tat ca cac receptor cua opioid dgu cap d6i vdi protein Gi. Khi kich thich
cac receptor cua opioid, gay uc che' adenylcyclase, uc che' md kenh Ca'" va hoat
hoa kenh K+(tang uu cue).Vivay, uc che' giai phong cac chat d~n truyen than kinh (chat P, acid glutamic) va ngan can d~n truyen xung d9ng than kinh.
Morphin n()i sinh: la cac peptid tu nhien duoc tao ra trong co th~, tac d9ng gi6ng nhumorphin, co vai tro hoat hoa receptor cua opioid. Hien nay nguoi ta da tim ra 3 ho morphin n9i sinh:
- Enkephalin: (Leu- enkephalin, Met- enkephalin) co tac dung uu tien tren receptor 8.
- Endorphin: (aNeo- endorphin, 13-Neo- endorphin) co tac dung uu tien tren receptor u,
- Dynorphin: (DynorphinA, Dynorphin B), co tac dung uu tien tren receptor k. Trong co th~, cac morphin n9i sinh tham gia VaGdigu hoa st;td~n truygn xung d9ng thlln kinh d nhigu ndi nhti nao, tllY s6ng. Chung thtidng dti<;lcgiai phong khi cd th~ g~p stress (dau). Cac tac d\lng clla chung bi giam ho~c mat bdi cac chat d6i khang voi opioid nhti naloxon, naltrexon.
1.3. Tac d1;lngva cdche chung cua thuoc giam dau trung lidng (xem them bang 3.7)
- Tac d\lng d~c hi~u tren receptor opioid va bi mat tac d\lng bdi chat d6i khang la naloxon va naltrexon.
- Tac d\lng giam dau ml;lnh,chQnlQcva sau n9i tl;lng. - Co tac d\lng an thlln, gay ngil.
- Gay lic che'h6 hap.
- Lam giam nhu d9ng ru9t. - Gay sang khoai va gay nghi~n.
Cd che: cac receptor clla opioid dgu c~p d6i voi protein Gi.Khi cac opioid g:ln VaGreceptor opioid (Il, k, 8) lam kich thich receptor nay, gay lic che' adenylcyclase.
1.4. Lien quan gifia cffu truc va tac d1;lng(hinh 3.4)
- Cac thu6c trong nhom dgu co cau truc nhan phenanthren ttidng tt;t morphin - la cau truc quye't dinh tac d\lng giam dau clla'cac thu6c.
- Khi thay d6i nhom-OHdvi tri c3va c6trong phan tit morphin thi m9t sO' tac d\lng dti<;lCly va d~c tinh dti<;lCd9ng hQccung thay d6i.
RO
o,
HO/
Morphin: R=-H Codein: R=-CH3
Hinh 3.4. Cau true hoa h9C chung cuaopioid
+Khi methyl hoa nhom -OH dvi tri C3, tac dung giam dau gay nghien giam, tac dung giam ho tang len, d6ng thoi sinh kha dung qua duong uong cua thuoc cling t6t hon morphin. Vi du: methyl morphin (codein).
+Acetyl hoa nhom -OH d C3va! hoac C6, thuoc xam nhap qua hang rao mau nao t6t hen morphin, tac dung giam dau gay nghien tang len. Vi du: diacetyl morphin (heroin).
+Khu H cua -OH d C6, tao nhorn ceton hoac ester hoa thi tac dung giam dau va d(>ctinh cling tang, nhung thoi gian tac dung lai ngan nhu oxymorphon, hydromorphon.
1.5. Phan loai
Dua VaGco che tac dung, chia cac thuoc giam dau trung uong thanh ba nhom: - Thuoc chu van tren receptor opioid:
+Cac opioid tv nhien: morphin, codein ...
+Cac opioid t6ng hop: pethidin, methadon ...
- Thu5c chu van - d6i khang han hop va chu van tung phan tren receptor opioid: pentazocin, nalorphin, nalbuphin, butorphanol...
- Thu6c d6i khang ddn thuftn tren receptor opioid: naloxon, naltrexon.
2. THUOC CUD V~ TREN RECEPTOR OPIOID
2.1. Cae opioid tljnhien
2.1.1. Morphin
Du(/e di)ng h(}c
Thuoc hffp thu duqc qua dUdng u6ng, dUdng tiem va dUdng h6 hffp. Hffp thu thu6c qua dUdng tiem nhanh va m:;tnh hdn, vi dUdng u6ng thuoc chuy~n hoa qua gan lftn dftu lon, sinh kha d\1llgthffp (khoang 25%). Sau khi u6ng 30- 60phut, d:;tt
nong dQ toi da trong mau, Lien ket vdi protein huyet tuong khoang 30%. T~p trung nhieu a co van, gan, ph6i, than. Thuoc qua duoc hang rao mau nao, nhau thai va sua me. Ndng dQ thuoc a nao thap hen cac noi khac, Morphin chuyen hoa a gan chu yeu lien hop vdi acid glucuronic tao chat chuyen hoa Ia morphin- 6- glucuronic con hoat tinh va morphin- 3- glucuronic khong co heat tinh. Thai tru chu yeu qua nude ti~u, mot phan thai qua ph an (co chu ky gan ruot), 90% thuoc thai trong vong 24 gio dllu. Thoi gian ban thai la 2- 3 gid a nguoi binh thuong va keo dai a nguoi suy than va tre so sinh (6- 30 gio),
Tac dung
Morphin va dfin xuat co tac dung chon loc tren receptor ~. Lieu cao, ngoai receptor ~, thuoc co tac dung tren cac receptor opioid khac. Tac dung cua morphin thay d6i theo lieu dung, gidi tinh, lua tu6i va loai. Tuy nhien, tac d\lng chinh la tic che thlln kinh trung udng.
- Tren thlln kinh trung udng:
+Tac d\lng giam dau: morphin co tac d\lng giam dau m:;tnh,giam dau nQi t:;tngva chQn lQc(chQnlQctren trung tam dau, kh6ng anh huang Wi cam giac khac va kh6ng maty thtic).
Cd che giam dau: morphin co tac d\lng chQn lQctren receptor ~, lam giam giai phong cac chat dfin truyen thlln kinh (nhu chat P, acid glutamic) va lam tang nguBngchiu dau.
+Tac d\lng an thlln, gay ngu: tac d\lng an thlln, gay ngu cua morphin chi r6 khi dung lieu thap hdn lieu giam dau va chi r6 a ngudi cao tu6i. Thuoc it gay bu6n ngli a ngudi tre tu6i. NguQcl:;ti,co nhieu trudng hQp l:;tithay b6n ch6n, btit dtit, th~m chi neu dung lieu cao cho tre em co th~ gay co gi~t.
+Tac d\lng tren tam thlln: gay cam giac sang khoai, md mang, tang tri tuang tUQng,mat cam giac doi khat, bu6n phien. Khi dung lau gay nghi~n thuoc.
- Tren h6 hap:
Ngay a lieu dieu tri, thuoc da gay tic che trung tam h6 hap, lam nhip thd ch~m va sau ... Lieu cao gay tic che m:;tnh,co th~ gay roi lo:;tnh6 hap. Cd che gay tic che h6 hap chu yeu do thuoc lam giam dap ting cua trung tam h6 hap doi voi CO2va tic che trung tam h6 hap a hanh nao. Ngoai ra, thuoc con gay co thllt cd
trdn phe quan (co th~ do tang giai phong histamin). Vi v~y, clln th~n trQng voi ngudi hen phe quan.
ThuOctic che m:;tnhtrung tam ho va lam giam phan x:;tho. - Tren tulln hoan:
Lieu dieu tri, thuoc it anh huang Wi tulln hoan. Lieu cao, thuoc lam ch~m nhip tim, gian m:;tchva h:;thuyet ap (co th~ do thuoc kich thich trung tam pho
giao cam, UC che trung tam van mach dhanh nao va tang tiet histamin). Cac chat doi khang vdi opioid, cac khang histamin va thuoc huy pho giao earn lam giam hoac mat tac dung tren twin hoan cua morphin va cac opioid.
- Tren tieu hoa:
Morphin lam giam truong luc va nhu d{mg SQico doc, giam tiet dich tieu hoa gay tao bon keo dai, Thuoc lam tang trucng luc soi co yang tieu hoa, co that mon vi, hau mon, co yang Oddi.
- Tren tiet nieu:
Morphin lam co co yang hang quang, gay hi ti~u tien. - Cac tac dung khac:
+D~ gay non do kich thich trung tam non dsan nao that IV.
+H~ than nhiet do kich thich trung tam tea nhiet,
+Tang tiet hormon tuyen yen.
+Giam chuyen hoa, giam oxy hoa,
+Co d6ng tIt do kich thich trung tam day III.
+Giam tiet dich, nhung tang tiet m6 hoi.
Chi djnh
- Dau nang hoac dau khong dap ung vOicac thuoc giam dau khac: sci th~n, sci m~t, ung thu, chan thudng, sau ph~u thu~t, san khoa, nh6i mau cd tim. - Phu ph6i cap th~ nh~ va vua.
- Tien me.
Tac d¥ng khong mong muon va d§c tinh
- Tac d1,lngkhong mong muon: thudng g~p nhat la hu6n non, non, tao hon, UCche ho hap, co d6ng tIt, tang ap h,tc dUdng m~t, hi ti~u, may day, ngua ... - DQctinh cap: khi dung lieu 0,05 - 0,06g, lieu gay chet la 0,1 - 0,15g.
Tri~u chung: hon me, co d6ng tIt, suy ho hap n~ng, tim tai, sau do gian d6ng tIt, tr1,lytim m~ch, ngung ho hap va tIt vong.
XIt tri: ngoai cac hi~n phap giai dQcthong thudng thi chat giai dQCd~c hi~u la cac khang opioid: naloxon, naltrexon phoi hQp voi atropin.
- DQctinh m~n (nghi~n thuoc)
Khi dung lien t1,lCkeo dai 2- 3 tu~n (doi khi 2- 3 ngay) gay hi~n tUQng quen thuoc (tuc la phai tang lieu moi d~t hi~u qua nhu han d~u). Di kem voi s1,iquen thuoc la s1,iph1,lthuQc ve th~ xac vao thuoc (nghi~n thuoc). Neu khong tiep t1,lC dung se co hQi chung cai thuoc voi hi~u hi~n la chay nuoc m:lt, nuoc miii, ngat, l~nh, giam than nhi~t, gian d6ng tIt, non mIta, tieu chay, dau cd, run, co th~ v~t va, co gi~t...
Xli tri (cai nghien): each ly vdi moi truong gay nghien, ke't hop giua lao
dong chan tay vdi tam ly tri lieu, Dung lieu phap thay the' b~ng methadon va
mot s6 thu6c cai nghien. Co th~ dung cac chat d6i khang la naloxon, naltrexon.
Ch{j'ng chi dinh. va thij,n trong
- Suy ho hap, hen phe' quan.
- Chan thuong nao hoac tang ap lucS9nao, - Trang thai co giat.
- Nhiern d9Crucu cap. - Dang dung cac IMAO. - Tre em dudi 30 thang tu6i. - Suy gan nang.
- Dau bung cap khong r6 nguyen nhan.
- Than trong vdi nguoi cao tu6i va nguoi mang thai.
Tuang tcic thuoc
_ Voi thu6c uc che than kinh trung uong khac: thu6c giam dau gay ngu, an than gay ngu, liet than ... lam tang tac dung lic che' than kinh trung uong cua morphin.
_ Voi lMAO gay truy tim mach, hon me, co th~ tli vong.Vivay, khong duoc phdi hop morphin vdi cac lMAO.
Che'phdm va lieu dung
Vien nen, vien nang 10- 200mg. Gng tiem 10mg/ mL; 20mgl 2mL. Gng
tiem 2mg/ mL; 4mg/ 2mL, 10mg/ mL khong co chat bao quan d~ tiem ngoai mang cling.
Tiem dtioi da, tiem blip: Ngtidi IOn5- 20mgx 2- 41ftnl 24h.
Tre em tren 30 thang: 0,1- 0,2mg/ kg/ Iftn.
U6ng: 10mg/ Iftnx 2- 4 Iftnl 24 gid. Co th~ tang de'n 60- 100mg/ 24 gid tuy theo mlic d9 quen thu5c va mlic d9 dau.
2.1.2. Codein
DU(jc d(Jng h9c
Thu6c hap thu qua dtidng u6ng t6t hdn. Sau khi u6ng 1- 2 gid, tac dl,lng xuat hi~n va keo dai 4- 6 gid. Dung tiem tinh m~ch, codein lam tang giai phong histamin, gay gian m~ch va h~ huye't ap nhieu hdn morphin vi v~y rat hie'm dung dtidng tiem tinh m~ch. Thu6c qua dtiQcnhau thai, chuy~n hoa dgan va thai tru qua th~n.
Tcic d¥ng va chi dinh