- Tac dung kich thich heM
5. THUOC trc cUEu¢ CHOLINERGIC (Thu6c huy ph6 giaocam)
5.1. Thuoc uc che' h~ muscarinic
5.1.1. Thuoc zic che'hf muscarinic ngu6n goc tunhien. 5.1.1.1. i\tropin
Ngu6ngoc
La alcaloid c6 trong belladon, ca d(k duoc.
Duac d()ng hoc
Thuoc d~ hap thu qua duong uongva tiern. Sinh kha dung qua duong uong khoang 50%. Sau khi tiern dudi da 20- 30 phiit hoac sau khi tiern tinh mach 5- 10 phut, thuoc dat nong de)toi da trong mau, Thuoc ph an bo khap cac t6 chuc cua co th~, qua dU<;IChang rao mau nao, nhau thai va sua me. Trong co th~, atropin duoc chuyen h6a d gan bang' ph an ling thuy phan dudi tac dung cua esterase tao acid tropic va tropanol, me)tphan bi oxy h6a. Thai tru chu ye'u qua nude ti~u ca dang chuyen h6a (50%) va dang chua chuyen h6a. Thoi gian ban thai khoang 2- 5 gic;
Ttic dlfng va cache'
Atropin va cac thuoc cung nh6m lic che' Clilnhtranh voi acetylcholin va cac chat kich thich h~ muscarinic khac, ngan can sl,1giin acetylcholin vao receptor muscarinic ca d thl1n kinh trung udng va ngolilivi. Gay kich thich thl1n kinh trung udng va huy ph6 giao cam.
- Kich thich than kinh trung lidng:dlieu dieu tri, thuoc kich thich nh~ me)t so trung tam d nao nhu vagus, trung tam ho hap va v~n mlilch.Lieu cao gay b6n ch6n, ao giac, me sang.
- Tac dl,mg huy pha giao cam:Atropin lic che'chQnlQctren h~ M(ittac d1,lng tren h~ N) gay tac d1,lnghuy ph6 giao cam, bi~u hi~n tren cac cd quan va tuye'n nhu sau:
+ Tren miit: thuoc gay gian d6ng ti'i do gian cd vong mong miit, gay li~t th~ mi dfln Wi mat kha nang dieu tie't cua miit va lam tang nhan ap.
+ Tren tul1n hoan: binh thudng thuoc it anh hUdng Wi tim, mlilch va huye't ap, nhung khi dung lieu cao ho~c h~ tul1n hoan bi lic che'do cUdng ph6 giao cam thi atropin phong be' h~ M, lam tim d~p nhanh, mlilnh,co mlilchva tang huye't ap.
+Tren cd trdn: atropin phong beh~ M tren cd trdn, lam giam trudng h;tc, giam nhu dQngva gian cac cd trdn ho hap, tieu h6a, tie't ni~u. Tac d1,lng gian cd trdn cang r6 khi cd trdn d trlilngthai co thiit.
+Tren tuye'n ngolilitie't: giam tie't dich ngolilitie't nhu giam tie't nuoc bQt, ddm, m6 hoi, dich m~t, dich vi, dich rue)t...
+ Tac dung khac: khi dung lieu nlt cao va tiem vao dQng mach c6 tac
dung gay te yeu, khang histamin nhe, phong he he N nhung khong
dang k~.
Chi dinh.
Nho mat gay gian d6ng tl'i d~ soi day mat, do khuc xa mat dtre lac.
Dau do co that da day, ruot, duong mat, duong nieu. Hen phe' quan,
Tien me.
Phong chong non khi di tau xe. B~nh Parkinson.
Nghen nhi that va cham nhip tim do cuong phe' vi. NgQ dQcthuoc kich thich cholinergic.
Ttic dung khong mong muon
Thuong g~p la kho mieng, kh6 nu6t, khat, s6t.
Gian d6ng tir,mat kha nang dieu tiet cua mat va tang nhan ap.
Twin hoan: nhip tim nhanh, danh trong nguc,
Th~n kinh: d~ hi kich thich, hoang tudng, hil~n.
Tiet nieu: hi ti~u.
Tieu h6a: giam nhu dong ruot, gay tao h6n.
Chong chi dinh
Tang nhan ap.
Bi ti~u do phi d:;lituyen tien li~t. Li~t rUQt, h~p mon vi va nhuQc cd.
Che'phdm va lieu dung
- Cheph~m:
Vien nen 0,25mg.
Dung dich tiem 0,25/ mL va 0,5mg/ mL va Img/ mL. Dung dich nho m~t 1%.
- Lieu dung:
Thong thudng u6ng ho~c tiem duoi da, tiem h~p 0,5- Img/ 24h.
Lieu t6i da tiem duoi da Img/ l~n, 2mg/ 24h; u6ng 2mg/ l~n, 3mg/ 24h
5.1.1.2. Scopolamin Ngu{Jngoc
La alcaloid trong mot so cay ho Ca.
Tae dl;lng
Scopolamin co 2 tac dung chinh:
- Tren than kinh thuc vat: scopolamin co tac dung tuong tu atropin nhung yeuhon va thoi gian tac dung ngan hen. Tac dung manh nhat la tren milt, bai tiet dich (xem them atropin).
- Tren than kinh trung uong: co tac dung an than (nguoc vdi tac dung cua atropin).
Chidinh. (tuong tu atropin) B~nh Parkinson.
Tign me.
Nho mat d~ soi day milt. Lam thuoc chong say tau xe.
5.1.2. Cae dan xuiit tong h!/p Hom atropin
La thuoc t6ng hop, co tac dung tuong tu atropin nhung nhanh va ngan hen (tac dung keo dai 24 gio),
Homatropin thuong dung thay the atropin d~ gay gian d6ng til, liet th~ mi. Dung dung dich nho milt 2- 5%.
Ngoai ra, con dung lam thuoc giam dau, chong co that co tron tieu hoa.
Cae thudc ehu yeu gay giiin dong tit
Cyclopentolat (Cyclogyl), tropicamid (Mydriacyl), tac dung tren d6ng til cua 2 thuoc nay ng!ln hdn atropin va homatropin. Thdi gian tilc d\lng cua cyclopentolat tit2- 12 gid, cua tropicamid tit30 phlit - 4 gid.
Thuoc ehu yeu lam giam tiet dieh
Cac thuoc nay tac d\lng chu yeu tren MI,lam giam tiet dich vi nen co tac d\lng digu tri loet d~ day ta trang va dl,1phong tai phat.
- Methanthelin (Banthin): lieu 50- 100mg,tac d\lllg duy tri duQC6 gid.Vien nen 50mg. Ligu dUng 15mgtilc dl,lIlgduy tri duQc6 gid.Vien nen 7,5 va 15mg. - Pirenzepin: kh6ng gay tilc d9ng len th~n kinh trung udng, it gay kh6
mi~ng va roi lo~n thi giac.
- Telenzepin: tac d\lng m~nh hdn pirenzepin tit4- 10 l~n.
Thuoc chit yeu die'u triParkinson
Benztropin (Cogentyl),trihexyphenidyl (Artane), biperiden.
Thuoc chit yeu chong cothiit co tran
Dycyclomin(Bentyl), oxybutylin (Ditropan).
5.2. Thuoc uc che' h~ nicotinic (h~ N)
5.2.1. Thuoc itc che' hf N dh.qch. (Thuoc liet hach, phong be'hach) Duac d{3ng hoc
La cac chat tflng hQP,co cau true la amin b~c 3 va 4 nen hap thu kern va cham qua duong tieu hoa. Thuoc thuong dung duong tiern. Bi chuyen hoa va thai tru nhanh ra khoi co th~.
Tacdung
Cac thuoc liet hach co tac d\lng tranh chap vdi acetylcholin tai receptor nicotinic a mang sau synap cua hach thuc vat lam ngan can d~n truyen xung dong than kinh til sci tien hach sang sci hau hach. Do do giam cac chuc nang thuc vat. Ngoai ra, thuoc con uc che nhe h~ N a ban van d9ng co xuong, ga.y gian co nhe. Tac dung tuy thu9C vao sl! phan bo cac h~ch giao cam va pho giao cam tren cac cd quan tfl chilc (bang 4.5).
Bang 4.5. Tomtat tac dl,lng clla thuoc phong beh~ch
CCIquan H~eo LnJthe Tae dl,mg
Ti~u d9n9 m~ch Giao cam Gian m~ch, h~ huyet ap
TInh m~ch Giao cam Gian m~ch, U tr~ tuan hoan, giam cung IlIgng tim.
Tim Ph6 giao cam Hmg nhip, tang suc co b6p tim
80ng tlt Ph6 giao cam Gian
Co mi Ph6 giao cam Li~t th~ mi
Tieu h6a Ph6 giao cam Giam trllcsng h,tc,giam nhu d9n9
Bang quang Ph6 giao cam Co bang quang, gay bf ti~u
Tuyen tiet Ph6 giao cam Giam tiet, kh6 mi~ng
Tuyen mo hoi Giao cam Giam tiet
Chi dinh
- Cdn tang huye't ap cap ho~c dung h~ huye't ap co ki~m soat trong ph~u thu~t. Cac trtidng hQptang huye't ap thong thtidng hi~n nay rat it dung. - Phu phfli cap (do co kha nang lam giam ap suat cua ph6i).
Ttic dung khong mong muon
Tren than kinh thuc v~t: r6i loan thi giac, liet cq mi, kho mieng, tao b6n, liet ruot, bi ti~u, ha huyet ap the' dung.
Tren than kinh trung uong: gay kich thich, hung cam, run, hi l~n, co giat, Khi qua lieu, dung cac thuoc kich thich adrenergic d~ giai d9C.
Cac thuoc va lieu dung
- Tetraetylamoni (TEA): 0,25- 0,5g/ Ian, 1- 2 lllni 24h, tiem blip. - Hexamethonium:
Tac dung manh hon TEA khoang lu- 20 Ian.
Uong 0,19/Ian, 3- 4 llln/ 24h. Tiem duci da, blip 20mg/ Ian, 1-2 lllni 24h. - Trimethaphan camsylat (Arfonat):
Tac dung manh hon TEA khoang 30 llln nhung ngan. Lieu dung: truyen tinh mach 0,1- 0,2 mgt kg/ 24h.
- Mecamylamin (lnuersine): Khdi dau 2,5mg/llln, 2l11nl24hsau d6 dieu chinh lieu theo dap ung cua nguoi benh.
- Cac thuoc khac: pentolinium, azamethonium, trimetinidium tuong tu TEA.
5.2.2. Thuoc ztc che' he N aco van (Thu6C mem. co, cura) 5.2.2.1. fJ(ic diem chung
Ngu6ngoc
v«ban chat h6a hQC,thuoc mem co deu la cac hop chat c6 chua nito, trong d6 c6 tac d\lng mli\nh nhat la h<;lpchat chua nitd b~c 4. Chung dU<;ICgQi ten chung la cac chat cura.
DUlJcdi)ng h(}c
Cac thu6c c6 cau truc amin b~c 4 nen kh6 hap thu qua dUdng tieu h6a, kh6 qua hang rao mau nao, thudng dung tiem tlnh mli\ch.
Cac thu6c c6 cau truc amin b~c 2, b~c 3 hap thu dU<;ICqua niem mli\ctieu h6a nen c6 th~ dung dUdng u6ng hol)c tiem (mellictin, condenphin). Trong cd th~ dU<;ICchuy~n h6a va thai tru chu ye'u qua nuoc ti~u.
Tac dung
Cac thu6c mem cd c6 tac d\lng phong be' h~ N d cd xUdng, lam ngung d~n truyen xung d9ng thlln kinh qua synap thlln kinh -cd d~n toi gian va mem cd
xudng. Ngoai tac d\lng gian mem Cd, thu6c con c6 tac d\lng phong be' h~ch thl,iC v~t nhung ye'u.
Tac d\lng gian mem cd khong xuat hi~n d6ng thdi rna theo m9t trinh tl,i nhat dinh va muc d9 mem cd ph\).thuQc vao lieu dung. Thong thudng, cac nh6m
co van d9ng tinh te'mem truce r5i de'n nhom co tho so: dllu tien co c6 gay, co mat (guc dau, S\lP mi mat, tr~ ham dudi, gian thanh quan) tie'p de'n nh6m co chi
(co tay, chan) r5i co than (co lung, bung, co gian suon cu6i cung la co hoanh).• ?
Khi co gian suon va co hoanh bi mern, benh nhan mat kha nang ho hap co the
tii vong. Thu tu phuc h5i theo chieu nguoc lai.
Chi dinh.
Tien me.
Co giat do u6n van, ng9 d9Cstrychnin, rna tien, s6c dien, Trang thai tang truong lucco,
Phiin loai
- Dua vao nguon goc, chia 2 loai:
Cac chat cura tu nhien: tubocurarin, mellictin, codenphin . Cac cura t6ng hop: galla min, suxamethonium, decameton . - Dua vao co che, chia 2 loai:
Cura chong' khu cue: tubocurarin, dimethyltubocurarin, gallamin ...
Cura gay khu cue lau ben: suxamethonium, decameton ...
Trong lam sang, phan loai dua vao co che'tac d\lng giup cho vi~c ll;iach9n thu6c d~ dang hdn.
5.2.2.2. Cura chong khli qtc
Tubocurarin
La alcaloid lay til cayCondrodendron tomentosum va m9t s610aistrichnos
co tac d\lng keo dai.
Tac dlfng va ed ehe'
Tubocurarin tranh chap voi acetylcholin tren h~ N d ban v~n d9ng cd xUdng,lam cho ban v~n d9ng khong khii cl;icdUQc,gay gian mem cd.
Thu6c co tac d\lng hi~p d5ng voi thu6c gay me, thu6c an thlln gay ngu. Khi qua lieu tubocurarin va cac thu6c cung nhom, co th~ giai d9Cb~ng cac thu6c khang cholinesterase nhu neostigmin.
Chi dinh
DUQcdung lam thu6c mem cd trong ph~u thu~t. Tang trudng ll;iCcd, tang v~n d9ng.
Tae dlfng khong mong muon
Gay co thllt khi phe' quan va hl;l.huye't ap do tang giru phong histamin.Vi v~y, nen dUngkhang histamin truOckhidUngtubocurarin va cac thuoc trong nhom.
Lieu dung
Lieu dung:6- 10mg tiem tinh mach, sau do dung tie'pneu thay can,
Cac thuoc khac
- Dimethyltubocurarin: la d~n chat methyl hoa cua tubocurarin co tac dung manh hon tubocurarin. Lieu dung: 2- 4mg/l~n, tiem tinh mach.
- Gallamin (Tricuran, Flaxedin): la chat t6ng hop co tile dung gay mem co ye'u hon tubocurarin 2 lan va thoi gian tac dung ngan hon, Lieu dung:
1mg/ kg tiem tinh mach.
- Mellictin: hap thu dU<;ICqua niem mac tieu hoa. Dung di~u tri tang truong luc co, tang van d9ng (h9i chung ngoai thap, liet rung ...). Lieu dung: uong' 20mg/l~n, 3 l~nI 24h, thoi gian di~u tri tit 3 tuan de'n 3 thang, Nghi 3- 4 tuan r6i dung dot maio
5.2.2.3. Cura gay khit cuelau. bin
Suxamethonium (Myorelaxin, Succinylcholin)
Duac d§ng hoc
Thuoc chu yeu dung duong tiem, Sau khi tiem tfnh mach khoang 1 phut xuat hien tac dung, duy tri khoang 10 phiit. Tac dung xuat hien sau khi tiem bl1p2- 3 phut va duy tri 10- 30 phUt. Thu5c qua dU<;ICnhau thai m9t lU<;Ingnho. Chuy~n hoa nhanh bdi cholinesterase trong huye't tudng. Thai trit chu ye'u qua nuac ti~u d~ng da chuy~n hoa.
Tcicdlfng va cd che'
La cac thu5c co tac d\lng gi5ng acetylcholin tren h~ N d ban v~n d9ng cd xudng, gay khi'i cl;icm~nh va lau b~n d~n Wi luc d~u trudng ll;iCcd hdi tang (th~m chi gay gi~t cd trong vai giay) sau do li~t cd, khong gay gian cd hoan toano
Chi djnh
Dung lam thu5c lam m~m cd trong ph~u thu~t, d~t n9i khi quan, nl1n xtidng gay...
Tcicdlfng khong mong muon
Tac d\mg khong mong mu5n co th~ g~p la m~m cd qua muc gay ch~m nhip tim, h~ huye't ap, ngiing thd. Ngoai ra, con g~p dau, cung ho~c gi~t cd khi mai dung thu5c.
Chong chi djnh
M~n cam vai thu5c. Ti~n si'is5t cao ac tinh. Glaucom goc dong.
Mdi bi bong nang hoac da chan thuong. Tang kali huyet.
cn«phdm valieu dung
Ong tiem dung dich 20,50, 100mglmL. LQthudc tiem 50mg va 100mg. Ngiroi IOn:tiem, truyen tinh mach 0,5- Img/ kg! lfuIhoac tiem blip 3-4mg!kg! lftn, tang lieu kh6ng qua 150mg.
Tre em: tiem blip 2,5mglkg, tang lieu kh6ng qua 150mg. Decameton
Tuong tu suxamethonium, nhung tac dung keo dai va d~ gay ngirng thd hen. Ngay nay it dung hon suxamethonium.