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BQYTE owe LV Hoe • • TAp! SACH f)Ao T~O DUQC SI f)~1 HQC Ma so: a.20.Y.06 ? ~ ~ Chu bien: PGS TS MAl TAT TO TS vO TH! TRAM " A' , NHA XUAT BAN Y HQC HA NQI- 2007 , ~ CHI £)~O BIEN SO~N: V~ Khoa h9C & Dim tao, B9 Y te , ~ CHU BIEN: PGS TS Mai Tat To TS vo Th! Tram NHaNG NGUeJlBIEN SO~N: PGS TS Mai Tat To TS vo Th! Tram ThS Bao Th! Vui THAM GIA TO CH(fC BAN THAo TS Nguyen Manh Pha ThS Phi van Tham © Ban quyen thuoc BQ Y te (Vu Khoa h9C va Dao tao) LOI Glen THII~U Thuc hien mot sCi dieu cua Luat Giao due, Be?Giao due & Dao tao va Be?Y te dii ban hanh chuong trinh khung dao tao Bac SI da khoa Be?Y te t6 chuc bien soan tai lieu day - hoc cac mon co sd, chuyen men va co ban chuyen nganh theo chuong trinh tren nham tung budc xay dung he?sach chuan cong tac dao tao nhan luc y teo Sach Duac If h9C - tg,p duoc bien soan dua tren chuong trinh giao due cua Truong Dai hoc DUQcHa Ne?itren co Sd chuong trinh khung dii duoc phe duyet Sach duoc cac nha giao giau kinh nghiem va tam huyet vdi cong tac dao tao bien soan theo phuong cham: Kien thuc co ban, h~ thong, ne?idung chinh xac, khoa hc; c~p nh~t cac tien be?khoa hc, ky thu~t hi~n d~i va tht;icti~n Vi~t Nam Sach Dztrjc If h9C - tg,p dii dUQcHe?id5ng chuyen mon th~m dinh sach va tai li~u d~y - hc chuyen nganh bac SI da khoa clla Be?Y te th~m dinh vao nam 2006, la tai li~u d~y - hc d~t chu~n chuyen mon clla Nganh Y te giai do~n 2006 - 2010 Trong qua trinh s11 d\lng sach phai dUQcchinh ly, b6 sung va c~p nh~t Be?Y te xin chan cam dn cac nha giao, cac chuyen gia ella Be?mon DUQcIt;ic,Trudng D~i hc DUQcHa Ne?idii danh nhieu cong sue hoan euCinsach nay; cam dn PGS TS Nguy~n Trng Thong va PGS TS Mai Phudng Mai dii dc, phan bi~n d~ cuCinsach dUQchoan chinh kip thdi ph\lc V\l cho cong tac dao t~o nhan It;icy teo L~n d~u xuat biin, chUng wi mong nh~ dUQcy kien dong gop clla d5ng nghi~p, cac b~ sinh vien va cac d9c gia d~ l~ xwlt ban sau duQchoan thi~n hdn Vl) KHOA HOC vA DAo Tft.,O BQYTE LOINOIDAU D~ dap ling muc tieu dao tao cua nganh, mQt nhiern vu quan cua nguoi duoc sl hien Ia phai bie't huang d~n si't dung thuoc hieu qua, an toan va hop IY.Duoc ly h9Cla mon h9Cnghien cuu nhiing tuong tac cua thuoc vdi co th~, da gop phan quan giup sinh vien duoc thuc hien duoc nhiern vu tren vdi muc tieu cua mon h9Cla: Cung cap nhfing kien thuc co ban, cap nhat vg duoc ly nhu: duoc dQngh9C, tac dung va co che tac dung, tac dung khong mong muon va ap dung dieu tri cua thuoc Giao trinh "Duoc ly h9C"do tap th~ can bQ-BQmon Duoc luc Truong dai h9CDuoc Ha NQibien so~n Chllyeu dung lam tai li~u h9Ct~p cho sinh viEmduqc nam thli ba, thli tu Ngoai ra, no ciing co th~ la tai li~u tham khao cho cac dQc gia quan tam Sach duqc chia hai t~p tudng dUdng vai hai h9Cph~n clla mon h9C T~p g6m Chllyeu phfin duqc ly d~i cudng va co them hai chudng: thu6c tac d\lng tren h~ thfin kinh th\iC v~t va thu6c tac d\lng tren h~ thfin kinh trung udng T~p g6m cac chudng: thu5c tac d\lng tren cac cd quan, nhom thu6c hoa tri li~u, ngQdQCva giai dQcthu6c Cac thu6c duqc trinh bay theo nhom vg cac di~m cd ban clla duqc dQng h9C, tac d\lng, cd che tac d\lng, nhung tac d\lng khong mong mu6n va ap d\lng digu trio Trong tung nhom, chung toi giai thi~u mQtso'thu6c d~i di~n ciing theo nQidung tren Do buac dfiu bien so~n nen du da co nhigu c5 g:1ng,song ch:1cch:1nkhong tranh khoi nhung thieu sot Chung Wirat mong nh~n duqc s\i chi'bao, gop y clla cac d6ng nghi~p va dQcgia d~ b5 sung, si'ta d5i cho nhung lfin bien so~n sau XIN TRAN TRQNG CAM ON cAc rAcGIA MUC LUC Lei gidi thieu Lei noi d~u Mdd~u Doi tuong man h9C Vi tri man hoc 10 Chu'dng Hap thu, phan bo, chuyen hoa, thai trir va dUQCdQng h9Cco ban 11 Hilp thu (absorption) 12 Phan bo (distribution) 22 Chuyen hoa (metabolism) 25 Thai tru (elimination) 32 Chu'dng Tac dung cua thuoc 40 MQt so khai niern 40 Co che tac dung cua thuoc 42 Cac ye'u to anh hudng de'n tac dung cua thuoc 47 Phan ling bilt loi cua thuoc (adverse drug reaction- ADR) 66 Chuong Thuoc tac dung tren h~ than kinh trung uong 71 D~i cuong 71 Cac chilt trung gian dftn truyen cua h~ than kinh trung uong 71 Kenh ion 74 Cac nhom thuoc tac dung tren he than kinh trung uong 74 Thuoc gay me 75 D~i cuong 75 ThuOc gay me duong' hf hap 77 Thuoc gay me duong tinh mach 83 'I'huec gay te 87 D~i cuong 87 Thu5c gay te co cau true ester 89 ThuOc gay te co cilu truc amid 91 ThuOc gay te co cilu true khac 93 Thuoc an th~n - gay ngU 94 D~i cudng 94 Dftn xuilt ella acid barbituric 95 Dftn xuilt benzodiazepin 99 Cae dftn xuilt khac 102 Thu6c giam dau trung uong Dliticubng 105 Thu6c ehu van tren receptor opioid Thu5c chu van - d6i khang h6n hop va chu v~n tung phan Thu6c d6i khang don thuan tren receptor opioid Thu6c chong dQng kinh Dliticuong Cac thu6c chong dQng kinh Thu6c kich thich than kinh trung uong Dliticuong Thu6c tac dung uu tien tren vo nao Thu6c kich thich uu tien tren hanh nao Thu6c tac dung uu tien tren s6ng Thu6c dieu tri r6i loan tam than Thu6c uc che tam than Dliticuong D~n xuat phenothiazin D~n xuat butyrophenon D~n xuat benz amid Cac thuoc khac Thu5c chong tram cam Dliticuong Thu6c uc che monoamin oxydase (IMAO) Thu6c chong tram cam ba vong Thu6c uc che chQn IQcthu h6i serotonin Thu6c ch6ng trftm cam khac Thu6c dieu hoa h0litt d9ng tam thftn Chu'dng Thu6c tac d1,lngtren h~ thftn kinh tht;tc v~t Dlitictidng Thu6c kich thich h~ adrenergic (Thu6c Ctidng giao cam) Thu6c uc che h~ adrenergic (Thu6c huy giao cam) Thu5c kich thich h~ cholinergic (Thu6c Ctidng giao cam) 105 107 114 116 117 117 118 126 126 127 128 130 132 132 132 133 135 137 138 140 140 140 142 144 145 147 149 149 162 172 180 M1,lc11,lctra cuu theo ten thu5c Tai li~u tham khao 195 199 ? ~ MOflAU DOl Tu'QNG MON HQC DUQcly h9C (pharmacology) la mon h9C nghien cuu ve su tac dong' gifia thuoc va co th~ Khi thuoc vao co th~, thuoc duoc co th~ tiep nhan nhu the nao va co th~ da phan ung dudi UtCdung cua thuoc 8\1 tac dong qua lai giua thuoc va co th~ da giup duoc ly h9C chia phan ro ret: - DUQcd9ng hoc (pharmacokinetics): nghien cuu ve su tiep nhan cua co th~ doi vdi thuoc, D6 la d9ng h9C cua su hap thu (absorption), phan phdi (distribution), chuyen h6a (metabolism) va thai tru (elimination) Cac kien thuc ve duoc d9ng hoc giup cho thay thuoc biet each dung thuoc hop ly, hieu qua (duong dua thudc vao co th~, lieu dung mot lan, lieu dung va dQt dieu tri ) - DUQcl\1Ch9C (pharmacodynamics): nghien cuu ve s\1 tac d9ng clla thuoc doi vai cd th~ sinh v~t Thuoc c6 th~ tac d9ng tren cac t6 chuc, cd quan holitc h~ thong clla cd th~ theo cac cd che khac d~ cho hi~u qua dieu tri (dieu chinh dUQCqua trinh sinh ly b~nh qua trinh sinh ly) holitc th~ hi~n cac tac dVng khong mong muon DUQcly h9C la m9t c~m nang cho cac th~y thuoc s11dVng thuoc va huang d~n s11dVng thuoc hi~u qua, hQp ly, an toano Ngoai ra, dUQcly h9C nghien cuu nhung v~n de chuyen sau: - DUQcly thCiikhiic (choronopharmacology): nghien cuu anh hUdng clla nhip sinh h9C (ho~t d9ng clla cd th~ bien d6i nhip nhang, c6 chu ky theo dem) Tac d9ng clla thuoc c6 th~ tang giam theo nhip nen th~y thuoc c~n biet d~ ch9n thCii di~m va lieu lUQng dung thuoc Vi dV: cortisol dUQc bai tiet tOt nh~t vao luc 8- giCisang Vi v~y c~n cho thuoc corticoid lieu b&ng t6ng lieu vao luc 8- giCisang thay vi cho l~n sang va chieu nhu truac day - Duoc ly di truyen (pharmacogenetics): nghien cuu tac d9ng cua thuoc tren nhirng benh ly mang tinh di truyen Vi du: nhfing nguoi thieu G6DP di truyen rat hay hi thieu mau tan mau dung thuoc chong sot ret - Duoc ly canh giac, goi la canh giac thuOc (pharmacovigilance): nghien ciru ve nhfmg phan ung khong mong muon cua thuoc (adverse drug reaction - ADR) xay qua trinh sli dung thuoc vdi lieu thuong dung ADRs giup cho thay thuoc canh giac cao sli dung thuoc vt TRI MON HQC Qua mot so net khai quat ve doi tuong cua mon h9C, duoc ly la mon h9C tich hop, lien quan mat thie't vdi nhfing mon y duoc khac: hoa duoc, duoc lieu, sinh h6a, giai phau- sinh ly, sinh ly benh, vi sinh, mien dich, dieu tri h9C, t6 chuc h9C 10 Chu'dng A' A A' A,? ? , "- HAP THU, PHAN BO, CHUYEN HOA, THAI TRlJ VA Dl1QC DQNG HQC CO BAN " ? Tuy theo muc dich dieu tri thuoc co th~ duqc dua vao co th~ theo cac duong' khac Du cho dung dUdng nao chang nita thuoc ciing duqc hap thu vao mau d nhirng mire de?khac nhau, sau se xay d6ng thoi hoac tuan W cac qua trinh phan be)',chuyen hoa va thai trii thuoc Cac qua trinh chiu anh hueng cua rat nhieu yeu to': cau true hoa hQCva 1y hoa tinh cua thuoc, dang bao che, duong dung, trang thai benh ly va yeu to' ca th~ ngiroi benh Co th~ trinh bay tom tiit cac qua trinh van chuyen cua thuoc co th~ theo so d6 hinh 1.1 Me Huyet Wong Nol dl,l'trlt Noi tac dl,lng Thuoc Thuoc Thuoc- receptor • Noi chuy~n h6a Chat chuy~n4-iIl-h6a -+- Chat chuy~nh6a Dl/dng khac Th~n Tieu h6a Hinh 1.1 Qua trinh vc;inehuy~n ella thuoe co th~ (theo E Singlas) 11 HAP THU (Absorption) Hap thu la su xam nhap cua thuoc vao vong twin hoan chung cua co th~ D~ co th~ xam nhap vao vong tuan hoan chung, ph an b6 de'n cac t6 chuc va thai tru, thuoc phai vuot qua cac mang sinh hoc cua cac t6 chuc khac theo cac phuong thuc van chuyen khac 1.1 V~n chuyen thuoc qua mang sinh hoc Co nhieu loai mang te' bao khac nhung chung dgu co nhfing thuoc tinh va chuc nang co ban giong Mang te' bao rat mong, co bg day til 7,5 de'n 10nm, co tinh dan h6i va co tinh tham chon loc, Thanh phan co ban cua mang la protein va lipid Mang duoc chia ldp; hai ldp ngoai g6m cac phan til protein va mot so' enzym, d~c biet la enzym phosphatase; ldp giira g6m cac phan til phospholipid Chinh ban chat lipid cua mang da can trd s\i khue'ch tan qua mang clla chat tan nUDCnhu glucose, cac ion v.v Nguc;1cl:;ticac chat tan lipid d~ dang chuy~n qua mango Do d~c di~m cau truc clla cac ph an til protein da t:;tothanh cac kenh (canal) chua d~y nUDcxuyen qua mango Qua cac 6ng cac chat tan nUDCco phan til nhi) d~ dang khue'ch tan qua mango So b9 vg cau truc clla mang duc;1C trinh bay d hinh 1.2 Hinh 1.2 Cau true eua mang [10] Px: protein xuyen Pr: protein ria 1.1.1 Khue'ch tan thl;l d(jng (passive diffusion) Khue'ch tan thl,1 d9ng can gQi la khue'ch tan don thu~n ho~c la s\i tham (permeation) la qua trinh thu6c khue'ch tan til noi co n6ng d9 cao de'n noi co n6ng d9 thap Muc d9 va t6e d9 khue'eh tan ty l~ thu~n vDi s\i ehenh l~eh vg n6ng d9 thu6e giua hai ben mang, di~n tieh bg m~t ella mang, h~ s5 khue'eh tan ella thu6e va ty l~ nghieh VDibg day ella mango 12