Phenothiazine derivatives yog ib pab pawg tseem ceeb tshaj plaws ntawm cov tshuaj hauv cov tshuaj niaj hnub no, siv los kho mob hlwb thiab lwm yam kab mob. Kev tshawb pom ntawm cov teebmeem neuroleptic thiab antipsychotic tau ua los ntawm lub sijhawm, thaum lub sijhawm tsim cov tshuaj antiallergic. Ntxiv nrog rau cov khoom tseem ceeb, lawv muaj ntau yam cuam tshuam rau tib neeg lub cev, uas feem ntau nyob ntawm cov qauv tshuaj ntawm cov tebchaw.
Kev piav qhia dav dav
Phenotiazine derivatives yog cov neeg sawv cev tseem ceeb ntawm cov tshuaj tiv thaiv niaj hnub no. Phenothiazine, los ntawm cov tshuaj ntawm pawg tshuaj no yog synthesized, yav tas los siv nyob rau hauv cov tshuaj raws li ib tug anthelmintic thiab antiseptic tshuaj, tab sis tam sim no nws tau poob nws qhov tseem ceeb. Tam sim no nws yog siv nyob rau hauv kev ua liaj ua teb raws li ib tug insecticidal thiab anthelmintic neeg sawv cev. Cov tshuaj no tsis muaj kev puas siab puas ntsws lossis neurotropic.
Xyoo 1945, Fabkis cov kws tshawb fawb pom tias thaum N-dialkylaminoalkyl radicals tau nkag mus rau hauv nws cov qauv.koj tuaj yeem tau txais cov tshuaj tiv thaiv kev puas siab puas ntsws.
Feem ntau, cov qauv tshuaj ntawm neuroleptic derivatives tuaj yeem sawv cev raws li hauv qab no:
Pharmacological action
Ntawm cov phenothiazine derivatives, cov tshuaj tau txais uas muaj cov nyhuv hauv qab no:
- tshuaj tiv thaiv kab mob;
- antispasmodic;
- tshuaj tiv thaiv kab mob;
- sedative;
- tshuaj tiv thaiv kev nyuaj siab;
- hypothermic (qis hauv lub cev kub);
- antiarrhythmic;
- vasodilating;
- antiemetic;
- nce kev ua haujlwm ntawm lwm yam tshuaj: tshuaj tua kab mob, tshuaj tiv thaiv kab mob thiab tshuaj tsaug zog.
Y
Vim qhov mob me me ntawm cov nyhuv sedative, cov tshuaj no hu ua tranquilizers (los ntawm Latin tran-quillns - ntsiag to, calm). Nrog rau txoj kev loj hlob ntawm cov txhais tau tias ntawm pab pawg no, cov kws kho mob muaj lub sijhawm los cuam tshuam cov txheej txheem kev puas siab puas ntsws ntawm ib tug neeg. Lub luag haujlwm tseem ceeb ntawm lawv qhov kev ua haujlwm yog txhawm rau thaiv cov nyhuv ntawm adrenaline ntawm kev tsim cov hlwb reticular. Lub pituitary-adrenal cortex system tau koom nrog hauv cov txheej txheem no.
thawj cov tshuaj siv dav yog Aminazine. 10 xyoo tom qab nws tau txais, nws twb siv li ntawm 50 lab tus tib neeg. Nyob rau hauv tag nrho, kwv yees li 5000 phenothiazine derivatives tau raug synthesized. Ntawm cov no, kwv yees li plaub caug tau nquag siv hauv kev kho mob.
Teb ntawm daim ntawv thov ntawm neuroleptics - phenothiazine derivatives
tshuaj tiv thaiv kab mob yog siv rau cov kab mob hauv qab no:
- Mental disorders: schizophrenia; neurasthenia; delirium, hallucinations; neuroses; insomnia; kev ntxhov siab thiab ntshai; kev ntxhov siab; nce excitability; delirium tremens thiab lwm yam.
- Vestibular disorders.
- Kev phais: raws li kev siv tshuaj loog ua ke.
Qee cov tshuaj muaj cov cuab yeej tiv thaiv kev puas siab puas ntsws ntau dua, thaum lwm tus yog cov tshuaj tiv thaiv kev puas siab puas ntsws. Phenothiazine derivatives ntawm aliphatic thiab piperazine series ua ke ua ke antipsychotic kev ua si (tshem tawm ntawm delirium, automatisms) thiab cov nyhuv sedative.
Lub cev thiab tshuaj lom neeg
Cov khoom tseem ceeb ntawm cov tebchaw no yog:
- Pom - Dawb crystalline hmoov (qee creamy), tsw tsw.
- Hygroscopicity (absorb noo ntawm huab cua).
- zoo solubility hauv dej, cawv, chloroform. Cov tebchaw yog insoluble hauv ether thiab benzene.
- nrawm oxidation. Hauv qhov no, ib qho radical tuaj yeem raug cais tawm, sulfoxides, nitric acid thiab lwm yam tshuaj raug tsim. Cov txheej txheem yog nrawm los ntawm kev txiav txim ntawm lub teeb. Hauv chemistry, sulfuric acid, poov tshuaj bromate los yog iodate, bromine dej, hydrogen peroxide, chloramine thiab lwm yam reagents yog siv los oxidize cov compounds.
- Oxidation khoom ntawm derivatives dissolve zoo nyob rau hauvorganic kuab tshuaj. Lawv pleev xim rau hauv cov xim ci (liab-liab, daj-liab, lilac). Cov cuab yeej no yog siv los txheeb xyuas thiab txheeb xyuas cov tshuaj phenothiazine nrog rau lawv cov metabolites hauv ntau lub cev kua.
- Kev tshwm sim ntawm cov khoom tseem ceeb. Thaum reacted nrog acids, lawv tsim cov ntsev uas muaj tib solubility zog.
- Nyob rau hauv lub teeb, cov tshuaj no thiab lawv cov kev daws tej zaum yuav tau ib tug pinkish xim.
Phenothiazine derivatives tsis tshwm sim hauv cov xwm txheej. Lawv tau txais synthetically los ntawm extraction nrog cov kuab tshuaj organic los ntawm alkaline aqueous daws. Cov tshuaj muab khaws cia rau hauv qhov chaw qhuav, tsaus, kaw nruj (kom tiv thaiv oxidation).
YPharmacokinetics
Neuroleptics, phenothiazine derivatives, yog absorbed rau hauv cov ntshav feem ntau hauv cov hnyuv. Txij li thaum lawv yog hydrophobic nyob rau hauv cov xwm, qhov no pab txhawb lawv kev sib raug zoo nrog cov proteins. Lawv feem ntau nyob hauv lub hlwb, daim siab thiab lub raum.
Kev tso tawm ntawm phenothiazine derivatives tshwm sim hauv cov zis thiab ib nrab hauv cov quav. Hauv cov zis, lawv raug kuaj pom tsuas yog hauv daim ntawv ntawm cov metabolites, uas tuaj yeem ua tau ntau lub kaum ob hom thaum noj cov tshuaj. Kev hloov pauv lom neeg ntawm cov tshuaj no hauv tib neeg lub cev tshwm sim raws li cov kev xav hauv qab no:
- oxidation, tsim ntawm sulfoxides, sulfones;
- demethylation;
- aromatic hydroxylation.
Toxicology
Raws li nrog rau lwm yam tshuaj psychotropic, sab thiab tshuaj lom kuj tshwm sim hauv phenothiazine derivatives. Hauv toxicological chemistry, ntau cov tshuaj lom tau piav qhia, uas feem ntau tshwm sim thaum ua ke nrog lwm yam tshuaj (cov tshuaj tua kab mob, insulin, barbiturates, thiab lwm yam). Kev noj cov tshuaj no ntau zaus tuaj yeem ua rau tuag taus.
Cov tshuaj no tuaj yeem sib sau hauv tib neeg lub cev. Cov koob tshuaj kho tau raug tso tawm maj mam (piv txwv li, "Aminazine" ntawm koob tshuaj 50 mg / hnub yog tawm hauv 3 lub lis piam). Qhov xwm txheej ntawm kev lom nrog tshuaj nrog phenothiazine derivatives nyob ntawm hnub nyoog, poj niam txiv neej, koob tshuaj thiab tsis muaj cov tsos mob tshwj xeeb. Tom qab kev tuag, cov tshuaj no thiab lawv cov metabolites tuaj yeem nyob hauv tib neeg lub cev rau 3 lub hlis. Kev kuaj mob ntawm cov neeg mob lom yog ua los ntawm kev tshawb fawb cov zis thiab ntshav.
Kev txiav txim siab ntau ntawm cov txiaj ntsig yog ua los ntawm ntau txoj hauv kev:
- acid-base titration;
- cerimetry (redox titration nrog cerium);
- spectrophotometric method (siv los tshuaj xyuas cov tshuaj uas tsim los ntawm lub Hoobkas);
- Kjeldahl method;
- iodometry;
- photocolorimetric method;
- gravimetry;
- indirect complexometric titration.
Kev faib tawm
Los ntawm qhov xwm txheej ntawm cov tshuaj siv tshuaj, 2 pawg tseem ceeb ntawm cov tshuaj no txawv:
- 10-alkyl derivatives (neuroleptic, sedative thiab antiallergiceffect);
- 10-acyl derivatives (siv hauv kev kho cov kab mob plawv).
Cov phenothiazine alkyl derivatives suav nrog "Promazin", "Promethazine", "Chlorpromazine", "Levomepromazine", "Trifluoperazine". Lawv muaj ib pab pawg lipophilic nrog tertiary nitrogen nyob rau hauv txoj hauj lwm 10 (saib daim duab qhia saum toj no). Cov acyl-derivatives muaj xws li "Moracizin", "Etacizin", uas muaj ib pawg carboxyl nyob rau hauv cov qauv ntawm active molecules.
Tseem muaj lwm qhov kev faib tawm - raws li qhov xwm txheej ntawm cov radicals ntawm nitrogen atoms. Cov yam ntxwv sib piv ntawm qhov kev txiav txim ntawm phenothiazine derivatives thiab lawv cov kev faib tawm ntawm lub hauv paus no yog muab rau hauv cov lus hauv qab no.
| Group of derivatives | Main pharmacological nyhuv | Tus Neeg Sawv Cev Zoo | Frequency of side effects |
| Aliphatic | Mild antipsychotic thiab sedative | YChlorpromazine | Nyob zoo ib tsoom phooj ywg |
| Piperazines | Muaj tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob nruab nrab, ua kom | YTrifluoperazine | High |
| Piperidine | Maj tshuaj tiv thaiv kab mob, sedative, tiv thaiv kev ntxhov siab, kev coj tus cwj pwm zoo | YThioridazine | qis |
Ntawm cov tshuaj tiam tshiab yog cov hauv qab no:
- tshuaj tiv thaiv kev nyuaj siab ("Ftorocyzine");
- txhais tau tias nthuav cov hlab ntsha ("Nonachlazine");
- tshuaj tiv thaiv kab mob ("Etacizin", "Etmozin");
- antiemetic ("Thiethylperazine").
Aliphatic derivatives
Aliphatic phenothiazine derivatives suav nrog tshuaj xws li:
- Chlorpromazine hydrochloride (cov npe lag luam yog Largactyl, Aminazine, Plegomazine).
- Levomepromazine ("Methotrimeprazine", "Tisercin", "Nozinan").
- Alimemazine ("Teralen", "Teraligen").
- Piportil ("Pipothiazine").
- Propazin ("Promazin").
Ib qho tshuaj siv dav hauv pab pawg no yog Chlorpromazine. Nws muaj cov nyhuv hauv qab no:
- tshuaj tiv thaiv kev puas siab puas ntsws (txo qis kev xav, hnov lus hauv cov neeg mob schizophrenia, txo qis aggressiveness);
- sedative (tawm ntawm kev cuam tshuam, txo qis kev ua lub cev, tshem tawm kev puas siab puas ntsws);
- tshuaj tsaug zog (hauv koob tshuaj ntau);
- anxiolytic (txo kev ntshai, ntxhov siab, ntxhov siab);
- antiemetic (qee zaum siv los tswj ntuav hnyav);
- antiallergic (thaiv cov tshuaj histamine);
- muscle relaxant (socov leeg);
- hypothermic (txo qis hauv lub cev kub vim kev cuam tshuam ntawm qhov chaw thermoregulatory hauv hypothalamus);
- nce ntxiv tshuaj loog, tshuaj tsaug zog thiab lwm yam tshuaj uas ua rau lub hauv siab hauv nruab siab.
YPiperazine derivatives
Piperazine phenothiazine derivatives suav nrog:
- Meterazine.
- Fluphenazine hydrochloride ("Fluphenazine", "Fluphenazine", "Moditen").
- Etalerazine.
- Fluphenazine-decanoate ("Moditen-depot").
- Majeptil.
- Trifluoperazine hydrochloride ("Triftazine", "Stelazine").
- Methophenazate ("Frenolon").
YProchlorperazine.
YThioproperazine.
Perphenazine.
Cov tshuaj no muaj zog dua li cov tshuaj tiv thaiv kev puas siab puas ntsws, tab sis lawv kuj ua rau muaj kev phiv ntau dua (kev mob tsis zoo ntxiv). Frenolon muaj tsawg kawg ntawm cov teeb meem no.
Trifluoperazine yog ib qho tshuaj tiv thaiv kab mob los ntawm pawg phenothiazine derivatives. Nws muaj cov txiaj ntsig zoo hauv kev kho mob hlwb ntau dua li Chlorpromazine. Kev txiav txim siab sedative thiab adrenoblocking yog txo. Perphenazine thiab trifluoperazine feem ntau yog siv los ua cov tshuaj tiv thaiv zoo hauv cov kab mob tshwm sim los ntawm hluav taws xob raug. Moditen-depot yog tus cwj pwm los ntawm kev ua haujlwm ntev dua li lwm cov tshuaj ntawm pab pawg no (cov nyhuv kho tau ntev li 1-2 lub lis piam).
YPipedine derivatives
Piperidine pawgphenothiazine derivatives suav nrog cov tshuaj hauv qab no:
YThioridazine (Sonapax).
YThiodazine.
Cov tshuaj no tsis tshua muaj zog thiab muaj kev phiv tsawg. Lawv muaj ib tug zoo sedative nyhuv tsis tsaug zog. Vim lawv txoj kev nyab xeeb ntau dua, lawv feem ntau raug muab rau cov neeg mob laus. Txawm li cas los xij, thaum noj cov koob tshuaj ntau, lawv tuaj yeem ua rau cov teebmeem cardiotoxic thiab kev puas tsuaj ntawm retina. Pipothiazine muaj cov nyhuv ntev rau ib hlis, yog li nws yog siv los kho cov kev puas siab puas ntsws loj hauv cov chaw kho mob sab nraud.
Contraindications thiab overdose
Contraindications hais txog kev siv cov tshuaj tiv thaiv kab mob ib txwm muaj ntawm txhua ntawm peb pawg uas tau teev tseg saum toj no tau qhia hauv cov lus:
| Drug name | Kev txwv | Ntau tshaj |
| Y"Chlorpromazine" |
1. Lub sijhawm cev xeeb tub thiab pub niam mis. 2. Individual intolerance rau lub Cheebtsam. 3. Coma, CNS kev nyuaj siab. 4. Mob siab lossis raum tsis ua haujlwm. 5. Cholelithiasis thiab urolithiasis. 6. Mob cerebrovascular raug mob thiab mob hlwb nyob rau lub sij hawm mob. 7. Txo kev tsim cov thyroid hormones. 8. Lub plawv tsis ua hauj lwm nyob rau theem ntawm decompensation, mob plawv pathologiesvascular system. 9. Thromboembolism, kab mob ntshav. 10. Ulcerative lesions ntawm gastrointestinal ib ntsuj av (thaum lub sij hawm mob). 11. Angle-close glaucoma. 12. Cov me nyuam hnub nyoog txog 1 xyoos. |
Neuroleptic Syndrome (cov leeg mob siab, mob hlwb, ua npaws), hypotension, toxic siab puas, hypothermia |
| "Trifluoperazine" |
1. Pp. 1-4, 8, 9 ntawm kev kho yav dhau los. 2. Cov menyuam yaus hnub nyoog qis dua 3 xyoos. |
Hypotension, arrhythmia, tachycardia, cuam tshuam hauv kev pom kev pom thiab rov qab, poob siab, convulsions, disorientation, ua pa nyuaj siab, nyob tsis tswm, hypothermia, pupillary dilation. |
| Y"Thioridazine" |
1. Pp. 1-4, 6, 8, 12 (saib "Chlorpromazine"). 2. Tus kab mob Porphyrin. 3. Kev nyuaj siab. 4. Nrog ceev faj, xaiv cov neeg mob nrog pathologies raws li kab lus. 4, 7, 10, 11 (saib "Chlorpromazine"), nrog rau kev haus cawv, mob qog noj ntshav, prostatic hyperplasia, qaug dab peg, ua tsis taus pa ua pa, Reye's syndrome thiab laus laus. |
Drowsiness, tso zis teeb meem, coma, tsis meej pem, qhov ncauj qhuav, hypotension, convulsions, ua pa nyuaj siab. |
Side effects
Feem ntau phenothiazine-raws li neuroleptics yog "tseem ceeb" hais txog cov kev mob tshwm sim, uas yog, lawv ua rau muaj kev cuam tshuam extrapyramidal (cov cim qhiaParkinsonism):
- nce nqaij pob txha;
- tremor;
- lub cev muaj zog retardation (slowdown ntawm nquag txav);
- daim npog ntsej muag, tsis tshua pom kev;
- khov hauv ib txoj haujlwm thiab lwm cov tsos mob uas maj mam nce.
Phenothiazine antipsychotics ua rau cov kev mob tshwm sim hauv qab no:
- kev tsis sib haum xeeb hauv qhov chaw;
- ua xua rau ntawm daim tawv nqaij thiab cov mucous daim nyias nyias, pigmentation, rhiab heev rau tshav ntuj;
- menstrual irregularity;
- galactorrhea (kev tso kua mis txawv txav los ntawm cov qog mammary, tsis cuam tshuam nrog kev pub niam mis);
- spastic contractions ntawm cov leeg ntawm lub ntsej muag thiab caj dab;
- impotence;
- mis augmentation;
- hyperthermia;
- txo qis ntshav siab thiab nws qhov hloov pauv;
- lub cev tsis muaj zog, tsis xis nyob;
- tachycardia;
- drowsy;
- txo qis ntawm cov qaub ncaug thiab cov qog ua kua, hnov qhov ncauj qhuav;
- pab plab plab motility;
- hemolytic anemia;
- tso zis tso quav.
Ntau yam tshuaj no yog hom tshuaj thaum noj mus ntev.
Kev sib tham nrog lwm yam tshuaj
Txoj kev txwv ntawm kev sib koom ua ke ntawm phenothiazine derivatives yog txuam nrog cov tshwm sim uas ua rau overdose, thiabkev mob tshwm sim. Nws tsis pom zoo kom muab lawv nrog cov tshuaj hauv qab no:
- cawv (nce sedative zog);
- tshuaj uas txo cov ntshav siab hauv ntshav siab, beta-blockers (kev txhim kho ntawm orthostatic hypotension);
- "Bromocriptine" (kev nce hauv cov concentration ntawm prolactin hauv cov ntshav, ua rau muaj kev cuam tshuam hormonal);
- tshuaj uas ua rau kev nyuaj siab rau hauv nruab nrab lub paj hlwb (anticonvulsants, narcotic painkillers, barbiturates, tshuaj tsaug zog) - tshwm sim ntawm kev nyuaj siab hnyav thiab lwm yam kev puas hlwb;
- tshuaj kho mob hyperthyroidism (overactive thyroid gland) thiab cov khoom uas muaj lithium, vim qhov no ua rau muaj kev cuam tshuam ntawm extrapyramidal thiab ua rau lawv qhov hnyav;
- anticoagulants (kev loj hlob ntawm agranulocytosis, kho mob tshwm sim nyob rau hauv daim ntawv ntawm cov kab mob nquag, ulcerative lesions ntawm mucous daim nyias nyias; nws cov teeb meem yog tshuaj lom kab mob siab, mob ntsws, necrotic enteropathy).
Yog xav paub ntxiv txog cov lus qhia, contraindications thiab phiv, saib cov lus qhia rau cov tshuaj no.
