Daawada Daawada Methotrexate ee Shilka ah ee Maalinlaha ah ee Shilka ah: Sababta Qaadashada Kiniinka Toddobaadlaha ah maalin kasta waa xaalad degdeg ah oo caafimaad¶

Methotrexate (Trexall, Rheumatrex, Otrexup, Rasuvo, Metoject) waa mid ka mid ah dawooyinka wax ka beddelka cudurrada ee ugu badan adduunka ee loogu talagalay rheumatoid arthritis-ka, psoriasis, psoriatic arthritis, lupus, iyo cudurka Crohn. Si ka duwan kaniini kasta oo kale ee ku jira golaha daawada bukaanka, daawada methotrexate ee afka laga qaato oo yar (7.5 mg to 25 mg, sida caadiga ah waxaa loo qaataa saddex ilaa toban 2.5 mg Kiniinnada jaalaha ah) ayaa loo qoray in la qaato ** hal mar todobaadkiiba hal maalin oo la doortay**. Sidaa awgeed, ** si shil ah u qaadashada daawada methotrexate-ka hal jeer hal mar maalin kasta *** - sababtoo ah calaamadda jahawareer ah ee warqad dhakhtar qoray, khaladka dib u heshiisiinta wareejinta isbitaalka, daryeel bixiyaha buuxinaya sanduuqa 7-maalmood ee kaniiniga ah si khaldan, ama hoos u dhac garasho fudud - waxaa aqoonsaday Machadka Caafimaadka Badbaadada ah ee Dhaqanka (ISMPHO), Ururka Caafimaadka Adduunka iyo Hay'adda Maraykanka ee ISMPHO Qaladaadka daawada "feejignaan sare" ee dadka waaweyn. Si ka duwan, ** liqidda hal mar oo xad dhaaf ah oo daawada methotrexate afka ah (sida ilmo ama qof weyn oo liqa labaatan 2.5 mg kaniiniyada hal mar) marar dhif ah ayay sababaan sunta daran** sababtoo ah xiidmaha bini'aadamka ee qaada folate-ka buuxa (PCFT) kaliya waxay nuugi karaan qadar xaddidan hal mar, kelyaha caafimaadka qaba ayaa inta soo hartay saacado gudahood ka soo saara. Si aad ah uga duwan, ** qaadashada xitaa 5 mg to 15 mg daawada methotrexate maalin kasta 4 ilaa 7+ maalmood oo isku xigta** waxay ilaalisaa soo-gaadhista daroogada oo joogto ah, saacad walba oo dhan wareega wareegga unugga, dabin methotrexate polyglutamates gudaha unugyada iyo kicinta* neutropenic septic shock. Xitaa si ka sii daran, ** Folic Acid (Vitamin B9) ee caadiga ah ma beddeli karo sunta methotrexate *** sababtoo ah ensaymka loo baahan yahay si uu u kiciyo folic acid (**dihydrofolate reductase, DHFR ***) waxaa si buuxda u xannibay methotrexate; Badbaadadu waxay u baahan tahay maamul degdeg ah oo isbitaal ah oo horay loo hawlgeliyay **Folinic Acid (Leucovorin / Calcium Folinate) ama Levoleucovorin **, dagaal badan ** sodium bicarbonate xididdada kaadida alkalinization , iyo, fashilka kelyaha, dib u habeynta ** Glucarpidase (Voraxaze).

Haddii adiga ama qof aad jeceshahay aad si lama filaan ah u qaadatay kiniinka methotrexate toddobaadlaha ah ** 3 ama maalmo ka badan oo isku xigta** (ama aad qaadatay qiyaasta labaad ee toddobaadlaha ah goor hore), ama haddii qof daawada methotrexate uu ku dhaco nabar afka ah oo xanuun leh, cune cayriin, qandho, nabar, ama saxaro madow, wac lambarka degdegga ah ee degaankaaga (911) gudaha Boqortooyada Midowday ee Ingiriiska iyo Kanada, 112 9 ee Midowga Yurub. nambarada degdega ah tusaha ama Xakamaynta Sunta isla markaaba, oo dib u eeg sepsis iyo shoog septic, 5-fluorouracil iyo capecitabine kiimoterabiga xad dhaafka ahiyo sumaynta gargaarka degdegga ah.

Hadda samee tan¶

1. ** JOOJI dhammaan qiyaasaha dheeraadka ah ee Methotrexate OO jooji dhammaan NSAIDs-yada iyo PPI-yada isla markiiba**: Ha qaadan kiniin kale oo methotrexate ah ama duritaan. Isla mar ahaantaana, isla markiiba qaado ** daawooyinka nonsteroid anti-inflammatory (NSAIDs: ibuprofen, naproxen, meloxicam, celecoxib, aspirin)**, proton pump inhibitors (PPI: omeprazole, pantoprazole), iyo **trimethoprim-sulfamethoxazole (Bactrim / Septra) dilid.
2. ** Aad Waaxda Gurmadka Degdegga ah ama wac Xakamaynta Sunta isla markiiba haddii daawada methotrexate la qaatay maalin kasta 3 maalmood ama ka badan oo isku xigta - XATAA HADDII QOFku 100% Fiican yahay ***: Waligaa ha sugin in ay calaamaduhu muuqdaan. Ka dib 3 ilaa 5+ maalmood oo isku xigta oo ah methotrexate maalinle ah, unugyada tarma ee dhuuxa lafta iyo xuubka mindhicirka ayaa durba si aamusan u dhimanaya, inkastoo maalinta koowaad ee tirinta dhiigga (CBC) iyo heerka methotrexate serum ay weli u muuqdaan kuwo si khiyaano leh u hooseeya ama "aan la ogaan karin." Horaantii Folinic Acid (Leucovorin) waxay bilaabantay ka hor intaanay nabarka afka iyo neutropenia soo muuqan nafo badbaadiya.
3. Waligaa ha u bedelin Folic Acid (Vitamin B9) oo aan laga soo iibsanin daawada Folinic Acid (Leucovorin)** 1 mg Kiniinnada folic acid ee farmashiyaha ma shaqayn doonaan oo kuma ilaalin doonaan. Folic acid dheef-shiid kiimikaad ahaan waa mid aan shaqayn ilaa uu beddelo ensaymka dihydrofolate reductase (DHFR) - enzyme saxda ah ee methotrexate uu xidhay. Bukaanku wuxuu u baahan yahay ** Folinic Acid (Leucovorin / Calcium Folinate / 5-formyltetrahydrofolate** ama Levoleucovorin, kaas oo si buuxda u dhaafaya enzyme-ka xannibay ee DHFR si uu dib ugu bilaabo isku-dhafka DNA-da.
4. Ka baar gudaha afka, faruuryaha, iyo ciridka si aad u ogaato goor hore "Herald Ulcers" (Oral Stomatitis / Mucositis): Sababtoo ah unugyada ku dahaaran afka iyo dhuunta waxay qaybsadaan 3 ilaa 5 maalmoodba mar, ** casaan xanuun leh, gubasho, boogaha cad ama jaalaha ah ee gudaha dhabannada, bushimaha, carrabka, ama ciridka* waa calaamadda digniinta ah ee #1. dhuuxa lafta iyo mareenka caloosha iyo mindhicirka (mucositis ayaa ka horreeya dhuuxa lafta dilaaga ah 24 ilaa 72 saacadood).
5. ** Hubi heerkulka qofka oo daaw qandho kasta (>= 38.0 C / 100.4 Fsida Sebsis Neutropenic oo nafta halis gelisa: Bukaanka qaatay daawada methotrexate ee maalinlaha ah (ama shaqadii kelyaha ay hoos u dhacday inta lagu jiro daawada methotrexate toddobaadlaha ah), qandho, qarqaryo, cune xanuun, qufac, ama jahawareer ayaa tilmaamaya ** qandho neutropenia (eber caabuq-la-dagaalanka neutrophils dhiigga unugyada cad cad)
6. **U dig dhakhtarka qolka xaaladaha degdega ah: Ha isku hallayn hal "hoos ama diidmo" Serum Methotrexate heerka dhiigga ee xad-dhaafka maalinlaha ah ee joogtada ah : Nomograms isbitaalka ee heerarka serum methotrexate (> 10 micromol/L at 24h) waxaa si adag loogu talagalay ** 24-saac oo degdeg ah faleebo faleebo oncology IV ah. In bukaan qaaday 10 mg afka maalin kasta 7 maalmood, serum heerka methotrexate waa la akhriyi karaa < 0.05 micromol/L halka ay dilaan ** polyglutamates methotrexate intracellularMTX-PGs waxay ku xiran yihiin dhuuxa lafta iyo unugyada mindhicirka taasoo keenta pancytopenia dilaa ah. ** Qiyaasta joogtada ah ee maalinlaha ah ee xad dhaafka ah waa in lagu daaweeyaa si adag Leucovorin iyadoo lagu saleynayo taariikhda iyo natiijooyinka shaybaarka iyada oo aan loo eegin heerka hoose ee heerka methotrexate serum.

Geedka go'aanka: Kala soocida hal liidnimo degdeg ah vs. Qalad qiyaaseedka subacute maalin kasta iyo sunta fashilka kelyaha¶

flowchart TD
    Start["Daawada la tuhunsan yahay ee Methotrexate (MTX) ee xad dhaafka ah, Khaladka Qaadashada, ama Sunta"] --> ClassifyType{"Qaabkee Kiliinikada Dhacay?"}

    ClassifyType -->|Pattern 1: Chronic / Subacute Daily Dosing Error (Weekly Dose Taken Daily for >= 3 Days) OR Weekly Dose + Acute Kidney Injury / Bactrim Interaction| ChronicDanger["Khatarta aadka u daran: Dabinnada Soo-gaadhista Unugyada Joogtada ah ee Methotrexate Polyglutamates (MTX-PGs) Gudaha Dhuuxa Lafta & Xadhkaha Goynta (Xusuusin: Heerka Serum MTX waxa laga yaabaa inuu u ekaado mid hooseeya/ caadi ah)"]

    ClassifyType -->|Pattern 2: Single Acute Oral Overdose in Healthy Child/Adult (e.g., Swallowed Multiple 2.5 mg Tablets All at Once)| AcuteOral["HOOS U-DHEXDHEXEEYA Khatarta Sunta Hababka: Qaadilaha Folate ee Mindhicirka (PCFT) Dheecaan ka sarreeya - 15-20 mg; Xad-dhaaf ah oo aan laga nuugin mindhicirka & si degdeg ah oo ay u nadiifiyaan kelyaha caadiga ah"]

    ClassifyType -->|Pattern 3: Massive IV / High-Dose Oncology Overdose OR Accidental Intrathecal (Spinal) Overdose| MassiveIV_IT["CATASTROPHE CAAFIMAAD: - Qiyaasta Sare ee IV + Fashilka Kelyaha -> Crystalline Nephropathy & Dhuxusha - Xad-dhaafka Xididdada -> Kiimikada Arachnoiditis ee Degdegga ah ee kor u kaca, Xaaladda Epilepticus, Kooma, Dhimasho"]

    ChronicDanger --> ImmediateWorkup["ED Workup & Ficil degdeg ah: 1. JOOJI Methotrexate, NSAIDs, PPIs, & Trimethoprim 2. Ku sawir STAT CBC oo leh Kala duwanaansho (ANC, Platelets), CMP (Creatinine, AST/ALT), & Serum MTX Heerka 3. Ka eeg Afka ee Boogaha & Neerfaha Feberaayo"]

    ImmediateWorkup --> LeucovorinStart["BADBAADINTA FOLINIC ACIID (LEUCOVORIN) (Ha sugin Heerka Serum MTX; Weligaa ha isticmaalin Folic Acid): - Qiyaasta Xad-dhaafka ah ee Joogtada ah: Leucovorin 15 mg ilaa 25 mg (ama 10-15 mg/m2) IV ama PO 6 saacadood kasta - Xanuun daran Leucovorin 100 mg/m2 (ama 100-150 mg) IV 3dii ilaa 6 saacadoodba ilaa inta dhiiga la tiriyo"]

    LeucovorinStart --> RenalSupport["Ciribtirka Kelyaha & Xidhmada Badbaadinta Dhuuxa Lafta: 1. Fuuq-baxa IV-ga daran + Soodhiyam Bicarbonate faleebooyin si loo ilaaliyo kaadida pH>= 7.5 ilaa 8.0 <1,000) + Antibiyootigyada Balaadhan ee Spectrum IV haddii Febrile 3. GLUCARPIDASE (VORAXAZE 50 Cutub/kg IV in ka badan 5 daqiiqo) haddii Dhaawac Kelyo Ba'an + Serum Joogto ah MTX (> 1-2 micromol/L)"]

    AcuteOral --> AcuteOralCare["1. Dhuxul firfircoon (1 g/kg) haddii <1-2 Saacadaha Ka-dib-u-qaadista 2. IV Fuuqbax + Hubi 6-saac & 24-saac Serum MTX Heerka, Creatinine, & CBC 50-100 mg) ama Ilmaha la qaatay> 0.5 mg/kg (ama> 10-20 mg)"]

    MassiveIV_IT --> IT_Emergency["Haddii Shilalka Gudaha ee Shilalka (Laf-dhabarka) Xad-dhaafka ah: DEGDEG DEGDEG ah Neefta-> Samee Dheecaan Degdeg ah Lumbar Puncture CSF Drainage + Isotonic Saline Ventriculolumbar CSF Lavage + Intrathecal Glucarpidase (2,000 Units IT) + IV Dexamethurine Lexamethuone Intrathecally - Fatal)"]

Pathophysiology: Waa maxay sababta qaadashada 10 mg Maalin kasta 7 Maalmood ayaa Dila Marka la Liqayo 70 mg Dhammaan hal mar waxay keenaan waxyeello eber ah¶

Mid ka mid ah xaqiiqooyinka ugu liddi ku ah sunta kiliinikada waa sababta mudada jadwalku ay aad uga badan tahay wadarta qiyaasta milligaraam ee soo-gaadhista daawada methotrexate ee afka:

1. Nuugista mindhicirka oo dhergaya (PCFT) iyo Nadiifinta Kelyaha ee Degdegga ah ee Hal Doose¶

1. ** Qoorta dhalo ee mindhicirka *: daawada methotrexate ee afka si aan fiicneyn ugu faafin gidaarka mindhicirka; waa in si firfircoon loogu shubaa duodenum-ka iyo jejunum-ka iyadoo uu raacayo ** Gaadiidleyda Folate-ku-xidhan ee Proton (PCFT / SLC46A1). Gaadiidleydan ** waxay ku dheregsan tahay qiyaasaha sare 15 mg to 25 mg (-0.2 to 0.3 mg/kg)**.
2. Haddii socod baradka ama qof weyni uu liqo soddon 2.5 mg kaniiniyada (75 mg wadarta guud) dhammaan isla isla daqiiqada saxda ah, qaadiyaha xiidmaha ayaa ka dherga: ** helitaan bioavailability ayaa hoos uga dhacaya 70% hoos ilaa < 15% to 20%**, sidaas darteed inta badan kaniiniyada ayaa si aan la nuugin u dhaafin saxarada.
3. ** Soo-gaadhista Plasma Gaaban vs. Wareegga Unugga Wajiga S**: Wax kasta oo jajab ah oo ka mid ah hal dose oo gala dhiigga waa ** 80% ilaa 90% ayaa laga soo saaraa iyadoo aan isbeddelin kelyaha caafimaadka qaba 12 ilaa 24 saacadood gudahood**. Sababtoo ah methotrexate waa **S-phase ( wajiga DNA synthesis) - antimetabolite gaar ah **, hal mawjadaha methotrexate ee 12-saacadood ah oo kooban waxay saameeyaan jajabka yar ee dhuuxa lafta iyo unugyada tarma ee mindhicirka kuwaas oo ku dhacay DNA-ga dhowr saacadood gudahood; sida ugu dhakhsaha badan ee daawadu nadiifiso, unugyada asliga ee nasashada ee hadhay ayaa si caadi ah u qaybiya oo dib u buuxiya dhuuxa lafta iyada oo aan dhaawac lahayn.

2. Waa maxay sababta qaadashada maalinlaha ah (>= 3 to 7 Days) Waxay sababtaa Polyglutamation Intracellular Intracellular¶

Marka bukaanku qaato wax yar 2.5 mg to 15 mg qiyaasta ** 24-kii saacba** (ama xitaa 12-kii saacba) ee 4, 5, 7, ama 14 days oo xiriir ah:

1. ** 100% Bioavailability maalin kasta ***: Sababtoo ah qiyaas kasta oo maalinle ah waa mid yar (<= 15 mg), Qaadaha folate-ka xiidmaha waligiis ma dhergo - nuugista 70% to 90% kaniini kasta.
2. ** Fulin S-Wejiga oo Joogta ah ***: Ku-ilaalinta methotrexate ee qulqulka dhiigga maalinba maalinta ka dambeysa waxay qabataa ** unug kasta oo dhuuxa lafta ah, unugga xuubka afka, iyo unugga crypt ee xiidmaha ** marka uu galo S-phase of mitosis, isagoo tirtiraya dhammaan barkada unugga unugga ee qaybisa.
3. ** Methotrexate Polyglutamate intracellularMTX-PGDabin *: Gudaha dhuuxa, beerka, iyo unugyada mindhicirka, enzyme ** folylpolyglutamate synthetase (FPGS) ** waxay ku dhejisaa silsiladaha 2 ilaa 7 unugyo glutamate dheeraad ah oo ku jira methotrexate, oo u beddelaya ** Methotrexate Polyglutamates (MTX-PG2 iyada oo loo marayo MTX-PG7).
4. Si ka duwan methotrexate-ka bilaashka ah ee dhiiga ku jira, ** polyglutamates-yadan waaweyn, ee si xun u dallacay kama bixi karaan xuubka unugyada ** waxayna ku sii xayirnaan karaan gudaha unugyada ** usbuucyo** ka dib marka heerarka methotrexate serum ay hoos u dhaceen eber.
5. MTX-PGs si aan leexleexad lahayn u quful Dihydrofolate Reductase (DHFR), Thymidylate Synthase (TS), iyo AICAR transformylase, oo gebi ahaanba joojiya dhammaan purineadenine/guanineiyo pyrimidine (thymidine) DNA synthesis.

Isbarbardhigga Master: Folic Acid (Vitamin B9) vs. Folinic Acid (Leucovorin) vs. Glucarpidase (Voraxaze)¶

Jadwalka caafimaad ee Subacute / Maalinlaha ah ee daawada Methotrexate ee xad dhaafka ah (maxaa dhacaya maalinba maalinta ka dambeysa)¶

Sababtoo ah bukaanada si lama filaan ah u qaata daawada methotrexate toddobaadlaha ah maalin kasta waxay dareemaan wax caadi ah dhowrka maalmood ee ugu horreeya, aqoonsiga horumarka bukaan-socodka ee saddex-heer ah waa muhiim:

1. ** Marxaladda 1: Wajiga Ururinta Unugyada Aamusan ee Unugyada (Maalmaha 1 ilaa 4 ee Qiyaasta Maalinlaha ah)**:
2. Bukaanku waxa uu dareemaa ladnaan ama lallabo khafiif ah, anorexia, ama daal MTX-PGs ku urura gudaha unugyada qaybinta.
3. ** Ficil : Haddii qaladka qiyaasta lagu qabto halkan (>= 3 consecutive days), laga bilaabo ** afka ama IV Leucovorin (15 mg every 6 hours iyo IV fuuq-celinta waxay ka hortagtaa ku dhawaad ​​dhammaan sunta hoose.
4. ** Marxaladda 2: Xabxabxabeedka Herald & Wajiga Hepatorenal (Maalmaha 4 ilaa 8)**:
5. Stomatitis afka oo xanuun badan, cuncun cuncun leh, boogo gacmeed oo xanuun badan oo bushimaha gudaha ah, xuubka xabka, carrabka, iyo saxarada adag, samaynta biyaha liqidda ama candhuufta ( odynophagia**).
6. Cutaneous Psoriatic Plaque Nabaad-guur: Bukaannada qaba cudurka psoriasis, taarikada maqaarka ee hadda jira waxay si lama filaan ah u noqdaan casaan, jilicsan, finan, iyo necrotic ("methotrexate epidermal necrosis", oo la mid ah Stevens-Johnson Syndrome / TEN), oo inta badan ay weheliyaan finan maqaarka ah oo cadceedda soo baxa.
7. **Calamadaha caloosha iyo mindhicirka iyo cagaarshow ***: matag, calool xanuun oo casiraad, shuban biyood ama dhiig leh (enteritis), beerka transaminases oo kor u kaca (AST/ALT, iyo kor u kaca serum creatinine.
8. ** Marxaladda 3: Masiibada Dhuuxa Lafta Aplasia & Neutropenic Sepsis (Maalmaha 6 ilaa 14+)**:
9. Maxaa yeelay unugyada dhiiga cad ee wareegayaneutrophils nolosha badhkeed 6 to 8 hours) iyo platelets (7 to 10 days) laguma beddelo dhuuxa lafaha burburay, ** Tirada Dhiiga Dhamaystiran (CBC) waxay ku dhacdaa inta u dhaxaysa Maalinta 6 iyo Maalinta 12 ***:
   • ** Leukopenia daran & AgranulocytosisANC < 500/mcL, inta badan 0/mcL*: Bakteeriyada iyo fangaska waxay u kala gudbaan afka boogaha iyo mindhicirka si toos ah u gala qulqulka dhiigga, taasoo keenta ** shoog septic ah, oof-wareen, iyo typhlitis.
   • ** Thrombocytopenia daranPlatelets < 20,000/mcL***: Dhiigbax cirrid iskiis ah, epistaxis, petechiae, melena ( saxaro dameer madow), iyo dhiigbax gudaha intracranial.
   • ** Dhiig-yaraan daran**: calool-xumo, dyspnea, iyo tachycardia.
10. (Xusuusin: Xataa si ka duwan qiyaasta xad-dhaafka ah, methotrexate waxay sababi kartaa doqonnimo ba'an Hypersensitivity Pneumonitis meel kasta oo lagu jiro daawaynta, oo soo bandhigta qufac qallalan, qandho, hypoxia, iyo sambabada laba geesoodka ah ee galaas sambabada ah).

Tillaabo-tallaabo Habka Maareynta Isbitaalka ee Methotrexate xad dhaafka ah¶

1. Folinic Acid (Leucovorin) Qiyaasta Badbaadinta & "Xeerka Kala Saarida 2-saac" ee Glucarpidase¶

1. Weligaa dib ha u dhigin Leucovorin: Maamul qiyaasta kowaad ee Folinic Acid faleebo (Leucovorin)1 saac gudahood marka la soo bandhigo 25 to 40 mg, ** had iyo jeer u adeegso marinka xididada suntan dhexdhexaad ilaa daran > 25 mg):
2. ** Qalad Qaadis Maalinle ah oo Hoosaysa (Astaam ah ama Fudud, Shaqada Kelyaha ee Caadiga ah, Serum Hoose MTX)**: Leucovorin 15 mg to 25 mg (ama 10 to 15 mg/m2IV (ama PO) 6dii saacadoodba ugu yaraan 3 ilaa 7+ maalmood ilaa CBC-yada taxanaha ahi ay xaqiijinayaan kor u kaca/dejinta neutrophils iyo platelet tirinta 48 saacadood.
3. Calaamad-qaadista xad-dhaafka ah ee daba-dheeraada (Mucositis, Leukopenia/Thrombocytopenia, ama AKI) AMA Serum Sare MTX (> 0.1 to 1.0 micromol/L: ** Leukovorin 100 mg/m2 (ama 100 mg to 150 mgIV 3dii ilaa 6dii saacadoodba* (oo uu hagayo Bleyer nomogram hadii ay aad u daran tahay,ama ay ku sii socoto suntan maalinlaha ah ee joogtada ah ilaa dhammaan cilladaha dhiiga iyo boogaha xabkaha ay xaliyaan, xitaa ka dib serum MTX waa < 0.05 micromol/L).
4. ** Waxyaalaha Serum MTX aad u daran>= 10 micromol/L 24h ama >= 100 micromol/L***: Kordhi Leucovorin ilaa 1,000 mg/m2 IV 6dii saacadoodba mar iyadoo loo sii marayo khadka dhexe (daawashada kalsiyumka serum, sida qiyaaso badan oo Kaalshiyam Folinate ah) waxay keentaa culaysyo badan oo calcium ah; si tartiib ah ugu geli <= 160 mg/minute ama u beddel Levoleucovorin at 50% ee qiyaasta jinsiyadda).
5. Glucarpidase (Voraxaze) 2-Saacadood Xeerka Kala Saarida:
6. Haddii bukaanku qabo ** dhaawac ba'an oo kelyo ah / nadiifin dib u dhac ah ** oo leh methotrexate balaasmaha oo si joogto ah u kacsan (> 1 to 2 micromol/Loo qaata ** Glucarpidase xididka50 Units/kg IV over 5 minutes***, xusuusnow in Glucarpidase uu sidoo kale jebiyo Leucovorin haddii ay isku mar ku jiraan dhiigga.
7. **Xeerka ***: Ha ku siinin Leucovorin 2 saacadood ka hor ama 2 saacadood ka dib faleebo Glucarpidase, ka dibna dib u bilaw qiyaas sare IV Leucovorin 2 saacadood ka dib Glucarpidase.
8. ( Digniinta Farshaxanka Shaybaarka: Ka dib markii Glucarpidase la siiyo, dheef-shiid kiimikaad ee dillaacay ** DAMPA* waxay la falgashaa cisbitaalka caadiga ah immunoassay 48 ilaa 72 saacadood, taasoo ka dhigaysa heerka serum methotrexate mid u muuqda mid been abuur ah haddii aan lagu cabbirin HPLC / LC-MS/MS***

2. Xidhmada Taageerada Gardarada leh: Kala saarida kaadida, G-CSF, iyo Daryeelka Mucositis¶

• ** Kala-saarista kaadida & Diuresis-ka-soo-saarka Sare**: Ku shub sodium bicarbonate isotonic (150 mEq NaHCO3 gudaha 1 L D5W at 150 to 250 mL/hr) in la joogteeyo ** kaadida soo baxda > 2 mL/kg/hr** iyo ** pH dipstick kaadida >= 7.5 to 8.0**; la soco oo beddel potassium iyo magnesium si dhow.
• Granulocyte Colony-Stimulating Factor (G-CSF / Filgrastim): Bukaan kasta oo qaba methotrexate-ku-dhacey ** neutropenia (ANC < 1,000/mcL, isla markiiba bilow ** Filgrastim subcutaneous (5 mcg/kg/day si loo dardargeliyo soo kabashada neutrophil dhuuxa lafta dhowr maalmood, yaraynta dhimashada shoogga septic.
• ** Antibiyootigyada Empiric Broad-Spectrum IV ee loogu talagalay Febrile Neutropenia *: Haddii heerkulku gaaro >= 38.0 C (100.4 F) ama ANC < 500/mcL, sawir laba qaybood oo ah dhaqamada dhiiga oo billow daawaynta beta-lactam anti-pseudomonal ( cefepime, piperacillin-tazobactam [ka digtoonow haddii MTX weli wareegayso], ama meropenem *) oo lagu daray ** vancomycin (haddii Fasalka 3-4 xuub afka laga qaato ama maqaarka dillaacay uu jiro)
• Taageerada afka laga qaato ee xuubka afka iyo Cholestyramine: Bixi Folinic Acid (Leucovorin)4 grams PO every 6 hours ama ** Dhuxul Dhaqdhaqaaq Dhaqaale-badan ah** si loo xiro methotrexate ee ku socota dib-u-wareejinta biliary enterohepatic ee mindhicirka.

Lambarada degdega ah ee gobolka iyo borotokoolka wakaalada¶

Su'aalaha soo noqnoqda¶

Waa maxay sababta aanan u qaadan karin kaniiniyada Folic acid (Vitamin B9) ee dheeraadka ah haddii aan si kama' ah u qaato Methotrexate-ka toddobaadlaha ah maalin kasta muddo toddobaad ah?¶

Folic acid (pteroylglutamic acid) oo aan dhakhtar qorin ama dhakhtar qorin waa horudhac fiitamiin aan shaqayn oo eber awood u leh inuu badbaadiyo unugyada inta lagu jiro qiyaasta xad dhaafka ah ee methotrexate. Si aad uga shaqayso gudaha jidhkaaga, folic acid waa in marka hore si kiimiko ah loo hawlgeliyaa enzyme la yidhaahdo Dihydrofolate Reductase (DHFR) - kaas oo ah enzyme saxda ah ee methotrexate si buuxda u quful oo naafo ah. Si loo badbaadiyo dhuuxa lafta iyo xuubka caloosha iyo mindhicirka, isbitaallada waa in ay siiyaan Folinic Acid (oo sidoo kale loo yaqaan Leucovorin ama Calcium Folinate), oo ah nooc horay loo sii hawlgeliyay ee folate kaas oo gebi ahaanba dhaafa enzyme-ka DHFR ee xannibay oo dib u bilaabaya isku-dhafka DNA-da isla markiiba.

Maxay tahay sababta qaadashada 10 mg ee Methotrexate maalin kasta muddo 6 maalmood ah (wadarta guud ee 60 mg) inta badan ay u geeriyooto, halka ilmaha liqa afar iyo labaatan kaniini 2.5 mg ah hal mar (60 mg) uu caadiyan leeyahay calaamado khafiif ah ama aan lahayn?¶

Marka qof uu liqo 60 mg oo methotrexate afka ah hal mar, gaadiidka folate ee xiidmaha yar wuxuu ka dhergaa qiyaastii 15 ilaa 20 mg, sidaas darteed inta badan kaniiniyada dheeraadka ah weligood lama nuugo dhiigga, kelyaha caafimaadka qaba waxay soo saaraan qaybta nuugista 12 ilaa 24 saacadood gudahood. Sababtoo ah methotrexate kaliya waxay dishaa unugyada inta ay si firfircoon u qaybsanayaan (isku-dubarid DNA-da ee S-phase), soo-gaadhis kooban oo 12-saac ah ayaa ka tagaysa inta badan unugyada tarma ee dhuuxa lafta iyada oo aan waxyeello gaarin. Taas bedelkeeda, qaadashada 10 mg maalin kasta 6 maalmood oo isku xigta waxay u ogolaataa 100% nuugista mindhicirka maalin kasta waxayna ilaalisaa heerarka daawada sunta ah ee joogtada ah ee wareegga unugyada unugyada usbuuc dhan, dabinnada methotrexate polyglutamates gudaha unugyada iyo tirtiridda dhammaan dhuuxa lafta iyo xuubka mindhicirka.

Haddii baaritaanka dhiigga isbitaalku muujiyo "Heerka Methotrexate Serum" waa eber ama lama ogaan karo ka dib markii aan qaatay daawada methotrexate maalin kasta muddo toddobaad ah, taasi miyay ka dhigan tahay inaan ammaan ahay?¶

Maya - tani waa mid ka mid ah dabinada ugu khatarta badan ee daawada degdega ah. Tijaabada caadiga ah ee dhiiga cusbitaalka ayaa kaliya cabbiraysa daawada methotrexate ee bilaashka ah ee ku dul sabbaynaysa balasmaha dareeraha ah ee dhiiga, iyo lambarada goynta nomogram-ka ee lagu daabacay warbixinada shaybaadhka waxay khuseeyaan KALIYA hal 24-saac oo keliya faleebooyin kansarka xididdada sare leh. Marka qof qaato daawada methotrexate afka laga qaato maalin kasta dhowr maalmood, methotrexate wuxuu galaa dhuuxa lafta iyo unugyada mindhicirka wuxuuna leeyahay dabo glutamate oo dheeraad ah oo ku dheggan (samaynta methotrexate polyglutamates) kaas oo ku xidha gudaha unugyada toddobaadyo halka heerka balaasmaha dhiiggu hoos uga dhaco xadka ogaanshaha shaybaadhka. Bukaanka qaba khaladaadka methotrexate ee joogtada ah ee maalinlaha ah waa in ay helaan samatabbixin buuxda oo Leucovorin ah oo xididka ah oo ku salaysan taariikhdooda qiyaasta qiyaasta, nabarrada afka, iyo tirada dhiigga - xitaa haddii heerka methotrexate serum uu akhriyo eber.

Waa maxay sababta nabarrada afka ee xanuunka leh (stomatitis) loogu tixgeliyo calan cas oo degdeg ah qofka qaadanaya Methotrexate?¶

Unugyada epithelial ee ku dahaadhan gudaha dhabannada, faruuryaha, ciridka, iyo cunaha ayaa kala qaybiya oo is beddela 3 ilaa 5 maalmoodba - ka dhaqso badan unugyada kale ee jidhka. Marka methotrexate uu gaaro heerarka sunta unugyada unugyada (ha ahaato qalad qiyaasta maalinlaha ah, hoos u dhaca shaqada kelyaha, ama isdhexgalka daroogada sida Bactrim), xuubka afku waa unuga ugu horreeya ee joojiya kala qaybinta oo u kala qaybsama boogaha cayriin ee xanuunka leh (mucositis). Nabarada afka waxay u adeegaan digniin hore oo degdeg ah oo 24-ilaa-72-saac ah taas oo ah in unugyada tarma ee dhuuxa lafta bukaanku ay sidoo kale joojiyeen qaybinta iyo in neutropenia nafta halis gelisa (eber unugyada dhiiga cad) iyo thrombocytopenia ay ku dhow yihiin inay garaacaan.

Waa maxay sababta antibiyootiga Trimethoprim-Sulfamethoxazole (Bactrim / Septra) ay si adag uga mamnuucday bukaanada qaadanaya Methotrexate?¶

Trimethoprim-sulfamethoxazole (sida caadiga ah loo qoro caabuqyada kaadi mareenka, boronkiitada, iyo caabuqyada maqaarka) waxay ku weeraraan bukaanka methotrexate iyada oo loo marayo laba waddo oo dilaa ah isku mar: marka hore, trimethoprim waxay xannibaysaa isla Dihydrofolate Reductase (DHFR) folate enzyme sida methotrexate, abuurista xannibaad isku dhafan oo joojisa soo saarista DNA-da dhammaan dhuuxa; Marka labaad, labada qayboodba waxay xannibaan tubbada kelyaha inay ka soo saaraan methotrexate kaadida waxayna garaacaan methotrexate borotiinnada dhiigga, taasoo keenaysa dhiigga iyo unugyada methotrexate inay sare u kacaan heerar dhimasho ah xitaa qiyaasta caadiga ah ee hal mar toddobaadkii.

Tilmaamaha la xidhiidha¶

• 5-Fluorouracil (5-FU) qaadashada kareemka kiimoterabiga ee xayawaanka iyo qaadashada kapecitabine ee bini'aadamka
• Sebsiis iyo shoogga septica ogaanshaha iyo jawaabta degdegga ah
• Dhaawac kelyo oo ba'an, rhabdomyolysis, iyo kala soocida kaadida mugdiga ah
• Xakamaynta dhiigbaxa daran iyo shoogga dhiigbaxa
• Sumeynta gargaarka degdegga ah iyo kala soocidda xakamaynta sunta

Ilaha iyo hanuuninta rasmiga ah¶

• Machadka Dhaqannada Daawaynta Badbaadada ah (ISMP): Dhaqanka ugu Wanaagsan ee Badbaadada Daawada ee loogu talagalay Cisbitaalada iyo Farmashiyeyaasha Bulshada: Ka Hortagga Fatal Maalin kasta halkii Todobaadle ah ee Khaladaadka Qiyaasta Methotrexate Oral.
• Ururka Caafimaadka Adduunka (WHO) & Wakaaladda Daawooyinka Yurub (EMA): Badbaadada Daawada ee Xaaladaha Khatarta Sare leh iyo Talooyinka PRAC si looga hortago Khaladaadka Qaadashada Khatarta ah iyo Khaladaadka ah ee Methotrexate.
• Daawaynta ka baxsan jidhka ee Sumowga (EXTRIP) Kooxda shaqada & Kulliyada Maraykanka ee Sunta Caafimaadka (ACMT): * Tilmaamaha Dhaqanka Kiliinikada ee Sumowga Methotrexate: Folinic Acid (Leucovorin), Alkalinization Urinary, Glucarpidase, iyo Hemodialysis-Flux Sare*.
• Adeegga Macluumaadka Sumowga Qaranka (NPIS, Boqortooyada Ingiriiska) & Daawooyinka iyo Alaabooyinka Daryeelka Caafimaadka Hay'adda Nidaaminta (MHRA): TOXBASE Maareynta Kiliinikada ee Daawada Ba'an iyo Joogtada ah ee Daawada Daawada ee Trimethoprim.
• Maamulka Cunnada iyo Dawooyinka ee Maraykanka (FDA): Qoritaanka Macluumaadka iyo Digniinaha Badbaadada Methotrexate, Leucovorin Calcium, iyo Voraxaze (Glucarpidase).

*Hagahan waxa loogu talagalay ujeeddooyin macluumaad mana beddelo qiimaynta caafimaadka ee xirfadleyda ah, la-talinta Xakamaynta Sunta, ama daryeelka Oncology/toxicology ee cusbitaalka. Sababtoo ah khaladaadka qiyaasta qiyaasta daawada methotrexate ee maalinlaha ah iyo isdhexgalka daroogada waxay keeni kartaa dib u dhac, dhuuxa lafaha oo nafta halis gelinaya iyo shoogga septic, waxaan si adag kuugula talineynaa inaad qaadato gacan la aqoonsan yahay ee gargaarka degdegga ah iyo koorsada CPR iyada oo loo marayo Xiriirka Caalamiga ah ee Laanqeyrta Cas iyo Bisha Cas (IFRC), bulshadaada Laanqeyrta Cas ee qaranka, St John Ambulance, ama bixiye maxalli ah oo la aqoonsan yahay.