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Tratamentul bolilor inflamatorii intestinale Flashcards

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1
Q

Bolile inflamatorii intestinale

A

Boala Crohn

Colita ulcerativa

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2
Q

Obiectivele tratamentului in BII

A

Controlul simptomelor digestive si extradigestive
Obtinerea si mentinerea remisiunii
Tratamentul si preventia complicatiilor

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3
Q

Clase de medicamente utilizate in tratamentul BII

A
  1. Antiinflamatoare intestinale
  2. Glucocorticoizi
  3. Imunosupresoare
  4. Terapia biologica anti TNFa
  5. Antibiotice
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4
Q

Antiinflamatoarele intestinale - reprezentanti

A

Derivatii de acid 5-aminosalicilic (5 ASA): SULFASALAZINA, OLSALAZINA, BALSALAZIDA

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5
Q

Sulfasalazina - structura chimica

A

MESALAZINA (componenta activa) si SULFAPIRIDINA (sulfamidic antibacterian - resp de RA) legate printr-o legatura DIAZO

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6
Q

Olsalazina - structura chimica

A

2 molecule de mesalazina legate prin leg diazo

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7
Q

Balsalazida - structura chimica

A

o molec de mesalazina legata de un compus inert

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8
Q

Farmacocinetica sulfasalazina

A

La nivelul colonului - leg diazo scindata de flora bacteriana -> elibereaza MESALAZINA cu efect local si SULFAPIRIDINA A din colon, M hepatic (acetilare, hidroxilare, conjugare), E urinara sub forma de metaboliti

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9
Q

Derivati 5-ASA - mecanism de actiune si efecte

A
  • COX, LOX -> scaderea prod de PG, LT
  • NF-kB
  • chemotaxia Ne
    efect antioxidant (inlatura SRO)
  • secretia de IL-1 si TNFa
    induc apoptoza LyT
    => efect local de inhibarea a inflamatiei
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10
Q

Derivati 5-ASA - indicatii

A

Prima linie de tratament in BII pentru obtinerea si mentinerea remisiunii (mai eficiente in CU)
Sulfasalazina - Terapie modificatoare de boala in boli osteoarticulare cu componenta inflamatorie

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11
Q

Sulfasalazina - RA

A

Dep de doza - cefalee, greturi, varsaturi, diaree
Idiosincrazice - rash, prurit cut
Hepatita toxica, pancreatita, leucopenie, anemie hemolitica, agranulocitoza, SJS, fibroza pulmonara, neurotoxicitate
Nefrotoxicitatea - !monitorizarea functiei renale
Scade nr si motilitatea spermatozoizilor
Scade abs de folati
Colorarea secr exocrine

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12
Q

Derivatii 5-ASA - CI

A

Alergie la salicilati, sulfamide

deficit de G6P-DH

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13
Q

Derivatii 5-ASA - interactiuni

A

Scad Bd digoxinului
- abd intest a Fe si acidului folic
azatioprina - creste riscul de leucopenie

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14
Q

Glucocorticoizii - indicatii

A

Tratamentul exacerbarilor acute de BC, CU

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15
Q

Glucocorticoizi - mecanism de actiune

A
  • sinteza unor citokine si chemokine proinflamatorii (TNF a, IL-1, IL-8)
    scade exprimarea moleculelor de adeziune
    moduleaza transcriptia genelor pt NOs, PLA2, COX2, NG-kB
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16
Q

Lipsa de raspuns la glucocorticoizi - cauze

A

Forme complicate de boala
Infectii intercurente
Particularitati genetice - polimorfismul MDR, niv alterat al CBP

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17
Q

Glucocorticoizi - mod de administrare si reprezentanti

A

Oral - PREDNISON, PREDNISOLON

iv - METILPREDNISOLON, HIDROCORTIZON

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18
Q

Budesonid - avantaje

A

Datorita metabolizarii extensive la primul pasaj hepatic, budesonidul are mai putine efecte adverse sistemice si poate fi folosit pe perioade mai indelungate in tratament

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19
Q

Glucocorticoizi - RA

A

HTA, exacerbare infectii, hiperglicemie, acnee, hirsutism, osteoporoza, miopatie, ICSR

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20
Q

Metode de diminuare a RA sistemice ale glucocorticozizilor

A

Administrarea de doze mari pe perioade scurte de timp
Budesonid
Administrarea la 2 zile

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21
Q

Terapia imunosupresoare - indicatie

Study These Flashcards
A

In formele refractare de BII sau la pacientii corticodependenti

22
Q

Azatioprina - mecanism de actiune

Study These Flashcards
A

Transformata in ACID TIOINOZINIC -> - competitiv sint ac inozinic (precursor al A si G) => - sinteza ADN, - proliferarea Ly => - rasp imun celular si umoral

23
Q

Azatioprina - farmacocinetica

Study These Flashcards
A

A buna dupa admin orala
M la 6-mercaptopurina -> ficat si eritrocite -> acid 6-tiouric
E urinar sub forma de metaboliti

24
Q

Azatioprina - indicatii

Study These Flashcards
A

CU si BC
Reactia de rejet a organelor transplantate
Boli autoimune cu comp inflamatoare

25
Azatioprina - RA
pancreatita acuta, artralgii, rash, febra, greturi, varsaturi toxic medular -> !monitorizare Hlg cresterea E hepatice -> !monitorizare fct hep scaderea rezistentei la infectii
26
Azatioprina - CI si precautii
Sarcina Scaderea dozelor in IR Incidenta crescuta de limfom non-Hodgkin Polimorfismul genei care codifica tiopurin-metil transferaza (E care metabolizeaza azatioprina)
27
Metotrexat - mecanism de actiune
- legarea acidului folic de DHFR => - sint purinelor => - sinteza ADN => moartea celulara
28
Metotrexat - mecanism de rezistenta
Cresterea nivelului de DHFR intracel Forma mutanta a DHFR cu afinitate scazuta pentru metotrexat Scadere transportului intracel al metotrexatului
29
Metotrexat - farmacocinetica
A buna dupa admin orala Cp scade in 3 faze: 1. distrib, 2. eliminare initiala, 3. eliminare prelungita (elib lenta din tes) E renala prin FG si secretie tubulara
30
Metotrexat - indicatii
Boala Crohn Leucemii acute limfoblastice, limfom Burkitt, coriocarcinom trofoblastiv cc mamar, pulm, micozis fungoid, tu cap si gat, osteosarcom psoriazis reactia de rejet a organelor afectiuni autoimune
31
Metotrexat - RA
Mielosupresie -> ! control Hlg febra, reactii anafilactice, necroza hepatica stomatita, ulceratii GI, conjunctivita, alopecie, osteoporoza, infertilitate leziuni renale acute - ! hidratare si alcalinizarea urinei CH - favoriz de varsta, DZ, consum alcool meningite la admin intratecala toxic pentru embrion, dismorfogen
32
Metotrexat - interactiuni
Salicilati, probenecid, sulfamide -> cresc Cp
33
Metotrexat - CI
Sarcina | IH si IR severe
34
Ciclosporina - mecanism de actiune
form un complex cu un R specif CICLOFILINA -> diminua activ enzimatica (serin treonin fosfataza) a CALCINEURINEI -> - sinteza unor citokine proinflamatorii (IL-2 - cu rol in activarea LyT) => X activarea ulterioara a LyT (mai ales LyTh)
35
Ciclosporina - farmacocinetica
A lenta si incompleta dupa admin orala M hepatic de E oxidative -> metaboliti inactivi E prin bila si scaun
36
Ciclosporina - indicatii
BII - mai eficienta in CU Prevenirea rejetului organelor transplantate - de electie Prevenirea reactiei grefa contra gazda Boli autoimune
37
Ciclosporina - RA
``` Nefrotoxicitate - necroza tubulara, nefropatie interstitiala -> ! control Cr Hepatotoxicitate HTA tremor, convulsii hiperplazie gingivala, hirsutism infectii frecvente limfoame maligne, leucemii ```
38
Ciclosporina - interactiuni
cresc Cp - ERITROMICINA, KETOCONAZOL, BLOC CA2+, CONTRACEPTIVE ORALE scad Cp - RIFAMPICINA, FENOBARBITAL, FENITOINA, CARBAMAZEPINA, CO-TRIMOXAZOL nefrotoxicitate additiva - AGZ, MEFALAN, CO-TRIMOXAZOL
39
Infliximab
Ac monoclonal himeric
40
Infliximab - mecanism de actiune
Leaga TNFa solubil si membranar -> previne leg citokinei de R specif => diminua activ proinflam a TNFa Fc a IgG1 -> + C' => declanseaza rasp imun mediat celular
41
Infliximab - indicatii
BII - forme care nu raspund la tratamentul imunosupresor conventional BC forma fistulizanta Colita fulminanta Boli inflamatorii reumatismale
42
Infliximab - RA
periinfuzionale - febra, frison, uritcarie, prurit cut, boala serului, soc anafilactic, manif cardio-pulm infectii - reactivarea unei TBC latente sau alte infectii granulomatoase Ac fata de comp murinica - RA intarziate: mialgii, artralgii, febra, rash, angioedem Ac anti ADNdc, ANA, sdr lupoid (extrem de rar)
43
Infliximab - CI
``` TBC activa infectii resp sau urinare acute ICC severa neoplazii citopenii sarcina ```
44
Adalimumab
Ac monoclonal umanizat IgG1
45
Adalimumab - mecanism de actiune
leaga TNFa solubil si membranar => complex stabil
46
Adalimumab - indicatii
BC care nu prezinta rasp sau care dezv RA la infliximab | idem infliximab
47
Certolizumab
Ac monoclonal umanizat (Fab al IgG) cu act anti TNFa
48
Natalizumab
Ac monoclonal complet umanizat cu actiune anti integrina a4 -> inducerea si mentiunea remisiunii in formele moderat severe de BC
49
Natalizumab - triunghi negru
monitorizare suplimentara - interactiune cu alte imunosupresoare si creste riscul de LEUCOENCEFALOPATIE MULTIFOCALA PROGRESIVA
50
Antibiotice
METRONIDAZOL, ciprofloxacina, claritromicina, rifamixina | Tratamentul complicatiilor, prevenirea recaderilor, inducerea remisiunii in asociere cu celelalte clase terapeutice

Farmacologie (8 decks)

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