Antifungice

POLIENE

Amfotericina B deoxycholate PK (AmB - d)

Amfotericina B lizozomala (L -AmB)

Amfotericina B  Complex lipidic (ABLC)

Mecanism actiune

- legare de ergosterol

- leziuni oxidative

- stimularea celulelor fagocitare

! Se absoarbtie in tubulatura ECMO!

! Concentratii in plaman, ficat, spina!

AMB-D

- 0.7 - 1 mg/zi in 2-4 ore 

- 1.5 mg/zi in PEV timp de 6 h

- activitate dependeta de concentratie

- legare ↑ de proteine plasmatice

- 𝛥t1/2 = 24 ore, per de eliminare 15 zile

- concentratie ↑ in ficat, splina, maduva, peritoneu, plaman, rinichi

- concentratie ↓ in LCR, lichidul amniotic

Ef adverse

- legat de adminsitrare - febra, HTA, frison, greata ← elibereaza IL6, IL8, TNF𝛼, MCP1, IL10

- nefrotoxicitate

- ↓ K, ↓ Mg

- ANafilaxie

- Encefalita demielininzanta

- anemie normocromica

ABLC

- 1 - 5 mg/kg/zi

- nefrootoxicitate mai scazuta

- efecte secundare - reactii legate de administrare

L-AMB

- neutropenie febrila 1 - 3 mg/kg/zi

- aspergiloza 3 - 5 mg/kg/zi

- eficacitate crescuta > Aspergilius

- 6 mg/kg/zi Cryptococus

AZOLI

Imidazoli

  • Miconazol
  • Ketoconazol
  • Clotrimazol
Triazoli

- tinta - Ergosterolul
- inhiba - 14𝛼Demethylase = Fungal CYP
- efecte adverse: rash, cefalee, gastro-intestinale, insuficienta hepatica, ↓ QT, defecte congenitale

  • 1 generatie - IMIDAZOLI
    • Fluconazol (Diflucan)
- forma IV/OR 
- excretie urinara crescuta
- timp de injumatatire crescut - o doza/zi
- obezi - cresti doza
- interactiuni medicamentoase +
    • Itraconazol 
- piele
- forma OR
- timp de injumatatire crescut - o doza/zi 
- metabolizare hepatica
- interactiuni medicamentoase +++

  • 2 generatie - TRIAZOLI
    • Voriconazol (Vfend) 
- forma IV/OR
- Candida auris, Candida  krusei, Candida  glabrata, Aspergilius fumigatus
- excretie in LCR
- metabolizare hepatica
- timp de injumatatire scazut - bid
- efecte adv: modificari oftalmologice, fotosensibilitate, toxicitate osoasa, cancer piele
- interactiuni medicamentoase +++
    • Posaconazol 
- forma IV/OR
- Candida auris, Candida  krusei, Candida  glabrata, Aspergilius fumigatus, Mucorales
- timp de injumatatire crescut - o doza/zi
- excretie fecala
- metabolizare hepatica
- interactiuni medicamentoase +++
    • Isavuconazol (Cresemba) 
- forma IV/OR 
- Candida auris, Candida  krusei, Candida  glabrata, Aspergilius fumigatus, Mucorales
- prodrug - Isavuconazonium sulfat
- timp de injumatatire crescut - o doza/zi
- metabolizare hepatica
- interactiuni medicamentoase +++

ECHINOCANDINE

Caspofungin (Cancidas)
Micafungin
Anidulafungin (Ecalta) 

- inhiba sinteza de đť›˝ 1,3 D glucagon

- efecte adverse: 

    - legate de adminsitrare flush facial, edem, prurit, bronhospasm

    - gastrointestinale, anemie, leucopenie, 

    - mai frecvente la Caspofungin

    - teratogen

- fungicide pentru Candida

- fungistatice depeendente de doza pentru Aspergilius

- metabolizare 

    • Caspofungin - citocromul P450
    • Micafungin - CYP
    • Anidulafungin - spontan in plasma

- penetranta minima in SNC

- eficiente in biofilm

- NU s emodifica doza pe ECMO

- EAGLE EYE EFFECT = scaderea eficacitatiila o doza mult peste MIC

ALTELE

Rezafungin 

- generatia a doua de echinocandine

Ibrexafungerp

- inhiba sinteza de glucagon
- OR

Fosmanogepix

- IV/OR
- sinergic cu AmB

Olorofim 

- OR
- Aspergilius

Odelconazol

- triazol inhalator

Volum lichid pleural

 Formula Balik

Volum lichid pleural (ml) = Distanta masurata ecografic (mm) x 20

pH lichid pleural < 7.2 = infectie

The fluid is considered an exudate if any of the following are found and a transudate if all are absent (Light’s criteria) –ratio of pleural fluid to serum protein > 0.5, ratio of pleural fluid to serum LDH > 0.6, pleural fluid LDH > two thirds of the upper limits of normal serum value. Pleural fluid cholesterol > 55 mg/dL (1.42mmol/L)may also be a useful in distinguishing an exudate from a transudate.

Pulmonary Arterial Hypertension / Pulmonary Venous Hypertension

Parametru PAH Pulmonary Arterial Hypertension PVH Pulmonary Venous Hypertension
RV ↑ ±↑
LA ↓ ↑
RA/LA
Size ratio		 ↑ N ( LA > RA)
Sept interatrial Impins spre stanga Impins spre stanga
RVOT  Frecvent Rar
E/A < 1 >1
Lat e' N ↓
Lat E/e' < 8 > 10
Ao pressure N / ↓ N / ↑
PCWP ⋜ 15 mmHg > 15 mmHg
PADP - PCWP > 7 mmHg < 5 mmHg

Rocuronium - blocare neuromusculara si reversie

 Administrarea de rocuroniu

- doza de IOT calculata la IBW

0.6 mg/kg IBW (doza se scade cu 15 % pentru femei)

Monitorizare EMG

- TOF count sau PTC

- evitare administrare in ultimele 30 min ale procedurii daca este posibil

Reversie

  • TOF Ratio ≥ 0.4 dar < 0.9

Neostigmina 15-30 𝜇g/kg + Glicopirolat 1:5 imediat dupa neostigmina

  • TOF Ratio < 0.4

Sugammadex 2 mg/kg

  • TOF Ratio ≥ 0.9

NU este nevoie de reversie

  • TOF Count = 0 (PTC ≥ 1)

Sugammadex 4 mg/kg


Daca TOF ratio < 0.9 dupa reversie initiala se adminsitreaza Sugammadex

- dupa 3 minute daca reversia initiala a fost cu Sugammadex

- dupa 10 minute daca reversia initiala a fost cu Neostigmina

Antitrombotice

Antiagregante plachetare

  • Analogi de prostaglandina PGI2

    • Beraprost
    • Iloprost
    • Prostaciclina (Epoprostenol)
    • Treprostinil

  • Inhibitori ai glicoproteinei IIb/IIIa

    • Abciximab
    • Eptifibatida
    • Tirofiban

  • Inhibitori ai receptorului P2Y12

    • Tienopiridine
      • Clopidogrel  
      • Prasugrel  
      • Ticlopidina 
    • Analogi nucleotidici/nucleozidici
      • Cangrelor  
      • Elinogrel  
      • Ticagrelor

  • Inhibitori ai ciclooxigenazei

    • Acid acetilsalicilic/Aspirina  
    • Aloxiprina  
    • Carbasalat calcic  
    • Indobufen  
    • Triflusal

  • Altele

    • Dipiridamol  
    • Ditazol  
    • Cilostazol  - inhibitor de fosfodiesteraza
    • Vorapaxar - antagonist protease-activated receptor-1 

Anticoagulante

  • AntagoniČ™ti ai vitaminei K
    • Cumarine: 
      • Acenocumarol  
      • Biscumacetat de etil  
      • Dicumarol  
      • Fenprocumona  
      • Warfarina
    • 1,3-indandione: 
      • Clorindiona  
      • Difenadiona  
      • Fenindiona
  • Inhibitori ai factorului Xa
    • Heparina
    • Heparina cu greutate moleculara mica
      • Certoparina  
      • Dalteparina  
      • Enoxaparina - Clexane  
      • Nadroparina  
      • Reviparina  
      • Tinzaparina
    • Oligozaharide 
      • Fondaparinux  
      • Idraparinux
    • Heparinoizi
      • Danaparoid  
      • Dermatan sulfat  
      • Sulodexid
    • Inhibitori direcČ›i Xa: 
      • Apixaban  
      • Betrixaban  
      • Edoxaban  
      • Rivaroxaban
  • Inhibitori direcČ›i de trombina (IIa)
    • BivalenČ›i
      • Hirudina  
      • Bivalirudina  
      • Desirudina  
      • Lepirudina
    • UnivalenČ›i
      • Argatroban  
      • Dabigatran  
      • Efegatran  
      • Inogatran  
      • Melagatran  
      • Ximelagatran
  • Altele
    • Antitrombina

Trombolitice/fibrinolitice

  • Activatori de plasminogen: 
    • Alteplaza  
    • Reteplaza  
    • Tenecteplaza  
    • Desmoteplaza  
    • Urokinaza  
    • Anistreplaza  
    • Monteplaza  
    • Streptokinaza
  • Altele
    • Ancrod  
    • Brinaza  
    • Fibrinolizina

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