Week 3 (cystic and drug induced) Flashcards
most common mutation in CF
F508 Delta
- 1 copy= hetero
- 2 copies= homo
Who can get Ivacaftor
(Kalydeco)
1 month and older w/ 1 copy of F508del OR another mutation that is responsive
Who can get Lum/Iva (Orkambi)
1 year and older w/ 2 copies of F508del
Who can use Tez/Iva (Symdeko)
6 years and older w/ 1 or 2 copies of F508del OR another mutation that responds to
Who can use Elex/Teza/Iva (Trikafta)
2 years and older w/ 1 or 2 copies of F508del
Most to least effacious modulator
Elex/Tez/Iva > Iva > Tez/Iva > Lum/Iva
Efficacy parameter
- FEV1 improved/inc
-Dec in acute pulmonary exac rates, inc BMI, inc in QOL
-Acute inc in lung function and sustained improved function longer than control
General SEs (7) of CF modulators
- Abdominal pain
- Diarrhea
- Rash
- Inc in ALT/AST
- inc blood creatine phosphokinase
- rhinorrhea
- Headhache
Monitoring
- Liver transaminase & bilirubin @baseline, q3 mon x 1 yr, then annually
When to dose adj CF (2)
-If AST/ALT is 3x upper limit of norm w/ bilirubin 2x upper limit norm
- mod- severe hepatic dysfunction
Counseling points
- Take w/ fat containing meal
- Avoid grapefruit (inhs CYP3A4)
Drug interactions : CYP3A4 mod inhs
- inc Cmax and AUC
- Erythromycin and fluconazole
- Dec Iva to QD and Tez/Elex alternate QD with Iva doses
Drug interactions : CYP3A4 strong inhs
- Inc AUC and Cmax
- Clarithromycin and Itraconazole
- Dec of Iva AND Tez/Elex dosing to BIW
Treatment for pulmonary aspects: asthma/ bronchospasms
- SABA (albuterol) > LABA
- brochospasms from hypertonic saline
Treatment for pulmonary aspects: Mucolytic/ hydrating agents (who get it, se, efficacy)
- ALL PATIENTS WITH CF
- Dornase alfa
-se: voice harshness & rash
-inc fev1 and dec ape - Hypertonic Saline
- se: bronchospasm
- dec ape
Treatment for pulmonary aspects: Inflammation (who, dosing, se)
- CF pt 6yr+
- Azithromycin
- m-w-f dosing
- se: n/d/v, AB resistance?
- improves all aspects of CF
- Alternative : high dose ibuprofen
Treatment for pulmonary aspects: Inhaled Abx (who, dose, se)
- CF pts 6yr+ w/ hx of pseudomonas
- Tobramycin 300 mg inh BID for 28 days on/off
-SE: Voice alternation, tinnitus - Azetronam 75mg inhaled for 2-5 min TID 28 days on/off
What vaccinations should CF pts get
- Flu, if 6 months+
What happens to home regimen during acute exacerbation of CF
- inc vest treatment and SABA to 4x daily
- inc dornase alfa and hypertonic saline to BID
- HOLD inhaled Abx
Treatment for CF APE w/ hx of MSSA no PA
- Anti-staphyococcal penicillin: Naficillin
or
-cephalosporin
Treatment for CF APE w/ hx of MSSA and PA
-Double PA coverage: Cefepime & Aminoglycoside (extended interval dosing)
Treatment for CF APE w/ hx of MRSA no PA
Vancomycin or Linezolid
Treatment for CF APE w/ hx of MRSA and PA
- Vancomycin or linezolid
AND - Double PA coverage: Aminoglycoside + B-Lactam (Ceftazidime)
CF APE ABx duration
- 10-14 days (can be continued at home in picc line or dec to oral)
- if no improv in 5-7 days reassess
APE ABx monitoring
- symptom persistance/ resolution
- sputum culture & susceptibilities
- pulmonary function test (FEV1, FVC) x weekly
- BUN/SCr
- ABx conct (draw conct q3-7 days)
ABx concentration monitoring (Amino)
- Aminoglycosides
- Traditional P 10-12 mcg/ml , T <1.5 mcg/ml
- Extended interval P 22.5-27.5 mcg/ml, T <0.1 mcg/ml, 18 hr <1 mcg/ml, AUC 80-100 mcg/ml
ABx concentration monitoring (Vanco)
T 10-20 mcg/ml
AUC/MIC > 400
Drug-related risk factors for DIP
- dose
- admin rate
- treatment duration
- O2 therapy
- Radiation therapy
- Cumulative dose
Patient-related risk factors
- Age (extremes)
- respiratory acidosis)
- pre-existing lung disease
- impaired renal or hepatic function
DI interstitial lung disease patho
Drug induced, fibrosis may lead to acute pneumonitis
DI interstitial lung disease symptoms
- Sudden onset dyspnea w/ non productive cough
- fever, rash
- crackles on expiration w/clubbing
CT: dec lung volume, bilat ground glass
DI interstitial lung disease causative agents
- Antimicrobals: Nitrofurantoin
- Anti- rheumatics: Leflunomide + Methotrexate
- Cardio: Amiodarone
- Anti-neoplastics : Bleomycin, Busulfan, cyclophosphamide, Gemcitabine
Treatment For DIILD
- Grade 2: hold med and give pred 1-2 mg/kg/day
- continue until it becomes grade 1 and monitor
- if no improv in 48-72 hrs inc grade
- Grade 3/4: permanent d/c med, give methylpred 1-2 mg/kg/day
- continue and taper over 4-6 weeks- if no improv give infliximab/IVIG/MMF
Treatment For DIILD caused by mTORI’s
- Grade 2 : Pred .75-1 mg/kg and dec dose or hold
- Grade 3: Pred .75-1 mg/kg and hold med
- Grade 4: Pred .75-1 mg/kg and permanently d/c
Treatment For DIILD Caused by Bleomycin
- Pred .75-1 mg/kg for 4-6 weeks with taper
Treatment For DIILD Caused by Carmustine
- pred taper 60 mg BID to 30 mg QD to 10 mg wkly to 5 mg weekly
Treatment For DIILD Caused by Amiodarone
Pred .5-1 mg/kg/day
*relapse if therapy given for <6 mons
-monitor baseline status, q3-6month x 1 yr
Pneumonia : BOOP symptoms and xray
- Cough, dyspnea, BL crackles
- chest x-ray: bilateral pathy, infiltrates
Pneumonia : Meds that cause BOOP (4)
-Bleomycin, Amiodarone, Carbamazepine, Cocaine
Pneumonia : Eosinophilic symptoms and xray
- Dry cought, chest pain, fever
- Xray: ground glass
Pneumonia : Meds that cause Eosinophilic
-Daptomycin, Mesalamine Sulfasalazine, Nitrofurantoin, and Minocycline
Pneumonia : Meds that cause Hypersensitivity pneumonia
NSAIDs, Methotrexate
Pneumonia : Meds that cause Pulmonary edema
Narcotics, treat w/ naloxone
Pneumonia : Meds that cause Lupus
Procainamide, Hydralazine, Isoniazid
