Week 3: Cystic Fibrosis/ Drug Induced Pulmonary Disease Flashcards
Root Cause of CF
defect in cystic fibrosis transmembrane (CFTR)conductance regulator. Transports Cl- and bicarbonate.
organs typically involved in cf
skin
pancreas lung
Epidemiology
most common lethal genetically inherited disease affecting caucasions
outcome of cf dependent on ..
disease/genotype
pt mangement
compliance w. therapies
CFTR mutation classes and order of Prevalence
Class I mutation: nucleus
Class II mutation: Golgi apparatus
both effect synthesis of CTFR mutation, and cannot reach epithelial surface
Class III, IV, V, : dysfunctional CFTR proteins. little to no Cl can be transfered outside of cell
Class II»>Class I>Class III~Class IV>Class V
Classes IV and V cause milder disease because of little transport
classes I-III have no cloride transport
Most common mutation of CFTR
F508del
can either be homozygous or heterozygous
homozygous F508del=44.2%
heterozygous F08del= 40.5%
CF patho
mutated CFTR gene
loss of CFTR function
Impaird Bacterial Eradication
Infection
Inflammation
Airway Remodeling
Airway Obstruction
Broncheiectasis
Most common pathogen affecting young children and adulthhod
children: staph. Aureus
1.s.aureus
2.H. influenzae
3.ps aeruginosa
adults: psudamonas aeruginosa
1.p. aeuginosa
2.s. aureus
3. MRSA
chronic infection in CF triggers inflammation involving what mediators
tnf-a
IL-
GM-CSF
Leukotrienes
Neutrophils etc.
further worsens obstruction and creates better environment for infection
Exocrine dysfunction due to CF
occurs in 85-90% of CF pts.
results in obstruction and consequently deficient in ..
Protease, amylase, lipase
bicarbonate
causes poor absoprtion of…
*fat soluble vitamins (ADEK),vit. b12, zinc
Long term xocrine dysfunction: Acinar celldestruction->fibrosis->progressive adipose replacement of pancreatic tissue
SS of poor digestoin and complications
abdominal distention,increased stool frequency w.loose consistency/foul odor
increased fecal fat content
endocrine dysfunction: CF related diabetes (5-30% prevelance)
complication:mal nutrition and poor weightgain (predictor of mortality)
CF comorbidities
depression
anxiety
manifestations: asthma, acid reflux, CF related diabetes, sinus disease
CFTR Modulators
ex: Ivacafter (Kalydeco)
moa:
age indication:
Class mutation indications:
specific mutation indications:
ex:
moa: Facilitates opening of the chloride channel (CFTR potentiator)”
age indication: >/4 months
Class mutation indications: class III-IV when used alone
specific mutation indications: G551D, R117H, etc.
considerations: can be used as monotherapy or combo
CFTR modulators
ex: Lumacaftor/ Ivacaftor (Orkambi)
moa:
age indication:
Class mutation indications:
specific mutation indications:
pearls:
CFTR modulators
ex:
moa: fixes the defective CFTR protein so it can move to the proper place on the airway cell surface (CFTR corrector). Ivacaftor serves as potentiator
age indication: >/2 years old
Class mutation indications: Class Ii
specific mutation indications: homozygous F508del
pearls:
CFTR modulators
ex: Tezacaftor/ Ivacaftor (Symdeko)
moa:
age indication:
Class mutation indications:
specific mutation indications:
pearls:
CFTR modulators
ex:
moa:T.fixes the defective CFTR protein so it can move to the proper place on the airway cell surface (CFTR corrector). Ivacaftor serves as potentiator
age indication: >/6 y.
Class mutation indications:
specific mutation indications: homo or hetero mutation of F508del CFTR, 3849+10kbC->T
pearls:
*MUST INCLUDE A mutation that is responsive to symdeko
CFTR modulators
ex: Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
moa:
age indication:
Class mutation indications:
specific mutation indications:
pearls:
CFTR modulators
ex: Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
moa: E and T fixes the defective CFTR protein so it can move to the proper place on the airway cell surface (CFTR corrector). Ivacaftor serves as potentiator
age indication: >/6 years old
Class mutation indications:
specific mutation indications: homo or hetero F508 delta
pearls: doesnt have limitations like symdeko has as far as specific mutation response
Ivacaftor Studies
STRIVE trial: ivacaftor improved FEV1
ENVISION trial: improved fe1 at 24 and 48 wks
PERSIST study:
Lumacaftor/ Ivacaftor
TRAFFIC &TRansport trials
improved FEV1 @ 24 weeks
PROGRESS studies:
Tezacaftor + Ivacaftor trials
EVOLVE trials: improvement of fev1 @24 WEEKS
EXPAND trial:
Considerations for general CFTR modulator use
must take w. fat containing meal.
get basline ast/alt levels
ast/alt q 3 mo. first 1 year, annually therafter
dose reduction required in mod-severe hepatic dysfunction
DDIs of CFTR modulators
Ivacaftor, Tezacaftor, Elexacaftor
mechanism of DDI:
EX:
Affect on AUC and CMAX:
dose adjustment :
I, Tz, El: cyp3a4 substrates
mechanism of DDI: moderate cyp3a4 inhibitors EX: erythromycin and fluconazole
Affect onAUC and CMAX: increase
dose adjustment :
*I once daily,
* Tz, El: qod alternating btw T+I( or E/T/I) and I
mechanism of DDI: STRONG cyp3a4 inhibitors EX: clarithromycin and itroconazole
Affect onAUC and CMAX: significant increase
dose adjustment :
*I : twice weekly
* Tz, El: twice weekly T/I or E/T/I
mechanism of DDI: CYP3A4 induction
EX: rifampin, carbamezapine, phenobarbital, pheytoin, st johns wort
Affect onAUC and CMAX: significant decrease
dose adjustment :
*T : avoid concomitant use
* Tz: avoid concominant use
DDIs of CFTR modulators
Lumacaftor/ Ivacaftor: STRONG cyp3a inducer
cotreatment w. cyp3a4 inhibitors (ex itraconazole),
if L/I added to a regimen w. storng inhibitor..
decrease lumacaftor/ivacaftor dose to 1 tab daily during first week, then rsume normal dose therafter
if string inhibitor added to L/I regimen.. no dose adjustment needed
Non Pharm Treatment of CF lung disease
high frequency chest wall oscillation (HFCWO) aka “vest” therapy
postural draining (PO)
Positive Expiratory pressure (PEP)
Oscillatory PEP-devices : flutter, Acapella, AerobikA and Corney
Exercise
Annual Influenza vaccination starting at age of 6 mo.
Topical Mucolytic/ Hydrating Agents
ex: Dornase Alfa
indication:
dose:
AE:
considerations:
ex:
indication: mucolytics
dose: 2.5 mg inhalation 1-2x daily
AE: hoursenss of voice, rash
considerations:
improves FEV and decrease acute pulmonary exacerbations.
well tolerated
chronic use recommended in mild and strongly recommended in mod-severe disease to improve lung function and increase qol
more commonly used in >/ 6y.o
Topical Mucolytic/ Hydrating Agents
ex: Hypertonic Saline
indication:
dose:
AE:
considerations:
ex:
indication: helps pull water into airway and derease thickness of scretion, making it easier
dose: 4mL inhalation BID
AE: bronchospasm, can be mitigated by albuterol
considerations:
limited impact on FVC OR FEV1, but does decreas rate of APE
well tolerated
chronic use recommended in mild-sev. disease to increase lung function and inc. qol
more commonlyused in adults >/6
broncodilator considerations
used in ~90% of pts
cf has asthma like component, makingthese beneficial
improve deposition of inhaled meds
SABAs such as albuterol commonly used
LABAs less comonly used such as salmeterol
anti-inflammtories: Azithromycin considerations
indication:
dose:
AE:
Azithromycin most commonly used antifinflammatory
most clear indication: in pts >/6 y.o chronically infected with P. Aeruginosa (and w.o) to improve lung function and reduce APE in mild-severe pts
dose:
10mg/kg PO MWF in pts. <25kg (off label dosing)
250mg PO MWF in pts. <40 kg
500 mg PO MWF in pts >40 kg
studies saww..
increase in FEV1 and fvc
increased ABW
decreased exacerbation
improv wol.
small studies saw abx resistance
ae: well tolerated. N,V wheezing
Considertions for inhaled abx
indication:
target organism:
dosing schedule
provide high conc directly to site of infection.
*targets bacterial colonization to decrease number of exacerbations
systemic absorbtion minimal
have on and off dosing (28 days on, 28 days off)to prevent adaptive resistance
target P. aeruginosa
indication: suppresive therapy chronic pulmonary infection due to p. aeruginosa in age >/6. recommended in milf and strongly recommended in mod-severe disease
inhaled ABX for CF
- Inhaled tobramycin
tobramycin (TOBI) 300 mg inhaled BID-28 days ON and 18 OFF
*nebulizer solution: administer over ~15 min
tobi Podhaler 112mg (4x28 mg caps) inhaled BID 28 days ON and 28 OFF
*DPI: administer over 2-7 min
AE: voice alteration, tinitis
- Inhaled Aztreonam
75 mg inhaled TID 28 days ON and 28 OFF.
*neb solution: administered over 2-3 min using altera nebulizer
AE: bronchospasm (can pretreat with SABA)
goal BMIs for CF pts
children: BMI> 50th percentile
adults:
MAle: BMI>23
Female: BMI>22
recommended diet for CF
MODERATE FAT, HIGH PROTEIN, AND HIGH CALORIES.
enteral feedings for children fallen off of the growth curve and asults not gaiing/maintaining weight
Nutrition: Pancreatic Enzyme Replacement Therapy(PERT) dose
emperic doses
maintenance dose
considerations for dose asjustments
recommended dose:based on lipase component
empiric dose:
infants: 2000-5000 U/ 120 mL formula
children<4 y.o: 1000U/KG w/ meals and 1/2 dose w. snacks
Children>4 and adults: 400-500 U/kg w. mals and 1/2 dose w. snacks.
*mean dose=1800-1950 units/kg/meal
maintenance dose:
*titate dose based on abw, STOOL FAT CONTENT, AND GI SYMPTOMS
consider decreasing dose if
*pt on high doses w. good effect
*pt having AE
consider increasing if
*poor weight gain
*pt experiencing bloating, increased # of fatty stools
PERT clinical pearls
brands and formulations not interchangeable
choose best dosage form: #after brand name is U/capsule. choose a formulation and round dose to nearest whole capsule
plan how it will be administered. (children<8 cant swallow tabs/caps well, so dose w. soft foods
Nutrients: Supplementation
multivitamins:
vitamin D:
vitamin k:
minerals:
multivitamins supplement s contaiing fat soluble vitamins(ADEK)
age<12 mo: 1mL PO QD age 1-3: 2 mL PO qd
AGE4-10 Y.: 1 TAB po qd AGE >10 2 TAB po qd
VitD supplements for pts hacing low 25-oH vit. D levels
Age 1-11 years: Vitamin D3 – 1000 IU QD
Age > 11 years: Vitamin D3 – 2000 IU QD
If level < 30 ng/ml after 3 months treatment…
o Age < 5 years: Vitamin D3 – 50,000 IU MWF X 1 month
o Age>5years:VitaminD3–50,000IUQDX1month
o May repeat course or refer if < 30 ng/ml after treatment course
Vit K supplemets during IV abx treatment.
*phytonadione (Vit.K( 5 mg PO twice weekly)
Minerals:
*Ferrous sulfate (iron),
*if poor weight gain-> zinc sulfate 1mg/kg/d divided bid
VITAMIN supplementation considerations
kids <8y.omay not be able to swallow tabs/caps
may crush tabs and take them w. soft foods
Acute Pulmonary Exacerbation
acute worsening of pullmoary symptoms
cough
increased sputum production
sob
chest pain
loss of appeitite
wightloss
lun function decline
airway clearance during APE of CF
increase vest treatment
increase dornase alfa
increase hypertonic sale
increase bronchodilator
abx trt of APE of CF considerations
abx selection:
*emperic abx based on population data in absense of culture data
*when culture is available , abx selection can be individualized based on historical culture data
abx dosing:
if pt has not been treated w. a given abx or if abx not monitored by tdm, dosig based on populaion pk data
if a pt trated w. a given abx tht required tdm, dosing can be individualized based on pt specific historical pk data. (this process helps get pts to goal quicker)
ex: if pt recieved tobramycin 10 mg and was titrated to 12 mg that pput them in the therepeutic range, next time they are admitted, they should be started on 12, assuming no change in clinical status or renal function
most common clinical situations requiring abx treatment in CF (empiris)
cf exacerbation w. hx MSSA ( no PA)
*anti-staph PCN/CEPH
cf exacerbation w. hx of MSSA AND PA
*double PA coverage: aminoglycoside+cefepime
cf exacerbation w. hx of MRSA (no PA)
*vancomycin or linezolid
cf exacerbation w. hx of MRSA and PA
*vanco or Linezolid PLUS
*double PA coverage: aminoglycoside+beta lactam (eg. ceftazidime)
when C&S. therapy can individualized
Less common clinical situations for abx treatment of APE
b cepacia and/or S. maltophilia
*combo therapy w. 2-3 drugs needed, guided by C&S
Abx dosing strategy
Extended dosing:
*dose q24 hrs.
*takes advantage of conc dependent killing strategies and maximizing peak/MIC interval
*increases drug free interval, dec amount in kidneys(reduce toxicity)
Abx dosing strategies
Extended Interval aminoglycioside dosing (EIAD):
*dose q24 hrs.
*takes advantage of conc dependent killing strategies and maximizing peak/MIC interval
*increases drug free interval, dec amount in kidneys(reduce toxicity). once daily dosing is preferable to TID dosing
Continous and extended/prolonged infusion beta lactam dosing
*beta lactama time dependent killing
*continous infusion-> maintains constant conc over course of regimen, dose individualized to target conc. above MIC
*extended infusion: conc graudlay increases until infuion stops. then decreases based on pts. pk parameters
*insufficient evidence to recommend continous (extended) infusion for beta lactams for APE trtment
duration of abx treatent of APE
duration of 14-21 days or longer
if no improvement in 5-7 days, reculture and or ajust abx
therapy may be completed at home w. PICC or port, or step down PO
monitoring efficacy and saftey for abx tretment in APE in CF
symptom persistence/ resolution
pulmonary function tests..FEV1 FVC
sputum culture and susceptibilities
BUN/ Scr
abx serum concentrations
Aminoglycoside monitoring for efficacy and efficacy
monitor peak and trough amg conc
traidiotnsl dosing: 10-12 mcg/mL/goal trough <1-2
EIAD: goal peak: 22.5-27.5 mcg/mL/ Goal 18hr level<1 mcg/mL
goal AUC 80-100 mcg/mlh
serum conc drawn initially and then q3-7 days
aminoglycose pk equations
Ke=ln(c1/c2)/deltaT
C=C0e^-kt
T1/2=0.693/ke
monitoring efficacy and safety : vancomycin
time dependent abx. trough concentrations needed only
goal 10-20 mcg/mL(to achieve AUC/MIC>/400
serum conc should be drawn initially once pt reaches Css (18-30 hrs), then q3-7d after
Unique issues for abx treatment acute cf exacerbations
multiple abx allergies: CHECK PT ALLERGIES BEFORE TRTMT
difficulty of penetration to site of infection due to thick mucus as well as mucoid layers on bacteria itself, especially on P. aeruginosa
more prone to AE of abx therpay, short term an dlong term
because reiceve multple abx therapies over lifetime, increase risk fo rmultidrug resistant organisms
abx pk:
*general rule. VD and CL INCREASEDDD (vs general population) of beta lactams and AMG in CF population
lung mechanisms of injury
oxidant injury
immune complex mediated
interferance with matrix formation
interferance with lipid metabolism
epidemiology of pulmonary toxicities
acute or chronic-> get good hx
ranges from reversible of toxicity to death
stopping med is most important step. corticosteroids can hellp, but not alot of good data
most present w. resp. symptoms and changes on xray
it is a dx og exclusion (Naranjo Scale)
lungs are capable of drug metabolism, co it can afect pulmonary vascular in a variety of ways
naranjob scale
estimates the probability of an adverse event
important questions in scale
*did the adverse event appear after suspected drug was administered
*was the reACTION MORE SEVER WHEN THE DOSE WAS INCREASED OR LELSS SEVERE WHEN THE DOSE WAS DECREASEd
score>/5 there is an advers eevent
risk factors for drug induced pulmonary diease
drug related
*dose or rate of administration
*treatment duration
*oxygen therapy
*radiation
cumulative dose (anything that can decrease antioxidants)
pt realted factors
*age (extremes of age)
*RA or preexisting lung disease
*impaired renal/hepatic function (review pkpd parameters)
genetics
Types of drug induced interstitial lung diseases
pulmonary fibrosis
pneumonitis
organizing pneumonia
eosinophilic pneumonia
hypersensitivity pneumonia
noncardiac pulmonary edema
diffuse alveolar damage/ diffuse alveolar hemorrhage (DAD/DAH)
drug induced insterstitial pneumonitis or fibrosis (DIP/F)
patho
onset
SS
Chronic
PE:
chest CT
patho:
usual or nonspecific interstitial pneumonia
*drug induced pulmonary fibrosis or idiopathic pulmonary fibrosis
*fibrosis can occur with many drugs and may be preceded by an acute pneumonitis
*fibrosis can lead to pulmonary HTN
onset: acute, subacute, chronic
SS: nonproductive cough and sudden onset dyspnea (hours), fever, rash, eosinophilia
Chronic: slowly progressing breathlessness, decreased physical activity
PE: crackles on expiration, clubbing
chest CT: fibrosis (decreased lung volumes, BL diffuse ground-glass opacities (honeycombing)
BAL: bronchoscopy alveolar lavage
DIPF mechanism of toxicity
direct toxic effect or oxidative stress
v
causses damage to
v
*alveolar epithelial cells
*platelet activation, release of
inflammatory cells and mediators,causes fibroblast recruitment
*or endothelial cells
*increases permeability and vascular leak
*impair cell repair and cell death
V
overall increases inflammation and excess deposition of extracellular matrix
v
causes remodeling, honeycombing,and fibrosis
causative agents of DIPF
antimicrobial
nitrofurzntoin
mechanism
presentation
incidence
mechanism: imbalance of oxidant/antioxidant
presentation:
*acute eosinophilic pneumonia
*pulmonary fibrosis (chronic):8. mo-16yrs
incidence: <10%, mortality: 8% (chronic)
causative agents of DIPF
antirheumatic: Leflunomide
mechanism
presentation
incidence
causative agents of DIPF
mechanism–
presentation–
incidence: incidense-1.46-0.63%
causative agents of DIPF
METHOTREXATE
mechanism
presentation
incidence
causative agents of DIPF
mechanism: hypersensitivity
presentation: onset days-years
incidence: incidence 0.43%
(low dose);5-10%
causative agents of DIPF(ANTINEOPLASTICS)
BLEOMYCIN
mechanism
presentation
incidence
mortality
causative agents of DIPF(ANTINEOPLASTICS)
mechanism: cytokine, inflmmatory cells and free o2 radical induction
presentation: weeks to months;can progress to fibrosis (well known)
incidence: 6.8-21%
mortality: 48%
causative agents of DIPF(ANTINEOPLASTICS)
BUSULFAN
mechanism
presentation
incidence
mortality
causative agents of DIPF(ANTINEOPLASTICS)
mechanism: direct alveolar injury
presentation: 4 years after monotherapy: months after high dose
incidence: 6%
mortality:25%
causative agents of DIPF(ANTINEOPLASTICS)
CARMUSTINE
mechanism
presentation
incidence
mortality
causative agents of DIPF(ANTINEOPLASTICS)
mechanism–
presentation- months-years after initiation. can progress to fibrosis (years)
incidence: 1.5-20%
mortality: –
causative agents of DIPF(ANTINEOPLASTICS)
CYCLOPHOSPHAMIDE
mechanism
presentation
incidence
mortality
causative agents of DIPF(ANTINEOPLASTICS)
mechanism: Direct alveolar injury
presentation: months of initiation (early), months-years (late)
incidence: 1%
mortality: 25%?
causative agents of DIPF(ANTINEOPLASTICS)
GEMMCITABINE
mechanism
presentation
incidence
mortality
causative agents of DIPF(ANTINEOPLASTICS)
mechanism: endothelial dysfunction after cytokine release
presentation: –
incidence” 1.1-1.9% or up to 20%
mortality: 22%
causative agents of DIPF
EGFRIs (epideral growth factor receptor inhibitors)
mechanism
presentation
incidence
mortality
causative agents of DIPF
mechanism: —
presentation: Acute-1 within 1 month
incidence:
*erlotinib/gefitinib: 1.2-1.6%
*mobocertinib/osimertinib: 3.3-4.3%
*cetuximab/panitumumab: 1%
mortality:
*erlotinib/gefitinib: 22.8%
*mobocertinib/osimertinib: 0.5-1.2%
*cetuximab/panitumumab:50%
causative agents of DIPF
ICPI’s(immune check point inhibitors)
mechanism
presentation
incidence
mortality
causative agents of DIPF
mechanism–
presentation: onset. 3 months (but many be faster if used in combo)
incidence:
PD-10-10%
PD-L1:0-10%
CTLA4: 0.01%
mortality–
causative agents of DIPF
mTORis
mechanism
presentation
incidence
mortality
causative agents of DIPF
mechanism DAD or hypersensitivity
presentation: varies 51 days-104 days:Daily regimens>weekly
incidence: <0.5%-42%
mortality:–
causative agents of DIPF
Taxanes
mechanism
presentation
incidence
mortality
causative agents of DIPF
mechanism:hypersensitivity: Direct Toxicity or organ
presentation: during cycle 2 and within 18 days after last cycle
incidence: Paclitaxel: 0.7-12%
mortality–
causative agents of DIPF
AMIODARONE
mechanism
presentation
Age:
incidence
mortality
causative agents of DIPF
mechanism:direct toxic effect
presentation: 4weeks-6 years
dose dpeendent: Yes; smaller doses_~200 mg) over years (>2 years) or larger doses shorter time frames;about 400 mg/day (>2 months)
Age: patients >60 years old, 3x increase in risk of toxicity each subsequent decade
incidence:1.2-8.8%
mortality: 3-37%
DRUG induced interstitial lung disease treatment due to ICPis
Grade 1:
Grade2:
Grade3,4
Grade 1 pneumonitis
*consider holding med
*reassess in 1-2 weeks
Grade 2
*hold meds
*prednisone/methylprednisolone1-2 mg/kg/day
V
*treat until improvement to grade 1>Then taper over 4-6 weeks
*if no improvement 48-72 hrs>treat as grade 3
grade 3,4:
*permanenet D/C
*methylprednisone 1-2 mg/kg/day
*taper over 4-6 weeks
* if no improvenent in 48hrs, give infliximab, IVIG, or MMF
Treatment of DIILD: mTORIs
Grade 1:
grade2:
grade3:
grade4:
grade 1: no recommendation
grade 2: dose reduce or hold med
*prednisone 0.75-1mg/kg/day>continue until grade 1
grade 3:*hold med
*prednisone 0.75-1mg/kg/day>continue until grade 1
Grade 4: permamntly D/C
*prednisone 0.75-1mg/kg/day>continue until grade 1
other treatments of DIILD: select medications
bleomycin: 0.75 mg/kg/day for 4-6 weeks, then taper
Carmustine: Prednisone 60 mg po BID then 30 mg po daily then tapered by 10 mg po weekly then 5 mg po weekly
amiodarone: Prednisone 0..5-1mg/kg/day. continue for several months to up to 1 year
Prevention of DIILD
baseline spirometry, DLCO, and chest xray in high risk agents
should occur q2weeks to q4mo.
amiodarone: Baseline then q3mo if clnically indicated
bleomycin: chest xray q1-2 weeks; and DLCO monthly
Drug induced Pneumonias
Bronchiolitis obliterans organizing pneumonia (BOOP)
what is it:
SS:
causative agents:
treatment:
what is it: acute inflammatory respons ein lung
SS:nonproductive cough, dyspnea, BL crackles, occasional fever/rash, xray: BL patchy infiltrates
causative agents: minocycline/nitrofurantoin, bleomycin, amiodarone, sulfasalazine, carbamezapine, cocaine
treatment: D/C agent or add steroids
Eosinophilic pneumonia
what is it:
SS:
causative agents:
treatment:
what is it: infiltration of pulmonary insterstitium w. eosinophils; drug or toxin mediated
SS:dry cough, dyspnea, echest pain, feevr;BL gorund glass opacities
causative agents: daptomycin, nitrofurantoin, minocycline,mesalamine, sulfasalazine (ALL)
treatment: Acute: treat w. steroids
chronic: not as common
HYpersensitivity pneumonitis
what is it:
SS:
causative agents:
treatment:
what is it: immediate reaction is more common
SS: urticaria, angioedema, rhinitis, dyspnea Chestxray: localized or BL alveolar infiltrates
causative agents:NSAIDS, methotrexate
treatment:D/C drug. antihistamines and possible steroids
Drug induced pulmonary edema (noncardiogenic)
what is it:
SS:
causative agents:
onset:
remits:
treatment:
what is it:
SS: cough, crepitation, cyanosis/hypoxemia, chest xray (acinar infiltrate and normal heart size
causative agents: narcotics, (iv heroin, morphine, methadone,meperidine, propoxyphene, naloxone, nalmefene, HCTZ
*dose dependent moderate to high dose narcotics
onset:minutes-2hrs
remits:24-48hrs (symptoms, 2-5days (xray), 10-12 weeks (PFTs)
treatment: naloxone, oxygen, ventilator support
Drug induced Lupus
what is it:
SS:
causative agents:
onset:
remit:
dose dependent?
treatment:
what is it:
SS:feever, myalgias, rash, althralgias, arthritis, and serositis, pleuritic pain
chest xrazy: pleural effusion, diffuse intersitial pneumonitis, and alveolar infiltrates
causative agents: !!procainamide!!, hydralazine, isoniazid, or anti-TNF alpha
compared to spontaneous lupus
*F:m ratio is 1:1 for DI lupus
rare in DIL(common in regular lupus): discoid lesions, malar erythema, renal disease, and CNS disease, no formation or complement and immune complexes
onset: up to 3 years after initiation
remit: 6 weeks
dose dependent? : no
treatment: drug withdrawal
