Pulm Exam 2 Flashcards
What is the most common site of ADR
skin, GI, CNS
Common presentations of drug-induced pulmonary disorders
apnea
bronchospasm
pulmonary edema
pulmonary eosinophilia
pulmonary fibrosis
Risk factors for drug-induced pulmonary disorders
age
pre-existing lung disease
combo therapy
cumulative doses
oxygen therapy
radiation therapy
occupational risk factors
Diagnosis for drug-induced pulmonary disorders
nonspecific clinical, radiologic, and histologic findings
often at diagnosis of exclusion
characteristic pattern of reaction to a specific drug
discontinuing the drug may reverse toxicity
Classification of drug-induced pulmonary disorders
histology/pathophysiology
med class
clinical manifestation
meds that cause drug-induced bronchospasm
aspirin
beta-blockers
sulfites
contrast media
ACE
N-acetylcysteine
natural rubber/latex allergy
Airway obstruction/bronchospasm
most common drug-induced pulmonary disorders
increased risk in patients with pre-existing bronchial diseases
Pathophysiological mechanisms for airway obstruction/bronchospasm
anaphylaxis (PCN, ceph, sulfa)
direct airway irritation (N-acetylcysteine, pollutants, DPI)
beta 2 receptor blockade
cyclo-oxygenase inhibition (NSAID, ASA)
anaphylactoid mast cell degranulation (contrast dye)
Causes of apnea/respiratory depression
CNS depression
respiratory neuromuscular blockade
Risk factors for apnea/respiratory depression
Age
COPD
alveolar hypoventilation/CO2 retention
dose
multiple agents
ACE inhibitor induced cough
women > men
African Americans and Chinese
seen with all ACE-inhibitors
occurs 3 days to 1 year after initiation
Drug-induced pulmonary edema is a failure of any one, or combo of homeostatic mechanisms:
increase in capillary hydrostatic pressure due to left ventricular failure
disruptions in osmotic and oncotic pressures in vasculature
damaged alveolar epithelium
disruption in interstitial pulmonary pressure
obstructed interstitial lymph flow
Drug-induced pulmonary eosinophilia (symptoms of loeffler’s syndrome)
fever
productive cough
dyspnea
cyanosis
bilateral pulmonary infiltrates
eosinophilia in the blood
Drug-induced pulmonary fibrosis
chemo agents make up largest group
caused by:
O2 therapy
chemo
radiation
infection
inflammatory injury
Drug-induced pulmonary HTN
cocaine
oral contraceptives
amphetamines
chemo agents
anorexic agents
Drug-induced pleural effusions
methysergide, practolol (idiopathic)
drug induced lupus syndrome:
procainamide, hydralazine
Beta blocker induced bronchospasm
may increase risk of asthma
less risk in cardio-selective agents
caution with topical admin of timolol for open angle glaucoma
Sulfite-induced bronchospasm
rare, severe, life-threatening asthmatic rxn after restaurant meals and wines
-food preservative potassium metabisulfite
-could be EDTA and benzalkonium chloride
Management pre-treatment drugs for sulfite-induced bronchospasm
cromolyn
anticholinergics
cyanocobalamin
N-acetylcysteine
use via inhalation as a mucolytic
direct airway irritation
admin beta 2 agonist w/ or APAP prior to N-acetylcysteine
Drugs that cause drug-induced pulmonary edema
cardiogenic
excessive IV fluids
blood and plasma transfusions
corticosteroids
opioids
idiosyncratic rxn to med/high dose narcotics
salicylate overdose
Treatment for opioid-induced edema
naloxone, oxygen, ventilator
sx improve 24-48 h
CXR clear 2-5 days
pulm fx test abnormalities may persist up to 10-12 wks
Drugs that cause drug-induced pulmonary eosinophilia
nitrofurantoin
para-aminosalicylic acid
methotrexate
sulfonamides
tetracyclines
chlorpropamide
phenytoin
NSAID
imipramine
Drug-induced pulmonary eosinophilia treatment
rapid improvement in sx following disc
-complete recovery in 15 days of w/drawl
anecdotal reports steroids may be beneficial
Signs and symptoms of drug-induced pulmonary fibrosis
dyspnea
hypoxemia
nonproductive cough
diffuse alveolar damage
interstitial pneumonitis
Risk factors for drug-induced pulmonary fibrosis: antineoplastics
cumulative dose
increased age
concurrent or previous radiotherapy
oxygen therapy
other cytotoxic drug therapy
pre-existing pulmonary disease
Drug-induced pulmonary fibrosis: Belomycin
dose dependent
generate superoxide anions
sx: cough and dyspnea
-chronic progressive fibrosis most common
-acute hypersensitivity rxn occur infrequently
Other chemotherapeutic agents that cause drug-induced pulmonary fibrosis
alkylating agents
antimetabolites
methotrexate
Risk factors for drug-induced pulmonary fibrosis: amiodarone
from wk to 6 yrs before onset
higher during first 12 months of therapy
cardiopulmonary surgery combined with the administration of high concentrations of oxygen
maintenance dose >400 mg for more than 2 months***
smaller doses for more than 2 years
Drug-induced pulmonary fibrosis amiodarone clinical features
exertional dyspnea (DOE)
nonproductive cough
wt loss
occasional low grade fever
radiographic changes are non-diagnostic
hypoxia, restrictive changes and diffusion abnormalities
Management for drug-induced pulmonary fibrosis
disc therapy
oxygen therapy
maybe corticosteroids
Classification of pleural disease
pleurisy (caused by viral pneumonia)
hemothorax, pneumothorax, chylothorax
pleural effusion
Pleuisy (aka pleuritis) symptoms can be treated with what
NSAIDS
cough suppressants
hemothorax, pneumothorax, chylothorax definition
a disruption in the pleural space and subsequent accumulation of air, blood, or lymph, resulting in compromised lung expansion
What is a tension pneumothorax
acute rapidly expanding pneumothorax; pressure exerted on the heart and greater vessels cause hemodynamic instability; may be fatal
Clinical presentation of hemothorax, pneumothorax, chylothorax
SOB
DOE
chest pain and dyspnea
tachypnea
cough
Management of hemothorax, pneumothorax, chylothorax
medical/surgical
-chest tube thoracostomy
adjunctive pharmacotherapy
-analgesia (opioides 1st line agent)
antimicrobial therapy
Antimicrobial therapy for management of hemothorax, pneumothorax, chylothorax
depend on circumstances of placement (use when placed in field)
1st gen cephalosporin (cedazolin x24 h)
Pathophysiology of pleural effusions
fluid movement into/out of pleural space determined by pressure gradient
(hydrostatic pressure from vessels, oncotic pressure from proteins in blood plasma)
“Fluid in”
“Fluid out”
Fluid accumulation due to loss of fluid homeostasis defines a pleural effusion
Pleural effusions: what does fluid in vs fluid out caused by
in: parietal pleura capillary hydrostatic pressure
out: lymphatic drainage
What is transudative pleural effusion
increased hydrostatic pressure, decreased oncotic pressure or both
pleural membrane not affected (pleurae are normal)
management: treat underlying cause
unresolved, severe, and recurrent effusions: thoracentesis, pleurodesis
What is exudative pleural effusion
result of pleural membrane disease
(caused by pneumonia or neoplastic disease)
management: treat underlying cause
requires direct intervention
What is pneumonia and neoplastic disease as a result of pleural membrane disease
pneumonia: parapneumonic effusion
neoplastic disease: lung, breast, lymph
Transudative: pleural fluid composition, pleural membrane involvement, most common etiology, often frequent cause
pleural fluid composition: low protein
pleural membrane involvement: no
most common etiology: HF
often frequent cause: cirrhosis, PE, nephrotic sydrome, SVC obstruction
Exudative: pleural fluid composition, pleural membrane involvement, most common etiology, often frequent cause
pleural fluid composition: high protein, cell count, LDH
pleural membrane involvement: Yes
most common etiology: pneumoniae
often frequent cause: neoplastic disease, infection (empyema), PE, drugs
Drugs that cause exudative pleural effusion
methotrexate
bromocriptine
nitrofurantoin
dantrolene
amiodarone
Diagnosis of pleural effusion
usually CXR (does not differentiate btw transudative and exudative)
Who gets treated in pleural effusions
symptomatic
recurrent
General approach to management of pleural effusions
stabilize the patient (ABC)
treat the underlying cause
provide symptomatic relief
prevent complications
prevent recurrence
Management of pleural effusions: thoracentesis (pleuracentesis)
needle drainage
one-time procedure
effective, but high incidence of recurrence
often diagnostic, not therapeutic
Management of pleural effusions: tube thoracostomy
drainage
instillation of pharm agents
tx of loculated effusions (intrapleural meds)
tx of loculated effusions in tube thoracostomy
streptokinase 250,000 units/urokinase 100,000 (units in 50-100 ml NS instilled once or twice daily)
alteplase 10 mg in NS 50 ml BID x6 doses
dornase alfa 5 mg in NS 50 ml BID x6 doses
alteplase + dornase alfa
Management of pleural effusions: pleurectomy
radical, side effects, rarely used
Management of pleural effusions: pleuroperitoneal shunt
impractical/inconvenient, complicated, rarely used
What is chemical pleurodesis
admin of a sclerosing agent into pleural space to induce a chemical pleuritis, which will form symphyses
Chemical pleurodesis: candidates
symptomatic, recurrent effusions
symptomatic improvement (decrease SOB) w/ complete lung re-expansion following thoracentesis
no intrabronical obstruction
Chemical pleurodesis: administration needs to have the following
ability of lung to expand
complete drainage of accumulated fluid
complete distribution of agent
absence of loculations
Chemical pleurodesis: agents commonly used
doxycycline (500-1000 mg x1-3 doses; repeat 2-3 d prn)
talc (must be sterile, asbestos-free, larger particle; thprascopic insufflation vs slurry via chest tube)
bleomycin (chemo agent)
Chemical pleurodesis: lidocaine
adjunctive therapy for local anesthesia
15-25 ml of a 1% soln (OR 3-4 mg/kg) instilled 15 min before procedure
What kind of channel is CFTR
cAMP activated anion (Cl-) channel it increased volume of secretions and decreased viscosity of lung mucus
What are the 6 different CFTR mutations
1: no protein
2: no traffic
3: no function
4: less function
5: less protein
6: less stable
What CFTR modulators are potentiators
ivacaftor
deutivacaftor
What CFTR modulators are correctors
lumacaftor
tezacaftor
elexacaftor
vanzacaftor
Potentiators do what
increase opening time of the CTFR channel resulting in higher ion flow
Correctors do what
facilitate the processing of mutated CFTR protein substrate leading to improved delivery to the cell membrane
Amplifers do what
selectively increase the amount of immature CFTR protein in the cell providing additional substrate for correctors and potentiators to act upon
Ivacaftor MOA
improve function of defective CFTR that reaches the cell surface
binds to defective protein at cell surface and opens chloride channel
improve gating capacity of CFTR activation of chloride channel of CFTR
Lumacaftor MOA
correct the processing and trafficking of defected CFTR
CFTR can reach the cell surface
at cell surface, the drug can further enhance the channel function
What drug causes chest discomfort and can increase bronchial secretions and productive cough
Orkambi
Trikafta (only does increase secretions)
What drug causes cataracts and can increase serum bilirubin and transaminases
Alyftrek
Trikafta (only does increase serum)
What is dornase alfa and its side effects
mucolytic agent
chest pain, voice disorder, pharyngitis, rhinitis, skin rash
Dornase Alfa MOA
rhDNase which hydrolyzes the DNA in mucus of CF patients which decreases mucus viscosity
In CF, impaired anion transport results in decreased secretion of more acidic fluid leading to what
precipitation of secreted proteins which decreases action of digestive enzyme causing malabsorption intraluminal obstruction of ducts leads to progressive pancreatic damage and atrophy
Pancreatic enzyme replacement therapy (pancrelipase)
Creon, pancreaza, pertyze, ultresa, viokace, zenpep
acts on GI tract
contain combo of lipase, amylase and proteases
natural product from porcine pancreatic glands
causes neck pain, ad pain, nasal congestion
What are the organs effected by CF
lungs, digestive system, reproductive organs
What is the most common mutation of CF
delta F508
autosomal recessive disease
Pathophysiology of gene mutations CF
mucosal obstruction
chloride transport
expression of other gene proteins involved in inflammatory processes, ion transport, cell signaling
Pathophysiology of sweat glands CF
CTFR regulates ion transport and salt homeostasis
chloride fails to be reabsorbed which impacts sodium ion reabsorption
results in sweat with high salt
Pathophysiology of lungs CF
abnormal Cl conductance on apical membrane, decrease airway surface liquid cause ciliary collapse and decreased mucociliary transport
causes mucus obstruction, infection, inflammation
Sinus and pulmonary clinical presentation of CF
chronic infection and nasal polyps in sinus cavity
SOB/cough w/ sputum production
flat chest, decreased FEV1
bacterial overgrowth
GI system clinical presentation of CF
obstruction of pancreatic ducts and intestinal tract, can not digest essential nutrients
infants: meconium ileus, steatorrhea, fail to thrive
older pt: severe constipation and insulin deficiency
reproductive system clinical presentation CF
male: blockage of or congenital bilateral absence of vas defs -> azoospermia
females: decrease water content in cervics which decrease fertility
Diagnosis of CF
IRT
QPIT (sweat chloride test)
<29 normal, 30-59 intermediate, >60 diagnostic (collect test from second site to confirm)
Non pharm tx for CF
want normal wt in adults and normal growth in kids
110-200% energy intake (eat more food)
What vitamins to take with PERT
A, D, E, K (fat soluble)
30 or greater ng/mL
Dosing for PERT
500-2000 lipase units/kg/meal
10,000 lipase units/kg/day
4,000 lipase units/gm of dietary fat/day
risk: <12 yo, doses >6,000 lipase units/kg/meal for >6 months, h/o meconium ileus, intestinal surgery, ibd
Formulations for PERT
capsules (can be mixed with food, do not let sit)
Do not crush tablets
can take with H2-antagonist or PPI
Risk factors for bone health and vitamin supplementation
malabsorption of vit D
poor nutritional status
physical inactivity
glucocorticoid therapy
antibiotics that require protection from sunlight exposure
DXA t/z score: >-1.0, >-2.0, <-2.0
> -1.0: repeat in 5 years (opt vit D, ca, vit K)
-2.0: repeat 2-4 years (improve nutrition, aggressive pulmonary tx, min steroid dosing, treat Cf-related diabetes)
<-2.0: repeat yearly (improve nutrition, consider bisphosphonate)
ACT airway clearance therapy steps
bronchodilator
hypertonic saline
dornase alfa
chest percussion
aerosolized antibiotics
What are the 2 types of anti-inflammatory therapy for CF
Ibu (20-30 mg/kg BID) for 6-17 yo and FEV >60%
Azithromycin (for pseudomonas)
Indications for antibiotic therapy for CF
acute pulmonary exacerbation, chronically infected w/ pasudomonas, require prevention of chronic psedudomonas
use aerosolized antibiotics
Pathogens for CF
early: staph
late: psedudomonas (need drug for cell wall destruction and inhibit cell wall synthesis)
pathogens never fully eradicated
What to use for CF pt with stenotrophomonas
SMZ-TMP
doxycycline
Vaccinations for CF pts
flu shot >6 months
PCV
COVID-19
Counseling for females and males with CF
female: OCP safe, DDI with OCP and antibiotics, patches may not adhere to skin
male: not infertile
CFRD (cystic fibrosis related diabetes) clinical features
18-21 years
females predominance
yearly beginning at age 10 with OGTT
insulin is therapy of choice
Ivacaftor indication and approved age
class 3, >1 month
lumacaftor/ivacaftor indication and approved age
delta F508 mutation, >1 year
tezacaftor/ivacaftor indication and approved age
delta F508 mutation, >6 year
elexacaftor/tezacaftor/ivacaftor indication and approved age
at least 1 delta F508 mutation, >2 years
vanzacaftor/tezacaftor/deutivacaftor indication and approved age
at least 1 delta F508 mutation or another responsive mutation in CFTR gene, >6 years
Pregnancy CF
high risk
monitor levels in first trimester to avoid toxicity while cont A, D, E, K vitamins
need more calories for breast feeding
complications: increased o2 uptake, blood volume, cardiac output, may cause right sided-HF
Peds CF
education of pt and child
Transplant CF
those for severe disease <30%
others: nutritional status, diabetes, number of CF exacerbations, compliance to care or immunosuppressant therapy
follow up for CF
q1-3 months
Desired outcomes in CF patients
sinopulmonary (prevent exacerbations, clearance of airways, bacterial colonization)
GI (optimize growth and nutrition, calorie intake)
psychosocial (education)
