Respiratory Pharmacology Flashcards
albuterol
class: inhaled SABA
clinical: bronchodilation
- prn quick relief of asthma sx
- exacerbations or pre-exercise
- prn only, lowest dose possible
- must be combined w/ ICS as SABA-only tx does not prevent exacerbations, and regular/frequent use may increase risk of exacerbations
route of administration: aerosol inhaler ± spacer ± nebulizer
metabolism: phase II liver (sulfotransferase)
adverse events:
- tachycardia
- tremor
- tolerance
- excess use w/o ICS -> increased risk of exacerbations
salmeterol
class: inhaled LABA
clinical: bronchodilation
- asthma
- COPD
metabolism: CYP3A4
formoterol
class: inhaled LABA w/ rapid onset
clinical: bronchodilation
- asthma
- COPD
- reliever and maintenance d/t rapid onset and long duration of action
metabolism: primarily glucuronidation
note: typically combined with ICS in ICS-formotorol dual formulation (Symbicort), which is preferred tx through most stages of asthma
vilanterol
class: inhaled LABA
clinical: bronchodilation
* COPD
- asthma
- once daily
- found in several combo products for COPD (both emphysema and chronic bronchitis)
metabolism: CYP3A4
ipratropium
class: inhaled SAMA
mechanism: pan-muscarinic ANTagonist
clinical:
- COPD maintenance
- acute asthma exacerbation in adults and peds (off-label)
route of administration:
- inhaler ± spacer ± nebulizer
- nasal spray
metabolism: CYP450
tiotropium
class: inhaled LAMA
mechanism: preferential M1 and M3 ANTagonist
clinical:
- maintenance COPD, asthma
metabolism: unmetabolized urinary
glycopyrrolate (glycopyrronium)
class: inhaled LAMA w/ fast onset
mechanism: preferential M3 ANTagonist
clinical:
- maintenance COPD
- fast-acting option for moderate to severe COPD
metabolism: unmetabolized urinary
umeclindinium
class: inhaled LAMA
mechanism: pan-muscarinic, preferential M3 ANTagonist
clinical:
- used in combo with vilanterol (LABA) for moderate to very severe COPD
route: once daily inhaled
metabolism: CYP450, but without changes in renal or hepatic impairment
beclomethasone
class: ICS
clinical:
- maintenance asthma
metabolism: prodrug; mostly fecal excretion
budesonide
class: ICS
clinical:
- budenoside-formoterol (Symbicort) is most common/preferred tx for asthma maintenance and relief
- decreased severity and duration of asthma attack
- maintenance COPD (off-label)
metabolism: CYP3A4
fluticasone
class: ICS; of ICS, highest binding affinity and selectivity for glucocorticoid receptors, longest tissue retention
clinical:
- asthma
- allergic rhinitis
- emphysema
route: nasal spray
metabolism: CYP3A4
mometasone
class: ICS
clinical:
- maintenance asthma
- seasonal and perennial allergic rhinitis
route: intranasal
metabolism: CYP3A4
omalizumab
class: humanized IgG1 mAb, anti-IgE
mechanism: anti-IgE
- binds free IgE (only), reducing its availability for binding
- no basophil degranulation or cross linking
clinical:
- moderate to severe allergic asthma
- refractory idiopathic urticaria (hives)
- severe food allergy (off-label)
route: sc, iv
AEs:
- anaphylaxis after 1st dose or ongoing tx; receive all doses in monitored clinical setting
mepolizumab
reslizumab
class: humanized mAb vs IL-5
- eosinophils and basophils
clinical:
- severe allergic asthma
route:
- mepolizumab: sc
- reslizumab: iv
benralizumab
class: humanized mAb vs IL-5R
- eosinophils and basophils
mechanism:
- IL-5R blocking, AND
- IL-5R neutralization (prevents hetero-oligimerization to blockade downstream signalling)
clinical:
- all asthma
- seasonal and perennial allergic rhinitis
route: intranasal
metabolism: CYP3A4
dupilumab
class: human mAb vs IL4 and IL13
mechanism: targets Th2 pathway (extrinsic)
- both IL4 and IL13 are involved in eosinophil recruitment, especially together
- IL13 also involved in smooth muscle contraction and proliferation involved in bronchospasm and fibrosis
clinical:
- add-on maintenance moderate-to-severe allergic asthma
limitation:
- NOT for acute bronchospasm
route: sc
tezepelumab
class: human mAb vs TSLP
clinical:
- add-on maintenance maintenance severe asthma
route: sc
montelukast
zafirlukast
class: cysteine leukotriene receptor ANTagonists
clinical:
- chronic asthma
- prevention of exercise-induced bronchospasm
- – esp in SABA-tolerant (i.e., SABA not effective)
- allergic rhinitis
- add-on medications only
- – montelukast + intranasal glucocorticoid for initial treatment of moderate to severe allergic rhinitis
limitations: NOT rescue medications
perfenidone
class: antifibrotic agent, anti-inflammatory
mechanism: TGF-beta ANTgonist
- inhibits collagen/ECM production, fibroblast proliferation
clinical:
- idiopathic pulmonary fibrosis (IPF)
- slows progression but does not halt or reverse disease
route: po
metabolism: primarily CYP1A2
- caution in liver pts
- d/c other CYP1A2-metabolizd drugs
nintedanib
class: antifibrotic agent
mechanism: TYRK inhibitor, multiple pathways:
- VEGFR
- FGFR (fibroblast growth factor)
- PDGF (platelet-derived growth factor)
clinical
- IPF
- systemic scleroderma (SSc) interstitial lung disease (ILD)
- other fibrotic ILDs
- slows progression but does not halt or reverse disease
route: po
metabolism: hydrolic ester cleavage + glucouronidation
AEs:
- GI
- c/i in pregnancy, childbearing potential; do not b/c pregnant for at least 3 mo after d/c
prednisone
class: systemic corticosteroid
mechanism: generalized immunosuppression
- inhibits migration of polymorphonuclear lymphocytes (PMNs)
- reverses capillary permeability p/w
- reduced immune cell count and activity
clinical: generalized immunosuppression ± targeted immunosuppressants; some specific indications in pulm:
- IPF
- cryptogenic organizing pneumonia (COP)
use:
- initial tx 4-8 wk
- when stable, taper as tolerated over 6-12 mo
route: po, iv, im
metabolism:
- prodrug –> prednisolone
- 4x potency of hydrocortisone
AEs: so many, dose and duration dependent
- hypothalamic-pituitary-adrenal (HPA) axis suppression
- infection
- hyperglycemia/metabolic syndrome
- osteoporosis
- cataracts
- myopathy
- adrenal suppression
- cushingoid
azathioprine
class: immunosuppressive antimetabolite mechanism: - inhibits purine and protein synthesis - reduced lymphocyte count - reduced Ig synthesis
clinical:
- connective tissue disease (CTD)/autoimmune-associated interstitial lung disease (ILD)
- transplant rejection prophylaxis
metabolism:
- prodrug –> 6-mercaptopuring (6-MP) –> 6-thioguanine (6-TGN) and others (active)
AEs:
- black box: malignancy
- infection
- GI
- BM suppression
- leukocytopenia (common)
- thrombocytopenia (less common)
- anemia (uncommon)
mycophenolate mofetil (MMF)
class: immunosuppressive antimetabolite
mechanism:
- inhibits purine synthesis via ANTagonism of inosine monophosphate dehydrogenase
- depletes guanosine preferentially in lymphocytes
- reduced lymphocyte count and activity
- reduced Ig synthesis
clinical:
- first-line in systemic sclerosis (SSc)
route: po, iv
metabolism:
- prodrug –> mycophenolic acid (MPA) (active)
- glucouronidation and excretion
AEs:
- black box:
- c/i in pregnancy
- malignancy
- serious infection
- hematologic leukopenia
- GI
abx for hospital-acquired pneumonia (HAP)
**antipseudomonals:
one of:
- piperacillin/tazobactam (most common iv, more severe cases)
- cefepime
- ceftazidime
- imipenem
- meropenem
if severe, +
- cipro
or
- aminoglycoside: amikacin, gentamicin, tobramycin
empirically, to cover MRSA b/f cultures are back:
- vancomycin
or
- linezolid
when cultures return:
- d/c vancomycin/linezolid if cultures confirm pseudomonas
- de-escalate to most narrow-spectrum antibiotic
- adjust per results of antibiotic sensitivity testing
outpatient abx for community-acquired pneumonia (CAP)
amoxicillin ± clavulanate
- no comorbidities
and
- low suspicion for mycoplasma, clamydophila, legionella
if comorbidities (diabetes, cancer, others):
- amoxicillin/clavulanate + azithromycin (preferred)
or
- cefpodoxime + azithromycin, levofloxacin, or moxyfloxacin
inpatient abx for community-acquired pneumonia (CAP)
third-get cephalosporins + macrolide, e.g.
- ceftriaxone + azithromycin (most common)
- cef covers “typicals” e.g. strep pneumoniae, H. influenza, M. catarrhalis
- macrolide covers “atypicals” e.g. chlamydophilia, mycoplasma, legionella
OR
respiratory fluoroquinolone
- levofloxacin
- moxifloxacin
(cover both typical and atypical)
abx for latent TB
- rifampin x4 mo or - isoniazid x9 mo or - isoniazid + rifampin or rifapentine x3 mo
abx for active TB
- rifampin + isoniazid + pyrazinamide + ethambutol
- consider transitioning to more narrow regimen after initial tx
- minimum total treatment >6 mo
tx for coccidioidomycosis
very long course of fluconazole (anti-fungal)
tx for histoplasmosis
mild: may clear spontaneously
mild-to-moderate: itraconazole
severe: amphoterrible
tx for blastomycosis
mild: may clear spontaneously
mild-to-moderate: itraconazole
severe: amphoterrible
