DRUG MOA (PULM)

SABAs/LABAs

1. Activate B-2 R in small bronchioles → activate AC → increase cAMP → bronchodilation

   1. increasing cAMP will also have PDE catalyze it into AMP → inhibition of SM relaxation

SABA drugs

albuterol (Ventolin), levoalbuterol (Xopenex), pirbuterol (Maxair), terbutaline (oral or SC)

LABA drugs

formoterol (Foradil), salmeterol (Serevent), arformoterol, indacaterol (Arcapta Neohaler)

Antimuscarinics (LAMAs) / Anticholinergics

Block muscarinic R (GPCR and mAChR) on PNS fibers → reduce vagal tone → antispasmodic, antisecretory, and BRONCHODILATORY effects

Antimuscarinics (LAMAs) Drugs

Ipratropium (Atrovent), Tiotropium (Spiriva), Aclidinium (Tudorzza), Umeclidinium (Incruse Ellipta)

Cholinergic Antagonists Drugs

Atropine

Glucocorticoids / ICS

1. restore Beta-agonist R sensitivity → restore effect of bronchodilators

2. directly stimulate cAMP by activating Gs-AC-cAMP to augment B-AR bronchodilation

Glucocorticoids / ICS Drugs

Beclomethasone (QVAR, Vanceril, Beclovent), budesonide (Pulmacort, Rhinocort, Respules), ciclesonide (Alvesco, Omnaris), fluticasone propionate (Flovent, Flonase), mometasone furoate (Nasonex)

Combined CCS and LABA

• Fluticasone / Salmeterol (Advair discus)

• Budesonide / formoterol (symbicort)

• Mometasone / formoterol (dulera)

Leukotriene Receptor Antagonist

inhibit LTD4

Leukotrienes Drugs

Montelukast (Singulair), Zafirlukast (Accolate)

Leukotriene Synthesis Blocker

inhibits 5-lipoxygenase → inhibit leukotriene formation (LTB4, C4, D4, E4) → decreases SM contraction + blood vessel permeability

Leukotriene Synthesis Blocker Drug

Zileuton (Zyflo)

Omalizumab (Xolair)

binds to human IgE’s high affinity Fc-R to prevent binding of IgE to mast cells and basophils (associated with allergic response) → lowers free serum IgE concentration (stops allergic rxn)

IL-5 Monoclonal ABs

IL-5 binding humanized IgG agents neutralize IL-5 produced by mast cells → prevent eosinophil migration to airway wall from bloodstream

IL-5 Monoclonal ABs Biologics

Mepolizumab, reslizumab, benralizumab

IL-4 R Monoclonal ABs

Block IL-4Ralpha → reduces signaling of IL-4 and IL-13 to B cell → reduce IgE release → reduce Mast cell activation

IL-4 R Monoclonal ABs Biologics

Dupilumab

Systemic CS

inhibit inflammation → block late phase reaction to allergens, reduce airway hyperresponsiveness, reduce inflammatory mediators

PDE4 inhibitor

inhibit PDE4 → increased cAMP activity → decrease immune + inflammatory activity

• SM relax (bronchodilation)

• suppress inflammatory cell fxn

• inhibit airway SN proliferation

Oral PDE4 inhibitor

Roflumilast (Daliresp)

PDE5 inhibitors

inhibit PDE5 → decrease cGMP conversion to GMP → vasodilation

PDE5 inhibitor Drugs

Theophylline, aminophylline, Sildenafil (Revatio), Tadalafil (Adcirca)

Eicosanoids / Prostacyclins

bind to IP R → activate AC → increase cAMP → activate PKA → inhibit MLCK → SM relax/vasodilation, anti-proliferation + inhibit of Plt aggregation (decrease thrombosis), decrease inflammation

Eicosanoids / Prostacyclin Drugs

epoprostenal, iloprost, treprostinil

Non-prostanoids Prostacyclin Agonist

selexipag (Uptravi) (same MOA as prostanoids)

Soluble Guanylate Cyclase Stimulators

• sensitize sGC to NO → stimulate sGC via binding site different than NO → stimulate cGMP production → reduces remodeling (fibrosis, constriction, proliferation, inflammation)

• reduced form of heme (Fe2+) binds to NO

Soluble Guanylate Cyclase Stimulator Drug

riociguat (Adempas)

Endothelin R antagonists

block ETa and ETb → decrease proliferation, hypertrophy, fibrosis, vasoconstriction, inflammation, increase vascular permeability → decreased pressure

Endothelin R antagonists Drugs

bosentran (Tracleer), ambrisentan (Letariris), macitentan (Opsumit)

Ivacaftor (Kalydeco)

• G551D / R117H mutation (have CFTR at membrane, no Cl- conduction)

• enhances Cl- conductance by increasing channel opening probability

Lumacaftor / Ivacaftor combo (Orkambi)

• lumacaftor = chaperone protein to get more CFTR channel to the apical membrane (help it escape destruction by the cell d/t misfolded proteins)

Tezacaftor / Ivacaftor combo (Symdeko)

• F508 mutation/deletion

• tezacaftor = chaperone to get more CFTR channel to membrane

Elexacaftor / Tezacaftor / Ivacaftor combo (Trikafta)

• at least one F508 mutation (hetero or homo)

• both elexacaftor and tezacaftor = chaperones to get more CFTR to membrane

Hypertonic saline

higher Na+ concentration → water follows → dilute/mobilize mucus

Dornase enzyme

cleaves extracellular DNA and decrease viscosity of mucus

Pancreatic enzyme supplementation (Creon, Pancreaze)

• a part of nutrition support

• increase fat absorption + ability to break down food

PPIs

• for if pt has GERD which can exacerbate reflex bronchospasm and increase airway inflammation

Insulin

• for CF associated DM (d/t destruction of islet cells)

Inhaled Abx for pseudomonas aeruginosa

• first line: inhaled tobramycin, aztreonam lysine

• second line: aztreonam

Oral azithromycin

anti-inflammatory effects (NO pseudo coverage)