asthma & COPD Flashcards
Short Acting Beta2 Agonists (SABA) Agents
Albuterol
Levalbuterol
SABA
- MOA: Stimulate adenylyl cyclase at beta2 receptor –> increase cAMP in bronchial smooth muscle –> bronchodilation
- Selective for beta2 receptor
- DOC for ACUTE ASTHMA ATTACKS and exercise induced asthma
- Onset: 5 min
- Duration: 3-4hr
- Given (almost) exclusively via inhalation
SABA ADE
- Well tolerated with PRN use: (as needed)
Mouth irritation, cough - ADE at high doses: Skeletal muscle tremor, atachycardia/palpitation, arrhythmia, tolerance with exercise use (decreased responsiveness and decrease in number of beta receptors)
Long Acting Beta2 Agonist (LABA) Agents
Long acting - Salmeterol - Formoterol Ultra-Long acting - Indacterol - Olodaterol - Vilanterol (in combo with ICS)
LABA
- MOA: Stimulate adenylyl cyclase at beta2 receptor –> increase cAMP in bronchial smooth muscle –> bronchodilation
- Slower onset of action (~30 min)
- Longer duration of action (12-24hrs)
- NOT for rescue therapy
- CANNOT be used as monotherapy in asthma
- OK in COPD
LABA ADE
- Well tolerated with PRN use: (as needed)
Mouth irritation, cough - ADE at high doses: Skeletal muscle tremor, atachycardia/palpitation, arrhythmia, tolerance with exercise use (decreased responsiveness and decrease in number of beta receptors)
Antimuscarinic Agents
Short Acting - Ipratropium Long Acting - Tiotropium - Aclidinium - Umeclidinium - Glycoprolate
Antimuscarinic
- MOA: competitively block muscarinic receptors (M1, M2, M3) and the effects of ACh in airway –> prevent vasoconstriction mediated by vagal discharge
- No effects on chronic inflammation
- bronchodilating effects last longer than Beta agonists
Antimuscarinic ADE
- Minimally absorbed, generally well tolerated
- Potential for: dry mouth, dry eyes, bitter/metallic taste, constipation, urinary retention
- NO Tremors or Arrhythmia
Methylxanthine derivative agents
theophylline - oral
Methylxanthine derivative
MOA: (1) non-selectively inhibits phosphodiesterase (PDE) –> Increases cAMP –> bronchodilatuon (2) Block adenosine receptors in CNS (inhibits bronchoconstriction)
- Available PO in IR and SR formulations
- Duration of action ~ 12hrs
- Requires high concentration to be effective
- Considered narrow therapeutic index drug
Theophylline
Metabolized via CYP450 1A2 enzyme system
- MANY drug-drug interactions – febuxostat, bupropion, carbamazepine, macrolide antibiotics, etc.
Clearance mediated by age, smoking status and other drugs
- Younger patients clear drug faster vs. elders
- Smokers clear the drug faster vs. non-smokers
Requires therapeutic monitoring
- Therapeutic range 10-20 mcg/mL
- Levels correlate with efficacy
Theophylline ADE:
- GI distress (enhanced gastric acid secretion)
- Tremor
- Insomnia
- In overdose, severe nausea and vomiting, hypotension, agitation, arrhythmia, cardiac arrest, seizures
PDE-4 Inhibitor Agents
Roflumilast - Oral
PDE-4 Inhibitor
MOA: not fully elucidated; electively inhibits PDE-4 –> increases cAMP –> bronchodilation
- Used for severe or very severe COPD (should be given in combo with at least one LAMA or LABA for COPD)
- Given by mouth once daily (duration of action >10-20 hrs)
Roflumilast
- Partially metabolized by CYP3A4 DDI with rifampin, phenobarbital, phenytoin, carbamazepine
- ADE: diarrhea, nausea, vomiting, abdominal pain, headache, dyspepsia, psychiatric events, weight loss
Cotricosteroids
MOA: binds to glucocorticoid receptors to:
- Inhibit inflammatory cell migration and activation
- Inhibit cytokine and mediator release
- Up regulate B2 receptors
- Inhibit IgE synthesis
DOC for persistent Asthma (prophylaxis)
- May take 4-6 weeks for effects
multiple dosage forms
- Do not abruptly d/c–> taper dose slowly
Inhaled Corticosteroids
Beclomethasone Budesonide - Safe in pregnancy Fluticasone propionate Fluticasone furoate Mometasone Flunisolide Ciclesonide
Oral/IV Corticosteroids
Prednisone
Prednisolone
Methylprednisolone
Hydrocortisone
ADE ICS
- Thrush (oral candidiasis) counsel patients to rinse mouth after each use
- Dysphonia
- Sore throat
- Cough
Oral Corticosteroids ADEs
- Adrenal suppression
- Cushing syndrome
- Growth retardation
- Osteoporosis
- Glucose intolerance
- Infection risk
- Mood changes
- Weight gain
- Edema
Coritcosteroids for Kids
- Potential growth stunting in children
- Still preferred DOC in children for asthma
- Lowest dose possible & monitor changes in growth
Bronchodilators
- SABA
- LABA
- Muscarinic Antagonsit
- Methylxanthine derivatives
- PDE-4 Inhibitors
Leukotriene Antagonists
- Lipoxygenase inhibitors
- Leukotriene receptor antagonists
Lipoxygenase inhibitors Agents
Zileuton - oral
Lipoxygenase inhibitors MOA
inhibits actions of 5-lipoxygenase to inhibit the synthesis of leukotrienes
Lipoxygenase Inhibitors ADE
- Headache
- Insomnia
- Somnolence
- GI upset
- Hepatotoxicity
DO NOT administer if LFTs>3XULN
Females > 65 years of age and those with pre-existing LFT elevations are at highest risk –> monitor
Leukotriene Receptor Antagonist Agents
Montelukast - oral
Zafirlukast - oral
Leukotriene Receptor Antagonist
MOA: Competitively block action of leukotrienes at the LTD4 receptor
Can be used for Asthma allergic symptoms, exercise-induced bronchospams, uricaria
Leukotriene Receptor Antagonists DDI
Zafirlukast - Warfarin –> may increase risk of bleed
Leukotriene Receptor Antagonists ADE
- Generally well tolerated
- Headache
- Hepatoxicity (Zafirlukast)
- Neuropsychiatric events (anmormal dreams, hostility, aggression, suicidality, agitation, hallucinations)
Mast Cell Stabilizers Agents
Cromolyn sodium
Nedocromil sodium
Mast Cell Stabilizers MOA
Block influc of Ca –> prevention of mast cell degranulation –> stabilize mast cell –> prevent release of inflammatory mediators
- Do not exert any direct bronchodilating, antihistaminic, or anti-inflammatory effects
Mast Cell Stabilizers
- Indicated for mild asthma cases (not used much)
- Not for rescue symptoms
- Requires multiple daily doses
- Clinical improvement may take 2-6 weeks for effect
- Well tolerated (mild throat irritation, couch, abnormal taste in mouth)
- NO DDI
Immunotherapy
Anti IgE agents
IL-5 Antagonists
Anti IgE Agents
Omalizumab
Anti IgE
- MOA: Monocolonal IgE antibody –> inhibits binding of IgE to surface of mast cells & basophils –> inhibits release of inflammatory mediators
- Indicated for allergic asthma not relieved with corticosteroid therapy (MUST have evidence of allergic sensitization)
- Dose based on IgE levels and body weight (SQ every 2-4 wk)
Omalizumab
- Indicated for >12 years of age
- Clinical improvement delayed (12 weeks to work)
- ADE: injection site reaction, Anaphylaxsis –> usually 1.5-2hr after dose, arthralgia, headache, pharyngitis, sinusitis, malignancies (immunosuppression)
- NO DDI
IL-5 Antagonist Agents
Mepolizumab
Reslizumab
IL-5 Antagonist
- MOA: Humanized interleukin -5 (IL-5) monoclonal antibody antagonist to reduce the amount of circulating eosinophils
- used for the maintenance of severe asthma for patients who continue to have exacerbation despite adequate therapy
- Administered SC (Mepolizumab) or IV (Reslizumab) every 4 weeks by HCP
- NOT recommended for monotherapy (must be >18yr of age with an eosinophilic phenotype
IL-5 Antagonist ADE:
- injection site reactions
- Headache
- Hypersensitivity reactions (anaphylaxis can be life threatening)
- Malignancy
- Muscle and face pain
