Respiratory Flashcards
Beta 2 Adrenoceptor
- MOA
GPCR (Gs)
- Increases cAMP
Beta 2 Adrenoceptor Agonist
- MOA
- Dilate bronchi by acting on Gs Beta 2 Adrenoceptors
- Inhibit mediator release from mast cells
- Inhibit TNFa release from monocytes
- Increase mucus clearance by acting on cilia
Beta 2 Adrenoceptor Agonist
- cAMP relationship to bronchi
Beta 2 Adrenoceptor activation = Increased cAMP
- More cAMP = Greater activation of PKA
–> Reduces Ca2+ levels leading to bronchidilation
Salbutamol
Beta 2 Adrenoceptor Agonist
- Oral/Injection
- Short Acting
Terbutaline
Beta 2 Adrenoceptor Agonist
- Short Acting
Salmeterol
Beta 2 Adrenoceptor Agonist
- Long Acting
Taken when asthma is not properly controlled by glucocorticoids
Formoterol
Beta 2 Adrenoceptor Agonist
- Long Acting
Taken when asthma is not properly controlled by glucocorticoids
Beta 2 Adrenoceptor Agonists
- Adverse Effects
- Tachycardia
- Dysrhythmias
- Tremor
Theophylline/Aminophylline
- MOA
- Inhibits PDE
–> Prevents breakdown of cAMP = Increase cAMP - Inhibits Adenosine Receptors
- Inhibits intracellular calcium release
–> Reduces smooth muscle contraction
Theophylline/Aminophylline
- Adverse Effects
Dysrhythmia
Seizures
Montelukast/Zafirlukast
- MOA
Cysteinyl Leukotriene Receptor Antagonist (CysLT1)
Antagonism reverses:
- Bronchoconstriction
- Hyperresponsive airways
- Mucosal edema
- Mucosa hypersecretion
Montelukast/Zafirlukast
- Comparison to Beta 2 Adrenoceptor Agonist
Not as effective as Beta 2 Adrenoceptor Agonist
Montelukast/Zafirlukast
- Route
Taken by mouth
Usually taken with inhaled corticosteroids
Beclometasone
Glucocorticoid
- Given as an inhalation
Anti-inflammatory
- Treats acute severe asthma
- Prevent chronic asthma
Adverse Effect:
- Adrenal Suppression
- Oropharyngeal candidiasis
Budenoside
Glucocorticoid
- Given as an inhalation
Anti-inflammatory
- Treats acute severe asthma
- Prevent chronic asthma
Adverse Effect:
- Adrenal Suppression
- Oropharyngeal candidiasis
Fluticasone
Glucocorticoid
- Given as an inhalation
Anti-inflammatory
- Treats acute severe asthma
- Prevent chronic asthma
Adverse Effect:
- Oropharyngeal candidiasis
Mometasone
Glucocorticoid
- Given as an inhalation
Anti-inflammatory
- Treats acute severe asthma
- Prevent chronic asthma
Adverse Effect:
- Oropharyngeal candidiasis
Ciclesonide
Glucocorticoid
- Given as an inhalation
Anti-inflammatory
- Treats acute severe asthma
- Prevent chronic asthma
Adverse Effect:
- Oropharyngeal candidiasis
Prednisolone
Glucocorticoid
- Given orally
Anti-inflammatory
- Used for patients with severe disease
Adverse Effect
- Risk of infection
- Osteoporosis
Glucocorticoids
- General MOA
Controls Gene Expression
- Binds intracellular receptor
- Dimerizes
- Complex translocates into the nucleus
- Modifies Gene Transcription
–> Transcription Factors
Basic Transactivation
Ligands binds to Glucocorticoid Receptor Dimer
–> Upregulates Transcription
Basic Transrepression
Ligands binds to Glucocorticoid Receptor Dimer
–> Complex binds to nGRE
–> Turns off transcription
Glucocorticoids
- Asthma MOA
Reduces transcription of
IL-2
–> Inhibits proliferation of Th Cells
–> Reduces formation of Th cytokines
–> Decreases activation of eosinophils
Reduces transcription of
IL-5/IL-13
Reduces transcription of lgE and lgE receptors
Glucocorticoids
- Adverse Effects
Oropharyngeal Candidiasis (Thrush)
Adrenal Suppression in Beclometasone and Budenoside
Systemic Side Effects are uncommon due to low systemic absorption and bioavailability from inhalation route of administration
Glucocorticoids
- Other Considerations
Are usually used in combination with Beta 2 Adrenoceptor Agonists for Chronic Asthma
- Dilation of Bronchial smooth muscles enhance deliver of glucocorticoids to the airway
- Glucocorticoids cause an increase in expression of Beta 2 Adrenoceptors in the airway
Omalizumab
Humanized Monoclonal Anti-lgE antibody
- Binds to free lgE and prevents it from interacting with
Mepolizumab
Humanized Monoclonal Antibody
- Binds to and inhibits IL-5
–> Prevents differentiation and recruitment of eosinophils
Treats Eosinophilic Asthma
Reslizumab
Humanized Monoclonal Antibody
- Binds to and inhibits IL-5
–> Prevents differentiation and recruitment of eosinophils
Treats Eosinophilic Asthma
Ipratropium
Inhaled Anticholinergic
(Muscarinic M1-M3 Antagonist)
- Treats Underlying symptoms of COPD
M3 Muscarinic Receptors
- Parasympathetic stimulation of these receptors causes bronchoconstriction and bronchial secretions
Tiotropium
Inhaled Anticholinergic
(Muscarinic M3 Antagonist)
- Treats Underlying symptoms of COPD
M3 Muscarinic Receptors
- Parasympathetic stimulation of these receptors causes bronchoconstriction and bronchial secretions
Aclidinium
Inhaled Anticholinergic (Newer Longer Acting)
- Treats COPD
Umeclidinium
Inhaled Anticholinergic (Newer Longer Acting)
- Treats COPD
Glycopyrrolate
Inhaled Anticholinergic (Newer Longer Acting)
- Treats COPD
Roflumilast
Long-Acting Phosphodiesterase 4 Inhibitor
- Prevents degradation of cAMP –> Increases cAMP
–> Increase PKA –> Decrease Calcium
–> Reduces Inflammation
Combined with bronchodilators to treat COPD
