Resp. Pharmacology Flashcards
What are the bolded drugs?
Cromolyn Sodium
Omalizumab
Theophylline
Albuterol
Salmeterol/Formoterol
Ipratropium Bromide
Beclomethasone
Zileuton/Zafirlukast
Azithromycin
N-acetylcysteine
- Dornase alpha*
- Ivacaftor*
What is asthma?
What is COPD?
Asthma: A reversible obstructive lung disease characterized by bronchoconstriction due to hyperresponsiveness of the airways to physical chemical and pharma stimuli
It is a chronic inflammatory condition with acute exacerbations.
_______________________
COPD: An obstructive lung disease over time making it hard to breathe. Involves inflammation and thickening of the airways. Involves destruction of the tissue of the lung whre oxygen is exchanged. Also referred to as either: Chronic bronchitis or emphysema.
What is the mechanism of asthma and what implication does that have for attacks?
IgE mediated hypersensitivity.
Significant because of Early and Late rxns
EARLY: Degranulation of histamine/leukotrienes/cytokines/**proteases **leading to immediate bronchoconstriction
LATE: Secretion of cytokines/chemokines leading to inflammation (late phase obstruction)
What are the major treatments categories for asthma pharma?
Bronchodilators and Antiinflammatory agents
How does Cromolyn Sodium work?
Uses?
But…?
Mast cell stabilizer
Uses: Chronic control of asthma/Prophylaxis of bronchospasm (allergen or exercise induced)
But: NOT A RESCUE MEDICINE and NOT AVAILABLE IN THE US FOR RESPIRATORY INDICATIONS. (so this slide was pointless?)
Omalizumab
Mech?
Uses?
Anti- IgE receptor antibody
Used for: Pts. w very severe asthma poorly controlled
Pts. with severe concomitant allergic rhinitis
Theophylline
What class is this
What is it used for
Mech
How is it taken
A methylxanthine
USES: Pt. with severe asthma and COPD.
Mech:
Nonselective PDE inhibitor (smooth muscle relaxation) and
Adenosine receptor antagonist (stops the constriction of airways through release of histamine and leukotrienes. However blocking this leads to lots of bad side effects like: headache palpitation dizziness hypotension tachycardia severe restlessness agitation seizures)
Taken orally
Albuterol and Salmeterol/Formoterol
Class/Mech?
Use?
Difference?
Why does this difference happen?
SE/CI?
Interesting fact about tolerance?
Inhaled Beta2 agonists/Directly stimulate airway smooth muscle through Gs/PKA/ decreasing calcium. ALSO 1. Prevents mediator release from mast cells. 2. Bronchial mucosal edema. 3. Enhances mucociliary clearance. 4. Reduces reflex cholinergic bronchoconstriction.
Uses: BEST BRONCHODILATOR TREATMENT WITH MINIMAL SIDE EFFECTS
Albuterol is short acting and for acute onset 3-6 hrs.
Salmeterol/Formoterol is slower onset and long acting >12 hrs. This may be due to a long aliphatic chain binding within the receptor binding cleft, anchoring.
SE/CI: Pts. with underlying CV disease but risks decreased with inhalation.
Muscle tremor/Tachycardia/Hypokalemia/Restlessness/Hypoxemia
Interestingly Side effects may become tolerized whereas bronchodilation never does. (this is good)
Specific uses for Albuterol Vs. Salmeterol
Dangers?
Why do some patients have adverse events/effects?
Important side effect to LABA?
Albuterol: Use as required to protect against various challenges. Increased use may indicate need for more anti-inflammatory therapy
Salmeterol: Treatment of asthma, bronchospasm, prophylaxis of exercise induced bronchospasm, COPD. Added if corticosteroids doesnt work, so it should not be the first med
Addition of long acting beta agonist increased risk for fatal/near fatal asthmatic attacks. Greatest risk for the 3-4 fold risk of asthma related death among children.
Polymorphisms of the Beta-2 adrenergic receptor. Arginine/arginine polymorphism may be a risk factor.
DO NOT STOP WITHOUT DISCUSSING W DOCTOR DUE TO TOLERANCE
Ipratropium Bromide
class?
Duration of action?
Mech?
Use?
Anti-cholinergic
Short acting
Competitive antagonist of ACh boinding to muscarinic cholinergic receptor (preventing constriction).
USES: Relaxes airway smooth muscle and decreases mucus secretion
Effective in acute severe asthma but less effective than beta-2 agonists.
CAN BE ADDITIVE for when Beta2 agonists are insufficient
Beclomethasone
Class?
Use?
What does it not do?
Interaction with Beta-2?
Steroid
BEST (most prescribed/effective) anti inflammatory for chronic inflammation underlying asthma. Used for persistent asthma as first line therapy. For when patients need to use beta agonist more than twice weekly for symptom control.
Does nto act on contractile response of airway smooth muscle. Nor does it effect the early response to allergen (because no mast cell effect). Does work on the late response.
Glucacorticoid receptors and Beta-2 receptors enhance each other. so using both are beneficial in asthma (there are combination inhalers with LABA [salmeterol] and corticosteroids [fluticasone]
What about Prednisolone/Prednisone and Hydrocortisone?
Prednisone/prednisolone are ORAL and Hydrocortisone is IV
Hydrocortisone used in acute asthma if lung function
Prednisone/prednisolone take several days to take effect, short course for exacerbations of asthma and then tapered over 1 week after resolved. Given as single dose in morning as coincides with normal diurnal increase in plasma cortisol and produces less adrenal suppression than if given divided or at night.
Zileuton/Zafirlukast
Mechanisms?
Use?
Zileuton- 5-lipooxygenase enzyme inhibitor stopping conversion of Arachidonic acid to LTC4 LTD4 LTE4
Zafirlukast- Antagonize leukotriene LT1 receptor.
Use: Mild to moderate asthma. Less effective than inhaled corticosteroids but indicated as add-on therapy in patients who are not well controlled on ICS
What do you use to treat COPD
Corticosteroids
Azithromycin
N-Acetylcysteine
Why use Azithromycin
Prevent and treat acute exacerbations of bronchitis (excessive cough and sputum secretions) accompanied by bacterial infection
