Drugs for the Management of COPD Flashcards
What is the difference between Salbutamol and Salmeterol (LABA) ?
Both are B2 selective adrenergic agonists.
-Salmeterol is a long lasting B2 agonist, while Salbutamol is a shorting lasting bronchodilator.
What are the 2 ways bronchial smooth muscle can be relaxed?
- Increased levels of cAMP (B agonists activate adenylyl cyclase and this pathway)
- Blocking bronchoconstriction mechanisms
True or False:
There is sympathetic innervation of the lungs.
False!
Parasympathetic stimulation only.
Isoproterenol:
- Non-selective beta agonist
- High affinity for both B1 and B2 receptors.
- Binds B1 receptors as well, causing an increase in heart rate.
What activates degranulation of mast cells?
Mast cells contain B2 receptors. When these agonists bind B2 receptors, there is a release of cellular contents from the cells, enhancing bronchoconstriction and an allergic reaction.
True or False:
B2 agonists develop tolerance easily.
True
Theophylline/ Aminophylline:
- PDE inhibitor (non selective)
- MAY increase cAMP levels which leads to bronchodilation
- Acts as an adenosine antagonist.
- Strong anti-inflammatory response
Adverse Effects:
- Nausea, Vomiting, Seizures and Cardiac Arrhythmias
- LOW Therapeutic index!
-Aminophylline= short term use only.
(Seizures and tachycardia)
Ipratropium bromide:
Anti-Muscarinic Agents:
- ->Inhalation increases sensitivity at the bronchioles.
- Increased adverse effects when Ipratropium enters the systemic circulation.
- Minimal effects when given by inhalation.
Which is administered first: B2 agonist such as Salbutamol or Ipratropium?
Salbutamol is administered first, and ipratropium is administered only when B2 agonists aren’t working… Ipratropium is used in moderate- severe asthma.
Cromolyn:
- Mast Cell Stabilizer
- ->Poorly absorbed across mucosal membranes, so when administered orally through inhalation, there are no vasodilator effects.
- Inhibits the secretion of mast cells*
- Does NO affect the cAMP pathway.
Mast cells release which contents which lead to Bronchoconstrictions?
-Cytokines, histamines and leukotrienes.
Beclomethasone:
Corticosteroids (GCs):
- Slow acting mechanisms which act to change the expression of genes in cells.
- Decreases the production of Eicosanoids.
- GC’s switch off Pro-Inflammatory Transcription Factors responsible for the release of inflammatory mediators.
- Likely do not cause bronchodilation due to late onset, but affect the secretion of inflammatory mediators/ bronchial hyper-reactivity (BHR).
- ->Short term use ONLY
What type of drugs are Zileuton and Montelukast, as well as there mechanism of action?
–>LK synthesis inhibitor/ antagonists
1) Zileuton is a 5-Lipoxygenase inhibitor (5-LOX-1)
2) Cys Leukotriene Antagonists
* These drugs are particularly effective in treating aspirin- induced asthma.
Describe why Aspirin can be problematic in inducing asthma:
–>Aspirin inhibits the production inflammatory mediators by blocking the enzyme cyclooxygenase (COX) and it’s inflammatory pathway. In doing this, arachidonic acid can only be converted into Leukotreines via the 5-lipoxygenase pathway which leads to the bronchoconstriction. (inhibited by Zileuton).
–>Aspirin induced asthma can be treated with the use of Zileuton to block the production of Leukotrines (LTC4 and LTD4) and decrease bronchoconstriction.
What are the 2 primary targets of the drugs affecting the Leukotriene’s System?
- Inhibition of 5-Lipoxygenase (Zileuton)
2. Leukotriene antagonists (Montelukast)
