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)
What are the main adverse effects of B2 agonist anti-asthmatic drugs?
- Tolerance is a major problem amongst B2 agonists.
- ->Can induce tremors and tachycardia
What are the main adverse effects of Theophylline as an anti-asthmatic drug?
PDE inhibitor/ mainly adenosine antagonist
- Narrow therapeutic window
- Several side effects due to toxicity
What are the main adverse effects of Ipratropium as an anti-asthmatic drug?
–>Anti-muscarinic,
-Poorly absorbed systemically (by inhalation)
Therefore increased sympathetic symptoms including a decrease in secretions (dry mouth- xerostomia)
What is the main use of Cromolyn in children?
Mast Cell Stabilizer
–>Used as a prophylactic in children (preventative measure)
Order of administration of Chronic Asthma?
1) Short acting B2 agonists (Salbutamol) and then longer lasting B2 agonists (Salmeterol- less likely to develop tolerance)
2) Inhaled Corticosteroids at a regular dose.
3) Inhaled Corticosteroids at a high dose.
4) 3+ Regulator Bronchodilator
- Besides inhaled corticosteroids, other bronchodilators such as LABA, Ipratropium and Zileuton or Montelukast could be added.
–>Cromolyn may be administered prior to an attack as a prophylactic to prevent adult onset asthma.
What is administered during a severe, life- threatening asthma attack?
During severe asthma attacks, there is no option but to use a corticosteroid (Beclomethasone) + suitable combination of the above bronchodilators (B agonists)
Adverse Effects of Corticosteroids?
-Growth retardation, peptic ulcers, CNS disturbances, hyperglycemia and superinfection (candidiasis)
–>Oral Thrush (fungal infection) is a problem with prolonged use of Beclomethasone aerosol drug.
NEW: Omalizumab:
- New horizon drug (Mast Cell Stabilizer)
- Humanized monoclonal antibody to IgE-R on mast cells.
- Cys LT’s and PGD2 can not be released, therefore there is no release of inflammatory mediated.
NEW: Etanercept:
-Tumour necrosis factor receptor (TNF-alpha receptor) antibody which neutralizes TNF mediated inflammation.
NEW: Cilomilast, Roflumilast:
Selective PDE4-inhibitors
-elevate cAMP levels in the bronchous with no effect on the heart (no increased heart rate- tachycardia)
