7. Drugs for Asthma or COPD Flashcards
What is asthma?
(Triggers, etc)
What is COPD
Episodic reversible obstruction of the airways
10-20% of people encounter bronchial asthma
Triggers- allergens (pollen), autoimmune disease
Characterized by airway inflammation & bronchial hyperresponsiveness to noxious stimuli
Initial bronchial hyper reactivity (BHR) later leads to asthma (severe bronchoconstriction and airway obstruction), if it persists, it becomes chronic obstructive pulmonary disease which is rigid unresponsive bronchial tree (COPD)
What are the 6 classes of drugs for asthma and COPD?
- β2 selective adrenergic agonists Albuterol (Salbutamol- SABA & Salmeterol- LABA)
- Adenosine antagonist + PDE inhibitor - theophylline
- Muscarinic antagonist- Ipratropium & Tiotropium
- Mast cell stabilizers- cromolyn, nedocromil, onalizumab
- Corticosteroid beclomethasone, fluticasone, prednisone
- Leukotriene (LT) Synthesis Inhibitor and LT antagonist- Zileuton and Montelukast
What are the bronchodilators division of anti-asthmatic drugs?
(3 of them)
(1 of 2 divisions)
Relax bronchial smooth muscle by elevating cAMP level or blocking bronchoconstrictor mechanisms which involve antagonists of parasympathetic cholinergic activity
- β adrenergic agonists- β2 selective agonists SABA and LABA
SABA short acting LABA long acting - Phosphodiesterase (PDE) inhibitor + an adenosine antagonist- theophylline, aminophylline
- M3 Muscarinic antagonist (cholinergic antagonist)- Ipratropium bromide
Slides 6-7
What are the decrease inflammation & reduce bronchial hyper responses (BHR) division of anti-asthmatic drugs?
(3 of them)
(2 of 2 division)
- Mast Cell Stabilizer- decrease release of mediators- Cromolyn, Omalizumab, given as prophylactic in children before the onset of asthma
- Leukotrienes- synthesis inhibitor & receptor antagonist
Zileuton and Montelukast - Corticosteroids- slow onset of action, reduce inflammation, most effective
Beclomethasone, Fluticasone, Prednisone (oral), Dexamethasone (oral)
What is theophylline?
Mechanism of action, adverse effects, etc
Phosphodiesterase (PDE) inhibitor
There is doubt it has sufficient intracellular concentrations to inhibit PDE and increase cAMP
So it’s focused more on acting as an adenosine antagonist
Adverse effects- narrow therapeutic index (5-20μg/mL)
Nausea, vomiting, anorexia, headache,
seizures, cardiac arrhythmias
Slides 8-9
What are antimuscarinic agents: Ipratropium?
Route of admin, effects, etc
Administration of anti-muscarinic agent by inhalation increase their selectivity at localized site, bronchioles
Ipratropium is more polar analog of atropine and it is poorly absorbed into the systemic circulation so the side effects are minimal when given through inhalation
Much more effective anti cholinergic effect in controlling mucus plug secretion and airway resistance in conditions of COPD
Ipratropium is considered in moderate to sever asthma when other agents fail
Can cause dry mouth
What is the mast cell stabilizer Cromolyn?
Mechanism of action, etc
Poorly absorbed across mucosal membranes
When given by inhalation, it has no bronchodilator effect
Given as a prophylactic prior to onset in children!!
Prevent early and late asthmatic response to inhaled allergen (inhibits secretion of mediators from mast cells in response to non specific noxious stimuli like cold air, chemical irritants, allergens)
Does not effect cAMP system
Ineffective in severe asthma
Slides 11-12
What so drugs that increase cAMP do?
Drugs that increase cAMP (like β2 agonists Salbutamol/Salmeterol or PDE inhibitors like theophylline) also inhibit antigen-induced mast cell secretion to some extent
What are corticosteroids (GCs)?
Mechanism of action, etc
Slow acts by blocking inflammatory mediators: decreases the production of Eicosanoids, reduces inflammation
GCs activated by GC receptor activation suppress the expression of genes for many inflammatory proteins
GCs switch off pro-inflammatory transcription factors
Administer steroid locally in a form that is not absorbed systematically (beclomethasone as an aerosol - inhaled corticosteroids ICS)
Slides 13-16
What are leukotriene inhibitors?
2 different approaches, etc
2 therapeutic approaches:
- 5-lipoxygenase inhibitor- Zileuton
- Leukotriene Antagonists- Montelukast
Effective in aspirin induced asthma
When COX is inhibited by Aspirin, AA will be shunted towards LO-derived leukotriene generation
Increase leukotriene promotes brinchoconstriction (admin of Zileuton or Montelukast overcomes this)
Zileuton inhibits biosynthesis of leukotrienes
Montelukast- antagonist that blocks leukotriene receptor
Slides 17-20
How are leukotrienes formed?
Formed by action of 5-lipoxygenase on arachidonic acid
The synthesis occurs in a variety of cells involved in the inflammatory response including eosinophils, mast cells, macrophages and basophils
Slide 17, 20
What β2 selective agonists?
Mechanism of action, adverse effects
Evoke bronchodilation by activating adenylate cyclase and enhancing cAMP level to evoke bronchodilation
Modest effect on late asthmatic response, presumably by inhibiting secretion of cellular mediators
Tolerance is major problem with these- avoid too many puffs (tolerance lower with long acting β2 (LABA))
Adverse effects- tremor, tachycardia
What are some of the side effects of taking corticosteroids orally?
Growth retardation, peptic ulcer, CNS disturbances, hyperglycemia, super infection (candidiasis)
What are the 5 steps in the management of chronic asthma?
- Short acting β2 agonists (Salbutamol), use LABA (Salmeterol) if tolerance is problem
- Cromolyn May be substituted prior to attack in childhood asthma (little value to adults)
- Dose of inhaled corticosteroids is increased
- Besides ICS, other bronchodilators such as LABA, Ipratropium (M antagonist), Zileuton, of Montelukast could be added (step 4 is combination therapy)
- In a very sever form asthma, no option but to rely on a suitable oral corticosteroid (prednisone, dexamethasone) and a suitable combo of the above bronchodilators
