Respi - asthma Flashcards
causes of asthma
- chronic airway inflammation
- hyperresponsiveness of the airway
- recurrent reversible airway obstruction
2 main groups of anti-asthma drugs
- prevention (controller) - anti-inflammatory drugs
2. provide relief - bronchodilators
6 groups of anti-inflammatory (control) anti-asthma drugs
[NIL]
- inhaled corticosteroids (ICS)
- inhaled Na cromoglygate
- leukotriene receptor antagonist (LTRA)
- anti-IgE
- anti-IL-5R
- anti-IL-4R
ICS drug
fluticasone - has high receptor binding affinity
-sonide/ -solide
ICS MOA
- Decrease secretion of inflammatory cells (T cells, mast cells, macrophages, eosinophils) in airways
- Decrease epithelial cell shedding
- Decrease macrophage phagocytosis and cytokine production and proteases
- Decrease PLA2, COX II, 5-LOX (inflammatory enzymes), increase annexins = downregulate leukotriene expression
- Increase airway SM b-receptors
- reduce plasma exudate/mucus secretion
ICS indication
nocturnal asthma
1st line asthma prophylaxis
reduce long term asthma complications like airway remodeling
ICS ADR
oropharyngeal candidiasis (candida infection) and irritation
dysphonia (hoarseness of voice)
- fluticasone: adrenal suppression
leukotriene modifiers (receptor antagonists) drugs
(-lukast)
- montelukast
- zafirlukast
- zileutone
montelukast and zafirlukast MOA
inhibit LTC4/LTD4
- inhibits bronchoconstriction,
- hyper-responsiveness,
- mucosal edema,
- mucus hypersecretion,
- SM hyperplasia
montelukast target receptor and indications
competitive antagonist of CysLT1 (cysteinyl leukotriene)
indications:
- prophylaxis + chronic treatment
- aspirin/ exercise induced asthma
(aspirin induced: aspirin inhibits AA -> prostaglandin, so AA -> LTA4 -> LTC4 -> asthma)
ORAL
montelukast ADR
psychological: agitation, hallucination, depression
Na cromoglycate MOA
inhibit mast cell degranulation (IgE mediated) -> prevent release of inflammatory cells (histamine, prostaglandins, leukotrienes)
Na cromoglycate clinical use
paeds asthma
prophylaxis for asthma & allergic rhinitis/ conjuctivitis
Na cromoglycate ADR
throat irritation, dryness, cough
Omalizumab (anti-IgE mAb) MOA
attacks Fc portion of IgE antibodies
- binds to IgE
- decrease expression of receptors
- decrease mediator release
- decrease inflammatory response and possible exacerbation
Omalizumab clinical use + method
allergic asthma, allergic rhinitis
injection every 2-4wks
Anti-IL-5R (-zumab) and anti-IL-4R (dupilumab) clinical use + method
severe asthma
subcutaneous injection
6 groups of bronchodilators (beta agonists) as asthma RELIEVERS
- non-selective (1-3hrs)
- short acting: SABA (4-6hrs)
- long acting: LABA (12hrs)
- long acting for COPD (24hrs)
- methylxanthine: theophylline
- muscarinic antagonists: SAMA (3-5hrs)/ LAMA (24hrs)
non-selective drug
epinephrine
SABA drug
salbutamol
salbutamol
rapid onset
hydrophilic
LABA drugs + clinical use
(-terol)
- salmeterol
- formoterol* - preferred choice (faster onset of action)
long term maintenance of asthma (esp nocturnal asthma)
formoterol
rapid onset
amphiphilic
salmeterol
slow onset - less useful for emergency use
lipophilic - slowly bind and release
LABA drug for COPD
indacaterol
beta agonists ADR
decrease muscle contraction: tremors, cramps peripheral vasodilation palpitations and tachycardia hypokalemia, hyperglycemia LABA: asthma related mortality
theophylline MOA
- inhibits PDE + blocks adenosine - increase cAMP -> relaxation
- release of epinephrine
- anti-inflammatory effects
but not as effective as a bronchconstrictor
theophylline clinical use + method
add on to inhaled beta agonists + ICS (inhaled corticosteroids)
nocturnal bronchospasm
COPD: improve lung fn
Oral/IV
theophylline ADR
narrow therapeutic range - be careful esp DDIs
GI: n/v, anorexia
CNS: anxiety, tremors
CVS: arrhythmia
muscarinic antagonists drugs
SAMA: short acting - ipratropium bromide
LAMA - tiotropium
(-tropium)
ipratroprium bromide MOA + method
inhibit m3 receptors = decrease inflammation
decrease bronchospasms and mucus secretion
less effective as a bronchodilator
inhaled, does not cross BBB
also used as a mucoregulator
ipratropium clinical use
add on to beta agonists + IHC
alternative for those intolerant to b agonists
COPD - bronchodilator effect
tiotropium clinical use
severe asthma
COPD - more potent than SAMA for COPD
MA ADR
dry mouth
urinary retention in elderly
(paradoxical) bronchospasm - supposed to decrease
