Bronchial Asthma Flashcards
Mention non-pharmacological treatment of asthma
Smoking cessation
Physical activity
Avoid NSAIDs
Mention as-needed reliever in all steps of BA & its alternative
Low dose ICS may be given ICS/formoterol as formaterol has rapid onset with rapid relief
A: SABA
Mention initial treatment in all 5 steps of BA
Step 1: Low dose ICS-formoterol Step 2: Low dose ICS or as-needed low dose ICS - Formoterol Step 3: Low dose ICS - LABA Step 4: Medium dose ICS + LABA Step 5: High dose ICS + LABA
Describe mechanism of selective beta2 agonist
Increase intracellular cAMP:
- Bronchodilatation
- Mast cell stabilization
- Increased bronchial mucocilirat clearnace
Mention examples of SABA & routes of administration
Salbutamol (albuterol) , terbutaline
Inhalation, oral, IV
Describe indications of action of SABA
-Rapid onset & short acting (4hrs) used as short-term reliever in Asthma & COPD, prophylactic in exercise induced asthma (10 min before).
Mention examples & routes of administration of LABA
Salmeterol - formeterol
Inhalation
Mention adverse effects of Selective beta2 agonists
Tremors, tachycardia, tolerance, hypokalemia, hypoxemia.
GR: Selective beta2 agonists cause tolerance & hypoxemia
T: down rehulation of beta receptor with regular use.
H: V/Q ratio worsens (b2 stimulation, vasodilation mora than BD, insufficient oxygenation)
Unlike other LABA, formeterol can be used as ….. + …..
Rescue medication (rapid onset) + ICS
GR: LABA should never be administered alone.
As their anti-inflammatory effect is insignificant & their bronchodilator effect masks the progression in asthma severity so inc risk of mortlaity.
GR: Epinephrine is rarely used in asthma
It is replaced by selective b2 agonists due to shorter action, non-selectivity leading to tachycardia, arrhythmia & inc BP.
Uses of epinephrine
Bronchospasm esp in anaphylaxis
GR: Ephedrine is rarely used
CNS side effects & availability of more effective agents
Route of administration of antimuscurinic drugs.
Inhalation alone or w/ b2 agonists
Mechanism of action of antimuscarinic drugs
M3 receptors in bronchial musculature, blockade of vagally-mediated bronchospasm and mucus secretion.
Indications of ipratropium
- Bronchodilator in BB-induced asthma, that due to psychogenic stimuli & patients intolerant to b2 agonists/ theophylline esp cardiac, elderly & thyrotoxic patients.
- Adujant to b2 agonists
- COPD
Disadvantages of ipratropium
- Tolerance: due to acting on M2 as well as M3
2. Delayed onset of action & less effective than b2 agonists in asthma
Use & advantage of tiotropium
Maintenance therapy in COPD
It is not associated with tolerance
Caffeine is more selective on ………, while theophylline is more selective on …….. .
CNS & cerebral vessels
Smooth muscles
Mechansim of action of methylxathines
- Inhibit phosphodiesterase, inc cAMP:
a. Direct BD
b. Anti-inflammatory, dec mast cell mediators & cytokines. - Block adenosine receptors, BD
Methylxanthines are metabolized in …. By ….
Liver, CYP450
Factors increasing theophylline serum level
Neonates & elderly, hepatoc disease, heart failure, viral infections, enzyme inhibitors (erythromycin, OC, cipro, zileuron, zafirlukast)
Factors decreasing theophylline serum level
Children, heavy smokers & drinkers, enzyme inducers (rifampicin, phenobarbital, phenytoin, carbamazepine)
Describe the anti-asthma & skeletal muscle effects of theophylline
- Bronchodilation (for acute) , anti-inflammatory (for chronic)
- Inc contractility & reverse fatigue of diaphragm in COPD
Mention CNS pharmacological & adverse effects of theophylline
P: alertness, respiratory stimulant
A: insomnia, anxiety, headache, convulsions, tremors.
Describe CVS pharmacological & adverse effects
P: VC of cerebral blood vessels
A: +ve inotropic & chronotropic, sinus tachycardia & arrythmia, VD & hypotension, cardiac arrest.
Mention adverse effects of theophylline on GIT
Anorexia, nausea, vomitting (CI: peptic ulcer)
Proctitis
Effect of theophylline on kidney
Weak diuretic action
GR: Increased risk of toxicity with theophylline (disadvatages of theophylline
Narrow safety margin
Saturation kinetics requiring drug monitoring
High Risk of drug interactions
Indications of theophylline
- 2nd or 3rd line of treatment in BA, for relief of acute bronchospasm, long-term control esp nocturnal asthma (SR), acute severse asthma.
- COPD
- Neonatal apnea
Aminophylline is
Theophylline & ethylenediamine to increase solubility
Indication of SR theophylline
Control medication & in nocturnal dyspnea, as it is long acting
Advantages of low dose theophylline
Full anti-inflammatory effect
No need to monitor level
What is the goal of asthma treatment?
To achieve and maintain clinical control (by suppressing inflammation using long term controller medication)
What is the mechanism of action of glucocorticoids in asthma?
Immunosuppresive & anti-inflammatory: inhibit phosphodiesterase, dec influx of inflammmatory cell/mediators, dec bronchial inflammation & hyper-responsiveness.
-Potentiate beta2 agonists: downregulate b2 receptors
Indications of corticosteroids in asthma
- Control medication
- Rescue medication in acute exacerbations not responding to b2 agonists
- Acute severe asthma
GR: Oral corticosteroids should be given in the early morning.
To coincide with circadian rhythm of CS to dec adrenal suppression.
Ciclesonide is a prodrug activated by ……
Bronchial esterases
Advantages of Ciclesonide over other ICS
High 1st pass metabolism & tight plasma protein binding, less systemic side effects
Less frequent candidiasis
Adverse effects of glucocorticoids
- Oropharyngeal candidiasis
- Hoarseness of voice
- Cataract - glaucoma
- Osteoporosis
- Retardation of growth
- Hypertension
- Diabetes
- Cushing syndrome
- Adrenal suppression
Side effects of glucocorticoids are minimized by
- Gargling & spitting following inflammation
- Use of spacer device
Mention limitations of zileuton
Liver toxicity & frequent dosing
Describe the mechanism of Zafirlukast-Montelukast.
LTs receptor anatgonists, bronchodilation & anti-inflammatory
Mention indications of Montelukast
- Control medications in persistent asthma:
- Alternatives to inhaled steroids in mild persistent asthma (for patients intolerant to steroids or cannot use inhalers)
- Added in moderate to severe cases - Aspirin induced asthma
- Exercise-induced asthma (prophylactic)
Advantages of Motelukast
- Oral therapy (easier than inhalation)
- Long duration of action
- Well-tolerated (minimal side effects)
Adverse effects of Leukotriene pathway inhibitors
- Headache & dyspepsia
- Elevated livers enzymes (zileutin, zafirlukast)
- Enzyme inhibition (zafirlukast)
Mechanism of action of cromolyn & nedocromil
- Inhibit mast cells degranulation, inhibit release of mediators, inhibit early response.
- Inhibit eosinophil activation, inhibit late inflammatory response to antigen.
Route of administration of cromolyn & nedocromil
Aerosol & microfine powder
Uses of cromolyn & nedocromil
Prophylaxis of antigen & exercise-induced asthma .
Chronic use for mild persistent asthma , dec bronchial hyper-responsiveness.
Allergic rhinoconjunctivitis
Adverse effects of cromolyn & nedocromil Na
- Throat irritation, cough, bronchospasm.
2. Stinging in the eye (with eye drops).
Mechanism of action of Ketotifen
Mast cell stabilization & antihistamine
Mechanism, usage, adverse effects of omalizumab
Anti-IgE monoclonal antibody
Add-on therapy in severe uncontrolled allergic asthma
Inc risk of anaphylaxis & reaction at the site of injection
Anti IL5 uses & adverse effects
Add-on therapy in severe uncontrolled allergic asthma
Headache & reaction at site
Anti IL4 uses & adverse effects
-Add-on therapy in severe uncontrolled allergic asthma on high dise ICS/LABA
-Atopic dermatitis
+injection site reaction, blood eosinophilia
Management of mild to moderate acute exacerbations
Give inhaled SABA
Prednisolone
Controlled oxygen
GR: Severe acute asthma is refractory to the usual lines of treatment.
Due to down regulation of beta receptors, mucus plug & acidosis.
Management of severe acute asthma
- Endotracheal intubation & suction of bronchial secretion
- Humidified oxygen inhalation
- IV fluids, correction of acid-base balance, electrolytes, dehydration.
- Drug therapy
Drug therapy of severe acute asthma
A. SABA +/- ipratropium B. Systemic glucocorticoids C. Aminophylline D. Artificial respiration E. Antibiotics/avoid sedatives