Respiratory Pharmacology Flashcards
β2-adrenergic agonists that are commonly used for asthma:
Albuterol, Pirbuterol and Terbutaline are called SABAs (Short Acting β2 Agonists) – they are used for acute symptoms.
Salmeterol & Formoterol –they are called LABAs (Long Acting β2 Agonists) –not used for acute symptoms
Albuterol, Pirbuterol and Terbutaline are rapidly acting β2–adrenergic agonists. They are the drugs of choice for acute relief of bronchospasm.
Salmeterol and Formoterol are long-acting β2 agonists (LABAs) – they are slow in onset of action.
LABAs available in combination with ICS (inhalational corticosteroid) for long term control and prevention of symptoms in moderate to severe persistent asthma.
Concern regarding long-acting beta agonists
A small percentage (<1%) of population may have genetic predisposition (genetic polymorphism in β2 receptors) that causes a slight risk of worsening asthma (severe asthma), exacerbations, or even death.
It is possible that the LABAs have other pharmacologic effects in asthma that have yet to recognize.
EIB –exercise induced bronchoconstriction:
SABAs used just before exercise will prevent EIB for 2–4 hours after inhalation.
LABAs will prevent up-to 12 hours.
Montelukast will decrease EIB in 50% of patients for up-to 24 hours.
Anticholinergics as bronchodilators:
Ipratropium: A short acting inhaled anticholinergic can be used in asthma, QID (four times daily). Prevent vagal mediated bronchoconstriction and drug induced bronchospasm such as β blockers.
Side Effects: Dry mouth and caution should be exercised in patients with glaucoma, BPH and bladder neck obstruction. The drug has very few side effects owing to poor systemic absorption.
Tiotropium is a long-acting anticholinergic, used once daily dosing, in COPD.
Methylxanthines drugs in asthma
Mechanism of Action:
Theophylline & Aminophylline are methylxanthine derivatives. They inhibit phosphodiesterase, the enzyme responsible for the metabolism of cAMP to AMP. Increased levels of cAMP result in bronchodilation. They have no significant anti-inflammatory effects. Blocks adenosine receptors.
Theophylline role in asthma:
Limited, because it has a very small therapeutic window. Drug interactions with theophylline:
Cimetidine, erythromycin and ciprofloxacin increase theophylline plasma levels.
Drugs that decrease plasma levels of theophylline:
Phenytoin, phenobarbitone and carbamazepine
Complications with theophylline overdose:
The most common are tremor, insomnia, GI distress, and nausea. Hypokalemia and hyperglycemia may occur. The most dangerous are seizures and arrhythmias.
Corticosteroids used in asthma:
Beclomethasone, Dexamethasone, Fluticasone, Budesonide, Flunisolide, and Prednisolone
Mechanism of action of corticosteroids:
They inhibit the synthesis of arachidonic acid by Phospholipase A2 consequently; various inflammatory mediators such as leukotrienes, cytokines, and prostaglandins are inhibited.
Steroids bind to intracellular receptors and activate glucocorticoid response elements (GREs) in the nucleus, result in the synthesis of substances that inhibit expression of inflammation and allergy.
Corticosteroids use in asthma management:
For both acute and maintenance asthma management:
Acute exacerbations –Systemic steroids are used primarily when the attack is severe
Maintenance therapy – Low dose inhalational corticosteroids suppress the inflammation and reduce the risk of exacerbations.
Higher inhaled corticosteroid doses may be needed for severe asthma.
Corticosteroids also increase β2–adrenoceptors responsiveness in the respiratory tract.
Corticosteroids are used once or twice a day. They help reduce the need for β2 agonists.
Corticosteroids prevent remodeling of respiratory tract which may occur in severe, progressive inflammation of chronic asthma.
Systemic Corticosteroids:
Dexamethasone and prednisolone: They are life saving steroids in status asthmaticus.
Oral glucocorticoids: Short course is used for exacerbations with incomplete response to β2 agonists, after which tapering is needed.
Pregnancy and Asthma
Safety to use anti-asthma drugs in pregnant women:
Pregnant women with asthma can be treated as aggressively as non pregnant asthmatic patients.
Risks of poorly controlled asthma include: pre- eclampsia, perinatal mortality, preterm labor and low birth weight.
Use of ICS (Inhaled Corticosteroids) during the 1st trimester: Congenital malformation may occur with ICS >1000 mcg/day
Another study with ICS use during pregnancy: Risks of endocrine and metabolic abnormalities
Leukotriene Inhibitors
Zileuton, Zafirlukast, Montelukast
Mechanism of action of each:
They either block the synthesis of leukotrienes from arachidonic acid or block the leukotriene receptor.
Zileuton – inhibits 5-lipoxygenase, which catalyzes the formation of leukotrienes from arachidonic acid.
Zafirlukast – LTD 4 receptor antagonist
Montelukast – LTD4 receptor antagonist
Clinical role of Leukotriene inhibitors in asthma:
Useful in prevention of exercise, antigen, and aspirin induced asthma.
They prevent bronchoconstriction and airway inflammation. Leukotriene inhibitors are used for chronic maintenance therapy of mild asthma; they are not beneficial in acute bronchospasm
Adverse effects of Leukotriene inhibitors:
Overall they have a very safe profile.
Zileuton – Some cases of elevated liver enzymes have been reported
Zafirlukast and Montelukast – Rarely patients develop as vasculitis and systemic eosinophilia resembling Churg-Strauss syndrome
Omalizumab:
Anti-IgE antibody –Omalizumab:
It is administered parenterally and an expensive drug.
MOA: It binds to the IgE on sensitized mast cells and prevents activation by triggers – prevents release of LTs and other mediators.
Used for prophylactic management in asthmatic patients and in cases of inadequate control with inhaled ICS in patients aged above 12 years.
Like other protein and antibody drugs, omalizumab causes anaphylaxis (a life-threatening systemic allergic reaction) in 1 to 2 patients per 1,000.
Release inhibitors used in asthma:
Cromolyn, and Nedocromil
Mechanism of action of cromolyn sodium and nedocromil:
They are effective prophylactic agents that stabilize the membranes of mast cells and prevent the release of inflammatory mediators.
They are not used for treating acute attacks of asthma:
They are used as prophylactic agents. Pretreatment with cromolyn or nedocromil blocks allergen- and exercise-induced bronchoconstriction.
Other uses: for preventing food allergy and hay fever. Available as oral, aerosol and drops
Potential toxicities of cromolyn and nedocromil:
Cromolyn – infrequent laryngeal edema, cough, and wheezing
Nedocromil – unpleasant taste
Opioids –ANTITUSSIVES (COUGH MEDICATIONS)
Codeine, Dextrometorphan
Use antitussives:
Antitussives have a limited role. Coughing is a symptom and, wherever possible, therapy is directed to its etiology. However, in acute respiratory tract infections where cough disrupts sleep, antitussives may be used.
Opiates suppress cough:
OpiatesdecreasetheCNScoughcenter’s sensitivity to peripheral stimuli. These actions occur at doses lower than those required for analgesia.
Opiates use as antitussives:
- Codeine
- Dextromethorphan: A synthetic derivative of codeine
Mechanism of action of dextromethorphan :
It suppresses the response of the cough center, but it does not have any analgesic or addictive potential and is less constipating than codeine.
N-acetylcysteine (abbreviated NAC)
Mucolytic agent:
N-acetylcysteine (abbreviated NAC) –cough:
• It is a used primarily as a mucolytic agent and in the management of acetaminophen overdose.
• Useful in cystic fibrosis (CF). Breaks disulfide bonds in mucus and liquefies it making it easier to cough out.
H1 antagonists
• Diphenhydramine
• Chlorpheniramine
• Loratadine
• Fexofenadine
• Cetirizine
Mechanism of action of antihistamines:
Blockers of H1 histamine receptors are useful in treating the symptoms of allergic rhinitis caused by histamine release.
Commonly used antihistamines in the treatment of rhinitis are:
Diphenhydramine, Chlorpheniramine, Cyproheptadine –they cross BBB and produce drowsiness.
Loratadine; Fexofenadine; Cetirizine are non- drowsy antihistamines
Rhinitis Agents
Treatment:
For allergic rhinitis, try avoidance therapy (avoiding contacts with all known allergens/irritants). If irritant avoidance is not realistically possible or if the rhinitis appears to be caused by a virus, medical options include: Nasal corticosteroids, Cromolynsodium, Antihistamines, α-Adrenergicagonists
Corticosteroids commonly used to treat chronic rhinitis:
Beclomethasone and flunisolide.
Chronic rhinitis does not show improvement until 2 weeks after the start of therapy.
Mechanism of action of α-adrenergic agonists:
α-Adrenergicagonistsconstrictdilatedarteriolesin the nasal mucosa and reduce airway resistance. When administered in aerosol form, these drugs have a rapid onset of action and show few systemic effects.
Examples of α-adrenergic agonists used in the treatment of rhinitis:
Phenylephrine and pseudoephedrine
Phenyephrine is also used to dilate pupil and to ↑BP
Effects of prolonged use of nasal decongestants:
Rebound nasal congestion often occurs after discontinuation from prolonged use.
