Asthma drugs Flashcards
(37 cards)
What is asthma?
Reversible airway obstruction as a result of bronchial hyper-reactivity, airway inflammation, mucous plugging and smooth muscle hypertrophy
What are the endogenous products that play important role in pathophysiology of lung?
Prostaglandins Acetylcholine Beta Adrenergics Histamine Adenosine ACE: inactivates bradykinin, which is enhanced by ACEI that cause cough and angioedema
How does Bradykinin and Substance P lead to a cough?
Bradykinin:
–Increases release of prostaglandins, Leukotrienes and Histamine leads to type J receptors at peripheral vagal afferents ending/non myelinated or C- fibers
Substance P:
—type J receptors at peripheral vagal afferent ending/non-myelinated or C-fibers
What is the role of methacholine in asthma?
Muscarinic Receptor (M3) agonist --used in bronchial challenge test to help diagnose asthma
Describe the role of inadequate surfactant in infants that leads to RDS.
Can be prevented if mothers who are about to deliver prematurely by dexamethasone administration
–test: lecithin to sphingolyelin ratio greater than 2.0m in amniotic fluid, indicated fetal lung maturity.
What factors precipitate an asthma attack?
Allergens: induce mast cell release of inflammatory mediators
Infections: viral URI or even bacterial/fungal
Pharmacological Factors: Beta Blockers, cholinergics
Exercise and Stress: Vagal and Adrenergic Influence
Moving on to the drugs used in asthma treatment, first are the bronchodilators (Beta receptor agonists, antimuscarinic drugs, methylxanthines). First lets start with the beta 2 receptor agonists, what are these drugs?
Albuterol Pirbuterol Terbutaline Salmeterol Formoterol
What is the MOA of beta 2 agonists?
Increasing intracellular concentrations of cAMP
–this leads to relaxation of bronchial smooth muscle and therefore bronchodilation
What are your short acting vs long acting beta 2 agonists?
SABA: albuterol, pirbuterol and terbutaline
LABAs: salmeterol and formoterol
–most of these drugs are inhaled, which minimizes their systemic side effects
–LABAs available in combination with ICS (inhalational corticosteriod) for long term control and prevention of symptoms in moderate to severe persistent asthma
What is a concern regarding long acting beta agonists?
Genetic Polymorphism in Beta 2 receptors
–causes slight worsening of asthma, exacerbations or even death
What are some clinical concerns of asthma?
Do not use LABAs inhaler for rescue medication!
LABAs should only be used in conjunction with an inhaled steroid
What drugs are used for exercise induced bronchoconstriction?
SABAs used just before exercise will prevent EIB for 2-4 hours after inhalation
LABAs will prevent up to 12 hours
What are the adverse effects of inhaled Beta 2 adrenergic agonists bronchodilators?
Tremors, Tachycardia, arrhythmias and hyperglycemia
–high doses of Beta 2 agonist can get into the systemic circulation and therefore into the blood stream
Next set of drugs for asthma are Anticholinergics as bronchodilators, Ipratropium and Tiotropium. What are their uses?
Ipratropium: a short acting inhaled anticholinergic can be used in asthma, QID
Tiotropium: a long acting anticholinergic used SID in COPD
What is the MOA of anticholinergics?
Parasympathetic stimulation causes bronchial constriction and mucous secretion.
–anticholinergics are used to block the muscarinic receptors in the smooth muscles and maintain bronchial dilation of the airway
What are the clinical uses for Ipratropium?
Prevent vagal mediated bronchoconstriction and drug induced bronchospasm such as beta blockers
What are the averse effects of Ipratropium?
Dry mouth
Careful in patients with glaucoma and BPH
The next drugs used in asthma are the Methylxanthines, Theophylline and Aminophylline.
Inhibit phosphodiesterase
–this enzyme converts cAMP to AMP
Increasing cAMP levels results in bronchodilation
also blocks adenosine receptors
What is the role, drug interactions, and complications of theophylline?
Role in Asthma:
–limited because it has a very small therapeutic window
Drug Interactions:
–Cimetidine, erythromycin and Ciprofloxacin all increase plasma levels
–Phenytonin, phenobarbitone and carbamazepine all decrease plasma levels
Complications with overdose:
—tremor, insomnia, GI distress and nausea.
Moving on to the corticosteroids used in asthma. What are they?
Beclomethasone Dexamethasone Fluticasone Budesonide Flunisolide Prednisolone
What is the MOA of corticosteroids?
Inhibit synthesis of arachidonic acid by phospholipase A2
–therefore inflammatory mediators like leuotrienes, cytokines and prostaglandins are inhibited
Steroids bind to intracellular receptors and activate glucocorticoid response elements in the nucleus, result in the synthesis of substances that inhibit expression of inflammation and allergy
How are corticosteriods used in asthma management?
Both acute and maintenance:
- –acute: 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
Corticosteroids also do what?
- Increase beta 2 adrenoreceptors responsiveness in the respiratory tract
- Used once or twice a day: reduce the need for beta 2 agonists
- Prevent remodeling of resp tract
- Patients who remain symptomatic in spite of compliance with inhaled corticosteroid treatment addition of long acting beta 2 agonists are recommended.
In regards to corticosteriods how are these processed in the system?
Ten percent deposited in the lung
Ninety percent swallowed
GI tract absorption from gut
First pass inactivation in the liver: therefore nothing gets passed to the systemic circulation
–however with long term use or high doses of drug from the liver and lungs can enter the systemic circulation and cause side effects
