Respiratory System - Asthma & COPD Flashcards
A chronic inflammatory disorder of the airways which involves complex interactions between many cells and inflammatory mediators which can result in inflammation, obstruction, increased airway responsiveness and episodic asthma symptoms.
Asthma
CLINICAL SIGNS & SYMPTOMS of Asthma:
- SOB
- Chest tightness
- Wheezing
- Tachypnea & tachycardia
- Pulsus paradoxus
HALLMARK Pathophysiologic Features of asthma:
- Reversible narrowing of the bronchial airway
- Marked increased in bronchial responsiveness to inhaled stimuli.
PATHOLOGIC Features
- Lymphocylic
- Eosinophilic
2 DOMAINS FOR THE SPECTRUM OF ASTHMA’S SEVERITY:
1. Impairment
2. Risk
Impairment: based on the frequency & severity of symptoms, severity of the airflow obstruction on pulmonary function testing & the intensity of therapy required for maintenance of asthma control.
Classification:
Mild Intermittent - interval
Mild persistent - not on a daily basis
Moderate persistent - everyday
Severe persistent - throughout the day
Risk: Based on susceptibility to asthma exacerbations
Precipitating factors of acute asthma:
- Allergens
- Occupational exposures
- Viral respiratory tract infections
- Exercise
- Emotions
- Exposure to initants
- Environmental exposures
- Drugs
Asthmatic bronchospasm:
- Allergenic stimuli
Mediated by IgE, produced in response to exposure to foreign proteins. - Non-allergenic stimuli
Exercise, Cigarette smoking, Cold air
Acute bronchoconstriction due to the release of histamine, tryptase, leukotrienes C4. D4 & prostaglandin D2
Early asthmatic response
Associated with an influx of inflammatory cells into the bronchial mucosa & with an increase in bronchial reactivity.
This is due to cytokines-produced by T2 lymphocytes especially interleukin (IL) 5,9 & 13.
Late asthmatic response
HYPOTHESIS:
Asthmatic bronchospasm (combination of mediators & exaggeration of responsiveness).
Drugs w/ different mode of action = effectively treat asthma.
Bronchospasm provoked by exposure to allergens might be reversed/prevented.
N/A
SYMPATHOMIMETIC AGENTS
ẞ2 Selective agonists:
Albuterol
Salmeterol
Metaproterenol
Pirbuterol
Terbutaline
(Short-acting)
a & ẞ Nonselective agonists:
Epinephrine
ẞ1 & ẞ2 agonists:
Isoproterenol
Available in SQ Indication is similar to epinephrine for severe asthma requiring emergency treatment when aerolized therapy is not available or has been ineffective.
Used to inhibit uterine contractions.
Principal A/E:
Skeletal muscle tremor
Nervousness
Occasional weakness
Dose:
Nebulizing solution:
- 2.5-5.0mg q 20 mins x3 doses,
- 2.5-10.0mg q 1-4 hrs pr
- or 10-15mg/hr continuously
MDI: 4-8 puffs q 20 mins up to 4 hrs, then q 1-4 hrs prn
Oral: SR tab,
0.3-0.6 mg/kg/day (pedia)
4mg q 12 hrs (adults)
Terbutaline
Long-acting B-agonists (LABA):
- Salmeterol
- Formoterol
interact with inhaled corticosteroids (ICS) to improve asthma control.
Not to be used as monotherapy.
W/ high lipid solubility
Ultra long-acting ß-agonists:
- Indacaterol
- Olodaterol
- Vilanterol
- Bambuterol
Used for monotherapy in COPD.
Used in combination w/ ICS for asthma
SYMPATHOMIMETIC AGENTS
-MOA: ẞ-agonists stimulate ẞ2 receptors activating adenyl cyclase, which increases intracellular production of cyclic adenosine monophosphate (cAMP).
Dose: Via inhalation, Systemic administration
Toxicity:
Worsened hypoxemia
Cardiac arrhythmias
Decreased arterial oxygen tension
Tachyphylaxis
N/A
Rapid-acting bronchodilator. Stimulates a, B and B2.
Used for the treatment of the acute vasodilation and bronchospasm of anaphylaxis.
Bronchodilation within 15 min that lasts for 60-90 min.
Epinephrine
Potent non selective B, and B2 bronchodilator.
Bronchodilation in 5 min that lasts for 60-90 min.
Isoproterenol
MOA: at high concentration inhibit several members of PDE enzyme family in vitro, increasing the intracellular CAMP & in some tissues cGMP.
Inhibition of cell surface receptors for adenosine.
Enhancement of histone deacetylation.
• Theophylline-tea (1,3 dimethylxanthine)
• Theobromine - cocoa (3,7 dimethylxanthine)
• Caffeine - coffee (1,3,7 trimethylxanthine)
The cause for the decline of theophylline use in asthma:
- Toxicities
- Serum level monitoring: narrow therapeutic index
Methylxanthine Drugs
A theophylline-ethylenediamine complex
Aminophylline
Selective inhibitor of PDE4.
Reduces the frequency of exacerbations of COPD Approved by the US FDA as treatment for COPD
ROFLUMILAST
METHYLXANTHINE DRUGS Effects:
CNS - mild cortical arousal with increased alertness & defence fatigue
Cardiovascular - (+) chronotropic and inotropic effects on the heart.
Gl - stimulates secretion of both gastric and digestive enzymes
Kidney - theophyline is a weak diuretic
- Smooth muscle - bronchodilation
- Skeletal muscle - improve contractility
N/A
Antimuscarinic agent:
Atropine
Ipratropium bromide
Longer acting antimuscarinic agent:
Tiotropium, aclidinium, umeclidinium - used for maintenance therapy of COPD.
A potent competitive inhibitor of acetylcholine at postganglionic muscarinic receptors, as a bronchodilator.
Atropine
A selective quaternary ammonium derivative of atropine which can be inhaled in high doses because of its poor absorption into the circulation and poor entry into the CNS.
As effective as albuterol in patients with COPD who at least partially reversible obstruction.
Ipratropium bromide
Suppress the inflammatory response and decrease hyperresponsiveness
MOA: Corticosteroids binds to glucocorticoid receptors on the cytoplasma of the cells.
Effect: Contraction of engorged vessels on bronchial mucosa.
Potentiation of the effects of beta receptor agonists.
Inhibition of the infiltration of asthmatic airways by lymphocytes, eosinophils and mast cells
Clinical use: improves all indices of asthma control.
Dose: for severe asthma exacerbations 30-60mg of prednisone per day.
IV dose of 0.5-Img/kg of methylprednisolone q 6-12 hr.
The dose is decreased after airway obstruction has improved.
Systemic treatment must be discontinued in 5 to 10 days
CORTICOSTEROIDS
