Asthma Flashcards
Classification of asthma
- Intermittent - < 2 days a week, not everyday. Lung function tests normal
- Mild persistent- > 2 days a week, not everyday. Lung function tests normal when person is not having an attack
- Moderate persistent- symptoms daily. Need to use short acting inhaler every day. Lung function tests abnormal
- Severe persistent- symptoms throughout each day. Severely limits daily activities. Lung function tests abnormal
Phases of asthma
Acute phase - excessive secretion of mucus that may clog the bronchi and bronchioles
Chronic phase - inflammation, followed by fibrosis, edema and necrosis of bronchial epithelial cells
Status asthmatic/refractory asthma?
Acute exacerbation of severe asthma that does not respond to standard treatments of bronchodilators
Risk factors and triggers
Stress
obesity
Drugs ( b blockers, aspirin)
Acetaminophen ( paracetamol)
Diagnosis of asthma
Spirometry - reduced Fev1, fev1/fvc ratio, and PEF
What is produced on initial exposure to allergens
IgE by plasma cells
IgE binds to what receptors?
High affinity receptors (FCeR-1) on mast cells
Re- exposure to allergens releases?
Mediators stored in mast cells. The histamine , tryptase, leukotrienes C4 and D4 and prostaglandin D2.
The mediators released cause?
Smooth muscle contraction and vascular leakage causing bronchoconstriction. EARLY ASTHMATIC RESPONSE
Late asthmatic response is mediated by?
TH2 cells (T lymphocytes)
What does TH2 cells secrete?
Interleukins (IL) 4,5 & 13, GM-CSF
What does the IL secreted by TH2 cells do?
- These cytokines attract and activate eosinophils.
- Stimulate IgE production by B lymphocytes
- Stimulate mucus production by bronchial epithelial cells
Early vs late response summary
EARLY
1. mast cell degranulation mediated by IgE.
2. Smooth muscle spasms, vasodilation
LATE
1. Initiated by cytokines produced by TH2 lymphocytes
2. Mucosal edema, mucosal secretion (by bronchial epithelial cells), more IgE production, activation of eosinophils
Treatment of asthma
MOA of Bronchodilators vs Controllers
Bronchodilators- relaxation of airway smooth muscle
Controllers- inhibit underlying inflammatory process
Classes of bronchodilators and examples
- Selective B2 agonists - Salbutamol, Salmeterol, Formoterol terbutaline, Bambuterol
- Non- selective sympathomimetics - epinephrine, ephedrine, isoprenaline, orciprenaline
- Anticholinergics / muscarinic antagonists - ipratropium bromide, tiotropium bromide
- Methylxanthines - theophylline, aminophylline, diprophylline
Mechanism of action of bronchodilators
SYMPATHOMIMETICS
Act on B2 adrenergic receptors of bronchial smooth muscles
Increase cAMP, causing bronchodilation
Mechanism of action of bronchodilators
METHYLXANTHINES
Decrease cAMP destruction.
By inhibiting Phosphodiesterases, causing bronchodilation
Mechanism of action of bronchodilators
MUSCARINIC RECEPTOR ANTAGONIST OR ANTICHOLINERGICS
Competitive antagonist of acetylcholine (ACH) at postganglionic nerve receptors, leading to smooth muscle relaxation and bronchodilation
B1 receptors found?
Cardiac and intestinal smooth muscles
B2 receptors found?
Bronchial, uterine and vascular smooth muscles Increase cAMP
B- adrenergic receptors action
Acts on b2 receptor (a G protein coupled receptor) > activates adenylyl cyclase > increase cAMP destruction > activates pkA > bronchodilation
Short acting b2 agonists (SABA) and function
Salbutamol
Terbutaline
For quick reversal of bronchospasm
(bronchodilation)
Long acting b2 agonists (LABA) and function
Salmeterol
Formeterol
Not used for treating acute attacks
Used for treating nocturnal attacks
Preventing asthma attacks along with steroids
Adverse effects of selective b2 agonists
Muscle tremor and palpitations
Mild hypokalemia
The Non-selective sympathomimetics ?
Epinephrine
Ephedrine
Isoproterenol
Isoprenaline
Orciprenaline
Side effects of non-selective sympathomimetics
Muscle tremor
Tachycardia
Palpitations
Hypokalemia
Restlessness
MOA of anticholinergics / antimuscarinic agents
Binds M3 receptors on airway smooth muscles, preventing the action of acetylcholine released from parasympathetic nerve - bronchodilation
Does not cross BBB - devoid of CNS side effects
Side effects of anticholinergics/ antimuscarinics
Dryness of mouth
GI distress
Use of anticholinergics/ antimuscarinics
DOC for bronchospasm caused by beta blockers
BRONCHODILATOR OF CHOICE in COPD
What are the short and long acting anticholinergic
Short-acting - Ipratropium
Long-acting - Tiotropium
The Methylxanthines?
Theophylline
Aminophylline
Diprophylline
(DAT)
MOA of Methylxanthines
- Inhibits Phosphodiesterase enzyme (PDE-III & IV) > elevating camp concentration leading to bronchodilation
- Blocking adenosine receptors > inhibiting bronchoconstriction
(Adenosine constricts bronchus smooth muscles via adenosine receptors)
Methylxanthines are NOT given to pt. with supraventricular tachycardia
Side effects of methylxanthines and plasma level
Plasma level > 20ug/mg - CNS stimulant effects
Plasma level > 40ug/mg - Tremors followed by seizures, agitation, arrhythmias
Side effects - Common: vomiting, headaches, nausea, diuresis, palpitations
High doses: arrhythmia, seizures & death
Methylxanthines drug interactions
CYP450 enzyme INDUCERS - rifampicin, phenytoin. Decreases theophylline
CYP450 enzyme INHIBITORS - cimetidine, ciprofloxacin. Increases plasma levels and prolongs half-life of theophylline
What are the controller therapies and use?
- Corticosteroids (inhalation and systematic)
- Mast cell stabilizers
- Leukotriene antagonists
- Monoclonal IgE antibody
Use - INHIBIT the underlying INFLAMMATORY process
Names of Corticosteroid Drugs and their route of use
Oral - Prednisolone, Prednisone, Methylprednisolone
Parenteral - Methylprednisolone, Hydrocortisone
Inhalation - Beclomethasone, Fluticasone, Triamcinolone, Budesonide
MOA of Corticosteroids
‘CONTROLLERS’ - provide long-term stabilization of symptoms due to their anti-inflammatory effects
Enhances the effectiveness of b2 receptors on the airway
INHIBITS THE RELEASE OF INFLAMMATORY MEDIATORS - prevents smooth muscle contraction, vascular permeability and airway mucus secretion
INHIBITS THE FORMATION AND RELEASE OF CYTOKINES thus prevents proliferation and activation of leukocytes
ICSs Use
Most effective controllers
Least absorbed into systemic circulation
ICS along with b2 agonist - FIRST CHOICE of drug for CHRONIC ASTHMA
Side effects of ICSs
Dryness of mouth
Voice changes
ORAL CANDIDIASIS or THRUSH
Systemic corticosteroids
Prednisone, methylprednisolone, hydrocortisone
Use of systemic corticosteroids
Reserved for patients who require urgent treatment
(SEVERE CHRONIC ASTHMA, STATUS ASTHMATICUS)
Side effects of systemic corticosteroids
Truncal obesity
Bruising
Osteoporosis
Diabetes
Hypertension
Gastric ulceration
Cataracts
Adrenal insufficiency
Cushing syndrome
Mast cell stabilizers
Sodium cromoglycate, Nedocromil
Use of Mast cell stabilizers
Not bronchodilators, non-steroidal drugs
Used for PROPHYLACTIC TREATMENT of bronchial asthma
Prevention the degranulation and release of chemical mediators from mast cells
Used solely for PROPHYLAXIS.
NOT for acute asthma attacks
To prevent bronchospasm associated with exposure to known precipitating factors, such as cold, dry air or allergens
Side effects of Mast cell stabilizers
Throat irritation
Dryness of mouth
Headache
Moa of leukotriene
Mediators of inflammation - causes bronchoconstriction and mucus production
Effects of leukotriene can be prevented by? And med?
- Inhibiting leukotriene synthesis
By inhibiting the 5-lipooxygenase enzyme - ZILEUTON - By blocking their stimulatory effects on Cys-LT receptors - ZAFIRLUKAST, MONTELUKAST
Uses of leukotriene antagonists
As an adjuvant with ICS in poorly responding patients
Prophylaxis and treatment of chronic asthma
Used for prophylaxis of mild to moderate asthma in children
NOT meant for the management of acute asthmatic attacks
Moa and adverse effects of leukotriene antagonists
ZILEUTON - CONTRAINDICATED in liver disease - Hepatotoxicity
ZAFIRLUKAST -
FOOD DECREASES BIOAVAILABILITY - administer 2 hours before meals (12hrs interval)
Adverse effects- git distress & headache
MONTELUKAST -
Administer once daily
Bioavailability is not affected by meals
Monoclonal anti-IgE antibody?
Omalizumab
Moa of Monoclonal anti-IgE antibody
Recombinant human monoclonal antibody which inhibits the binding of IgE to mast cells and basophils
Inhibits the activation of IgE that is already bound to mast cells and prevents its degranulation
Management of Chronic Asthma
Mild intermittent -
short-acting b2 agonist as required for symptom relief
Mild persistent -
short-acting b2 agonist as required for symptom relief + Low dose ICS
Moderate persistent -
short-acting b2 agonist as required for symptom relief + Low dose ICS + LABA
Severe persistent -
short-acting b2 agonist as required for symptom relief + High dose ICS + LABA
Very Severe persistent - short-acting b2 agonist as required for symptom relief + High dose ICS + LABA + OCS
Treatment of Acute Severe Asthma
A high conc. of OXYGEN, given by face mask to achieve oxygen saturation of >90%
The mainstay of treatment are HIGH DOSES of SABA
Treatment of Acute Severe Asthma in severely ill pt. with impending respiratory failure
IV B2 agonist may be given
A NEBULIZED ANTICHOLINERGIC MAY BE ADDED if there is not a satisfactory response to b2 agonist alone
Treatment of Acute Severe Asthma for pt. with respiratory failure
INTUBATE and INSTITUTE VENTILATION
Treatment of Acute Severe Asthma in severely ill pt. with chest infection
Treated with intensive antibiotic therapy
Correct dehydration and acidosis
CHRONIC BRONCHITIS
Chronic productive cough and excessive sputum
Enlargement of mucus glands
Increase in mucus production
Thickening of the bronchial wall
Dyspnoea, bronchospasm and respiratory tract infections
Complications of CHRONIC BRONCHITIS
Pt. suffers from RT-sided heart failure (corpulmonale: pulmonary hypertension, RT Ventricular hypertrophy, RT Heart failure)
EMPHYSEMA
Enlargement of air spaces
Destruction of lung parenchyma
Loss of elasticity and closure of small airways
Management of COPD
COPD - Irreversible dz.l, drugs only relieve the symptoms without treating underlying pathophysiology
Management of COPD
Aims of the treatment
To lessen the airflow obstruction
Reduce respiratory symptoms and improve quality of life
Prevent secondary complications like hypoxaemia, infections and corpulmonale
Treatment of COPD
Stop smoking
FIRST LINE DRUG THERAPY - BRONCHODILATORS - to reduce bronchospasm and wheezing
Methylxanthines - to improve respiratory muscle functions
Corticosteroids
O2 therapy
