Asthma Flashcards
What is asthma?
- An inflammatory disease of lung airways
- reversible airway obstruction
What is asthma characterized by?
- Narrowed airways; ↓ gas exchange
- Inflammation of airways with inflammatory cells
- Bronchoconstriction + bronchospasm
- Mucus production
- cholinergic nerve over-activity
- smooth muscle hypertrophy
What factors contribute to allergic asthma?
eosinophilic
- Allergens (most common)
- Occupational (industrial chemicals)
- Air pollutants
- Infections (RSV, influenza)
- Exercise
- Medicines (aspirin, B-blockers)
- Stress
- Genes
What factors contribute to non-allergic asthma?
non-eosinophilic
- Adults
- Nasal polyps
- Drug hypersensitivity; aspirin, penicillin
- COPD
- poor prognosis
does not respond to corticosteroids
What tests are done for asthma?
- Family history
- Physical exam
- Spirometry
- Bronchodilator reversibility test
- Allergy test
in more sever cases CT scan
What happens to bronchioles during SNS?
- Bronchodilation
- Adrenaline activates β2 receptors
What happens to bronchioles during PNS?
- Bronchoconstriction
- Ach binds to M3 receptors
- increased mucus secretion
- vagus nerve
Muscarinic M3
What are the types of bronchodilators?
- β2 agonists
- Muscarinic antagonists/Anti-cholinergic
- Methylxanthines
SNS activation, PNS inactivation
What are SABAs?
Short acting Beta agonists
- Salbutamol
- Terbutaline
- acute asthma attacks + exercise relief
- short term relief for COPD
- last 4-6 hrs
- bind directly to orthosteric B2 receptor sites
What are LABAs?
Long acting beta agonists
- Salmeterol / Formoterol / Indacaterol / Vilanterol
- used for clients with more frequent attacks with corticosteroids
- last 12-24 hrs
- bind to orthosteric and exo-sites for prolonged receptor activation
What are the contraindications of beta-blockers?
- can precipitate asthma
- Non-selective BB: cause bronchoconstriction
- Cardioselective: safer but still risky
non-selective targets B1 + B2, cardioselective target B1 only
What are some side effects of B-agonists?
- hypersensitivity to drug
- hypertension
- tremors
- muscle cramps
- thyroid disease
- DM
- tachyarrhythmias
- CAD
- seizures
- hypokalaemia
What is the MOA of B2 agonists?
- Bind to B2 adrenoreceptors
- Increase cAMP via G-protein linked activation of AC
- Bronchodilation of smooth muscle
- inhibit mediator release from mast cells
What are Muscarinic receptor antagonists?
Ipratropium (the only SAMA)
- antagonist for M1, M2, M3
- bronchodilator
- reduces mucous secretion
- slower acting that B2 agonist
Tiotropium (LAMA)
- inverse agonist for M1,M3
can be ipratropium/tiotropium bromide
What are side effects of Muscarinic receptor antagonists?
- usually well tolerated
- dry mouth and urinary retention
What are methylxanthines?
- have immunomodulatory effects
- found in tea, coffee, cocoa
- Caffeine, Theophylline, Aminophylline
What is the MOA of methylxanthines?
- bronchodilation
- inhibit phosphodiesterase
- more cAMP, cGMP
- anti-inflammatory actions
- improves diaphragm strength
Give information about theophylline
- most common xanthine drug
- taken orally
- low TI
- drugs interact with theophylline, affecting its metabolism with CYP1A2
- macrolides inhibit CYP1A2, ↑ toxicity of theo
- smoking + caffeine also effect theo
- rifampicin increases CYP1A2, ↓ theo
aminophylline taken by IV - ICU, macrolides: clarithromycin, erythromycn
What are side effects of methylxanthines?
low TI, so SE with high concentrations:
- nausea
- arrhythmias
- tremor, seizure
TI = therapeutic index
Where are methylxanthines metabolised?
- liver
- Cytochrome P450; CYP1A2
Explain the pathophysiology of asthma?
- Initial phase: interaction of allergen with mast cell IgE, release of histamine + PGD2 - bronchoconstriction
- Intermediate phase: chemokine release - IL4, IL5 and IL13, leukocyte release
Mucosal oedema - Late phase: Influx of Th2 cells, neutrophils and eosinophils activated - TNF-a, IFN-y released
Lung epithelial damage
What anti-inflammatory drugs are used in asthma treatment?
- Glucocorticoids
- Cromones
- Leukotriene synthesis inhibitors
- Leukotriene receptor antagonists
What are corticosteroids?
- Beclomethasone (inhaled)
- Prednisone (oral)
- Hydrocortisone (IV)
What are side effects of inhaled corticosteroids?
- Oral candidiasis (thrush)
- Dysphonia (myopathy of laryngeal muscles)
What are systemic side effects of oral corticosteroids?
- adrenal suppression
- infections
- hypertension, fluid retention
- osteoporosis, myopathy, obesity, growth stunting, catarcts, glaucoma
- glucose intolerance
What do we give first in an acute asthma attack?
Bronchodilators FIRST, then corticosteroids
How do anti-leukotrienes work?
- most effective in exercise induced bronchioconstriction
- not for acute attacks
- low s/e
- orally
Leukotriene receptor antagonism:
- blocks cysteinyl leukotriene type 1 receptors
Leukotriene synthesis inhibition:
- Inhibitis 5-lipooxygenase enyzme, stops formation of leukotriene
How do glucocorticoids work?
as anti-leukotriene
- inhibit arachadonic acid synthesis
- suppresses phospolipase A2
What are cromones?
- mast cell stabilisers
- sodium cromogylate + nedocromil
- inhibit dengranulation and reduce mediator release
- inhibit eosinophil accumulation
- inhaled
blocks release of histamine, chemokines and leukotrienes from mast cells
What are some newer anti-inflammatory approaches for asthma?
- Omalizumab; Anti-IgE
- methotrexate
- gold
- cyclosporin
- anti-TNF-a agents
How is acute asthma managed?
- SABA: salbutamol
- Muscarinic antagonist: ipratropium (inhaled)
- Corticosteroid: prednisolone (oral)
- hospitalization
Magnesium sulphate in IV used for life threatening situations
How is chronic asthma managed?
- give SABA as reliever (optional)
- low does ICS for controller
- leukotrine modifier
- methylxanthine: theophylline
- LAMA
from 2 onwards switch SABA to LABA and increase ICS dose as needed
What are the microscopic features of asthma?
- neutrophils + eosinophils
- mast cell degranulation
- basement membrane thick
- lumen filled with mucus
- hypertrophy of smooth muscle + goblet cells
What are the cardinal symptoms of asthma?
- Cough (nocturnal)
- Wheeze
- SOB
- usually onset in childhood
- rhinitis and eczema
What is the classic triad in asthma?
- Dyspnoea
- Wheeze
- Cough (non-productive)
no sputum in cough
What are the cardinal signs of asthma?
- wheezing upon auscultation
- reduced PEFR
- reduced FEV1
- accessory muscle use
- cyanosis
- hyperinflation of chest
Why are asthma symptoms worse during the night and in the morning?
- cortisol ↓ 12am
- adrenaline ↓ 4am
- nocturnal symptoms 2-3am onwards
