Asthma Flashcards
Asthma
Non-communicable disease that is a chronic inflammatory disease of the airways of the airwasy
COPD
a group of diseases that cause airflow blockage and breathing-related problem
Asthma pathophysiology(tissue changes)?
-Increase in eosinophils in the mucus and tissue which will modulate inflammatory response
-Increase in goblet cells and thus an increase in mucus production
-Thickened basement membrane
-Increase in mast cells in lamina propria and thus increase in histamine
-Increase in T-helper cells
-Increase in neutrophils and highly inflmaation
Mediators of asthma
- IgE antibodies
- Mast cells-IgE complex
- Eosinophils
- Increase TH2-in lungs more than TH1 ad this causes inflammation
- Histamine
- LTD4
- Prostaglandin D2
Asthma key markers?
- Airflow obstruction
- Bronchohyperresponsive (due to histamine release)
- Inflammation(due to increase in neutrophils and other immune cells)
Asthma Symptoms
- Shortness of breath
- Wheezing associated with coughing
- Chest tightness
- Dry irritating cough
5.Mucus secretion
Phases of asthma?
-IgE binds FCεR-1 receptors on mast cells in the airwaymucosa
-Re-exposure to the allergen triggers the release of mediators from mast cells as well as other mediators
-Histamine, tryptase, LTC4 and D4, PGD2
-Smooth muscle contraction and vascular leakage → acute
bronchoconstriction of the “early asthmatic response.”
What is an early asthmatic response ?
Acute bronchoconstriction & vascular leakage
What is a late asthmatic response ?
–6 hours later more sustained phase of bronchoconstriction
Asthma categories?
Mild
Moderate
Severe/life-threatening
Status asthmaticus?
- Extreme form
- Severe & continuous.
- Poorly responsive to standard therapeutic measures
Asthma drugs for bronchodilators?
B-2 agonist selective drugs
What are the bronchodilator drugs used for asthma and their durations?
- Short-acting( Suffocating for truth)
- Salbutamol
-Fenoterol
-Terbutaline
- Salbutamol
- Long acting B2 agonists(Swallow food)
-Salmeterol
-Formoterol - Ultra-long acting( Inner Voice)
-Indacetrol
-Vilanterol
Which long-acting B2 agonist has a delayed onset?
Salmeterol
Which duration of B2 bronchodilators have increased lipids?
Long-acting B2 agonist
Monotherapy for asthma/COPD?
-Monotherapy for COPD
-B2 agonists are used in combination of IC
-NO MONOTHERAPY FOR ASTHMA
B-2 agonist S/E?
-Muscle tremors
-Tachycardia
-Hypokalemia
-Restlessness
-Hypoxemia
-Metabolic effects
-Increase in plasma: Glucose, FFA, Lactate, Pyruvate, Insulin
Mast cell stabilizers ?
Stabilizers mast cell by decreasing mast cell degradation to prevent histamine release
Mast cell stabilizers drugs?
Can Kids Need Mast?
Cromolyn Sodium
Ketotifen
Nedocromil Sodium
Mast
Mast cell indications?
Treat allergic and exercise-induced bronchospasm in asthmatic patients
Corticosteroid indications?
-Anti-inflammatory
-First-line in asthma
Corticosteroid 2 MOA?
Inhibit phospholipase A-2
Upregulation of annexin A1
Corticosteroid 2 MOA?
Inhibit phospholipase A-2
Upregulation of annexin A1
Corticosteriods drugs?
BBFF-CMT
Beclomethasone
Budisonide
Ciclesonide
Flunisolide
Fluticasone
Mometasone
Triamclionolone
Asthma corticosteroid side effects?
-Oropharyngeal candidiasis
-Dysphonia(hoarseness)
Leukotriene pathway?
- Phosphoilipids
- Phospholipiase A2 converts phopholipids to arachidinoic acid
- Arachidonic acid is coverted to PGs by COX and leukotriene by 5-lipooxygenase
Effect of leukotriene pathway?
Causes bronchoconstriction(mainly) and contributes to overall inflammation, vasodilation and oedema
Leukotriene pathway inhibitor?
Inhibits the production Leukotriene?
Which drugs are leukotriene inhibitors and state where they act?
- Montelukast-LTD4 receptor antagonist
- Zafirlukast-LTD4 receptor antagonist
- Zileuton-5-lipoxygenase and LTB4 receptor antagonist
How does aspirin cause asthma?
Aspirin is a COX inhibitor. Thus all the arachnoid acid will be converted into leukotriene and causes an increases in inflammation bronchoconstriction
Leukotriene inhibitor indications?
-Aspirin-induced asthma or aspirin-excerbated respiratory disease(AERD)
Leukotriene inhibitor admin?
Oral administration & thus can easily be take in children over the age of 12months
Leukotriene inhibitor and children?
Ideal for children from 12 months of age
Monoclonal antibody therapy MOA?
Recombinant antibody activity that selectively bind to cell receptor to decrease teh activity of that cell
Monoclonal antibody therapy for asthma drugs?
BROM
- Omalizumab
- Mepolizumab
- Reslizumab
- Benralizumab
Omalizumab MOA?
Selectively bind to free IgE and prevents them from binidng to mast cell receptor ans thus decreasing histamine release and bronchial constriction
MOA for Mepolizumab, Reslizumab & Benralizumab
Anti-IL5(involved in the pathway binding to an asthma attack) monoclonal antibody
For asthma associated with peripheral eosinophilia
Mepolizumab ADR and cure?
Can lead to herpes zoster infection
The varicella zoster vaccine 4 weeks before initiating mepolizumab
Which drug is given adjunct to the monoclonal antibody and its MOA?
Dupilumab
Anti-IL4/IL3 receptor antibody
Which asthma treatment is first-line for severe asthma?
Corticosteroids
Which asthma treatment is first-line for mild and moderate asthma?
Dupilumab with oral corticosteriod dependent asthma
Monoclonal antibody therapy S/E?
Associated with anaphylactic reactions or other hypersensitivity
Antimuscuranic asthma MOA?
Acetylcholine binds to muscarinic receptors to play a key role in the pathophysiology of asthma, leading to bronchoconstriction, increased mucus secretion, inflammation and airway remodelling.
Muscarinic antagonists increase airflow in asthma by blocking cholinergic tone and also by blocking reflex bronchoconstriction mediated by the vagus nerves. They may also inhibit secretion and clearance of mucus
Antimuscuranic drug mnemonic?
GTI
Glycopyrrolate
Tiotropium
Ipratropium
MOA of long-acting antimuscarinic drug for asthma?
(GT)I
Bind to M1, M2 & M3 receptors and this increases selectivity for these receptors compared to ipratropium
Long-acting anti-muscarinic drugs and association?
Fast dissociation from M2 may allow ACh to bind to M2 receptor thus inhibiting further ACh release
Short-acting anti-muscarinic drugs indication?
Patients with partially reversible obstruction
Why can short-acting antimuscuranic drugs be inhaled and why does it not have any effect on the peripheral circulation ?
Does not cross the BBB and thus decreases CNS effects and can be inhaled in high doses because of its poor absorption into the peripheral circulation and decreases lipid solubility
Methylxanthines the three MOA?
- Phosphodiesterase(PDE) inhibitor
PDE inhibit cAMP degradation
Thus, there will be an increase in intracellular cAMP and that causes the relaxation of smooth muscles and bronchodilation results - Inhibit adenoside receptor
- Increase histone deacetylation
What is the role of adenosine in asthma?
Adenosine will cause bronchoconstriction and an increase histamine release from the airway mast cells + inflammation
What is the role of histone in asthma?
Histone acetylation causes inflammatory gene transcription and that increases inflammation.
Therefore histone deacetylation by methylxanthines inhibits inflammation
Methylxanthine drugs?
CATT
1. Theophylline
2. Theobromine
3. Aminophylline
4. Caffeine
What is the result of the inhibition of PDE-3 and PDE-4?
PDE-3 Inhibition: Bronchodilation
PDE-4 Inhibition: Inhibits the release of inflammatory cytokines and chemokines
Roflumilast?
Selective PDE-4 inhibitor ad effective for reducing the frequency of exacerbations of COPD
Which xanthine drug is the most effective bronchodilator ?
Theophylline is the most selective in its smooth muscle effects
Which xanthine drug has the most CNS effective ?
Caffeine has the greatest CNS effects
Methylxanthines and mild cortical arousal?
All methylxanthines especially caffeine, cause mild cortical arousal with increased alertness and reduction of fatigue
Which enzyme metabolises theophylline?
CYP1A2 metabolism
Methylxanthines ADR?
-Abdominal discomfort
-Restlessness
-Headache
-Nausea & vomitting
-Diuresis
-Increased acid secretion
-Cardiac arrhythmias
-Seizures
Which drug do we use to treat severe/life threatening no response?
MgSO4/IV
Asthma drug categories?
ASTHMA(2)
Albuterol, ,ecT (B2-agonists)
Steriods (Corticosteroids)
Theophylline(Methylxanthines)
Histamine release blocker
Muscuranic antagonist(GTI)
Anti leukotrienes(MZZ)
AntiIgE((Monoclonal antibody)
Which classes of drugs are bronchodilators?
- Sympathomimetics (B-agonists
- Phosphodiesterase(PDE) inhibitors
- Anticholinergic agents
What are B1 agonists drugs?
EEI
- Epinephrine (Adrenaline)
- Ephedrine
- Isoproterenol/isoprenaline
Tx for Epinephrine ?
-Acute vasodilation
-Severe bronchospasm
-Bronchospasm of anaphylaxis
ADR for Epinephrine ?
Tachycardia, arrhythmias and worsening of angina pectoris_B1 receptors
Duration of action between Ephedrine and Ephinephrine?
Ephedrine>Epinephrine
Why is Ephedrine used less in the tx of asthma?
Ephedrine thus infrequently used to treat asthma
Which class of drugs was substituted by B2 selective agonists?
Isoproterenol
What causes tolerance for asthma?
Tolerance is from continued use and may be from the down regulation of the receptor
What is the benefit of ipratropium bromide?
Doesn’t cross BBB. Fewer CNS effects
Which anticholinergic drug is used for COPD and when?
Ipratropium bromide used patients have reversible obstruction
Immunological effects of corticosteroids ?
.1 Anti-inflammatory
2. Inhibit inflammatory cytokines
3. Induce apoptosis of eosinophils
4. Inhibit multiple inflammatory genes
5. Prevent and reverse vascular permeability
6. Inhibit mucus glycoproteoin secretion
What is the tx of oral candidiasis ?
Nystatin drops
Which cells synthesis leukotrienes?
Eosinophils
Mast cells
Macrophages
Basophils
What causes increased clearance in Theophylline?
Enzyme induction(mainly CYP1A2)
- Rifampicin, Barbiturates, Ethanol, Ritonavir
- Smoking
- High-protein, low-carbohydrate diet
- Barbecued diet
5 .Childhood
What causes decreases clearance in Theophylline?
CYP Inhibition
1. Cimetidine, Erthryomycin, Ciproflaxacin, Allopurinol, Fluvoxamine, Zafirlukast
- Congestive heart failure
- Liver disease
- Pnemonia
- Viral infection & vaccination
- High-carbphydrate diet
- Old age
Effect of LAMA’s in asthma and COPD
Effect is small in normal airways but is greater in COPD
LAMA/LABA dual combination inhalers?
- Indacaterol/glycopyrronium
- Vilanterol/umeclidinium bromide
- Olodaterol/tiotropium bromide
- Formoterol/glycopyrronium bromide
TSLP
Thymic stromal lymphopoietin(TSLP)- is an epithelial cell-derived cytokine-role in the induction od type 2 inflammation via both innate and acquired immune system
Anti-TSLP drug and MOA?
Tezepelumab
Human IgG2 monoclonal antibody that inhibits the binding of TSLP to the TSLP receptor
Asthm aCI?
B-blockers & NSAIDS
