Asthma Flashcards

1
Q

Asthma

A

Non-communicable disease that is a chronic inflammatory disease of the airways of the airwasy

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2
Q

COPD

A

a group of diseases that cause airflow blockage and breathing-related problem

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3
Q

Asthma pathophysiology(tissue changes)?

A

-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

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4
Q

Mediators of asthma

A
  1. IgE antibodies
  2. Mast cells-IgE complex
  3. Eosinophils
  4. Increase TH2-in lungs more than TH1 ad this causes inflammation
  5. Histamine
  6. LTD4
  7. Prostaglandin D2
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5
Q

Asthma key markers?

A
  1. Airflow obstruction
  2. Bronchohyperresponsive (due to histamine release)
  3. Inflammation(due to increase in neutrophils and other immune cells)
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6
Q

Asthma Symptoms

A
  1. Shortness of breath
  2. Wheezing associated with coughing
  3. Chest tightness
  4. Dry irritating cough
    5.Mucus secretion
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7
Q

Phases of asthma?

A

-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.”

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8
Q

What is an early asthmatic response ?

A

Acute bronchoconstriction & vascular leakage

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9
Q

What is a late asthmatic response ?

A

–6 hours later more sustained phase of bronchoconstriction

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10
Q

Asthma categories?

A

Mild
Moderate
Severe/life-threatening

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11
Q

Status asthmaticus?

A
  • Extreme form
  • Severe & continuous.
  • Poorly responsive to standard therapeutic measures
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12
Q

Asthma drugs for bronchodilators?

A

B-2 agonist selective drugs

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13
Q

What are the bronchodilator drugs used for asthma and their durations?

A
  1. Short-acting( Suffocating for truth)
    • Salbutamol
      -Fenoterol
      -Terbutaline
  2. Long acting B2 agonists(Swallow food)
    -Salmeterol
    -Formoterol
  3. Ultra-long acting( Inner Voice)
    -Indacetrol
    -Vilanterol
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14
Q

Which long-acting B2 agonist has a delayed onset?

A

Salmeterol

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15
Q

Which duration of B2 bronchodilators have increased lipids?

A

Long-acting B2 agonist

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16
Q

Monotherapy for asthma/COPD?

A

-Monotherapy for COPD
-B2 agonists are used in combination of IC
-NO MONOTHERAPY FOR ASTHMA

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17
Q

B-2 agonist S/E?

A

-Muscle tremors
-Tachycardia
-Hypokalemia
-Restlessness
-Hypoxemia
-Metabolic effects
-Increase in plasma: Glucose, FFA, Lactate, Pyruvate, Insulin

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18
Q

Mast cell stabilizers ?

A

Stabilizers mast cell by decreasing mast cell degradation to prevent histamine release

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19
Q

Mast cell stabilizers drugs?

A

Can Kids Need Mast?

Cromolyn Sodium
Ketotifen
Nedocromil Sodium
Mast

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20
Q

Mast cell indications?

A

Treat allergic and exercise-induced bronchospasm in asthmatic patients

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21
Q

Corticosteroid indications?

A

-Anti-inflammatory
-First-line in asthma

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22
Q

Corticosteroid 2 MOA?

A

Inhibit phospholipase A-2
Upregulation of annexin A1

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23
Q

Corticosteroid 2 MOA?

A

Inhibit phospholipase A-2
Upregulation of annexin A1

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24
Q

Corticosteriods drugs?

A

BBFF-CMT

Beclomethasone
Budisonide
Ciclesonide
Flunisolide
Fluticasone
Mometasone
Triamclionolone

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25
Asthma corticosteroid side effects?
-Oropharyngeal candidiasis -Dysphonia(hoarseness)
26
Leukotriene pathway?
1. Phosphoilipids 2. Phospholipiase A2 converts phopholipids to arachidinoic acid 3. Arachidonic acid is coverted to PGs by COX and leukotriene by 5-lipooxygenase
27
Effect of leukotriene pathway?
Causes bronchoconstriction(mainly) and contributes to overall inflammation, vasodilation and oedema
28
Leukotriene pathway inhibitor?
Inhibits the production Leukotriene?
29
Which drugs are leukotriene inhibitors and state where they act?
1. Montelukast-LTD4 receptor antagonist 2. Zafirlukast-LTD4 receptor antagonist 3. Zileuton-5-lipoxygenase and LTB4 receptor antagonist
30
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
31
Leukotriene inhibitor indications?
-Aspirin-induced asthma or aspirin-excerbated respiratory disease(AERD)
32
Leukotriene inhibitor admin?
Oral administration & thus can easily be take in children over the age of 12months
33
Leukotriene inhibitor and children?
Ideal for children from 12 months of age
34
Monoclonal antibody therapy MOA?
Recombinant antibody activity that selectively bind to cell receptor to decrease teh activity of that cell
35
Monoclonal antibody therapy for asthma drugs?
BROM 1. Omalizumab 2. Mepolizumab 3. Reslizumab 4. Benralizumab
36
Omalizumab MOA?
Selectively bind to free IgE and prevents them from binidng to mast cell receptor ans thus decreasing histamine release and bronchial constriction
37
MOA for Mepolizumab, Reslizumab & Benralizumab
Anti-IL5(involved in the pathway binding to an asthma attack) monoclonal antibody For asthma associated with peripheral eosinophilia
38
Mepolizumab ADR and cure?
Can lead to herpes zoster infection The varicella zoster vaccine 4 weeks before initiating mepolizumab
39
Which drug is given adjunct to the monoclonal antibody and its MOA?
Dupilumab Anti-IL4/IL3 receptor antibody
40
Which asthma treatment is first-line for severe asthma?
Corticosteroids
41
Which asthma treatment is first-line for mild and moderate asthma?
Dupilumab with oral corticosteriod dependent asthma
42
Monoclonal antibody therapy S/E?
Associated with anaphylactic reactions or other hypersensitivity
43
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
44
Antimuscuranic drug mnemonic?
GTI Glycopyrrolate Tiotropium Ipratropium
45
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
46
Long-acting anti-muscarinic drugs and association?
Fast dissociation from M2 may allow ACh to bind to M2 receptor thus inhibiting further ACh release
47
Short-acting anti-muscarinic drugs indication?
Patients with partially reversible obstruction
48
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
49
Methylxanthines the three MOA?
1. 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 2. Inhibit adenoside receptor 3. Increase histone deacetylation
50
What is the role of adenosine in asthma?
Adenosine will cause bronchoconstriction and an increase histamine release from the airway mast cells + inflammation
51
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
52
Methylxanthine drugs?
CATT 1. Theophylline 2. Theobromine 3. Aminophylline 4. Caffeine
53
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
54
Roflumilast?
Selective PDE-4 inhibitor ad effective for reducing the frequency of exacerbations of COPD
55
Which xanthine drug is the most effective bronchodilator ?
Theophylline is the most selective in its smooth muscle effects
56
Which xanthine drug has the most CNS effective ?
Caffeine has the greatest CNS effects
57
Methylxanthines and mild cortical arousal?
All methylxanthines especially caffeine, cause mild cortical arousal with increased alertness and reduction of fatigue
58
Which enzyme metabolises theophylline?
CYP1A2 metabolism
59
Methylxanthines ADR?
-Abdominal discomfort -Restlessness -Headache -Nausea & vomitting -Diuresis -Increased acid secretion -Cardiac arrhythmias -Seizures
60
Which drug do we use to treat severe/life threatening no response?
MgSO4/IV
61
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)
62
Which classes of drugs are bronchodilators?
1. Sympathomimetics (B-agonists 2. Phosphodiesterase(PDE) inhibitors 3. Anticholinergic agents
63
What are B1 agonists drugs?
EEI 1. Epinephrine (Adrenaline) 2. Ephedrine 3. Isoproterenol/isoprenaline
64
Tx for Epinephrine ?
-Acute vasodilation -Severe bronchospasm -Bronchospasm of anaphylaxis
65
ADR for Epinephrine ?
Tachycardia, arrhythmias and worsening of angina pectoris_B1 receptors
66
Duration of action between Ephedrine and Ephinephrine?
Ephedrine>Epinephrine
67
Why is Ephedrine used less in the tx of asthma?
Ephedrine thus infrequently used to treat asthma
68
Which class of drugs was substituted by B2 selective agonists?
Isoproterenol
69
What causes tolerance for asthma?
Tolerance is from continued use and may be from the down regulation of the receptor
70
What is the benefit of ipratropium bromide?
Doesn't cross BBB. Fewer CNS effects
71
Which anticholinergic drug is used for COPD and when?
Ipratropium bromide used patients have reversible obstruction
72
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
73
What is the tx of oral candidiasis ?
Nystatin drops
74
Which cells synthesis leukotrienes?
Eosinophils Mast cells Macrophages Basophils
75
What causes increased clearance in Theophylline?
Enzyme induction(mainly CYP1A2) 1. Rifampicin, Barbiturates, Ethanol, Ritonavir 2. Smoking 3. High-protein, low-carbohydrate diet 4. Barbecued diet 5 .Childhood
76
What causes decreases clearance in Theophylline?
CYP Inhibition 1. Cimetidine, Erthryomycin, Ciproflaxacin, Allopurinol, Fluvoxamine, Zafirlukast 2. Congestive heart failure 3. Liver disease 4. Pnemonia 5. Viral infection & vaccination 6. High-carbphydrate diet 7. Old age
77
Effect of LAMA's in asthma and COPD
Effect is small in normal airways but is greater in COPD
78
LAMA/LABA dual combination inhalers?
1. Indacaterol/glycopyrronium 2. Vilanterol/umeclidinium bromide 3. Olodaterol/tiotropium bromide 4. Formoterol/glycopyrronium bromide
79
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
80
Anti-TSLP drug and MOA?
Tezepelumab Human IgG2 monoclonal antibody that inhibits the binding of TSLP to the TSLP receptor
81
Asthm aCI?
B-blockers & NSAIDS