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Medsci305 > Lecture 18: Asthma > Flashcards

Lecture 18: Asthma Flashcards

1
Q

What is asthma?

A

chronic inflammatory disease of the airways.

  • main feature = airway obstruction caused by bronchospasm
  • very old disease first reported 3,500 years ago
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2
Q

What are the symptoms of asthma?

A
  • wheezing
  • cough
  • sputum production
  • chest tightness
  • shortness of breath
  • variable episodic air flow obstruction (reversible either spontaneously or with treatment)
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3
Q

How does asthma differ from COPD?

A

the airway obstruction in COPD is generally not reversible

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4
Q

What is the prevalence of asthma?

A
  • 1/6 adults and 1/4 children have asthma symptoms
  • most common cause of hospital admissions in children
  • one of the highest ranking disease in DALYs lost in males and certain females
  • male children and female adults have highest prevalence of asthma
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5
Q

What are the features of asthma?

A
  • episodic. Symptom will vary from day to day and season to season
  • generally worse in winter and night time
  • chronic disease which could be life threatening
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6
Q

What are the 3 key differences in the airways between asthmatics and healthy people?

A
  1. airways are smaller
  2. airways are thicker
  3. oedema, swelling and lots of sputum
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7
Q

What are risk factors that trigger Asthma?

A
  • exercise
  • viral infection
  • animal fur
  • house dust mites (common in NZ)
  • moulds, smoke, pollen
  • changes in weather
  • strong emotional expression (laughing or crying hard, breathing heavily)
  • airborne chemicals or dust
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8
Q

What lab studies are used in the diagnosis of asthma?

A
  • history of coughing, wheezing, chest tightedness
  • lung function tests
  • allergy tests and serologic studies
  • radiographic studies to confirm diagnosis
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9
Q

Which lung function tests are used in the diagnosis of asthma?

A

-PEFR: this only measures difference of lung function. It cannot diagnose asthma, but is used to measure the efficacy of treatment

-FEV1 (spirometry) is a better measure for asthma. Often done before and after beta 2 agonist treatment
if FEV1 is reversible this strongly indicates asthma

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10
Q

How can a skin test help with asthma diagnosis?

A

helps to identify the allergen which sets off the asthma

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11
Q

What is the response to allergen challenge?

A

there are 3 main types:

  1. acute phase response - which occurs 5-10 min after exposure
  2. late phase response - which occurs 4-6 hours after the lung function reduces
  3. mixture of the 2 phases.

after the allergen challenge, lung function stops and becomes worse at around 1 hour. then at the late phase response, lung function reduces at 4 hours

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12
Q

What is the mechanism of asthma?

A
  • the acute phase response stimulates the release of cytokines and inflammatory cells
  • the late phase activates TH2 cells and IL-13 and IL-9. These activate B cells and cytokines to activate mast cells
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13
Q

What are the two main treatments of asthma?

A

preventors and relievers

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14
Q

What are the treatment goals for asthma?

A
  • control chronic symptoms
  • achieve normal activity levels for exercise
  • maintain near normal pulmonary function
  • prevent eacerbations
  • minimise ED visits and hospitalisations
  • avoid adverse effects of asthma medications
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15
Q

What is the difference between preventors and relievers?

A

preventors: do not provide relief from asthma attack but are long term control medications which have anti-inflammatory effects and therefore prevent asthma attacks
relievers: drugs which provide relief from asthma symptoms for acute asthma attacks

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16
Q

How to relievers work to treat asthma?

A

Beta 2 agonists bind to beta 2 adrenoreceptors which si a post membrane receptor.

  • triggers adenylate cyclase to conver ATP -> cAMP which increase PKA levels to induce further functions
  • Na/K ATPase is increased, pi hydrolysis is reduced
  • Na/Ca exchanger is increased and MLCK is reduced
  • Resulting in bronchial relaxation
17
Q

What is the mechanism for side effects induced by relievers?

A
  • There will be upregulation of the K+ channel (hypokalaemia)
  • There are also beta 2 receptors in the heart which will cause increased HR, contractility and contraction (tachycardia)
  • also increase contractility in skeletal muscles (tremors)
  • activates alpha 1, beta 1 and beta 2 in fat cells resulting in lipolysis and thermogenesis
18
Q

What are the different types of forms of relievers?

A 
MDI
dry powdered device
spacer
nebuliser
oral
19
Q

What are short acting relievers good for?

A
  • they have a short duration but act quickly
  • useful for EIB or non specific triggers
  • acute and severe asthma
  • normally used prn
20
Q

Why should salbutamol be combined with an ICS?

A
  • If you use salbtuamol more than 6x /day the effects of the drug is reduced.
  • combined use with an ICS can help to recover some of the beta 2 receptors so they are used together in therpay to retain the potency of salbutamol
21
Q

When are long acting relievers used?

A
  • these have a long duration but will take some time to have onset
  • cant last for more than 24 hours so are for regular use
22
Q

How are anticholinergics used?

A
  • these can also reduce smooth muscle contraction and increase secretion of glands
  • majority of these agents are non selective
  • ipratropium has a slow onset of 1-2 hours, and lasts fr 6-12 hours. It is used regularly with low side effect and can reduce the mucous

-tiotropium can last longer than 24 hours and has equal affinity for the M1, M2 and M3 receptors

23
Q

What are the xanthines?

A

These are the nonselective phosphodiesterase inhibitors

  • activation of histone deacetylase has an anti-inflammatory effect
  • relaxes muscles too
  • increases cAmp and PKA levels to inhibit inflammatory cells resulting in bronchodilation and increase ciliary beat frequency to help clear the mucous
24
Q

What are the non respiratory effects of xanthines?

A
  • improve CV performance
  • decrease pulmonary pressure
  • improve diuresis
25
Q

What are the side effects of xanthines?

A
  • narrow TI range, requires close monitoring
  • nausea and vomtiing
  • hypoglycaemia
  • seizures
26
Q

What are the preventors of asthma?

A
  • glucocorticoids
  • leukotriene receptor anatgonists
  • mast cell stabilisers
  • future treatments (immunotherapy, anti-IgE therapy, Mg sulfate, therapies against TNF-a, IL-5, gene therapy
27
Q

What are the relievers of asthma?

A

beta 2 agonists
anticholinergics
xanthines

28
Q

What are glucocortiosteroids?

A
  • the main preventor treatment is inhaled glucocorticosteroids
  • These are glucocorticoid agonists which downgregulate the inflammatory response by altering transcription of inflammatory and non-inflammatory genes
29
Q

What are the cellular and molecular effects of glucocorticoids in asthma?

A
  • suppress circulating eosinophils

- inhibit synthesis, release and expression of cytokines and peptides to prevent unwanted inflammatory responses

30
Q

When are oral GCs used in asthma?

A
  • e.g. prednisone
  • for acute and very severe patients
  • these can decrease asthma symptoms and improve lung function, but won’t see many effects until 4 weeks later (alteration of gene transcription takes time)
  • patient needs to be compliant.
31
Q

What are the common problems with GCs therapy?

A
  • patients not accepting ‘steroid’ (need to explain ICS is different to anabolic steroids)
  • safety: high doses long term leads to problems like cushing’s syndrome and the redistribution of body fat to the trunk, back and neck causing a buffalo hump
  • increases gluconeogenesis
  • increases protein breakdown
  • increases OP risk
  • increases CNS activity which can decrease depression, but cause the patient to become euphoric
  • salt and water retention
  • hoarseness, dysphonia, cough, oral candidiasis (reduce by rinsing mouth after use. spacer also reduces chance of thrush.)
32
Q

What are leukotriene receptor antagonists?

A

e. g. zafirlucast (given orally)
- these prevent aspirin induced and EIB
- can be used for early and late responses to the allergen
- relaxes airways in mild asthma
- used as add-on drug to beta 2 agonist due to different mode of action

33
Q

What are the side effects of zafirlucast?

A
  • headache
  • GI disturbance
  • reversible hepatitis
  • hyperbilrubinemia
34
Q

What are mast cell stabilisers?

A
  • e.g. cromolyn sodium, nedocromil sodium
  • these prevent mast cell degranulation and the release of histamine which causes the inflammatory symptoms.
  • doesn’t work for everyone so requires a 4-6 week trial period
  • it is non steroidal and able to prevent early and late asthmatic responses to inhaled allergens
  • also reduces airway reactivity resulting from exposure to a range of inhaled irritants like SO2 and cold air
35
Q

What is the mechanism of mast cell stabilisers?

A

-inhibits IgE mediated release from mast cells by preventing the degranulation

36
Q

What are the local side effects of mast cell stabiliers?

A
  • cough.

- almost no systemic effects.

37
Q

What are possible future treatments for asthma?

A 
immunotherapy
anti-IgE therapy
-magnesium sulfate
-therapies against TNF-a
-anti interleukin 5 
-gene therapy

Medsci305 (17 decks)

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