Asthma Flashcards

1
Q

Outline the aims of asthma control. Outline the steps of asthma control.

A

Aims:

  • minimise symptoms (day & night)
  • minimal need for reliever medication
  • no exacerbations
  • no limitation of physical activity
  • normal lung function (FEV1 & PEFR > 80% of predicted)
  1. Short-acting beta-2 agonists (SABAs)
  2. Inhaled corticosteroids
  3. Long-acting beta-2 agonists (LABAs)
  4. Leukotriene receptor antagonists/methylxanthine/long-acting anti-cholinergic (M3)
  5. Oral corticosteroids
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2
Q

What should be done before initiating new drug therapy in asthma?

A

Check compliance with existing therapies

Check inhaler technique

Eliminate trigger factors

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3
Q

What is the first step in asthma control? What is its mechanism of action? When is it indicated?

A

Short-acting beta-2 agonists (SABAs)
e.g. salbutamol, terbutaline

Indicated for mild, intermittent asthma

Acts on airway smooth muscle & inhibits mast cell degranulation

Symptom relief (reversal of bronchoconstriction)

Use as required (regular use reduces asthma control by increasing mast cell degranulation in response to allergens)

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4
Q

Give some examples of ADRs associated with beta-2 agonists.

A
  • tachycardia
  • palpitations
  • tremor
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5
Q

What is the second stage of asthma control? What is its mechanism of action? When is it indicated? What are the aims of treatment?

A

Inhaled corticosteroids

Reduce eosinophilic inflammation (therefore patients respond better if they have eosinophilic asthma)
- up-regulates beta-2 receptors, inhibition of inflammation & inflammatory mediators (induces apoptosis)

Indicated when:

  • using beta-2 agonist 3+ times/wk
  • symptoms 3+ times/wk
  • waking 1+ times/wk
  • exacerbation requiring oral steroids in last 2yrs (point of consideration)

Aims:

  • improve symptoms
  • improve lung function
  • reduce exacerbations
  • prevent death
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6
Q

Outline the pharmacokinetics and pharmacodynamics of inhaled corticosteroids.

A

10um particles enter mouth and oropharynx —> absorbed in gut —> inactivated in the liver (first pass) —> systemic circulation

1-5um particles settle in small airways —> absorbed in lungs —> systemic circulation

0.5um particles too small (inhaled to alveoli and exhaled without being deposited in lungs)

Few systemic ADRs as metabolised in lungs and poorly absorbed

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7
Q

What is the third step in asthma control? When is it indicated?

A

Long-acting beta-2 agonists (LABAs) e.g. salmeterol, formoterol

Indicated when not controlled on 400ug/day of inhaled corticosteroids (flat dose-response curve, therefore no improvement when increasing dose), nocturnal asthma

note: co-prescribed with inhaled steroids (not anti-inflammatory on their own - COPD can be used on their own) —> combination inhalers increase compliance, cheaper, safer, etc.

Subsequently:

  • if control is inadequate increase the concentration of inhaled steroid
  • if no response, stop LABA and institute leukotriene receptor antagonist/theophylline
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8
Q

What is the fourth step of asthma control? What is their mechanism of action?

A

High dose inhaled corticosteroids (biopsy to check if non-eosinophilic asthma)

OR leukotriene receptor antagonists
(leukotrienes released by mast cells & eosinophils; cause bronchoconstriction, mucus secretion, mucosal oedema, inflammatory cell recruitment)

OR methyxantine e.g. theophylline
(inhibits TNF-alpha & leukotriene synthesis)

OR long-acting anti-cholinergic (M3) e.g. tiotropium bromide
(reduced smooth muscle contraction & mucus secretion; reduces exacerbations in COPD & asthma)

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9
Q

Give some examples of ADRs associated with leukotriene receptor antagonists.

A
  • angioedema
  • dry mouth
  • anaphylaxis
  • fever
  • arthralgia
  • gastric disturbances
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10
Q

What is the fifth step of asthma control? When is it indicated?

A

Oral corticosteroids

OR anti-IgE (prevents IgE binding to allow cross-linking and activation of mast cells)

Indicated in exacerbations and residual eosinophilia

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11
Q

What are the different classes of beta-2 agonists? Give examples for each.

A

RELIEVERS:

  • Fast onset, short duration (3-5hrs) e.g. inhaled terbutaline, inhaled salbutamol
  • Fast onset, long duration (12hrs) e.g. inhaled formoterol

PREVENTERS:

  • Slow onset, short duration e.g. oral terbutaline, oral salbutamol, oral formoterol
  • Slow onset, long duration e.g. inhaled salmeterol, oral bambuterol
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12
Q

What are methylxanthines? What is their mechanism of action?Outline their pharmacokinetics. Give some examples of ADRs associated with methylxanthines.

A

e.g. theophylline, aminophylline

Antagonist adenosine receptors + inhibition of phosphodiesterase in smooth muscle

Poor efficacy
Narrow therapeutic window

ADRs. (freq.):

  • nausea
  • headache
  • reflux
  • psychomotor agitation (wringing hands, pacing)
  • arrhythmias
  • fits
  • affected by CYP450 (many drug-drug interactions)
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13
Q

What are some important points to remember regarding inhaler techniques and management of asthma?

A

Inhaler techniques:

  • if patient is unable to use a device satisfactorily, must find an alternative
  • assess ability to use an inhaler in clinical reviews
  • medication titrated against clinical response to ensure optimum efficacy

Once asthma is controlled, stepping down is recommended (otherwise may receive higher dose than necessary)

Every asthmatic should have a self-management plan with written instructions on when and how to step-up and step-down treatment (better outcomes)

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14
Q

What is required to diagnose an episode of acute, severe asthma in adults?

A

Any one of:

  • unable to complete sentences
  • pulse > 110bpm
  • resp. rate > 25/min
  • peak flow 33%-50% of best/predicted
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15
Q

Give some examples of life-threatening features in an episode of acute, severe asthma.

A
  • spO2 4.5kPa
  • silent chest
  • cyanosis
  • feeble resp. effort
  • hypotension
  • bradycardia
  • arrhythmias
  • exhaustion
  • confusion
  • coma

NEAR FATAL: paCO2 > 6kPa OR mechanical ventilation

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16
Q

Outline the treatment of an episode of acute, severe asthma.

A
  1. High flow O2 (spO2 94%-98%)
  2. Nebulised salbutamol (continuous if necessary)
  3. Oral prednisolone: 40mg/day for 10-14 days OR IV hydrocortisone
    (can stop without tapering down - no risk of adrenal suppression)
  4. If not responding/acute/life-threatening: add nebulised ipratropium bromide (anti-cholinergic)
  5. No improvement/life-threatening features still present: consider IV aminophylline (BEWARE IF ON ORAL THEOPHYLLINE)
17
Q

Reminder: outline the pathophysiology of asthma.

A

Th2-driven inflammation (eosinophilic OR neutrophilic)

  • –> mucosal oedema
  • –> bronchoconstriction
  • –> mucus plugging
  • –> airway remodelling
  • –> bronchial hyper-responsiveness

Smooth muscle dysfunction:

  • increased contraction
  • increased mass
  • increased cytokines & chemokines

Airway remodelling:

  • mucous gland hyperplasia
  • subepithelial fibrosis
  • epithelium desquamation
  • airway wall thickening
  • increased smooth muscle mass

Immune cells:

  • T-cells
  • mast cells
  • eosinophils
18
Q

When are anti-cholinergic muscarinic antagonists indicated in asthma and why?

A

Prevent bronchoconstriction but do not cause bronchodilation
- good for preventing exacerbations but not for managing symptoms of asthma

+ inhibit mucus secretion
+ when inhaled reduces systemic ADRs

19
Q

How do corticosteroids exert their primary effect in asthma on a molecular level?

A

TRANSACTIVATION = up-regulation of beta-2-receptors —> anti-inflamamtory mediators up-regulated

TRANSREPRESSION = inflammatory mediators down-regulated at different points