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Semester 4 - Clinical Pharmacology And Therapeutics > Respiratory Medication > Flashcards

Respiratory Medication Flashcards

1
Q

Describe the pathophysiology of asthma

A

Th2-drive / eosinophilic inflammation leading to:

Mucosal oedema
Bronchoconstriction (increase smooth muscle dysfunction causing increase in contractions and cytokines)
Mucous plugging

Airway remodelling (mucous gland hyperplasia, sub epithelial fibrosis, epithelium desquamation, airway wall thickening, increased smooth muscle mall)

causing bronchial hyper responsiveness.

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2
Q

What are the 5 steps of asthma control?

A

Step 1: Mild intermittent asthma

Step 2: Regular preventer therapy

Step 3: Add on therapy

Step 4: Persistent poor control

Step 5: Continuous or frequent use of oral steroids

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3
Q

What are the results of asthma control?

A 
Minimal symptoms during day and night
Minimal need for reliever medication
No exacerbations
No limitation of physical activity
Normal lung function
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4
Q

What is step 1?

A

Step 1 is for mild intermittent asthma.

Use short-acting B2-agonists (salbutamol, terbutaline)

Used for symptom control through reversal of bronchoconstriction
Prevention of bronchoconstriction i.e. on exercise
Should only be used on an as-required basis.
If used regularly, they reduce asthma control.

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5
Q

How do B2-agonists works?

A

Predominant action is on airway smooth muscle

Potentially inhibit mast cell degranulation if only used intermittently

On regular use of B2-agonists, mast cell degranulation in response to allergen increases.

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6
Q

What are the different classes of inhaled B2-agonists?

A

Fast onset, short duration: Terbutaline, Salbutamol

Fast onset, long duration: Formoterol, olodaterol, indacarerol

Slow onset, long duration: Salmeterol, vilanterol

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7
Q

What are the side effects of B2-agonist side-effects?

A

Adrenergic - tachycardia, palpitations, tremor

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8
Q

When should step 2 (corticosteroids) be started?

A

Start when:

Using B2 agonists >3 times/week
Symptoms >3 times/week
Waking>1time/week
Exacerbation requiring oral steroid in last 2 years

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9
Q

How do steroids work?

A

Prevent inflammation

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10
Q

What do corticosteroids do?

A

Improve symptoms
Improve lung function
Reduce exacerbations
Prevent death

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11
Q

What are the molecular actions of steroids?

A
  1. Transactivation -B2 receptors, inhibitors

2. Transrepression - Inflammatory mediators, cytokines, chemokines

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12
Q

Three key properties of steroids

A

A very high affinity for the GCS receptor

Increased uptake and dwell time in tissue local application

Rapid inactivation by hepatic biotransformation following systemic absorption

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13
Q

Describe the systemic availability of inhaled drugs

A

Mouth and pharynx -> lung deposition -> systemic circulation

Mouth and pharynx -> GI tract -> Liver -> systemic circulation

Beclomethasone absorbed through gut and lungs.
Budesonide and fluticasone undergo extensive first-pass metabolism

Lung absorption is still relevant and at high doses all ICS have the potential to produce systemic side-effects.

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14
Q

Who has a better response to steroids?

A

Eosinophilic asthma have a better treatment response to inhaled steroids than non-eosinophilic patients.

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15
Q

What do you do before adding step 3?

A

Re-check patient’s medication compliance

Check inhaler technique:

  • Right inhaler?
  • using it correctly?

Eliminate trigger factors

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16
Q

What do you add in step 3?

A

First choice - long acting B2-agonsits (formoterol, salmeterol)

Add in LABA when patient not controlled on steroids

17
Q

What are the effects of long-acting B2-agonists?

A

Reduce asthma exacerbations
Improve asthma symptoms
Improve lung function

Not anti-inflammatory in their own, must alway be prescribed in conjunction with an inhaled steroid.

18
Q

What are combined inhalers? How do they work?

A

Combined inhalers contain both ICS and long B2-agonist.

You take most of them twice daily.

19
Q

Why do they combine LABA and ICS in a single inhaler?

A 
Ease of use
Compliance
1 vs 2 prescriptions to worry about
Potentially cheaper than 2 individual inhalers.
Safety
20
Q

What are some alternative step 3/4 add-ons?

A

High dose ICS
Leukotrienes receptor antagonists
Theophylline
Tiotropium

21
Q

How do leukotriene receptor antagonists work?

A

LTC4 released by mast cells and eosinophils can induce bronchoconstriction, mucus secretion and mucosal oedema and provost inflammatory cell recruitment.

LRAs block the effect of cysteinyl leukotrinenes in the airways at the CysL1 receptor

Some anti-asthma activity but only useful in about 15% of patients as add-on therapies

22
Q

What are the side effects of Leukotriene Receptor Antagonists?

A 
Angioedema
Dry mouth
Anaphylaxis
Arthralgia
Fever
Gastric disturbances
Nightmares
23
Q

How do methyxanthines work?

A
  1. Antagonise adenosine receptors
  2. Inhibit phosphodiesterase - increasecAMP - unlikely to be relevant in vivo
  3. Often poorly efficacious
  4. Narrow therapeutic window
  5. Frequent side-effects -nausea, headache, reflux
  6. Potentially life-threatening toxic complications - arrhythmias, fits
  7. Drug interactions - increased by CYP P450 inhibitors (erythromycin)
24
Q

How do long acting anticholinergics (LAMAs) work?

A

Tiotropium bromide (SPIRIVA)

Long acting once daily anti-cholinergic
Licensed for COPD and severe asthma
Reduces exacerbations in both COPD and asthma, small improvements in lung function and symptoms
Relative selectivity for M3 receptors

Side effects:
Dry mouth, urinary retention, glaucoma

25
Q

Other than Tiotropium bromide, what other LAMAs are licenced for COPD?

A

Aclidinum
Umeclidinium
Glycopyrronium

26
Q

What things can you add in step 5?

A

Oral steroids

Biological therapies:
Anti-IgE
Anti IL-5

27
Q

What is Anti-IgE?

A

Omalizumab

Strict criteria for use. Reduces exacerbation rates in patients not controlled on oral steroids, may allow oral steroid tapering.

Works by preventing IgE binding to high affinity IgE receptor

Cannot bind to IgE already bound to receptor, so cannot cross-link IgE and activate mast cells.

28
Q

What is anti-IL-5?

A

Mepolozumab, Reslizumab

Reduced peripheral blood and airway eosinophilic numbers

Most effective at reducing rate of severe asthma exacerbations

More effective at reducing rate of severe asthma exacerbations.

More effective if >3 exacerbations/year with high blood eosinophils

Also allow steroid tapering

29
Q

How can people self manage their asthma?

A

Self-management plans (asthma action plans)

Self-management plan with written instructions on when and how to step-up and step-down treatment.

Leads to better outcomes in terms of day-to-day control, frequency and severity of exacerbations.

30
Q

When should patients step down treatment?

A

One asthma is controlled, stepping down is recommended

If stepping down does not take place these patients may receive a higher dose than is necessary.

Patients should be maintained at the lowest possible dose of inhaled steroids.

31
Q

Wh is the best size particles?

A

1-5microns - most effective as they settle in the small airways

32
Q

What are the characteristics of severe asthma?

A

Any one of:

  1. Unable to complete sentences
  2. Pulse >110bpm
  3. Respiration >25/min
  4. Peak flow 33-50% of best or predicted
33
Q

What are the features of life threatening asthma?

A 
PEF <33%
sPO2 <92%
PaO2 <8kPa
PaCO2 >4.5 kPa
Silent chest
Cyanosis
Feeble respiratory effort
Hypotension, bradycardia, arrhythmia
Exhaustion, confusion, coma

Near-fatal: PaXO2 >6kPa, mechanical ventilation

34
Q

How do you treat acute severe asthma?

A
  1. Oxygen - high flow - aim to keep O2 94-98% sat
  2. Nebulised salbutamol - continuous if necessary, oxygen driven
  3. Oral prednisolone
  4. If moderate exacerbation not responding, or acute severe / life threatening, add nebuliser ipratropium
  5. IV aminophylline
35
Q

What are anticholinergics and when are they used?

A

Iprotrapium bromide (ATROVENT)

A quaternary anticholinergics agent

Bronchodilation develops more slowly and less intense than adrenergic agonists. Response may last up to 6 hours.

Useful add-on in acute severe / life-threatening asthma, or moderately exacerbation with poor response to initial therapy

Semester 4 - Clinical Pharmacology And Therapeutics (26 decks)

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