Therapeutics for airflow obstruction

Question 1

What are preventors and relievers?

Answer 1

Preventor = anti-inflammatory 
Reliver = bronchodilator

Question 2

What are anti-inflammatories?

Answer 2

Corticosteroids
Cromones
Theophylline

Question 3

What stops mediators and TH2 cytokines

Answer 3

Antileukotrines or antihistamines

Monoclonal antibodies - Anti-IgE, Anti-interlukin 5

Question 4

What can calm twitchy smooth muscles - hyper-reactivity?

Answer 4

Beta2 agonists

Musarinic antagonists

Question 5

What is the asthma treatment pyramid?

Answer 5

Reliever - beta2 agonist as needed
Preventor (1st line) - inhaled steroid such as beclomethasone
Controller (2nd line additive to ICS) - theyophylline, LTRA, LABA/LAMA, Anti-IgE/Anti-IL5
Oral steroid

Question 6

When are coricosteroids used?

Answer 6

In asthma and COPD but may cause pneumonia in COPD due to local immune suppression and impaired mucociliary clearance especially with fluticasone due to prolonged lung retention

Question 7

What is an example of an oral steroid?

Answer 7

Prednisolone has a low theraputic ratio and is only used for acute exacerbations not maintenance

Question 8

What is an example of an inhaled steroid?

Answer 8

Beclomethasone has a high theraputic ratio which is used for maintenance monotherapy in asthma

Question 9

How are corticosteroids used in COPD?

Answer 9

In a combo of ICS and LABA not as a monotherapy. This helps to reduce exacerbations in esoinohpilic COPD and optimises lung delivery

Question 10

What are the actions of a spacer device?

Answer 10

Avoids the coordination problems with pMDI
Reduces oropharyngeal and laryngeal side effects
Reduces systemic absorption from swallowed fraction
Acts as a holding chamber for aerosol
Reduces particle size and velocity
Improves lung deposition

Question 11

When are cromones used?

Answer 11

Only used in asthma - cromoglycate
Mast cell stabiliser - weak anti-inflammatory when compared to steroids
Cromoglycate effective in atopic children
Inhaled route only
Not used much due to poor efficacy

Question 12

What is the role of leukotrines in asthma?

Answer 12

Increased mucus secretion
Eosinophil influx
Edema
Contraction and proliferation of airway smooth muscles

Question 13

When are leukotrine receptor agonists used?

Answer 13

Only used in asthma as an anti-inflammatory
Montelukast - oral route, once daily, high theraputic ratio
Less potent anti-inflammatory than inhaled steroid
Used as a second line as a compltemntary drug to non steroidal anti-inflammatory additive inhaled steroid
Effective in allergic rhinitis

Question 14

When are anti-IgE’s used?`

Answer 14

Omalizumab which prevents the binding of high-affinity IgE receptors and inhibits TH2 response and associated meditator release from basophils/mast cells
Injection every 2/4 weeks for asthma only
Only used in patients with severe persistent allergic asthma - a raised IgE
Very expensive

Question 15

When is anti-IL5 used?

Answer 15

Mepolizumab
Blocks the effects of TH2 cytokine IL-5 which is responsible for eosinophilic inflammation in asthma
Injection every 4 weeks for patients with severe refractory eosinophilic asthma
Very expensive
Little effect on pulmonary function or symptoms but reduces exacerbations and oral steroid sparing effect

Question 16

What do beta agonists do?

Answer 16

They stimulate bronchial smooth muscle B2-receptors by increasing cAMP

Question 17

What is an example of a short acting and long acting b2-agonist?

Answer 17

Salbutamol -SABA

Salmeterol/formoterol LABA

Question 18

How are B2 agonists prescribed in asthma and COPD?

Answer 18

Combo inhalers such as beclometasone and formeterol
ICS/LABA used in asthma
ICA/LABA/LAMA used in COPD

Question 19

Why is the inhaled route prefered?

Answer 19

High theraputic ratio. There is b2 down regulation and tachyphylaxis with chronic LABA use
High nebulised doses given in acute attacks

Question 20

When are muscarinic antagonists used?

Answer 20

To block post junctional end plate M3 receptors
Short acting - Ipratropium
Long acting - Tiotropium
Inhaled route only, high therapeutic ratio
Used mostly in COPD to reduce exacerbations on its own or as a LAMA/LABA/ICS
Beclometasone/formoterol/glycopyrronium
High doses of neb ipratropium used in acute COPD and asthma

Question 21

When are methylxanthines used?

Answer 21

Theophylline for maintenance therapy. SR formulation used for nocturnal drips. Used as an add on to inhaled steroids as a complementary non steroidal anti-inflammatory
Low theraputic ratio but used in asthma and COPD

Question 22

When are PDE4 inhibitors used?

Answer 22

Roflumilast as an oral tablet used in COPD only. Has minimal effect on FEV1 - anti-inflammatory action
Reduces exacerbations - additive to LABA or LAMA
Adverse effects - nausea, diarrhoea, headache, weight loss

Question 23

How is chronic asthma treated?

Answer 23

Abolish symptoms, mininum B2-use, normalise FEV1, reduce PEF variability, reduce exacerbations, prevent long term airway remodeling. Avoid triggers
Supress the inflammatory cascade with ICS
Non steroidal anti-inflamm therapy such as theophylline ,anti-leukotrine, cromoglycate
Stabilise smooth muscles with LABA/LAMA

Question 24

How is acute asthma treated?

Answer 24

Oral prednisolone or IV hydrocortisone
Nebulised high dose salbutamol, neb ipratropium, IV aminophylline/magnesium
At least 60% O2
ITU assisted mechanical intubated ventilation if falling PaO2 and rising PaCO2 but never use a resp stimulant

Question 25

How is COPD treated non-pharmacologically?

Answer 25

``` To reduce exacerbations, improve pulmonary functino , improve QOL Prevent pulmonary heart disease Smoking cessation Immunisation Pharmacotherapy Pulmonary rehab Oxygen ```

Question 26

How is COPD treated pharmacologically?

Answer 26

``` LAMA/LABA mono LABA/LAMA combo ICS/LABA combo ICS/LABA/LAMA combo PDE4I - Roflumilast Mucolytic - carbocisteine Antibiotics - aithromycin ```

Question 27

How is acute COPD treated?

Answer 27

Nub high dose sabutamol + ipratropium Oral prednsiolone Antibiotic (amoxycillin/doxycycline) if infection 24-28% O2 titrated against PaO2/PaCO2 Physio to aide sputum expectoration Non-invasive ventilation to allow a higher FiO2 ITU intibated assisted ventilation only if reversibel component

Question 28

What leads to patients retainig CO2?

Answer 28

V/Q mismatch Haldane effect Hypoxic drive

Question 29

What is V/Q mismatching?

Answer 29

Areas of poor ventilation have reactive vasoconstriction Give excess oxygen and that reactive vasoconstrction reverses Perfusion becomes good but the ventilation is still poor

Question 30

What is the haldane effect?

Answer 30

Chronically hypoxaemic pateints have a low Hb saturation CO2 occupies the empty binding sites on the Hb Giving a high FiO2 pushes the CO2 off the Hb into the system

Question 31

What is the hypoxic drive?

Answer 31

Normal respiration is driven by CO2 chemoreceptors Chronic hypercarbia leads to the denstisation of these receptors Oxygen chemoreceptors then become important

Question 32

What are the characteristics of hypoxaemia?

Answer 32

Altered mental status, cyanosis, dyspnoea, tachypnoea, arrhythmias Hyperventilation increases dramatically when pO2 is less than 5.3 kPa Loss of consciousness occurs at around 4.3 kPa

Question 33

What are the different types of hypoxia?

Answer 33

Circulatory Anaemic Toxic Hypoxaemic

Question 34

What can cause the alveolar endothelial interfaces to fail?

Answer 34

``` Interstitial thickening Pulmonary fibrosis Sarcoidosis Lymphangitis Vascular dysfunction Pulmonary vasculitis Endothelial malignancy ```

Question 35

What is shunting?

Answer 35

Perfusion without ventilaion

Question 36

What is dead space

Answer 36

Ventilation without perfusion

Question 37

What is type 1 resp failure?

Answer 37

Hypoxemic respiratory failure (type I) is characterized by an arterial oxygen tension (PaO2) lower than 60 mm Hg with a normal or low arterial carbon dioxide tension (PaCO2). This is the most common form of respiratory failure, and it can be associated with virtually all acute diseases of the lung, which generally involve fluid filling or collapse of alveolar units. Some examples of type I respiratory failure are cardiogenic or noncardiogenic pulmonary edema, pneumonia, and pulmonary hemorrhage.

Question 38

What is type 2 resp failure?

Answer 38

Hypercapnic respiratory failure (type II) is characterized by a PaCO2 higher than 50 mm Hg. Hypoxemia is common in patients with hypercapnic respiratory failure who are breathing room air. The pH depends on the level of bicarbonate, which, in turn, is dependent on the duration of hypercapnia. Common etiologies include drug overdose, neuromuscular disease, chest wall abnormalities, and severe airway disorders (eg, asthma and chronic obstructive pulmonary disease [COPD]).