Resp Part 1

Question 1

Indications of β2-agonists (short-acting and long-acting)?

Answer 1

Asthma:
- SABA (relieve breathlessness)
- LABA (used alongside ICS for chronic asthma; ALWAYS give LABA with ICS)

COPD:
- SABA (relieve breathlessness)
- LABA (2ND LINE to reduce exacerbations + improve symptoms)

Hyperkalaemia
- nebulised salbutamol

Question 2

Mechanism of action of β2-agonists?

Answer 2

Activates beta2 receptors in smooth muscle of bronchi/gut/uterus/blood vessels.
→ stimulates GPCR (G protein-coupled receptor) signalling cascade.
→ causes smooth muscle relaxation.
→ As a result, improves airflow in constricted airways and reduces breathlessness.

β2-agonists stimulate Na/K ATPase pumps.
→ causes K+ to move from outside of cells to inside.

Question 3

Examples of SABA?

Answer 3

Salbutamol
Terbutaline

Question 4

Examples of LABA?

Answer 4

Salmeterol
Formoterol

Question 5

Adverse effects of β2-agonists?

Answer 5

Tachycardia
Palpitations
Anxiety
Tremor

Promote glycogenolysis →increase serum glucose conc

At high doses →serum lactate may rise

LABA -muscle cramps

Question 6

Warnings of β2-agonists?

Answer 6

ALWAYS offer LABA + ICS
- LABA alone is associated with increased asthma deaths.

CVD pts:
- tachycardia may provoke angina/arrhythmias
→occurs in tx of hyperkalemia when high doses are given.

Question 7

Important interactions of β2-agonists?

Answer 7

Effectiveness may be reduced by β-blockers.

Concomitant use of high-dose nebulised β2-agonists with theophylline and corticosteroids can cause hypokalemia
→ so monitor serum K conc

Question 8

How are β2-agonists monitored?

Answer 8

Asthma:
- monitor disease severity by assessing their symptoms and serial measurements of PEFR (peak expiratory flow rate).

COPD:
- monitor disease severity by assessing their symptoms and exacerbation rate.

Question 9

Patient education on β2-agonists?

Answer 9

Aim to make their airways relax and improve breathing.

Seek medical advice if they use the inhaler very frequently
- increase other tx (e.g. ICS) according to their written action plan.

Ensure they know how and when to take the inhaler (e.g. for acute episode, before exercise, or regular long-acting medication).

Multiple doses in a short time period can cause pt to feel shaky and anxious.

Question 10

Indications of anti-muscarinics (short-acting and long-acting)?

Answer 10

Asthma:
- SAMA (relieve breathlessness during acute exacerbation; given in addition to SABA).
- LAMA (offered to pts one or more severe asthma exacerbation in the past year; given alongside ICS + LABA).

COPD:
- SAMA (relieve breathlessness during acute exacerbation/exercise).
- LAMA (prevent breathlessness and exacerbation)

Question 11

Mechanism of action of anti-muscarinics?

Answer 11

BRONCHODILATORS

Anti-muscarinics bind to muscarinin receptor by acting as a competitive inhibitor of acetylcholine
→ increases HR and conduction
→ reduces smooth muscle tone and secretions from glands in the resp and GI tract

In the eye:
→ causes relaxation of the pupillary constrictor, hence results pupillary dilation.

→ causes relaxation of ciliary muscles, hence prevents accommodation.

Question 12

Adverse effects of anti-muscarinics?

Answer 12

Irritation of resp tract:
- Nasopharyngitis​
- Sinusitis ​
- Cough

GI disturbance:
- Dry mouth​
- Constipation​
- Urinary retention

Blurred vision
Headaches

Question 13

Warnings of anti-muscarinics?

Answer 13

Use with caution in pts:
- susceptible to acute angle closure glaucoma (can increase intraocular pressure)
- with/at risk of arrhythmias/urinary retention

Question 14

Important interactions on anti-muscarinics?

Answer 14

Not generally a problem due to LOW SYSTEMIC ABSORPTION.

Question 15

Monitoring of anti-muscarinics?

Answer 15

Effectiveness assessed by:
- improvement of symptoms
- review PEFR (for asthma)

Check inhaler technique at every review and correct it to optimise potential tx benefits.

Question 16

Pt education on anti-muscarinics?

Answer 16

Aims to open airways and improve breathing.

Ensure they know how and when to take the inhaler (e.g. for acute episode, before exercise, or regular long-acting medication).

Discuss SEs e.g. dry mouth →advise pt to keep a bottle of water or chew gum or suck sweet to relieve this symptom.

Question 17

Examples of SAMA (shorting-acting anti-muscarinics)?

Answer 17

ipratropium

Question 18

Examples of LAMA?

Answer 18

tiotropium

Question 19

Indications of ICS (inhaled corticosteroids)?

Answer 19

Asthma:
- for airway inflammation and control symptoms if SABA not effective alone

COPD:
- for symptom control and prevent exacerbation in severe airflow obstruction on spirometry and/or recurrent exacerbation

Question 20

Adverse effects of ICS?

Answer 20

Oral candidiasis
Hoarse voice

In COPD:
- risk of pneumonia

In high dose ICS:
- adrenal suppression
- growth retardation (in CHILDREN)
- osteoporosis

Question 20

MOA of ICS?

Answer 20

Corticosteroids pass through the plasma membrane and activate receptors in the cytoplasm.
→ activated receptor passes into the nucleus and DOWNREGULATES interleukins/cytokines/chemokines and UPREGULATES anti-inflammatory proteins.

→ this reduces mucosal inflammation, widens the airways, reduces mucus secretion

→ hence improve symptoms and reduce exacerbation in asthma and COPD

Question 21

Warnings of ICS?

Answer 21

High dose ICS (specifically FLUTICASONE)

Use with caution in:
- COPD pts with a hx of pneumonia
→ children due to growth retardation (suppression) risk.

Question 22

Important interactions of ICS?

Answer 22

None significant.

Question 22

Monitoring ICS?

Answer 22

Asthma:
- monitor disease severity by assessing their symptoms and serial measurements of PEFR.

COPD:
- monitor disease severity by assessing their symptoms and exacerbation rate.
- review after 3-6months tx to see if tx needs to be adjusted or maintained.

Question 23

Pt education on ICS?

Answer 23

Aims to reduce inflammation in the lung.

Steroid is unlikely to be absorbed into the body except in high dose tx.

Advise rinse mouth and gargle after taking inhaler to prevent development of a sore mouth or hoarse voice.

Ensure they know how to use the inhaler at each review, correct if needed.

Question 24

Examples of ICS?

Answer 24

beclometasone
budesonide
fluticasone

Question 25

Indications of oral corticosteroids?

Answer 25

Allergic or inflammatory disorders (e.g. anaphylaxis, asthma)

Suppression of autoimmune disease (e.g. IBD, inflammatory arthritis)

Cancer (reduces tumour-associated swelling)

Hormonal replacement (in adrenal insufficiency or hypopituitarism)

Question 26

MOA of oral corticosteroids?

Answer 26

Drug binds to glucocorticoid receptors, which then translocate to the nucleus and bind to glucocorticoid-response elements.
→this regulates gene expression.

Drug modifies the immune response by:
→UPREGULATES anti-inflammatory genes.
→DOWNREGULATES pro-inflammatory genes (e.g. cytokines, TNFα)
→this suppresses circulating monocytes and eosinophils.

Metabolic effects include:
- INCREASED gluconeogenesis (due to increased AA and fatty acids, released by catabolism of muscle and fat)

-MINERALOCORTICOID EFFECTS (stimulating sodium and water retention AND potassium excretion in renal tubule)

Question 27

Adverse effects of oral corticosteroids?

Answer 27

Immunosuppression (increase risk of infection, alters host response)

Metabolic effects:
- DM
- Osteoporosis

Mood and behavioural changes:
- Insomnia​
- Confusion​
- Psychosis​
- Suicidal thoughts

Mineralocorticoids actions results in: ​
- Hypertension​
- Hypokalemia​
- Oedema

Prolonged tx causes:
- adrenal atrophy (prevents endogenous cortisol secretion)

Sudden tx withdrawal causes:
- acute Addisonian crisis with CVS collapse
→hence easing off tx is required.

Chronic glucocorticoid deficiency can occur during tx withdrawal:
- fatigue
- wt loss
- arthralgia

Question 28

Warnings of oral corticosteroids?

Answer 28

Prescribe with caution in people with:​
- Infection​
- children (can suppress growth)

Question 29

Important interactions of oral corticosteroids?

Answer 29

Corticosteroids + NSAIDs:
- peptic ulceration
- GI bleeding

Corticosteroids + β2-agonists/loop or thiazide diuretics/theophylline:
- hypokalaemia

Efficacy of corticosteroids REDUCED by cytochrome P450 inducers.

Corticosteroids REDUCE immune response to vaccines.

Question 30

Monitoring of oral corticosteroids?

Answer 30

Efficacy monitored:
- peak flow for asthma
- blood inflammatory markers

In prolonged tx, monitor for adverse effects:
- glucose and HbA1c (diabetes)
- DEXA (bone density)

Question 31

Pt education on oral corticosteroids?

Answer 31

Tx should suppress the underlying process.

Start to feel better within 1-2 days.

Prolonged tx -advise pt to not stop tx suddenly.

Give pts a steroid card to carry with them at all time and show if they need tx.

Discuss benefits and risks, including osteoporosis, bone fractures, and diabetes so that pt can make an informed decision.