Pharmacology of respiratory drugs 2

Question 1

Learning outcomes

Answer 1

• Describe the role of short-acting and long-acting bronchodilator therapies (beta2 agonists, muscarinic antagonists) in the management of chronic obstructive pulmonary disease (COPD)
• Discuss the place for corticosteroids in patients with moderate or severe airflow obstruction
• Briefly discuss novel immunological agents and their use in COPD
• Briefly describe nicotine dependence and outline smoking cessation therapies
• Discuss the properties of mucokinetic agents and their place in the management of COPD
• Briefly outline the place for antibiotics and prophylactic vaccination in the management of COPD

Question 2

COPD (chronic bronchitis and emphysema)- definition

Answer 2

Defn: A preventable and treatable disease of airflow limitation not fully reversible, usually progressive and associated with an abnormal inflammatory responseto noxious gases or particles, may be associated with other extrapulmonary effects

Question 3

Spirometry- reversibility

Answer 3

• Significant (> 12%) reversibility (increase) of FEV1 or FVC
• 15 minutes after bronchodilator
• COPD if FEV1/FVC < 0.7
• Steroid reversibility testing:–ICS for (6–8 weeks) may be undertaken with repeat spirometry (> 12% or 200 mL increase FEV1 or FVC)

Question 4

Fundamentals of COPD care

Answer 4

Confirmed diagnosis: (offer these) treatment and support to stop smoking

• pneumonoccoal and influenza vaccine
• pulmonary rehabilitation if indicated
• co-develop a personalised self management plan
• optomise treatment for co-morbidities (these treatments and plans should be revisited at every review)

> start inhaled therapy only if:

• all other interventions have been offered, and
• if inhaled therapies are needed to relieve breathlessness or exercise limitation

Question 5

Smoking cessation

Answer 5

• Very brief advice for smoking cessation•Local NHS Stop Smoking Services
• Withdrawal symptom reduction:–NRT (patch + inhaler, lozenge, spray – combo best)–Varenicline (nicotinic receptor partial agonist)–Bupropion (selective neuronal re-uptake of catecholamine inhibitor)
• E-cigs (vaping)

Question 6

Roflumilast

Answer 6

• Oral selective phosphodiesterase-4 enzyme (PDE4) inhibitor, once daily
• MOA: phosphodiesterase-4 enzyme (PDE4) inhibitor increasing cAMP especially in lung tissue reducing recruitment of neutrophils and eosinophils (anti-inflammatory action)
• Reduces number of exacerbations
• Add-on to bronchodilator therapy in severe COPD (FEV1< 50%) and > 2 exacerbations in previous 12 months despite ×3 therapy (LAMA + LABA + ICS)
• Specialist only (Respiratory clinic)
• Adverse drug effects: diarrhoea, weight loss, nausea and headache
• Caution – psychiatric illness

Question 7

Mucolytic/kinetic agents

Answer 7

Mainly carbocysteine (or acetylcysteine)
-Reduces the hypersecretion of glycoproteins by mucus cells (response to irritants)
-Add-on therapy for COPD with excessive viscous mucus, oral capsule
NICE:
-Trial if chronic productive cough (level B)
-Continue if benefit (level D)
-Avoid if active peptic ulcer disease (increases GI Haemorrhage)

Question 8

Modes of delivery

Answer 8

Breath activated- inhalation triggers release of powder/spray
Spacing device (kids)
Nebuliser- most efficient way to provide large dose of medication

Question 9

Acute exacerbation- asthma

Answer 9

• Assess severity:
• PEFR
• Mild: > 75% previous best or predicted
• Mod: 50–75%
• Severe: < 50%
• Life threatening: < 33%
• Clinical condition
• Heart rate/Resprate/O2Sats

Question 10

Acute exacerbation- asthma

Answer 10

STAT Nebulised salbutamol (SABA) 5 mg

• Repeat every 15–20 mins
• STAT steroid Prednisolone 40 mg oral or Hydrocortisone 100mg IV (will need regular dose 7 days)
• If repeated salbutamol nebuliser required then add in STAT nebulised ipratropium bromide (SAMA) 500 micrograms
• Call senior help/999 –?admit to hospital
• IV salbutamol and IV magnesium sulphate can be considered in severe/life-threatening asthma

Question 11

Acute exacerbation- COPD

Answer 11

STAT Nebulised salbutamol (SABA) 5 mg (air driven Neb +/−controlled oxygen)

• Repeat every 15–20 mins
• STAT steroid Prednisolone 30mg oral or Hydrocortisone 100mg IV (will need regular dose 7 days)
• If repeated salbutamol nebuliser required then add in STAT nebulised ipratropium bromide (SAMA) 500 micrograms (stop LAMA while on SAMA)
• Call senior help/999 –?admit to hospital
• Non-invasive ventilation if required, ?antibiotic
• IV aminophylline may be considered (if not on oral)

Question 12

End-stage COPD

Answer 12

• Advanced care planning
• Non-invasive ventilation (NIV)
• Long term oxygen therapy (LTOT)
• ?Opioids for distressing dyspnoea
• Community COPD team +/−MacMillan support services

Question 13

In summary 1

Answer 13

•Confirm diagnosis
•Consider non pharmacological interventions
–Stop Smoking team referral
–Pulmonary rehab
–All patients should be offered pneumoccacalvaccine and annual influenza vaccine
•Initially SABA (or SAMA)
•If not steroid responsive
– add LABA and LAMA (stop SAMA) if recurrent exacerbations
– trial ICS (×3 therapy)
•If steroid responsive– add LABA + ICS, if recurrent exacerbations
– add LAMA (×3 therapy)

Question 14

In summary 2

Answer 14

With respiratory specialist input can consider:
•Azithromycin prophylaxis
•Roflumilast
•Mucolytic agent trial
•Theophylline•Oxygen requirement (LTOT)
•Non-invasive ventilation (NIV)
•End-stage symptom management

(Don’t forget co-morbidities (Corpulmonale))