COPD

Question 1

Short-acting Beta Agonist

Common indications

Answer 1

1. COPD- releive breathlessness brought on by exercise
2. Asthma- used in conjunction with other agents
3. Hyperkalaemia- nebulised salbutamol may be used in conjunction with other treatments for the urgent treatment of hyperkalaemia

Question 2

B₂-agonist MOA

Answer 2

• B₂-receptors are found on the smooth muscle of the bronchi, GIT, uterus and blood vessels
• Stimulation of the GPCR activates a signalling cascade that leads to the relaxation of smooth muscle
• Improves airflow reduce SOB
• B₂-agonist stimulates Na/K/ATPase pumps on the cell surface
  
  • Shifting K into the cell- useful for hyperkalaemia

Question 3

B2-Agonist important side effects

Answer 3

• Tachycardia
• Palpitations
• Anxiety
• Tremor
• Increase serum glucose levels- diabetes
• Muscle cramps

Question 4

B2-agonist

Warnings

Answer 4

• Only use LABA in asthma if there is an ICS treatment used as well
• Without the steroid there is an increase mortality rate
• Care should be given to people with CVD
  
  • Tachycardia= worsen angina, provoke arrhythmias
  • Especially important when using as part of the hyperkalaemia treatment

Question 5

B2-agonist important interactions

Answer 5

• Beta blockers- may reduce the effectiveness of the agonist
• Extensive use of B2 with ICS and theophylline may lead to hypokalaemia monitor U&E

Question 6

B2- agonist

Monitoring + advise

Answer 6

• Symptom severity
• Peak flow meter
• Spirometry
• Exacerbations
• Tell patients this will help there breathing (symptoms) but not treat/cure the disease.
• If they need to use B2-agonist regularly then they need to get there other inhalers stepped up
• Make sure they clean their inhaler regularly

Question 7

ICS

Common indications

Answer 7

• Asthma- treat airway inflammation and control symptoms at step 2 of asthma therapy when SABA fails
• COPD- to control symptoms and prevent exacerbations in patients who have severe airflow obstruction on spirometry and or recurrent exacerbations
  
  • Can be used in combination with LABA + LAMA

Question 8

ICS

Mechanism of action

Answer 8

• Corticosteroids pass through the plasma membrane and interact with receptors in the cytoplasm
• The activated receptor then passes into the nucleus to modify transcription of a large number of genes
  
  • Pro-inflammatory cytokines, interleukins and chemokines are downregulated
  • While anti-inflammatory proteins are upregulated
• In the airways this reduces mucosal inflammation, widens the airways and reduces mucus secretion
• Improves symptoms

Question 9

ICS

Important adverse events

Answer 9

• Immunosupressive effect in the mouth increases risk of oral thrush
• Hoarse voice
• In COPD, they can increase the risk of pneumonia
• Very little is absorbed into the blood, so there are few systematic adverse effect unless very high doses are used

Question 10

ICS

Warnings

Answer 10

• High doses- use in caution in COPD patients with a history of pneumonia
• Children- growth suppression

Question 11

Antimuscarinic bronchodilators

Common indications

Answer 11

• Asthma
• COPD

Question 12

Antimuscarinic bronchodilators

MOA

Answer 12

• Antimuscarinic drugs bind to the muscarinic receptors, where they act as a competitive inhibitor of acetylcholine
• Stimulation of the muscarinic receptors brings about a wide range of parasympathetic rest and digest effects
• In blocking the receptor, antimuscarinic have the opposite effect
  
  • Reduce smooth muscle tone
  • Reduce secretion from glands in the respiratory and GIT
  • Relaxation of pupillary constrictor, ciliary muscles preventing accommodation in the eye

Question 13

Antimuscarinic bronchodilators

Adverse effects

Answer 13

• When antimuscarinic bronchodilators are taken by inhalation, there is relatively little systematic absorption
• Adverse effects, apart from dry mouth are uncommon

Question 14

Antimuscarinic bronchodilators

Warnings

Answer 14

• Antimuscarinics should be used with caution in patients susceptible to angle-closure glaucoma, in whom they can precipitate a dangerous rise in intraocular pressure
• They should be used with caution in patients with or at risk of arrhythmias
• However, in practice, most patients can take these drugs by inhalation without major problems

Question 15

Antimuscarinic bronchodilators

Question 16

Corticosteroids (Glucocorticoids) systemic

Common indications

Answer 16

• Allergic or inflammatory disorders- anaphylaxis and asthma COPD
  
  • Only use in COPD on advise of a specialist
• Suppression of autoimmune disease e.g. inflammatory bowel disease, inflammatory arthritis
• In the treatment of some cancers as part of chemotherapy or to reduce tumour-associated swelling
• Hormone replacement in adrenal insufficiency or hypopituitarism

Question 17

Corticosteroids (Glucocorticoids) systemic

MOA

Answer 17

• These corticosteroid exert mainly glucocorticoid effects
• They bind to cytosolic glucocorticoid receptors, which then translocate to the nucleus and bind to glucocorticoid-response elements, which regulate gene expression
• Corticosteroids are most commonly prescribed to modify the immune response
• They upregulate anti-inflammatory genes
• Down regulate pro-inflammatory proteins
• Direct actions on inflammatory cells include suppression of circulating monocytes and eosinophils
• Their metabolic effects include increased gluconeogenesis from increased circulating amino and fatty acids, released by catabolism (breakdown) of muscle and fat
• These drugs also have a mineralocorticoid effects, stimulating Na+ and water retention and K+ excretion in the renal tubles

Question 18

Corticosteroids (Glucocorticoids) systemic

Important adverse effects

Answer 18

• Immunosuppression increases the risk and severity of the infection and alters the host response
• Metabolic effects include diabetes mellitus (gluconeogenesis)and osteoporosis
• Increased catabolism causes proximal muscle weakness, skin thinning with easy bruising and gastritis
• Mood and behavioural changes- insomnia, confusion, psychosis and suicidal ideas
• Hypertension, hypokalaemia, oedema can result from mineralocorticoid action
• Corticosteroid treatment suppresses the pituitary adrenocorticotropic hormone (ACTH) secretion, switching off stimulus for normal adrenal cortisol production
  
  • In prolonged treatment, this causes adrenal atrophy- preventing endogenous cortisol secretion
  • If corticosteroids are abruptly withdrawn suddenly, an acute Addisonian crisis with cardiovascular collapse may occur
  • Withdraw slowly and allow recovery of adrenal function
  • Symptoms of chronic glucocorticoid deficiency that occur during treatment withdrawal include fatigue, weight loss and arthralgia

Question 19

Corticosteroids (Glucocorticoids) systemic

Warnings

Answer 19

• Corticosteroids should be prescribed with caution in people with infection- worsening of infection
  
  • And in Children- growth suppression

Question 20

Corticosteroids (Glucocorticoids) systemic

Interactions

Answer 20

• Corticosteroids increase the risk of peptic ulceration and GI bleeding when used with NSAIDs
• Enhance hypokalaemia in patients taking B₂-agonists, theophylline, loop or thiazide diuretics
• Their efficacy may be reduced by CYP P450 inducers (Carbamazepine, phenytoin, rifampicin)
• Corticosteroids reduce the immune response to Vaccines

Question 21

Corticosteroids (Glucocorticoids) systemic

Administration + Communication

Answer 21

• OD corticosteroid treatment should be taken in the morning to mimic the natural circadian rhythm and reduce insomnia
• State to patients that treatment should suppress the underlying disease process and that the patient will usually start to feel better within 1-2 days
• For patients who require prolonged treatment, warn then NOT to stop treatment suddenly as this could make them very unwell
• Give them a steroid card to carry with them at all times and show if they need treatment
• Discuss longer-term risk: diabetes, osteoporosis + bone fractures
• Patients on long term won’t be able to increase secretion in response to stress so should always carry steroids around with them