Asthma

Question 1

Lung function test

Answer 1

• Spirometry-
  
  • Forced expiratory volume in 1 second / Forced vital capacity (FEV1/FVC) ratio of less than 70% as a positive test for obstructive airway disease
• Bronchodilator reversibility
  
  • Offer a BDR test to adults with obstructive spirometry. Regard improvement in FEV1 of 12% or more, together with an increase in volume of 200ml or more as positive

Question 2

Short acting B2 agonist (SABA)- MOA

Salbutamol

Answer 2

• B₂-receptors are found in the smooth muscle of the bronchi, GI tract, uterus and blood vessels
• Stimulation of this GPCR activates a signalling cascade that leads to smooth muscle relation
• This improves airflow in constricted airways, reducing the symptoms of breathlessness
• Like insulin, B2-agonists also stimulate Na+/K+- ATPase pumps on cell surface membranes, thereby causing a shift of K+ from the extracellular to intracellular compartment

Question 3

SABA + LABA (Long acting beta-agonist)

Salmeterol

Side effects + Warnings

Answer 3

• Activation of B2-receptors in other tissues accounts for the common fight or flight adverse effects
  
  • Tachycardia, palpitations, anxiety and tremor
• Increase serum glycose
• LAMA cause muscle cramps
• LABA should be used with inhaled corticosteroid is also part of therapy
• Cardiovascular disease- tachycardia may provoke angina or arrhythmias,
  
  • This is especially pertinent in the treatment of hyperkalaemia, when high doses may be necessary

Question 4

SABA + LABA

Interactions

Answer 4

• Beta-blockers- reduce the effectiveness
• Nebulised B2 agonist with theophylline and corticosteroids can lead to hypokalaemia, so serum potassium concentrations should be monitored

Question 5

Inhaled Corticosteroid (ICS)

Beclometasone, budesonide, fluticasone

Answer 5

• Corticosteroid pass through the plasma membrane and interact with receptors in the cytoplasm
• The activated receptor then passes into the nucleus to modify the transcription of a large number of gene
• Pro-inflammatory interleukins, cytokines and chemokines are downregulated, while anti-inflammatory proteins are upregulated
• In the airways, This reduces mucosal inflammation, widens the airways, and reduces mucus secretion
• This improves symptoms and reduces exacerbations in asthma and COPD

Question 6

ICS

Side effects + Warnings

Answer 6

• The main adverse effects of ICS occur locally in the airway, where their immunosuppressive effect can cause Oral thrush
• They can also cause a Hoarse voice
• In COPD, there is some evidence they may increase the risk of Pneumonia
• Only systemic effects at high doses
  
  • Adrenal suppression, growth retardation and osteoporosis
• History of pneumonia and in children

Question 7

Leukotriene receptor antagonist

Montelukast

MOA

Answer 7

• Prophylaxis of asthma
• Symptomatic relief of seasonal allergic rhinitis in patients with asthma

Question 8

LRA

Montelukast

MOA

Answer 8

• Leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released by various cells (mast/eosinophils)
• These important pro-asthmatic mediators bind to cysteinyl leukotriene receptors found in the human airway and other pro-inflammatory cells
• In asthma, LT effects include bronchoconstriction, mucous secretion, vascular permeability and eosinophil recruitment
• In allergic rhinitis- increase nasal airway resistance and nalsal obstruction

Question 9

LRA

Montelukast

Warnings

Answer 9

• Hypersensitivity
• Rarely this can cause Chrug-strauss syndrome

Question 10

LRA

Adverse effects

Answer 10

• Increased risk of infection
• GI disorders
• Elevated ALT, AST
• Rash
• Uncommonly cause psychiatric disorders
• Pyrexia

Question 11

Montelukast

Interactions

Answer 11

• Phenobarbital- reduced montelukast exposure

Question 12

Theophylline

Indications

Answer 12

• Chronic asthma
• Reversible airway obstruction
• Severe acute asthma
• Chronic asthma

Question 13

Theophylline
MOA

Answer 13

• Phosphodiesterase inhibition- likely to be involved but are plasma concern (too low)
• Adenosine antagonist- Stimulates myocardium and produces diminution of venous pressure in CHF leading to a marked increase in cardiac output
• Inhibition of inflammatory cells- suppressor of T-lymphocyte activity + reduction in eosinophils and neutrophils
• Potentiation of diaphragm contractility- useful action unique to these agents

Question 14

Theophylline

Warnings

Answer 14

• Cautioned in
  
  • Cardiac arrhythmias
  • Other cardiac diseases
  • Elderly (increase theophylline concentration)
  • Epilepsy
  • Fever
  • HTN
  • Peptic ulcers
  • Risk of hypokalemia
  • Thyroid disorders

Question 15

Theophylline

Adverse events

Answer 15

• OVERDOSE- Vomiting, agitation, dilated pupils, tachycardia, hyperglycaemia, convulsions, ventricular arrhythmias, severe hypokalaemia can rapidly develop

Question 16

Theophylline

Interactions

Answer 16

• CYP inducers- increased clearance of theophylline
• CYP inhibitors- Decreased clearance of
• Smoking and alcohol can increase the clearance of theophylline
• Ciprofloxacin- Elevated theophylline levels
• Adenosine receptor agonists
• Oppose sedatory effects of BZs
• Theophylline may decrease steady state of phenytoin
• Anything causes hypokalemia- B2agonist
  *

Question 17

Conditions that can effect theophylline clearance

Answer 17

• Elderly patients with
  
  • Cardiac
  • Hepatic
  • Lung disease exacerbation
  • Hypothyroidism
  • Fever
  • Viral infection

Question 18

Theophylline

Monitoring

Answer 18

• Theophylline has a narrow TI with a range of 10-20mg/L
• Toxicity can occur above 20mg/mL
• Plasma theophylline concentration should be measure 5 days after starting oral treatment and at least 3 days after dose adjustment
• Bloods should be taken 4-6hrs after oral dose of MR product
• Rate of adsorption can vary between preparations therefore should stick to specific brands and not switch.