Leukotriene Receptor Antagonists Vs Inhaled Corticosteroids Biology Essay

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The desire to write this report came after witnessing firsthand on placement, the difficulties that disabled children have in taking asthma medication. The use of inhaled medication to treat asthma takes a degree of coordination, and this is often difficult to achieve in children with both physical and mental disabilities. On many occasions on my placement at a special needs school, I observed children resisting the efforts of the staff to administer the child's medication. This poor coordination can lead to oral deposition of the drug and thus means that the drug is not being delivered efficiently. Poor delivery reduces the efficacy of the treatment and in the case of inhaled corticosteroids, oral deposition can lead to local side effects such as oral candidiasis.

When coordination of inhaled therapies is poor, it results in poorly controlled asthma in patients, and in the case of children with specific disabilities, this can be life threatening. An alternative to inhaled drug treatments may help reduce asthmatic exacerbations in patients with poor coordination and reduce the risk of potentially severe episodes. Oral corticosteroids are a possible treatment, however they are not recommended for long term control in children due to their side effects. Therefore an alternative treatment is required, and oral leukotriene receptor antagonists have been shown to be beneficial in the treatment of asthma, and are relatively free of side effects.

I hope by the end of this report.....

Ideally I would like to discuss the benefit of leukotriene receptor antagonists in children with special needs, however the literature on this subject is limited, so instead I will focus on children in general.

Literature Review

Asthma is one of the most common chronic diseases in the world affecting over 300 million people worldwide with 7% of the UK population and 1 in 11 children affected . It is a chronic inflammatory disease of the airways characterised by bronchial hyperreactivity and obstruction of the airway, which results in attacks of wheeze, dyspnoea chest tightness and coughing. (chaytor lecture cvrr 44)

It is recognised from the patient's previous medical history, as well as a pattern of signs or symptoms as shown in (figure....). It is best confirmed by evidence of reversible airflow obstruction accompanying these symptoms. (GINA_PG_2010 ref) A diagnosis of asthma is normally given when inhaled bronchodilators cause >15% improvement in forced expiratory volume in 1 second (FEV1) or peak expiratory flow rate (PEFR). (Need another ref)

Clinically asthma is classified according to the frequency of symptoms and lung function tests. It can also be classified as either extrinsic or intrinsic asthma, where extrinsic (atopic) asthma has a definite external cause e.g. allergens and intrinsic asthma when there is no apparent external cause.(need ref for both in/extrinsic)

What causes asthma

Asthma is a multifactorial disease in origin which arises from a complex interaction of genetic and environmental factors. The most common antigen which elicits a type I hypersensitive response (mention about type 1 hypersensitivity in sentence before) is from house dust mites. Other common allergens are grass pollen and animal fur. There is a direct correlation between raised levels of IgE and asthma [Mechanisms of IgE Inflammation ref]. (ref pos from book)

What happens during an asthma attack

An asthma attack is the term commonly to describe an acute asthma exacerbation. (Factors accounting for asthma variability ref) There are three factors which contribute to the obstruction of the airways during an asthma attack: increased mucus production, inflammation of the airways, and bronchospasm.

Inhalation of allergens in atopic individuals results in an immediate response and subsequent bronchoconstriction usually lasting for up to 2 hours, however this can be reversed using bronchodilators such as the β2-adrenergic receptor agonist salbutamol. The immediate response phase is normally followed by a late-phase response after around 3-12 hours later which causes bronchoconstriction which is less responsive to bronchodilators as well as inflammation of the airway. Recurrent asthma attacks which last for several days are due to the late-phase response where there is an increased airway hyperresponsiveness.

How do you treat and asthma attack

Drugs used to treat asthma can be categorised as being either 'relievers' or 'controllers' Bronchodilator drugs are used to treat the symptoms of bronchoconstriction and so are classified as 'relievers', where as anti-inflammatory drugs which treat the underlying chronic inflammatory processes in asthma are known as 'controllers'

Relievers

β2-agonists act on the smooth muscle of the airways, activating β-adrenergic receptors which result in the relaxation of the smooth muscle and hence bronchodilation. These can be either short-acting β2-agonists (SABA) such as salbutamol whose action last 4-6 hours or long-acting β2-agonists (LABA) like salmeterol which last for over 12 hours.

Muscarinic receptor antagonists are another type of bronchodilator which act on parasympathetic nerves by blocking the release of acetylcholine and as such prevent bronchoconstriction in the airways. Muscarinic receptor antagonists are less effective the β2-agonists however their action is longer-lasting.

Theophylines

magnesium

Controllers

Inhaled corticosteroids (eg beclomethasone/budesonide) are the most effective therapy used to achieve long term control over asthma. They are anti-inflammatory drugs which when inhaled, bind to glucocorticoid receptors within the cytoplasm and inhibit the transcription of many inflammatory proteins and signalling molecules. This results in a subsequent decrease in the numbers of mast cells and eosinophils present within the mucosa of the airway in patients with asthma.

A reduction in the number of mast clls and eosinophils equals.....

Asthmatic inflammatio is characterised by

What does this mean in terms of asthma attacks

Although inhaled corticosteroids inhibit the transcription of inflammatory proteins locally, they also have systemic effects, altering the transcription of other proteins which gives rise to their in their various side effects.

The use of inhaled corticosteroids is associated with fewer exacerbations, improved lung function as airflow obstruction is reversed and improved asthma-specific quality of life. However long term high doses of inhaled corticosteroids can result in the development of cataracts, osteoporosis and the stunting of growth in children (refs from Wikipedia) Discontinuation of treatment with inhaled corticosteroids results in return of asthmatic symptoms and airway inflammation.

Inhaled corticosteroids can be taken at low/moderate doses in combination with a long-acting β2 agonist (LABA) to control symptoms, and has been shown to be more effective than high doses of inhaled corticosteroids alone, so much so that this is the recommended treatment for asthma. It has also been shown that taking leukotriene modifiers in conjunction with inhaled corticosteroids has an additive effect in asthma prevention. (ref) The combination of either LABA or leukotriene antagonists enables clinicians to reduce the levels of ICS to prevent side effects. (ref)

Inhaled corticosteroids and long-acting β2 agonists are typically administered via dose-metered inhalers, and so if the patient has difficulty using these, for example due to poor coordination,the medication will be less effective. Relate to placement

Oral corticosteroids are less specific than inhaled corticosteroids as their actions are systemic....side effects are more profound. Not viable option to take corticosteroids orally long term and only recommended in a small number of patients with severe asthma (bourke book ref). Need alternatives

Use of oral CS (prednisolone) are more susceptible to some infections such as chicken pox, plus peptic ulceration, myopathy, osteoporosis, growth suppression, depression, psychosis, cataracts and cushingoid features. (Ref)

Alternatives...

Unlike other asthmatic therapies which tend to be administered via inhalation, leukotriene receptor antagonists such as montelukast can be given orally, which is often beneficial for young children where inhalation is difficult. The use of a leukotriene receptor antagonist is recommended for children who are unable to take inhaled ICS to control their asthma. ( NICE technology appraisal guidance 131)

This could be a possible situation in regards to my placement as the children are not able take their asthma inhalers due to physical and mental disabilities, however taking one tablet is much easier for their compliance.

Leukotriene receptor antagonists (montelukast, zafirlukast) are drugs which act the type 1 cysteinyl leukotriene receptor and block the action of leukotrienes C4, D4 and E4. Cysteinyl leukotrienes have both bronchoconstrictor and pro-inflammatory actions, and so blocking their actions is beneficial in asthma. (ref)

Leukotriene receptor antagonists improve lung function and reduce bronchial hyper responsiveness (bourke book ref)

Leukotriene receptor antagonists result in a reduction in the levels circulating eosinophils in the bloodstream Leukotriene receptor antagonists are virtually free of side effects.(other refs needed)

Normally used to treat mild asthma

Patients with asthma who are obese, smoke may benefits from treatment with leukotriene antagonists Patients who suffer from aspiring-induced asthma (pulmonary pathophysiology book ref)

Conclusion

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