Respiratory System Case Studies: Case study level 1 – Asthma-Community

Learning outcomes

Level 1 case study: You will be able to:

1. describe the risk factors
2. describe the disease
3. describe the pharmacology of the drug
4. outline the formulations available, including drug molecule, excipients, etc. for the medicines
5. summarise basic social pharmacy issues (e.g. opening containers, large labels).

Scenario

An 18-year-old man, VB, presents with a history of recurrent episodes of wheeze after walking 200 meters. VB has recently started to go to a gym and his episodes of wheeze have worsened. He goes to see his GP. He can talk in sentences but his respiratory rate is increased. His peak flow is 420 L/min which is 80% of predicted result. A diagnosis of mild asthma is made. He is started on salbutamol metered dose inhaler (MDI) two puffs when required and beclomethasone (Qvar) 50 micrograms twice daily.

Questions

1. What is asthma?
2. What are the risk factors for developing asthma? What risk factors does the patient have?
3a. What is the pharmacology of beta2-agonists and inhaled corticosteroids?
3b. What are the side-effects of beta2-agonists?
4. What formulations of salbutamol and inhaled corticosteroids are available and what are the advantages and disadvantages?
5. Describe how to use an MDI.
6. What are the social implications of this man’s asthma?

Answers

1. What is asthma?
Asthma is a chronic inflammatory disease affecting the airways. Symptoms are cough, wheeze, a feeling of tightness in the chest and shortness of breath.
Asthma is characterized by:

• airway obstruction (bronchoconstriction), which is usually reversible either spontaneously or with therapeutic intervention,
• airway hyperresponsiveness to a range of stimuli,
• inflammation of the respiratory bronchioles due to eosinophils.

T lymphocytes and mast cells are involved in the production of mucus, edema, smooth muscle hypertrophy and this can lead to mucus production and epithelial damage. If asthma is chronic it can lead to inflammation associated with irreversible bronchoconstriction.

Asthma can be classified as either extrinsic or intrinsic.

• Extrinsic – there is a known external stimulus. This is usually in patients that are atopic and show reactions to allergens. This is common in childhood asthma
• Intrinsic – there is a causative agent identified. This usually starts in middle life, but there may be some evidence of allergy in younger life.

Patient VB may have had mild asthma as a child and this has now been exacerbated by the increased incidence of wheeze.

2. What are the risk factors for developing asthma? What risk factors does the patient have?
The risk factors for developing asthma are as follows:

• Atopy in a patient, which refers to a group of disorders which include asthma, eczema and hay fever.
• Positive family history.
• Circulating antibodies and developing IgE class against common environmental factors.
• Genetic and environmental factors influencing levels of IgE.
• Occupational hazards (e.g. exposure to reactive chemicals such as isocyanates or IgE-related, such as allergens from animals, flour and grain).
• Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. aspirin), which can precipitate an attack in 5% of people with asthma.
• Beta-blockers. There is some evidence that beta-adrenergic blocking drugs such as propranolol can cause bronchoconstriction in some patients. Some selectivity with beta2-adrenergic drugs can minimise this effect but caution should be exercised.
• Atmospheric pollutants (e.g. cigarette smoke, car pollutants, dust).
• Cold air and exercise. People with asthma should ensure they are using effective medication since the latter can precipitate hyperresponsiveness of the airway.

This patient has limited risk factors, however, recurrent episodes of wheeze and exposure to cold and exercise may have precipitated the attack.

3a. What is the pharmacology of beta2-agonists and inhaled corticosteroids?
Beta2-adrenergic agonists are available as short- and long-acting agents. These drugs have limited gastric absorption and are only effective when inhaled, following which they exert a local effect in the lungs. Beta2-adrenergic agents cause bronchodilation by increasing the levels of cyclic adenosine monophosphate (cAMP) following stimulation of the beta2-receptors in smooth muscle. They act throughout the respiratory tract. Short-acting beta2-adrenergic agents are the drugs of choice for the acute management of asthma. Longer-acting beta2 adrenergic agonists are used in patients with moderate to severe asthma in combination with corticosteroids.

Corticosteroids are anti-inflammatory drugs and are available in a range of formulations. These drugs are used in the management of short- and long-term control of asthma. A wide range of formulations and types of corticosteroids varying in potency are available.
Inhaled corticosteroids are minimally absorbed and have a local effect. However, depending on the dose and potency of the inhaled corticosteroid, inhaled forms can produce systemic side-effects. Oral prednisolone is rapidly absorbed and is metabolized by the liver. Some corticosteroids may be administered intravenously.

Corticosteroids have a complex mechanism of action. They can affect the production of cytokines, leukotrienes, and prostaglandins. This affects the production of eosinophils and release of other markers of the inflammatory response. Corticosteroids can affect other areas of the body and hence have a range of side-effects.

3b. What are the side-effects of beta2-agonists?

Adverse effects include:

paradoxical bronchospasm
tachycardia
palpitations
tremor
headache
blushing
dry mouth
hypertension
arrhythmia
low potassium levels.

4. What formulations of salbutamol and inhaled corticosteroids are available and what are the advantages and disadvantages?

Salbutamol

Salbutamol is available as tablets, inhalers, nebulizer solution and intravenous injection. In the management of asthma at step 1 and 2 the inhaled formulation is the best option since it targets the drug and minimizes side-effects. Oral tablets of salbutamol are rarely used and there is limited evidence of their effectiveness.

Patients who have difficulty in coordination with inhalers can use a spacer device. These remove the need for coordination between actuation of a pressurised metered dose inhaler and inhalation. The spacer device reduces the velocity of the aerosol and subsequent impaction on the oropharynx. In addition, the device allows more time for evaporation of the propellant so that a larger proportion of the particles can be inhaled and deposited in the lungs. The size of the spacer is important, the larger spacers with a one-way valve (Nebuhaler, Volumatic) being most effective. Spacer devices are particularly useful for patients with poor inhalation technique, for children, for patients requiring higher doses, for nocturnal asthma, and for patients who have poor coordination.

Nebulised and intravenous salbutamol is required for more severe and acute status asthmaticus.

Corticosteroids

Corticosteroids are available in tablet, inhaled and intravenous dosage forms. Inhaled corticosteroids allow the control of asthma with minimal systemic absorption and thus reduce the risks associated with corticosteroids such as osteoporosis and adrenal suppression. These risks are greatly increased when taking systemic corticosteroids.
Oral tablets and intravenous steroids are used in more severe and acute status asthmaticus.

5. Describe how to use an MDI.
Patient education is vital for the management of asthma. Patients should be guided in their use of the asthma inhaler. It is important that you then observe the patient’s use. Instructions given to the patient are as follows:

• Sit in a comfortable, upright position.
• Remove the cap of the inhaler.
• Shake the inhaler.
• Breathe out and then put the mouthpiece into your mouth and take a deep inhalation, simultaneously pressing the inhaler.
• Hold your breath, then exhale slowly.
• Wipe the mouthpiece and replace the lid.
• The inhaler should be stored in a cool dry place.
• The essential counseling points should be taken from the inhaler package insert
• If you are to take two puffs, wait half a minute before repeating the steps above.

6. What are the social implications of this man’s asthma?

VP is entering adult life and will need to be aware of the importance of effective asthma management. He has to be mature enough to take responsibility for his asthma management and must not feel inhibited by having to carry inhalers with him. He needs to ensure prophylactic cover with beta2-agonists when undergoing strenuous exercise. He needs to be counseled on issues of sex education and the regular use of his inhalers. There is limited evidence of genetic malformation from his medicines, but the patient needs to be aware that when he considers a family, his child may be prone to asthma due to the genetic predisposition.

General references

1. Joint Formulary Committee (2008) British National Formulary 55. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, March.

Author:

1. Soraya Dhillon, MBE, BPharm (Hons), PhD, FRPharmS
2. Andrzej Kostrzewski, BSc, MSc, MMedEd, PhD, FHEA, MRPharmS