Respiratory system

Inhaled corticosteroids

The inhaled corticosteroids used in respiratory medicine are in fact synthetic agonists of the glucocorticoid receptor (GR), a nuclear hormone receptor in the same family as the androgen, progesterone and mineralocorticoid receptors. GR agonists act to modulate expression of genes containing the glucocorticoid response element (GRE). Although complex, the response appears to include inhibition of the biosynthesis of pro-inflammatory prostaglandins and leukotrienes. Hence GR agonist drug action results in reduced airway inflammation, when administered by inhalation.

Inhaled corticosteroids, if used regularly, provide effective asthma control and are the preferred treatment for long-term control of mild, moderate, or severe persistent asthma symptoms. Common side-effects of taking inhaled corticosteroids can include a hoarse voice, sore throat and mild throat infections (e.g.. thrush). Inhaled corticosteroids prescribed at the low doses recommended for asthma control have not been shown to cause weak bones, growth suppression, weight gain or cataracts, which are some of the side-effects of high dose corticosteroid use. Systemic absorption may follow nasal administration particularly if high doses are used or if treatment is prolonged.

Corticosteroid tablets or liquid are used when a higher dose is needed to effect asthma control and this level of usage can cause some of the deleterious side-effects listed above.

Inhaled corticosteroids can be prescribed in combination medications which also contain long-acting bronchodilator (LABA) drugs, providing effective concomitant control of the two major contributors to asthma symptoms; inflammation and bronchoconstriction. Common side-effects of combination medications include rapid heart beat, tremor or nervousness, cough, throat irritation or hoarseness.

Single agent inhaled corticosteroids

Budesonide, prescribed for prophylaxis of asthma, allergic and nonallergic (vasomotor) rhinitis, nasal polyps and Crohn's disease and collagenous colitis. Rectal administration is used to treat ulcerative colitis involving rectal and recto-sigmoid disease.

Fluticasone, prescribed for prophylaxis of asthma, prophylaxis and treatment of allergic rhinitis and perennial rhinitis, nasal polyps, severe inflammatory skin disorders such as dermatitis and eczemas unresponsive to less potent corticosteroids and psoriasis

Ciclesonide, prescribed for prophylaxis of asthma, by inhalation of aerosol.

Beclometasone dipropionate, prescribed for prophylaxis of asthma, management of oral ulceration, prophylaxis and treatment of allergic and vasomotor rhinitis, , severe inflammatory skin disorders such as dermatitis and eczemas unresponsive to less potent corticosteroids, psoriasis and as an adjunct to aminosalicylates in acute mild to moderate ulcerative colitis

Combination medications

Budesonide plus formoterol (LABA), prescribed for maintenance therapy for asthma, and for patients with chronic obstructive pulmonary disease with forced expiratory volume <50% of predicted (per second)

Fluticasone plus salmeterol (LABA), prescribed for prophylaxis of asthma

Theophyllines

Theophylline is a xanthine (or methylxanthine) used as a bronchodilator indicated for asthma and chronic obstructive pulmonary disease (COPD). Theophylline is an adrenoceptor antagonist, acting primarily on the A2A and A2B adrenoceptors. Antagonism of adenosine action at these receptors results in relaxation of the smooth muscle of bronchial airways and pulmonary blood vessels.

Concomittant therapy with beta2 agonists in patients with severe asthma should be monitored closely, as this dual therapy can cause potentially serious hypokalaemia.

Theophylline can be prescirbed as oral medication for reversible airways obstruction, severe acute asthma, and chronic asthma.

It can also be given by injection as aminophylline, a mixture of theophylline and ethylenediamine (increases the solubility of theophylline by ~20-fold).

Antimuscarinic bronchodilators

Antimuscarinic (anticholinergic) bronchodilators provide an alternative, complementary approach to the treatment of airways obstruction, to the use of beta2-adrenergic agents. They are useful for the treatment of asthmatic patients who are poorly controlled by, or who experience troublesome side-effects from, adrenergic agents. Antimuscarinic agents delivered by inhalation block activity of acetylcholine at muscarinic acetylcholine receptors on the smooth muscle cells of the airways, to induce bronchodilation.

Tiotropium, prescribed for maintenance treatment of chronic obstructive pulmonary disease and as an adjunct to inhaled corticosteroids and long-acting beta2 agonists for the maintenance treatment of patients with asthma (experiencing one or more severe exacerbations in the last year)

Glycopyrronium bromide, indicated for maintenance treatment of chronic obstructive pulmonary disease

Umeclidinium, indicated for maintenance treatment of chronic obstructive pulmonary disease

 

Combination medications

Umeclidinium with vilanterol (beta2 receptor agonist), indicated for maintenance treatment of chronic obstructive pulmonary disease

Tiotropium with olodaterol (beta2 receptor agonist), indicated for maintenance treatment of chronic obstructive pulmonary disease

Beta-2 adrenoceptor agonists

The beta2-adrenoceptor agonist drugs used in respiratory medicine function as long-acting bronchodilators (LABAs). They are prescribed as single agents or in combination with inhaled corticosteroids or muscarinic receptor antagonists.

 

Single agent long-acting beta2 agonists

Salmeterol, prescribed for reversible airways obstruction, nocturnal asthma, and prevention of exercise-induced bronchospasm in patients requiring long-term regular bronchodilator therapy. Also used to treat chronic obstructive pulmonary disease. Only used in severe asthma in patients taking regular inhaled corticosteroid. As the duration of drug action is around 12 hours it is adminsitered twice daily.

Formoterol, prescribed for the same indications as salmeterol

Indacaterol, prescribed for maintenance treatment of chronic obstructive pulmonary disease

Olodaterol, prescribed for maintenance treatment of chronic obstructive pulmonary disease

Bambuterol hydrochloride, a pro-drug of terbutaline, prescribed for asthma and other conditions associated with reversible airways obstruction

 

Combination medications

Budesonide (corticosteroid) plus formoterol, prescribed for maintenance therapy for asthma, and for patients with chronic obstructive pulmonary disease with forced expiratory volume <50% of predicted (per second)

Fluticasone (corticosteroid) plus salmeterol, prescribed for prophylaxis of asthma

Vilanterol plus fluticasone (corticosteroid), prescribed for prophylaxis of asthma and vilanterol plus umeclidinium (a muscarinic receptor antagonist), prescribed for maintenance treatment of chronic obstructive pulmonary disease

Incadaterol is available combined with glycopyrronium (a muscarinic receptor antagonist), for Maintenance treatment of chronic obstructive pulmonary disease

Formoterol is available combined with the corticosteroids budesonide, fluticasone or beclometasone

Olodaterol is available combined with the muscarinic receptor antagonists glycopyrronium or tiotropium

 

 

Oxygen therapy

Oxygen therapy takes many forms depending on the requirements of the condition being treated. Oxygen therapy might be advised for lung diseases, heart conditions, carbon monoxide poisoning, and may be used in surgical settings.

Hyperbaric oxygen therapy, which takes place inside a pressurised chamber is used to treat decompression sickness and carbon monoxide poisoning. Hyperbaric oxygen therapy increases the partial pressure of oxygen in the tissues of the body much more effectively than normobaric oxygen can.

Oxygen tents utilise normobaric pressure to deliver oxygen at a higher level than normal inside an airtight enclosure.

Supplemental oxygen can also be delivered via an oxygen mask, nasal cannula or non-rebreather mask (NRB). Nasal cannulae deliver 1–5 litres of oxygen per minute, providing an oxygen concentration of 28–44%. If a patient requires a higher flow rate to meet their inspiratory flow demands, respiratory gas humidification (of an oxygen/air mixture) allows higher flow rates (> 6 litres/min) to be delivered comfortably via a nasal cannula, whilst maintaining the patient's ability to eat, drink and talk while receiving therapy. Disposable medical oxygen masks deliver oxygen more effectively than nasal cannulae, but are also more restrictive. NRBs can deliver a higher flow of oxygen (up to 15 litres/min) and use a one-way valve to prevent the re-inhalation of expired gases. Use of NRBs can achieve oxygen concentratiions of 60-80%. They are useful for patients who require high-concentration oxygen and who can breathe on their own (e.g. to treat smoke inhalation or chronic airway limitation).

A more intrusive delivery system is the continuous positive airway pressure (CPAP) device, often used to treat sleep apnea. The CPAP mask fits snugly over the patient's nose and the oxygen is delivered via a short hose connected to the CPAP machine. Unfortunately compliance using these devices is limited by the wearer's discomfort due to the tight-fitting and restrictive nature of the mask (the CPAP machine is also quite noisy).

The aim of oxygen therapy is to improve patients' function and activity in the least invasive yet effective manner.

Leukotriene receptor antagonists

Leukotriene receptor antagonists (LTRAs) block the action of leukotriene D4 (and to a lesser extent leukotrienes C4 and E4) on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes. This action reduces the inflammatory bronchoconstriction caused by leukotriene. LTRAs are not suitable for treating acute asthma attacks. They do not interact with theophyllines, as they operate by different molecular mechanisms.

Zafirlukast, tablets are prescribed for prophylaxis of asthma, suitable for adults and children. Zafirlukast is often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. Tablets are taken on an empty stomach (one hour before, or two hours after food). Avoidance advised in patients with hepatic impairment, and moderate to severe renal impairment. Common side-effects include gastrointestinal disturbances, headache and respiratory infections.

Montelukast, orally administered drugs are prescribed for prophylaxis of asthma and to provide symptomatic relief of seasonal allergic rhinitis in asthmatic patients. Montelukast is primarily used as a complementary therapy in adults in addition to inhaled corticosteroids, if these are insufficient in controlling their asthma. In addition to film-coated tablets, montelukast is available in chewable tablets and granules that can be mixed in to cold soft food for administration. Like zafirlukast, these medications should be taken on an empty stomach. Common side-effects include gastrointestinal disturbances, headaches, hypersensitivity reactions and drowsiness. The original trade name (under patent coverage) was Singulair, but since patent expiry generic montelukast is sold under a range of brand names.

A drug acting on the same inflammatory pathway is zileuton, which inhibits the 5-LOX (5-lipoxygenase) enzyme that catalyses the formation of leukotrienes LTB4, LTC4, LTD4, and LTE4 from arachidonic acid. Although not approved for use in the UK, zileuton is approved in the US for the maintenance treatment of asthma. Common side-effects include headache and gastrointestinal disturbances (heartburn, mild stomach pain, nausea).