Nocturnal asthma

It is newer long acting selective P2 adrenergic agonist with slow onset of action, used for maintenance therapy in asthma, nocturnal asthma and asthma induced by exercise. 

Common side effects of theophylline therapy include headache, dyspepsia, and nausea. More serious side effects such as lethal seizures or cardiac arrythmias can occur if blood levels are too high. Many derivatives of theophylline have been prepared in an effort to discover an analogue without these limitations (60,61). However, the most universal solution has resulted from the development of reHable sustained release formulations. This technology limits the peaks and valleys in semm blood levels that occur with frequent dosing of immediate release formulations. ControUed release addresses the problems inherent in a dmg which is rapidly metabolized but which is toxic at levels ( >20 7g/mL) that are only slightly higher than the therapeutically efficacious ones (10—20 p.g/mL). Furthermore, such once-a-day formulations taken just before bedtime have proven especially beneficial in the control of nocturnal asthma (27,50,62). 

Fig. 12. Profile of patterned dehvery of salbutamol, for nocturnal asthma, from an elementary osmotic pump. A delayed pulse of salbutamol, superimposed...

Monitor symptoms such as wheezing, shortness of breath, chest tightness, cough, and nocturnal awakenings due to asthma symptoms. Daytime symptoms should occur no... 

In nocturnal asthma, long-acting inhaled /T-agonists are preferred over oral sustained-release / -agonists or sustained-release theophylline. However, nocturnal asthma may be an indicator of inadequate antiinflammatory treatment. 

P -Adrenergic receptor R16G Nocturnal asthma/severity Agonist-dependent down- (6,12(258)... 

Severe cases may, however, require an intensified bronchodilator treatment with systemic jk-mimetics or theophylline (systemic use only low therapeutic index monitoring of plasma levels needed). Salmeterol is a long-acting in-halative P2-mimetic (duration 12 h onset -20 min) that offers the advantage of a lower systemic exposure. It is used prophylactically at bedtime for nocturnal asthma. 

Extensive studies have been done on a clearly defined asthma syndrome produced by exposure to western red cedar. ° Plicatic acid has been identified as the etiologic agent. The western red cedar asthma syndrome includes rhinitis, conjunctivitis, wheezing, cough, and nocturnal attacks of breathlessness characterized by a precipitous decline in FEVi. There is no apparent relation between skin sensitivity and respiratory changes. No precipitating IgG antibodies are found in the serum of sensitized individuals, and circulating IgE antibodies are present in about one-third of affected individuals. 

Inhaled salmeterol has a pharmacological half-life in excess of 12 hours, much longer than either albuterol or terbutaline. The likely basis for this long half-hfe is that the long lipophilic tail of salmeterol promotes retention of the molecule in the cell membrane. Its long duration of action makes salmeterol particularly suitable for prophylactic use, such as in preventing nocturnal symptoms of asthma. Because of its relatively slow onset of action, salmeterol should not be used to treat acute symptoms. 

Urgent treatment is often begun with an oral dose of 30-60 mg prednisone per day or an intravenous dose of 1 mg/kg methylprednisolone every 6 hours the daily dose is decreased after airway obstruction has improved. In most patients, systemic corticosteroid therapy can be discontinued in a week or 10 days, but in other patients symptoms may worsen as the dose is decreased to lower levels. Because adrenal suppression by corticosteroids is related to dose and because secretion of endogenous corticosteroids has a diurnal variation, it is customary to administer corticosteroids early in the morning after endogenous ACTH secretion has peaked. For prevention of nocturnal asthma, however, oral or inhaled corticosteroids are most effective when given in the late afternoon. 

Asthma is best thought of as a disease in two time domains. In the present domain, it is important for the distress it causes—cough, nocturnal awakenings, and shortness of breath that interferes with the ability to exercise or to pursue desired activities. For mild asthma, occasional inhalation of a bronchodilator may be all that is needed. For more severe asthma, treatment with a long-term controller, like an inhaled corticosteroid, is necessary to prevent symptoms and restore function. The second domain of asthma is the risk it presents of future events, such as exacerbations, or of progressive loss of pulmonary function. A patient s satisfaction with his or her ability to control symptoms and maintain function by frequent use of an inhaled 32 agonist does not mean that the risk of future events is also controlled. In fact, use of two or more canisters of an inhaled 3 agonist per month is a marker of increased risk of asthma fatality. 

Sutherland ER, Ellison MC, Kraft M, Martin RJ (2003) Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunology 112 513-517... 

Arkinstall WW (1988) Review of the North American experience with evening administration of Uniphyl tablets, a once-daily theophylline preparation, in the treatment of nocturnal asthma. Am J Med 85 60-63... 

Simonsson BG, Sjoberg A, Rolf C, et al. 1985. Acute and long-term airway hyperreactivity in aluminum-salt exposed workers with nocturnal asthma. Eur J Respir Dis 66 105-118. 

Turki J, Pak J, Green SA, Martin RJ, Liggett SB. Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Glyl6 correlates with the nocturnal phenotype. J Clin Invest 1995 95(4) 1635-1641. 

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. 

A 37-year-old man who had taken lithium and sulpiride for 14 years and who was a long-time smoker without respiratory symptoms or a history of asthma had lithium withdrawn because of an asymptomatic bradycardia (44 beats/minute) (125). Six weeks later, he developed symptoms of asthma, including nocturnal cough, exertional wheezing, increased airway resistance, and a low FEV1, attributed to lithium withdrawal. 

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