Archive for the ‘chronic diseases’ Category

The Role of Inhaled Long-Acting Beta-2 Agonists in the Management of Asthma. LABAs as Adjunctive Therapy

BudesonideThe various guidelines have defined the role of LABAs as adjunctive, given concurrently with an inhaled corticosteroid, and the combination is now considered preferred therapy for moderate and severe persistent asthma. This is supported by a large body of evidence that adding a LABA to the inhaled corticosteroid in patients poorly controlled on just the inhaled corticosteroid is superior to doubling the dose of the inhaled corticosteroids. These studies have been extensively reviewed elsewhere. Most were of short duration (12-24 weeks) and, while virtually all demonstrated greater improvements in symptom control and lung function with combination therapy than with inhaled corticosteroid monotherapy at the same or increased dosage, their short duration precluded definitive analysis of effects on rates of asthma exacerbation. When the studies were grouped together and subjected to meta-analysis, however, these studies collectively suggested that the combination of a LABA and an inhaled corticosteroid decreased the rate of asthma exacerbations overall.

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The Role of Inhaled Long-Acting Beta-2 Agonists in the Management of Asthma. Clinical Use of LABAs

The LABAs are approved for chronic maintenance therapy of asthma, chronic obstructive pul¬monary disease and exercise-induced bronchospasm (EIB). Numerous trials have demonstrated the superiority of maintenance therapy with an inhaled LABA (administered twice daily) to maintenance therapy with an inhaled short-acting beta-2 agonist (administered four times daily). Therapy with LABAs improves lung function, bronchial hyperre-sponsiveness and symptom control during chronic administration. The LABAs also provide superior control of asthma with fewer adverse effects than sustained-release theophylline. However, the LABAs are less effective than low-dose inhaled corticosteroids as monotherapy for persistent asthma, particularly in preventing asthma exacerbations. In the studies comparing monotherapy with LABAs to inhaled corticosteroids, no improvement in bronchial hyperresponsiveness compared to placebo was noted, and one 12-month trial in children reported a decrease in lung function and increase in bronchial hyperresponsiveness for LABA therapy. However, there was no placebo group and the differences between active treatments were similar to those seen in the other studies that showed no difference in these outcomes from the placebo control group. This suggests the changes were most likely a result of patients not receiving the inhaled corticosteroid as opposed to the putative effect of LABAs on worsening asthma.

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Clinical Pharmacology of the LABAs

LABAs differ from short-acting inhaled beta-2 agonists principally in having large side chains, increasing their lipophilicity. The greater water solubility of short-acting inhaled beta-2 agonists, such as albuterol, leads them to diffuse away from the beta-2-adrenergic receptors, limiting their duration of action. The greater lipophilicity of formoterol and salmeterol facilitates their partitioning and retention in the phospholipid region of the cell membrane lipid bilayer, prolonging the duration of action.

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Management of Asthma

Management of Asthma

National and international guidelines for the management of concur on the goals of therapy (Table 1)  and on the components of the care necessary to achieve them (Table 2). The components of care involve eliminating or avoiding disease exacerbating factors, monitoring, education and pharmacotherapy. The guidelines agree that pharmacotherapy should consist of the treatment that can most effectively reduce symptoms, prevent exacerbations and maintain lung function as near to normal as possible while producing the least amount of adverse effects.

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The Role of Inhaled Long-Acting Beta-2 Agonists in the Management of Asthma

Management of AsthmaThe role of inhaled beta-2 agonists in the management of asthma has changed significantly over the last several years. This review outlines the most recent understanding of the pathophysiology of asthma and the studies that define the roles lhat both short- and long-acting beta-2 agonists play in therapy for this disease. A concentration on the clinical pharmacology and genetic implications for clinical use of this class of drugs in accordance with the national and international guidelines are described.

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CHRONIC FATIGUE SYNDROME – Pharmacologic Therapy

Chronic Fatigue SyndromeNo treatment has been proved to benefit patients with CFS in large randomized controlled trials that have been replicated by other investigators in other populations of patients. Moreover, without a better understanding of the pathogenesis of CFS, it is unlikely that definitive treatment will be identified. Indeed, the pharmacologic treatment of CFS primarily involves the treatment of the symptoms associated with CFS. In my experience, patients with CFS are unusually sensitive to any drug or substance (e.g., alcohol) that affects the central nervous system; one should start with a low dose and then gradually escalate it as necessary.

Low-Dose Tricyclic Agents

The most widely used treatment of CFS is sedating tricyclic antidepressant agents in low doses: amitriptyline or doxepin, 5 to 20 mg at bedtime. For unusually low doses, the liquid form of the medication may be necessary. Low-dose tricyclic agents have been proved efficacious in randomized trials of a similar illness (fibromyalgia) and in a number of sleep disorders. No such trials have been conducted in patients with CFS. In my anecdotal experience, most patients immediately notice that their sleep is less frequently interrupted and that they awaken feeling somewhat more refreshed.

Patients with concomitant depression do not report an improvement in the core symptoms of depression when given these low doses of tricyclic agents. Patients should be warned that during the first week of therapy, even extremely low doses of tricyclics may cause them to feel groggy in the morning; that reaction usually dissipates after about 1 week. When this reaction does not dissipate, patients can be switched to a less sedating tricyclic agent, such as desipramine (Norpramin),* 20 to 50 mg at bedtime, or to the triazolopyridine trazodone (Desyrel),* 25 to 50 mg at bedtime.

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MANAGEMENT OF CHRONIC FATIGUE SYNDROME

Nonpharmacologic Management

Orthoses often prescribed for osteoporotic patients.Management of the patient with CFS requires more than pharmacotherapy. First, the clinician must make a personal judgment as to whether patients are accurately relating their symptoms -both those that they admit to and those that they deny. CFS is an illness defined only by symptoms. Thus, an occasional patient seeking secondary gain may fabricate a “perfect story” for CFS. Somewhat more commonly, patients who have been told that they are suffering from major depression and who find that diagnosis to be stigmatizing read about CFS in the media and come to believe that it explains their fatigue. So, the first task of the clinician is to make an admittedly arbitrary judgment as to the veracity of the symptoms reported. In my experience, with CFS and other illnesses, it is generally wisest to believe what the patient tells you.

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