Treatment of asthma. New and time-tested strategies

Early, aggressive therapy in conjunction with good communication with a knowledgeable, caring physician may reverse the trends of increasing morbidity and mortality from asthma. Allergen avoidance and immunotherapy are helpful in some patients. For those who need medication, bronchodilation with a beta 2-adrenergic drug, often in conjunction with an anticholinergic and theophylline, is the current treatment of choice for acute symptoms. For prophylaxis of chronic symptoms, sustained-release theophylline is still an excellent drug. However, an anti-inflammatory agent (eg, cromolyn sodium [Intal]) or, in some cases, an inhaled corticosteroid, may be an effective alternative. Whatever treatment is used, its success depends on effective self-management, which begins with education of the patient and family.     

Exercise-induced asthma

Exercise-induced asthma can appear as one of many forms of airway hyperreactivity or as a unique clinical entity. Simple spirometry confirms the suspected clinical diagnosis in most instances, although more sensitive measurements of airway obstruction may be required. In general, the asthmatic need not restrict physical activity because of exercise-induced attacks. The disease responds well to prophylactic management with a wide variety of antiasthmatic agents, such as theophylline preparations, beta-agonists, and cromolyn sodium.     

Asthma in primary care patients. Challenges and controversies

Asthma varies in intensity, and patients must be treated as individuals to whom formulas do not apply. Often, the most difficult person to treat is the first-time patient whose clinical course is unknown and whose response to medications is totally untested. Although exacerbating substances should be avoided whenever possible, medication unfortunately is still needed by most asthmatic patients. At present, the choice of initial medication is subject to individual physician preference; beta 2-adrenergic agonists, cromolyn sodium (Intal), theophylline, and aerosol corticosteroids are all acceptable as first-line treatment. Addition of a second, third, or fourth medication again depends on individual response and physician choice. Patients with asthma need to be educated regarding the nature of the disease and its almost total unpredictability. Equally important is a frequent review of medications and a willingness to alter regimens as situations require.     

Evidence-based asthma management

In 2002 the National Asthma Education and Prevention Program published evidence-based guidelines for the diagnosis and management of asthma, but there are some unresolved asthma-management issues that need further research. For asthmatic children inhaled corticosteroids are more beneficial than as-needed use of beta(2) agonists, long-acting beta(2) agonists, theophylline, cromolyn sodium, nedocromil, or any combination of those. Leukotriene modifiers are an alternative but not a preferred treatment; they should be considered if the medication needs to be administered orally rather than via inhalation. Cromolyn sodium and nedocromil are effective long-term asthma-control medications, but they are not as effective as inhaled corticosteroids. There is insufficient evidence to determine whether cromolyn benefits maintenance of childhood asthma. Cromolyn sodium and nedocromil are alternatives, but not preferred treatments for mild persistent asthma. Cromolyn may be useful as a preventive therapy prior to exertion or unavoidable exposure to allergens. Regular inhalation of corticosteroids controls asthma significantly better than as-needed beta(2) agonists. No studies have examined the long-term impact of regular inhaled corticosteroids on lung function in children 相似文献   

Advances in pediatric drug therapy of asthma.

Most pediatric patients requiring medication to prevent or treat asthmatic symptoms require only the use of inhaled beta 2 agonists. Children younger than 6 years old usually require use of the nebulized or oral forms of beta 2 agonists. Theophylline or cromolyn is added as a second-line agent to the regimens of children who need an additional agent. Anticholinergic agents are added as third-line agents for resistant cases of asthma. Inhaled and oral steroids are reserved for resistant cases of childhood chronic asthma, even though adults frequently are given inhaled steroids as second-line agents. Parenteral steroids are used for the treatment of status asthmaticus.     

Outpatient management of asthma in adults.

The diagnosis of asthma is made by demonstrating episodic and reversible airway obstruction. Office spirometry or peak flow meters should be used to objectively measure pulmonary status, since the history and physical examination do not correlate well with asthma severity. Reducing exposure to indoor and outdoor allergens may prevent exacerbations. Asthma medications are prescribed in a step-wise fashion. Inhaled beta 2 agonists should be used by patients with mild asthma during brief and limited symptomatic episodes. Anti-inflammatory agents, such as inhaled corticosteroids or cromolyn, should be added for moderate degrees of asthma. If symptoms persist, a long-acting bronchodilator, such as an oral beta agonist or oral theophylline, may be added in the evening. A short course of oral steroids may also be prescribed as needed. Patients should be taught to correctly use metered-dose inhalers, to keep a daily record with home peak flow measurements that monitor their pulmonary status and to follow a prescribed medication plan for exacerbations.     

Model for theophylline overdose treatment with oral activated charcoal

The effect of repeated oral doses of activated charcoal on theophylline kinetics was studied in six subjects with hepatic cirrhosis and five patients with moderate theophylline poisoning to determine whether an activated charcoal regimen would be a useful strategy in patients with theophylline poisoning who did not require hemoperfusion. Six subjects with cirrhosis were injected IV with 6 mg/kg aminophylline followed by either water or water with activated charcoal (140 gm) in divided doses over 12 hr. In these subjects, treatment with activated charcoal decreased the mean (+/- SE) serum theophylline t1/2 from 12.7 +/- 4.0 hr to 4.0 +/- 0.7 hr. Subjects with the longest control t1/2s demonstrated the greatest charcoal effect. We developed a mathematical model that predicts that treatment with repeated oral doses of activated charcoal would result in an average serum theophylline t1/2 of 7.1 hr or less even if the subject's endogenous theophylline t1/2 is very long. In a pilot study of five patients with moderate theophylline poisoning, treatment with repeated oral doses of activated charcoal was well tolerated and led to a mean (+/- SE) t1/2 that was shorter than expected (4.9 +/- 0.8 hr, range 3.1 to 7.1 hr). We conclude that repeated oral doses of activated charcoal are relatively more effective in decreasing the serum theophylline t1/2 in persons with long endogenous t1/2s and that this may be useful for certain patients with mild or moderate theophylline poisoning.     

Topical pharmacotherapy for allergic rhinitis: new agents.

The advantages of topical (as opposed to systemic) therapy for allergic rhinitis include the avoidance of undesirable systemic effects and the concentration of therapeutic effect on the target organ. Successful topical therapy requires establishment of a proper diagnosis, followed by effective delivery of the medication to the nasal mucosa. In addition to currently available preparations such as cromolyn sodium and various corticosteroids, several other topical nasal preparations for the treatment of allergic rhinitis are under investigation. These include antihistamines (eg, levocabastine), anti-inflammatory/mast cell stabilizing drugs (eg, nedocromil), new corticosteroids (eg, triamcinolone, budesonide, fluocortin, fluticasone), anticholinergics (eg, ipratropium), and miscellaneous agents (eg, HEPP [IgE pentapeptide]).     

Asthma therapy. Advantages and limitations of various approaches

The physician who understands the various physiologic mechanisms that result in bronchospasm can choose the appropriate management approach. Recommended initial outpatient treatment of sporadic asthma consists of administration of an inhaled beta 2 agent, followed as necessary by a systemic beta 2 agent, a long-acting theophylline preparation, cromolyn, and inhaled ipratropium. Chronic steroid therapy should be used only after a trial of combination therapy with the foregoing drugs, and the daily dose of steroids should be minimized by use of a beclomethasone inhaler. Treatment of acute attacks depends on their chronicity and severity and on the medications the patient has already taken.     

Need for theophylline in severe steroid-requiring asthmatics

Concern about side-effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi-medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti-asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in-patients, 12-15 years old, completed a double-blind, cross-over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long-acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10-30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids.     

Repetitive doses of activated charcoal in the treatment of poisoning

Activated charcoal has found a renewed role in the management of overdosed patients. Routinely administered to reduce the gastrointestinal (GI) absorption of many drugs, growing evidence indicates that repeated doses of charcoal also may enhance drug elimination. Some drugs are excreted into the bile or gastric fluids (phencyclidine, digoxin) and are reabsorbed. Other drugs (theophylline, phenobarbital) can diffuse from the plasma into the lumen of the GI tract. Activated charcoal is administered at regular intervals to sequester these toxins in the GI tract, eventually causing their excretion in feces. This article reviews the evidence for the safety and efficacy of repetitive charcoal therapy. While supportive management remains the mainstay of therapy in poisoned patients, activated charcoal is inexpensive, effective, simple to administer, and may obviate the need for more invasive methods of toxin removal.     

Cost-effectiveness of including cromolyn sodium in the treatment program for asthma: a retrospective, record-based study

The treatment of chronic mild to moderately severe asthma is expensive for families and for society. Controlling the costs of asthma-related medications, physician visits, emergency room visits, and hospital admissions is therefore an important consideration. A retrospective, record-based study was undertaken to determine the costs of treating asthma in patients for whom cromolyn sodium was included in the routine treatment plan (n = 27) and those for whom treatment did not include cromolyn sodium (n = 26). Significant reductions in the number of emergency room visits and hospital admissions were obtained in patients who were treated with cromolyn sodium. The estimated average cost of emergency room visits was $33 a year for the patients given cromolyn sodium compared with $624 a year for patients in the comparison group. The estimated average cost of hospital admissions was reduced by $1,298 for the cromolyn sodium group compared with a $357 reduction for the comparison group. Computed for the entire course of treatment, the average (+/- SD) daily cost of medications for the comparison group was $0.84 +/- $0.37 versus $0.93 +/- $0.25 for the cromolyn sodium treatment group. Thus dramatic savings in costs of emergency room visits and hospitalizations when cromolyn sodium was included in therapy were effected at a small increase in the overall cost of medications. Analyzed visit by visit, the average daily cost of treatment that included cromolyn sodium decreased while that of the comparison group increased. We conclude that including cromolyn sodium in a regular anti-asthma regimen is a cost-effective and therapeutically effective treatment strategy.     

Asthma therapy: present trends and future prospects

The short-term treatment of asthma has for years included supplemental oxygen, IV theophylline, and subcutaneously administered and inhaled beta-adrenergic agonists, anticholinergics, and corticosteroids. This regimen has not really changed. What have changed, however, are the specificity of the drugs and the mode of their administration. Metered-dose inhalers can deliver selective beta-adrenergic agonists, anticholinergics, and corticosteroids directly to the airway mucosa. Topical delivery of medication has dramatically reduced the side effects of all classes of medication. As experience accrues, more studies indicate that inhalation therapy may become the mainstay of asthma treatment, even in the emergency department. Metered-dose inhalers have also aided in the resurgence of the use of cromolyn. There is certainly improved ease of administration and perhaps a reduced incidence of rebound bronchospasm. The appearance of newer beta 2-adrenergic agonists with improved beta 2-adrenergic selectivity and longer half-lives underscores the activity in asthma research. There is hope that selective bronchodilating corticosteroids or calcium-channel blockers can be developed. Bronchodilating prostaglandins and leukotrienes, or inhibitors of prostaglandins and leukotrienes that cause bronchoconstriction, are being investigated. An oral mast-cell membrane stabilizer is available and hopefully can be improved. Finally, the transdermal delivery of medication may open an entirely new avenue for the treatment of those suffering from asthma.     

Pharmacologic therapy of asthma.

Asthma is treated by avoiding the precipitants of symptoms, by a trial of hyposensitization (immunotherapy) if the precipitant cannot be avoided, and principally by pharmacologic therapy. Acute attacks have been most widely treated with epinephrine, but adrenergic aerosol bronchodilators and aminophylline are being used increasingly. When an acute attack of asthma does not respond to treatment, a diagnosis of status asthmaticus should be considered and the patient treated in a hospital intensive care unit because of the potentially life-threatening sequela of respiratory failure. Periodic mild episodes of asthma usually respond to administration of an oral bronchodilator. Chronic low-grade asthma is best treated with an around-the-clock regimen of theophylline. Patients whose asthma is not under satisfactory control with conventional bronchodilators may be given a trial of cromolyn sodium. Chronic severe cases may be treated with corticosteroids, but these drugs must be skillfully administered to avoid adverse effects.     

Randomized double-blind placebo-controlled study of drugs with anti-ulcer action and their use in associated pathology

The effect of lithium preparations (lithium carbonate, lithium oxybutyrate), calcium channel blocking agents (verapamil, nifedipine), beta 2-adrenoagonist (salbutamol), cromolyn sodium and cimetidine on clinical efficacy and frequency of ulcer cicatrization was assessed in 201 patients (33 women, 168 men) with endoscopically verified stomach ulcer (52 patients) and duodenal ulcer (166 patients) during treatment for 4 weeks as compared to placebo and standard antiulcerative therapy (cholinolytics, antacids and reparents). All the tested drugs (excluding cromolyn sodium) significantly increased as compared to placebo the frequency of ulcer cicatrization (p less than 0.001 in the use of lithium preparations and cimetidine; p less than 0.01 in the use of salbutamol and verapamil; p less than 0.05 in the use of nifedipine). The effect of lithium preparations and cimetidine exceeded that of standard antiulcerative multimodality therapy.     

Bronchial asthma: some aspects of pathogenesis and therapy.

The first step in management of bronchial asthma is to exclude other diseases which may present as wheezing dyspena. Once the diagnosis is confirmed beyond a reasonable doubt, therapy can be initiated. Treatment depends on the type, severity, and duration of the disease. Other factors which dictate the choice of drug are the patient's response, metabolism of the drug, and complications of the disease. Theophylline forms the backbone of asthma therapy. Because of the wide variation in half-life of theophylline in different individuals due to variation in rate of metabolism and elimination, serum levels of theophylline should be monitored whenever possible. Newer antiasthmatic drugs, such as cromolyn sodium and inhaled steroids, are playing an increasing role in treatment of selected patients.     

Rational use of sulfonylureas.

The clinical use of sulfonylureas described in this article is both rational and effective for diabetic patients. Sulfonylureas are not used (1) in patients with insulin-dependent (type I) diabetes, because they are completely ineffective or (2) in patients with non-insulin-dependent (type II) diabetes who respond satisfactorily to diet, because they are unnecessary. In a patient with type II diabetes who has few or no symptoms but does not respond satisfactorily to diet, a sulfonylurea is introduced at a low dose, with gradual increases until a satisfactory response occurs, thus avoiding hypoglycemia. When symptoms of type II diabetes are marked, initiation of therapy with maximum doses of a sulfonylurea quickly distinguishes patients who need insulin therapy from those who have a good chance of responding to an oral drug. Abuse of sulfonylureas occurs when patients who could benefit from diet alone are treated with the drugs unnecessarily or, more often, when patients with poorly controlled disease continue to take maximum doses of the drugs. The usual situation is one in which the patient refuses insulin therapy or the physician does not suggest starting it. In other cases, the poorly controlled patient may be allowed to continue with a combination of a sulfonylurea and an ineffective dose of insulin. In this circumstance, the oral drug should be discontinued and insulin doses increased until control is more satisfactory. Because evidence is so compelling that near euglycemia has a beneficial effect on diabetic retinopathy, nephropathy, and neuropathy, physicians really do patients a disservice by misusing sulfonylureas.     

Practice and Economics Cost Considerations in Headache Treatment Part 2: Acute Migraine Treatment

Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication.
Over-the-counter medications such as aspirin ($0.02/325 mg), Excadrin· ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal ant-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet.
Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are given for more effective use of these agents.
Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as Indirect costs to the patient, family, and society.     

Outpatient management of asthma.

Oral administration of xanthine compounds represents the first line of therapy in most patients with asthma. Establishment and maintenance of a therapeutic blood level of the medication requires regular dosgae. Oral sympathomimetic agents with predominantly beta-2 adrenergic activity, if tolerated, are often useful adjuncts to xanthine therapy. Sympathomimetic aerosols are not recommended. Cromolyn is often a valuable prophlactic agent. Corticosteroid aerosols may be useful in limiting adrenal suppression when steroids are necessary.