DRUGS USED IN TREATMENT OF ASTHMA

Asthma is a chronic inflammatory disorder of the airways. All patients need a short-acting inhaled β2-agonist to use as needed for symptoms. Patients with mild, moderate, or severe persistent asthma need daily long-term control medication. Start treatment at a higher "step" to achieve rapid control and then "step down" to the minimum therapy needed to maintain control, or start treatment at the "step" that is appropriate to the severity of the patient's asthma and then gradually "step up" therapy until control is achieved and maintained (see chart in this section). The "step-down" approach is preferred. Increases or decreases in medication(s) may be needed over time. 

CORTICOSTEROIDS 

(eg, triamcinolone, hydrocortisone, dexamethasone, methylprednisolone, prednisolone, prednisone): Corticosteroids are steroid hormones indicated for the treatment of adrenocortical insufficiency, steroid-responsive dermatoses, inflammatory disorders, autoimmune disorders, allergic reactions, and other conditions requiring immunosuppressive effects. Corticosteroids exert their effects by binding to specific intracellular receptors and translocating into the nucleus to subsequently regulate gene expression. 

Physiologic actions of corticosteroids depend on their glucocorticoid or mineralocorticoid activity:

Glucocorticoids also play an active role on the modulation of carbohydrate, protein, and lipid metabolism. They stimulate hepatic gluconeogenesis, inhibit glucose uptake in muscle and adipose tissues to conserve glucose, and provide substrates for gluconeogenesis by mobilizing amino acids from extrahepatic tissues and stimulating lipolysis in adipose tissues. Glucocorticoids also produce potent anti-inflammatory and immunosuppressive activity through the suppression of polymorphonuclear leukocytes migration, decreased inflammatory mediator production and reduction of capillary permeability. 

Mineralocorticoids, on the other hand, play a role in the maintenance of fluid and electrolyte homeostasis. Their actions include promoting Na+ and K+ ion exchange in the distal tubule of the kidney, increasing the resorption of sodium and water and the renal excretion of K+ and H+, and stimulating the expression of sodium channels to facilitate sodium uptake from the tubular lumen.

Systemic corticosteroids with predominant glucocorticoid activity in order of decreasing potency include dexamethasone, methylprednisolone, and triamcinolone. Prednisone and prednisolone are less potent glucocorticoids with weak mineralocorticoid activity, while hydrocortisone is the least potent glucocorticoid but has increased mineralocorticoid activity compared to others in this group.

LONG-TERM CONTROL MEDICATIONS are taken daily to achieve and maintain control of persistent asthma.

Inhaled corticosteroids (eg, beclomethasone, budesonide, flunisolide, fluticasone, triamcinolone) are used in the long-term control of asthma. Systemic corticosteroids are used in long-term therapy to gain prompt control of the disease and also to manage severe persistent asthma. It is possible to prevent disease progression with their early use. Low doses are used for mild persistent asthma; medium doses are used for moderate persistent asthma; high doses are reserved for the most severe cases. To reduce the potential for adverse effects with inhalers: Use a spacer or holding chamber; rinse mouth and spit after inhalation; consider adding a long-acting inhaled β2-agonist to a low-to-medium dose of inhaled steroid rather than using a higher dose of inhaled steroid (especially for nocturnal symptoms); monitor linear growth in children; when inhaled corticosteroid doses exceed 1000mcg per day, consider supplements of calcium (1g-1.5g/day), Vitamin D (400Units/day) and estrogen replacement therapy for postmenopausal women; may reduce doses of inhaled steroids by about 25% every 2–3 months until the lowest dose required to maintain control is reached.

Cromolyn sodium and nedocromil are mild-to-moderate antiinflammatory medications. They may be used as an initial choice in addition to a bronchodilator for long-term control in children. They can also be used as preventative treatment before unavoidable exposure to known allergens and in some cases of exercise-induced asthma. They should not be used to treat acute symptoms or exacerbations.

Long-acting β2-agonists (eg, salmeterol, formoterol, sustained-release albuterol) are used with inhaled corticosteroids for long-term control of symptoms (especially nocturnal symptoms). They may also be used to prevent exercise-induced bronchospasm. They should not be used to treat acute symptoms or exacerbations.

Leukotriene antagonists (eg, zafirlukast, montelukast) may be considered alternative therapy or adjunctive therapy to low doses of inhaled corticosteroids, or cromolyn or nedocromil in mild persistent asthma. Zafirlukast may be used in children ≥5 years of age; montelukast in patients ≥12 months of age.

Theophylline, a methylxanthine, is a mild-to-moderate bronchodilator. Blood levels must be maintained within a safe but effective range.

QUICK-RELIEF MEDICATIONS are used to provide prompt treatment of acute airflow obstruction and accompanying symptoms.

Short-acting β2-agonists (eg, albuterol, levalbuterol, bitolterol, pirbuterol, terbutaline) are preferred for the relief of acute symptoms. Increase in use or use of more than one canister in one month indicates inadequate control of asthma and the need for initiating or intensifying antiinflammatory therapy. Regularly scheduled, daily use of a short-acting β2-agonist is generally not recommended; they may be considered first for preventing exercise-induced asthma.

Systemic corticosteroids (eg, methylprednisolone, prednisolone, prednisone) are used for moderate-to-severe exacerbations to speed recovery and prevent recurrence of exacerbations. The addition of a 3- to 10-day course of oral corticosteroids may be needed to reestablish control during periods of gradual deterioration or for a moderate-to-severe exacerbation. 

Anticholinergic agents (eg, ipratropium) may provide additive benefit to inhaled β2-agonists in severe exacerbations. They may also be used as an alternative bronchodilator for patients who cannot tolerate an inhaled β2-agonist.

by

AKSHAYA SRIKANTH

Pharm.D* Intern

Hyderabad, India