{"id":593,"date":"2020-02-17T20:19:05","date_gmt":"2020-02-17T14:49:05","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=593"},"modified":"2020-02-17T20:19:05","modified_gmt":"2020-02-17T14:49:05","slug":"inhaled-glucocorticoids","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/inhaled-glucocorticoids\/","title":{"rendered":"Inhaled glucocorticoids"},"content":{"rendered":"\n
Inhaled glucocorticoids<\/strong><\/p>\n\n\n\n Inhaled glucocorticoids (commonly called inhaled steroids or ICS) are considered the agents of choice in all patients with persistent asthma according national and international guidelines<\/p>\n\n\n\n ICS have fewer and less severe adverse effects than orally-administered glucocorticoids, and they are widely used to treat asthma and chronic obstructive pulmonary disease (COPD).<\/p>\n\n\n\n However, there are concerns about the systemic effects of ICS, particularly as they are likely to be used over long periods of time, in infants, children, and older adults. The safety of ICS has been extensively investigated since their introduction for the treatment of asthma 30 years ago<\/p>\n\n\n\n DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant metered dose inhaler<\/p>\n\n\n\n Efficacy<\/strong> \u2014 <\/p>\n\n\n\n Representative studies demonstrating the efficacy of inhaled glucocorticoids include the following:<\/p>\n\n\n\n \u25cfA multicenter, double-blind trial randomly assigned over 7000 patients with mild persistent asthma to treatment with low-dose inhaled\u00a0budesonide\u00a0(400 mcg once daily) or placebo for three years<\/p>\n\n\n\n budesonide \u00e0<\/p>\n\n\n\n Not all patients with asthma are responsive to inhaled glucocorticoid therapy. Studies suggest that up to 35 percent of patients may not experience improvements in FEV1<\/sub> or bronchial hyperresponsiveness<\/p>\n\n\n\n patients with mild asthma who smoke cigarettes appear relatively resistant to the effects of low-dose inhaled glucocorticoids.<\/p>\n\n\n\n Initial dosing<\/strong> \u2014 <\/p>\n\n\n\n low-dose range, corresponding to Step 2 treatment<\/p>\n\n\n\n Among the low-dose inhaled glucocorticoids,\u00a0mometasone\u00a0is approved for once-daily dosing.<\/p>\n\n\n\n The other inhaled glucocorticoids have traditionally been administered twice daily, although it is likely that they can be used once daily in many patients with mild asthma, which might improve compliance.<\/p>\n\n\n\n More evidence supports the safety of\u00a0budesonide\u00a0during pregnancy<\/strong> than for the other inhaled glucocorticoids.<\/p>\n\n\n\n Delivery devices and spacers<\/strong> \u2014 <\/p>\n\n\n\n Inhaled glucocorticoids are available via MDI, breath-actuated MDI, dry powder inhaler (DPI), soft mist inhaler, and as a solution for nebulization.<\/p>\n\n\n\n Use of a valved holding chamber (“spacer”) device with MDI glucocorticoids is recommended in order to maximize medication delivery to the bronchi and to minimize oropharyngeal deposition.<\/p>\n\n\n\n Spacers are not used with DPIs, SMIs, or breath-actuated MDIs<\/p>\n\n\n\n Side effects<\/strong> \u2014 <\/p>\n\n\n\n Oral candidiasis and dysphonia (hoarse voice) are the most common side effects<\/strong> of low-dose inhaled glucocorticoids.<\/p>\n\n\n\n EFFECTS OF LOCAL DEPOSITION<\/strong><\/p>\n\n\n\n Side effects due to the local deposition of inhaled glucocorticoid in the oropharynx and larynx may occur. The frequency of complaints depends on the specific drug, dose, frequency of administration, inhaler technique, and the delivery system used.<\/p>\n\n\n\n Dysphonia<\/strong> \u2014 <\/p>\n\n\n\n Reported incidences vary from 1 to 60 percent, depending on the patient population, device, dose, length of observation, and manner of data collection<\/p>\n\n\n\n The mechanism of ICS-associated dysphonia may involve factors such as myopathy of laryngeal muscles (manifest as incomplete closure or bowing of the vocal cords on adduction), mucosal irritation, and laryngeal candidiasis<\/p>\n\n\n\n Dysphonia is sometimes reduced by using a spacer with the MDI, although results are variable<\/p>\n\n\n\n Topical candidiasis<\/strong> \u2014 <\/p>\n\n\n\n Oropharyngeal candidiasis (thrush) \u00e0 particularly elderly patients, patients taking concomitant oral glucocorticoids or antibiotics.<\/p>\n\n\n\n For patients using MDIs, large volume spacer devices may protect against thrush by reducing the amount of drug deposited in the oropharynx.<\/p>\n\n\n\n In addition, rinsing the mouth and throat with water and expectorating the rinsate after use of all forms of ICS is preventative.<\/p>\n\n\n\n reported in up to 15 percent of patients complaining of dysphonia during ICS therapy.<\/p>\n\n\n\n Contact hypersensitivity<\/strong> \u2014 <\/p>\n\n\n\n Allergic contact dermatitis has occasionally been described due to ICS, particularly\u00a0budesonide. An erythematous, eczematoid eruption is typically noted around the mouth, nostrils, or eyes.<\/p>\n\n\n\n Other<\/strong> \u2014 Cough and throat irritation, sometimes accompanied by reflex bronchoconstriction, may occur<\/p>\n\n\n\n SYSTEMIC ADVERSE EFFECTS<\/strong><\/p>\n\n\n\n The addition of intranasal glucocorticoids to high-dose ICS (eg, in patients with allergic rhinitis and asthma) likely increases the systemic exposure to glucocorticoids, although the contribution to adverse effects has not been specifically quantified<\/p>\n\n\n\n Adrenal suppression<\/strong> \u2014 <\/p>\n\n\n\n Systemic administration of glucocorticoids causes hypothalamic-pituitary-adrenal (HPA) axis suppression by reducing corticotropin (ACTH) production, which reduces cortisol secretion by the adrenal gland.<\/p>\n\n\n\n The degree of HPA suppression is dependent on dose, duration, frequency, and timing of glucocorticoid administration.<\/p>\n\n\n\n The risk of symptomatic adrenal suppression or acute adrenal crisis by ICS therapy is small, particularly when the doses used are within the recommended ranges.<\/p>\n\n\n\n To screen for adrenal insufficiency, the first step is measurement of serum cortisol in the morning (eg, 8 AM). Because cortisol normally peaks in the morning, a low level suggests adrenal insufficiency. The results are interpreted as follows:<\/p>\n\n\n\n \u25cfA morning cortisol <3 mcg\/dL, suggests probable adrenal insufficiency. This is sufficient to make the diagnosis if the patient is symptomatic.<\/p>\n\n\n\n If the patient is asymptomatic, an\u00a0ACTH stimulation test\u00a0should be performed to evaluate further for adrenal insufficiency.<\/p>\n\n\n\n \u25cfA morning cortisol 3 to 10\u00a0mcg\/dL\u00a0is inconclusive. In most cases, the child should be further evaluated with an\u00a0ACTH stimulation test\u00a0<\/p>\n\n\n\n \u25cfA morning cortisol level >10\u00a0mcg\/dL\u00a0is reassuring, but does not completely exclude adrenal insufficiency. Further evaluation with an\u00a0ACTH stimulation test\u00a0may be appropriate if the patient is symptomatic.<\/p>\n\n\n\n When the\u00a0ACTH stimulation test\u00a0is performed, the guideline recommends using the low-dose of ACTH (1 mcg intravenously), with measurements of cortisol at baseline and 30 minutes at a minimum.<\/p>\n\n\n\n A peak cortisol level below 18 mcg\/dL is consistent with adrenal insufficiency.<\/p>\n\n\n\n Lung infection<\/strong> \u2014 <\/p>\n\n\n\n \u25cfPneumonia<\/strong> \u2013 Data are somewhat mixed regarding the risk of pneumonia among patients with COPD or asthma taking ICS, although a small increase in risk is usually reported<\/p>\n\n\n\n \u25cfTuberculosis<\/strong>\u00a0\u2013 In a nested case-control study that included over 400,000 patients with asthma or COPD (564 cases of tuberculosis), the risk of tuberculosis was slightly increased among all users of ICS (RR 1.26, 95% CI 1.18-1.56), particularly those using doses equivalent to\u00a0fluticasone\u00a0propionate 1000 mcg per day or more (RR 1.97, 95% CI 1.18-3.3)<\/p>\n\n\n\n