Inhalation, administration steroids

The peak response to steroids is delayed by 6-12 hours after intravenous administration. Steroid therapy may be administered by inhalation or intravenous injection. The inhaied route is unreiiabie in acute attacfe and is most suitabie for prophyiaxis as a means of reducing the frequency of acute attacks. Hydrocortisone 0.5 mg-kg-l h-l or 4 mg-kg-1 intravenousiy 4-houriy is wideiy... 

Systemic corticosteroids (Table 80-4) are indicated in all patients with acute severe asthma not responding completely to initial inhaled /J2-agonist administration (every 20 minutes for three to four doses). Prednisone, 1 to 2 mg/kg/day (up to 40 to 60 mg/day), is administered orally in two divided doses for 3 to 10 days. Because short-term (1 to 2 weeks), high-dose systemic steroids do not produce serious toxicities, the ideal method is to use a short burst and then maintain the patient on appropriate long-term control therapy with inhaled corticosteroids. 

A major breakthrough in asthma therapy was the introduction in the 1970s of aerosol corticosteroids These agents (Table 39.3) maintain much of the impressive therapeutic efficacy of parenteral and oral corticosteroids, but by virtue of their local administration and markedly reduced systemic absorption, they are associated with a greatly reduced incidence and severity of side effects. The success of inhaled steroids has led to a substantial reduction in the use of systemic corticosteroids. Inhaled corticosteroids, along with 2-(tdreno-ceptor agonists, are front-line therapy of chronic asthma. 

Glucocorticoids are available in a wide range of preparations, so that they can be administered parenterally, orally, topically, or by inhalation. Obviously the oral route is preferred for prolonged therapy. However, parenteral administration is required in certain circumstances. Intramuscular injection of a water-soluble ester (phosphate or succinate) formed by esterification of the C21 steroid alcohol produces peak plasma steroid levels within 1 hour. Such preparations are useful in emergencies. By contrast, acetate and tertiary butylacetate esters must be injected locally as suspensions and are slowly absorbed from the injection site, which prolongs their effectiveness to approximately 8 hours. 

Inhaled glucocorticoid preparations, such as be-clomethasone dipropionate and betamethasone valerate, provide an effective alternative to systemic steroids in the treatment of chronic asthma, with lesser side effects than oral or parenteral glucocorticoids (see Chapter 39). In fact, inhaled glucocorticoids have become a mainstay of asthma therapy. Inhalation delivers the agent directly to the target site in relatively low doses, with the potential for more frequent administration. Moreover, inhaled glucocorticoids are metabolized in the lung before they are absorbed, which reduces their systemic effects. However, even modest doses of... 

The first inhaled glucocorticoid, beclomethasone dipropionate, revolutionized asthma therapy, when it was found that topical delivery to the lung resulted in reduced systemic side-effects (adrenal suppression, oseteoporosis and growth inhibition) typically seen with oral steroid treatments. Interestingly, a further reduction in systemic exposure was achieved with the introduction of fluticasone propionate (1). The evolution of this drug stemmed from observations with the steroid 17-carboxylates that showed that these esters were active topically when esterified, while the parent acids were inactive. Thus it was realized that enzymatic hydrolysis of the ester would lead to systemic deactivation. SAR studies led to a series of carbothioates, which were very active in vivo when topically applied to rodents, but were inactive after oral administration. It was shown that fluticasone propionate (1) underwent first pass metabolism in the liver to the corresponding inactive 173-carboxylic acid (la) (Scheme 1). This observation was... 

Tukiainen H, Rytila P, Hamalainen KM, Silvasti MS, Keski-Karhu J. Finnish Study Group. Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients. Respir Med 2002 96(4) 221-9. 

Posterior subcapsular cataracts (PSCs) can occur with all routes of administration (Figure 12-2), including systemic, topical, cutaneous, nasal aerosols, and inhalation corticosteroids. In a study of 44 rheumatoid arthritis patients treated with various steroids, including prednisone and dexamethasone, 17 (39%) developed bilateral PSCs. Dosage and duration of therapy appeared to be correlated with the incidence of cataract development. Patients who received prednisone therapy for 1 to 4 years showed an 11% incidence if the dose range was less than 10 mg/day a 30% incidence if the dose was... 

Corticosteroid administration by systemic (oral or intravenous), topical (ophthalmic and cutaneous), injected (periocular and subcutaneous), and inhalation and possibly nasal routes can elevate lOP In patients who are steroid responders, oral steroids produce approximately 60% the increase in lOP as compared with topical agents, most likely because of differences in achieved anterior chamber concentrations of the drug. Those with primary open-angle glaucoma respond to steroids at a rate of 46% to 92% compared with 18% to 36% of... 

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

Dichlorodifluoromethane is used as an aerosol propellant in metered-dose inhaler (MDI) formulations, either as the sole propellant or in combination with dichlorotetrafluoroethane, trichloromonofluoromethane, or mixtures of these chlorofluorocarbons. Dichlorodifluoromethane may also be used as a propellant in an aerosolized sterile talc used for intrapleural administration and is also used alone in some MDIs containing a steroid. 

After acute inhalation exposure to high concentrations of vanadium and/or compounds, pulmonary edema may result. If so, oxygen administration may be necessary. Experimental evidence suggests that the administration of steroids such as prednisolone succinate or phthalate may prevent the development of a chemical lung edema (Stutz and Janusz 1988). 

Bronchospa may orxur after administration of the inhaled cortisteroids If an immediate increase in wheezing indicating brond ospasm occurs after administration of a corticosteroid inhalant, the nurse immediately administers a shortacting inhaled bronchodilator. The inhaled corticosteroid is discontinued and an alternate treatment started. 

Miscellaneous - Treatment of severe steroid-dependent asthmatics with high dally doses of Inhaled steroids in order to reduce oral steroid requirements continues to attract attentlon Budesonide was much more effective In chronic asthma by Inhalation than by oral administration. Its low oral bloavallabillty (11%), a short half life and extensive liver metabolism may explain why It produces few systemic side effects... 

Whereas NSAIDs have both anti-inflammatory and analgesic properties and are used for a variety of aches and pains of muscles and joints, the steroidal anti-inflammatory agents are not analgesic. Members of this class are used by oral administration, by topical application to the skin and eye and by inhalation to the lung. Figure 4.18 shows the structures of several such drugs. Cortisone (Roussel, 1952) and hydrocortisone (Pfizer, 1954) were first obtained by isolation from adrenal glands and shown to have powerful anti-... 

In a case study of a 17-year-old male with mixed S. haematobium-S. mansoni infection for >4 months, after administration of PZQ 60mg/kg he developed fatigue, fever, cough and dyspnoea with wheezing within 24 h of treatment. Hypoxaemia, leucocytosis (28 x 10 /uL with eosinophilia up to 70.5%) and abnormal pulmonary function tests (forced expiratory volume in 1 s of 54% and forced vital capacity of 48%) were also seen which resolved after treatment with prednisolone and inhaled steroids. Authors speculated that this reaction constituted a arish-Herxheimer-like reaction which is unique since the patient was considered to be in the chronic course of the disease [60 j. 

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