Corticosteroids administration route

There is no evidence that intravenous corticosteroid administration is more effective than oral administration, and the oral route is preferred in acute severe asthma.3 There are also few data to guide selection of initial corticosteroid doses. Recommended doses for acute severe asthma are shown in Table 11-5, page 227 however, recent data indicate that... 

Table 12-3 Advantages and Disadvantages of the Three Routes of Corticosteroid Administration ...

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... 

Induction of ocular hypertension after corticosteroid administration depends on the specific drug, the dose, the route and frequency of administration, and the corticosteroid responsiveness of the patient. Generally, patients with elevated lOP are asymptomatic, so examination with applanation tonometry is the key to diagnosis. If the patient shows a steroid responsiveness, the onset of lOP elevations is not immediate but occurs after approximately 2 weeks of use. However, it can occur many weeks later, and this time to onset is generally longer for systemic steroids. In responsive patients the level of lOP rise with systemic steroids averages approximately 60% of that produced by topically applied steroids. 

Corticosteroids should only be used during acute exacerbations of ulcerative colitis. The total duration of therapy should not exceed 4 to 8 weeks. Many different corticosteroids are available and differ in anti-inflammatory potency and mineralocorticoid activity (Table 38-2). Choosing a corticosteroid and route of administration depends on the clinical presentation. 

Fluid/Solute overload Excessive amounts of sodium chloride by any route may cause hypokalemia and acidosis. Administration of IV solutions can cause fluid or solute overload resulting in dilution of serum electrolyte concentrations, CHF, overhydration, congested states, or acute pulmonary edema, especially in patients with cardiovascular disease and in patients receiving corticosteroids or corticotropin or drugs that may give rise to sodium retention. 

Shortly after the introduction of corticosteroids to ocular therapeutics, clinical use indicated that local treatment was equal to or superior to systemic administration, provided that the diseased tissue could be brought in contact with sufficient concentration of steroid. In general, when possible topical administration is indicated for anterior segment disease. Ease of application, comparatively low cost, and relative absence of systemic complications make it the preferred route of steroid therapy. Selection of a particular topical steroid and the dosage... 

The success of intravitreal implants, such as achieved with ganciclovir, has renewed interest in developing an intravitreal corticosteroid implant to further enhance the intravitreal route of administration, thus reducing the need for multiple injections. Bausch and Lomb and Control Delivery Systems have developed an intravitreal implant that can deliver the corticosteroid fluocinolone acetonide (Retrisert) to posterior eye tissue for up to 3 years. The implant, which was approved in 2005 by the U.S. Food and DrugAdministration (FDA), delivers 0.59 or 2.1 mg of fluocinolone acetonide. The long-term ocular side effects of this device are unknown at this time. 

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... 

Deeper or more severe forms of uveitis may not respond to topical therapy hence, injectable and/or oral routes of administration may be required. Periocular corticosteroids may be used occasionally for anterior uveitis however, this therapy is more often used in cases of intermediate uveitis or, less commonly, unilateral posterior uveitis.A small amount of depot corticosteroid (e.g., 1 ml of 40 mg/ml triamcinolone acetonide injected superiorly or inferiorly in the orbit) is considered acceptable and appropriate treatment in such situations. In cases of chronic posterior uveitis or uveitis associated with CME, intravitreal triamcinolone has also been used with some success. A retrospective study in 2005 demonstrated that intravitreal injection of 4 mg/0.1 ml triamcinolone acetonide can effectively reduce CME and improve visual acuity and, in some eyes, allow for the reduction of immimosuppressive therapy. 

The ocular side effects of corticosteroids are many and are related to the route of administration. The most common concerns are increased intraocular pressure (lOP) and cataracts, but delayed epithelial woimd healing and increased risk of infection due to immime modulation and decreased tear lysozyme levels are issues for the cornea. Changes to other ocular tissues have been noted (subconjunctival hemorrhages, blue sclera, eyelid hyperemia and edema, retinal emboUc events, central serous choroidopathy) and neurologic compUcations reported (diplopia, nerve palsies, intracranial hypertension) (see Appendix 35-1). 

For any minor injuries sustained during athletic training NSAIDs and corticosteroids (topical, intra-articular) suppress symptoms and allow the training to proceed maximally. Their use is allowed subject to restrictions about route of administration, but strong opioids are disallowed. Similarly, the IOC Medical Code defines acceptable and unacceptable treatments for relief of cough, hay fever, diarrhoea, vomiting, pain and asthma. Doctors should remember that they may get their athlete patients into trouble with sports authorities by inadvertent prescribing of banned substances. ... 

When would you consider different routes of administration of corticosteroids ... 

Drugs have been administered nasally for several years both for topical and systemic effect. Topical administration includes agents for the treatment of nasal congestion, rhinitis, sinusitis, and related allergic and other chronic conditions. Various medications include corticosteroids, antihistaminics, anticholinergics, and vasoconstrictors. The focus in recent years has been on the use of nasal route for systemic drug delivery. 

Absorption and systemic toxicity observed using special routes should be compared with the more usual intravenous or oral routes of administration to identify and assess the relevance of any significant differences observed. Plasma levels will obviously depend on the amount of drug absorbed. Higher systemic (i.e. circulating) levels of drug may help explain the differences in toxicity between routes. Corticosteroids, for example, are more toxic on the basis of administered dose when given by the inhalation compared with the oral route. It is the ratio of the AUC for the plasma... 

When used in combination with corticosteroids, cyclophosphamide is dosed at 1-3 mg/kg for oral therapy and 0.5-1.0 g/m of body surface area for intravenous therapy. The most common route of cyclophosphamide administration is intravenous, although there is little evidence that this is better than oral administration. Likewise, there is no evidence to suggest the optimal duration of treatment. Based on empirical experience, cyclophosphamide generally is dosed monthly for 6 months and then every 3 months for a period of either 2 years or for 1 year after the nephritis is in remission." " Of course, cyclophosphamide therapy is not without risk. Serious toxic effects include suppression of hematopoiesis, opportunistic infections, bladder complications (e.g., hemorrhagic cystitis and cancer), sterility, and teratogenesis. White blood cell counts must be monitored during cyclophosphamide therapy, and if the nadir is less than 1500/mm, the dose must be adjusted to keep the white cell count above 1500/mm. Nausea and vomiting associated with cyclophosphamide can be controlled with oral ondansetron plus dexamethasone. ... 

The degree of systemic side effects is dose-dependent, related to the half-life of the drug, frequency of administration, time of day when administered, and route of administration. In other words, the higher the plasma corticosteroid concentration and longer the half-life, the greater the systemic side effects will be (Table 33.3). 

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