Therapeutically corticosteroids

Sustained intraocular corticosteroid delivery can overcome systemic side effects associated with oral topical and periocular therapy while at the same time provide effective suppression of intraocular inflammation (5-9). However, sustained intraocular therapeutic corticosteroid levels are required to adequately treat uveitis that typically has a chronic and recurrent course. Some corticosteroids such as dexa-methasone phosphate are less suitable for treatment of chronic intraocular inflammation as they have half-lives of < 4 hours when administered intravitreally and are rapidly removed from the eye (5,9). 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

Corticosteroid clearance may be increased, resulting in reduced therapeutic effects. 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

The most commonly used corticosteroids are methylpred-nisolone (IV and oral) and prednisone (oral), although prednisolone and dexamethasone also have been shown to be effective for organ transplantation. Corticosteroid doses vary by center-specific protocols, organ type, and patient characteristics. A typical taper would include an IV 100 to 500 mg bolus of methylprednisolone at the time of transplant and then a taper over 5 to 7 days to a maintenance dose of prednisone 20 mg/day or complete cessation.2,7 It is important for practitioners to know that approximately 4 mg methylprednisolone is equivalent to 5 mg prednisone and 0.75 mg dexamethasone.11 At most transplant centers, therapeutic drug monitoring of corticosteroids is not employed. Corticosteroids are associated with a variety of acute and chronic toxicides. The most common adverse events have been summarized in Table 52-5. 

Corticosteroids also exert inhibitory effects on the overall immune process. These drugs impair the function of the leukocytes responsible for antibody production and destruction of foreign cells. As a result, corticosteroids are also used therapeutically in the prevention of organ transplant rejection. 

Achievement of efficacy by any therapeutic regimen requires days to weeks. Initial dramatic response may be achieved with some agents such as corticosteroids. However, sustained benefit with pharmacologically specific antipsoriatic therapy may require 2 to 8 weeks or longer for clinically meaningful response. 

Treatment of fixed drug reactions involves removal of the offending agent. Other therapeutic measures include corticosteroids, antihistamines to relieve itching, and perhaps cool water compresses on the affected area. 

The following therapeutic measures should be instituted promptly (1) suppression of thyroid hormone formation and secretion (2) antiadrenergic therapy (3) administration of corticosteroids and (4) treatment of associated complications or coexisting factors that may have precipitated the storm (Table 20-2). 

Although leukotriene antagonists represent a new therapeutic alternative, published studies to date have shown them to be no more effective than peripherally selective antihistamines and less effective than intranasal corticosteroids. However, combined use with antihistamines is more effective than antihistamine treatment alone. 

The use of Thera Wise bioactive natural therapeutic ointment, so-called Miracle oil obtained from Tamanu oil in the South Pacific has been reported.This ointment has been used as a skin healing remedy in the treatment of skin burns, eczema and can be used both for infants and adults. The wide range of the Thera Wise agents include the SHO Natural Skin Healing Ointment which has been reported to be an excellent alternative to corticosteroids, anti-itches and antibacterials, while the HmR Natural Hemorrhoidal Ointment has been reportedly used in the treatment of hemorrhoids and hemorrhoids associated with pregnancy. The Ac-f Natural Acne Ointment has been employed as a gentle, balanced supportive care for the treatment of acne. 

Combination with prednisone Combination therapy of inhaled corticosteroids with systemic corticosteroids may increase the risk of HPA suppression compared with a therapeutic dose of either one alone. Use inhaled corticosteroids with caution in patients already receiving prednisone. 

Concomitant therapy - Concomitant therapy with other second-line drugs (eg, gold salts) demonstrates additional therapeutic benefit. Use with partially effective doses of corticosteroids for a steroid-sparing effect and result in greater improvement is not established. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Pharmacology The primary therapeutic effects of the topical corticosteroids are caused by their antiinflammatory activity, which is nonspecific (ie, they act against most causes of inflammation including mechanical, chemical, microbiological, and immunological). 

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Figure 1.7. Structure of some of the major corticosteroids that have found routine therapeutic application...

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