Hydrocortisone administration route

Amphotericin B is the mainstay of treatment of patients with severe endemic fungal infections. The conventional deoxycholate formulation of the drug can be associated with substantial infusion-related adverse effects (e.g., chills, fever, nausea, rigors, and in rare cases hypotension, flushing, respiratory difficulty, and arrhythmias). Pre-medication with low doses of hydrocortisone, acetaminophen, nonsteroidal anti-inflammatory agents, and meperidine is common to reduce acute infusion-related reactions. Venous irritation associated with the drug can also lead to thrombophlebitis, hence central venous catheters are the preferred route of administration in patients receiving more than a week of therapy. 

Topical routes of drug administration are where the drug is applied directly to the site of action. Many medicines are applied directly for example, hydrocortisone can be rubbed into the skin to relieve a local area of inflammation. The anticholinesterase neostigmine is dropped directly onto the eye surface to relieve glaucoma, a condition characterised by raised intra-ocular pressure which if untreated can lead to blindness. 

They are given by oral, parenteral and topical route. Oral bioavailabiHty of synthetic cortico-steroids is high. Hydrocortisone after oral administration undergoes extensive first pass metabolism in liver. 

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... 

In 1951-1952, Sulzberger et al. showed that systemically - but not topically -applied cortisone acetate was effective in the treatment of eczema and other der-matitides, whereas hydrocortisone was effective with both routes of administration [8,9]. Because the topical route promised a relative freedom from troublesome systemic side effects (e.g., salt retention). Schering recognized the need for an effective synthesis of the latter. 

The use of glucocorticoids is associated with reduced bone mineral density, bone loss, osteoporosis, and fractures. This has been described during the long-term use of glucocorticoid by any route of administration (SEDA-19, 377) (SEDA-20, 374). The effects of glucocorticoids on bone have been reviewed (SEDA-21, 417) (165). Biochemical markers of bone mineral density are listed in Table 4. In patients with secondary hypoadrenaUsm, hydrocortisone 30 mg/day for replacement produced a significant fall in osteocalcin, indicating bone loss. Lower doses of hydrocortisone (10 mg and 20 mg) produced similar efficacy in terms of quality of life but smaller effects on osteocalcin concentrations and therefore a reduction in bone loss (166). 

Unfortunately, only relatively few of the many papers published on povidone deal with its influence on bioavailability in vivo. However, where results are available, they almost always show an improvement in bioavailability. Figs. 49 to 51 show the effect of coprecipitation with povidone on the bioavailability of different active substances administered by different routes. Fig. 49 shows, as a typical example, the oral bioavailability of a nifedipine coprecipitate in the rat, Fig. 50 shows the rectal bioavailability of a phenobarbital coprecipitate in rabbits, while Fig. 51 shows the effect of a hydrocortisone coprecipitate on the human skin after percutaneous administration. In all three cases, the same dose of the pure active substance without povidone was applied for reference. 

The formulation chosen for particular drugs is not random, but the degree to which it is critical varies from drug to drug. For example, hydrocortisone is available for at least seven routes of administration, as tablets, several creams and ointments, intraocular solutions, suppositories, intrarectal foams, injections and eardrops. Even newer drugs, with fewer indications than hydrocortisone, seek greater market acceptability by providing a variety of alternative formulations (e.g. sumatriptan is available as an injection, intranasal spray, suppository and tablets). 

Hydrocortisone is metaboiized by the iiver foiiowing administration by any route, with a haif-iife of approximateiy i.O to 1.5 hours (23). Hydrocortisone is mainiy excreted in the urine as inactive 0-giucuronide conjugates and minor 0-suifate conjugates of urocortisoi, 5(3-dihydrocortisoi, and urocortisone (Fig. 33.9). The... 

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