Prednisone

Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other corticosteroids. It is generally considered safe in pregnancy and low doses appear to be safe while the user is breastfeeding. After prolonged use, prednisone must be stopped gradually. Prednisolone then binds to glucocorticoid receptors, activating them and triggering changes in gene expression.

Prednisone was patented in 1954 and approved for medical use in the United States in 1955. Prednisone is a therapeutic alternative on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

Medical uses

Prednisone is used for many different autoimmune diseases and inflammatory conditions, including asthma, gout, COPD, CIDP, rheumatic disorders, allergic disorders, ulcerative colitis and Crohn's disease, granulomatosis with polyangiitis, adrenocortical insufficiency, hypercalcemia due to cancer, thyroiditis, laryngitis, severe tuberculosis, hives, eczema, lipid pneumonitis, pericarditis, multiple sclerosis, nephrotic syndrome, sarcoidosis, to relieve the effects of shingles, lupus, myasthenia gravis, poison oak exposure, Ménière's disease, autoimmune hepatitis, giant cell arteritis, the Herxheimer reaction that is common during the treatment of syphilis, Duchenne muscular dystrophy, uveitis, and as part of a drug regimen to prevent rejection after organ transplant. Prednisone is used as an antitumor drug.

Prednisone is often also prescribed as a form of treatment for sudden sensorineural hearing loss (SSNHL).

Prednisone can be used in the treatment of decompensated heart failure to increase renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. In terms of the mechanism of action for this purpose: prednisone, a glucocorticoid, can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, thereby inducing a potent diuresis.

At high doses, it may be used to prevent rejection following an organ transplant. The mineralocorticoid effects of prednisone are minor, which is why it is not used in the management of adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly.

It can also cause depression or depressive symptoms and anxiety in some individuals.

Long-term side effects include Cushing's syndrome, steroid dementia syndrome, truncal weight gain, glaucoma and cataracts, diabetes mellitus type 2, and depression upon dose reduction or cessation. Long-term steroids can also increase the risk of osteoporosis, but research has found that few of these people were taking medications to protect bones. Prednisone also results in leukocytosis.

Major

Source:

Unusual fatigue or weakness
Mental confusion
Memory and attention dysfunction (steroid dementia syndrome)
Muscle atrophy
Blurred vision
Abdominal pain
Peptic ulcer
Painful hips or shoulders
Steroid-induced osteoporosis
Stretch marks
Osteonecrosis – same as avascular necrosis
Insomnia
Severe joint pain
Cataracts or glaucoma
Anxiety
Black stool
Stomach pain or bloating
Severe swelling
Mouth sores or dry mouth
Avascular necrosis
Hepatic steatosis
Hiccups and burping
Weakening and breakage of tendons

Minor

Source: if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addisonian crisis. For those on chronic therapy, alternate-day dosing may preserve adrenal function and thereby reduce side effects.

Glucocorticoids act to inhibit feedback of both the hypothalamus, decreasing corticotropin-releasing hormone (CRH), and corticotrophs in the anterior pituitary gland, decreasing the amount of adrenocorticotropic hormone (ACTH). For this reason, glucocorticoid analogue drugs such as prednisone down-regulate the natural synthesis of glucocorticoids. This mechanism leads to dependence in a short time and can be dangerous if medications are withdrawn too quickly. The body must have time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again.

Prednisone may start to result in the suppression of the hypothalamic–pituitary–adrenal (HPA) axis if used at doses 7–10 mg or higher for several weeks. This is approximately equal to the amount of endogenous cortisol produced by the body every day. As such, the HPA axis starts to become suppressed and atrophy. If this occurs the patient should be tapered off prednisone slowly to give the adrenal gland enough time to regain its function and endogenous production of steroids.

Withdrawal

The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:

received more than 40 mg prednisone (or equivalent) daily for more than one week
been given repeat doses in the evening
received more than three weeks of treatment
recently received repeated courses (particularly if taken for longer than three weeks)
taken a short course within one year of stopping long-term therapy
other possible causes of adrenal suppression

Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse who have received treatment for three weeks or less and who are not included in the patient groups described above.

During corticosteroid withdrawal, the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.

Pharmacology

Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties. Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone.

Pharmacokinetics

Prednisone is absorbed in the gastrointestinal tract and has a half-life of 2–3 hours. The drug is cleared by hepatic metabolism using cytochrome P450 enzymes. Metabolites are excreted in the bile and urine.

Industry

thumb|Prednisone 20 mg oral tablet

The pharmaceutical industry uses prednisone tablets for the calibration of dissolution testing equipment according to the United States Pharmacopeia (USP).

Chemistry

Prednisone is a synthetic pregnane corticosteroid and derivative of cortisone and is also known as δ<sup>1</sup>-cortisone or 1,2-dehydrocortisone or as 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione.

History

The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile. The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation, by Arthur Nobile and coworkers. They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone.

The enhanced adrenocorticoid activity of these compounds over cortisone and hydrocortisone was demonstrated in mice. and Delta-Cortef, respectively.

Research

Fibromyalgia

One small study found that prednisone was ineffective in the treatment of fibromyalgia and that there was actually a trend towards deterioration.