Prednisone

Not to be confused with Prednisolone.

Prednisone

Systematic (IUPAC) name
17,21-dihydroxypregna-1,4-diene-3,11,20-trione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a601102
Pregnancy category	C
Legal status	Rx Only (US)(AUS)
Routes of administration	Oral, Nasal, Rectal, Injection, IV
Pharmacokinetic data
Bioavailability	70%
Metabolism	prednisolone (liver)
Biological half-life	Biological half-life of prednisone is 18 to 36 hours.
Excretion	Renal
Identifiers
CAS Number	53-03-2 Y
ATC code	A07EA03 (WHO) H02AB07
PubChem	CID: 5865
IUPHAR/BPS	7096
DrugBank	DB00635 Y
ChemSpider	5656 Y
UNII	VB0R961HZT N
KEGG	C07370 Y
ChEBI	CHEBI:8382 Y
ChEMBL	CHEMBL635 Y
Synonyms	Deltasone, Liquid Pred, Orasone, Adasone, Deltacortisone, Prednisonum
Chemical data
Formula	C21H26O5
Molecular mass	358.428 g/mol
SMILES O=C(CO)[C@@]3(O)CC[C@H]2[C@@H]4CC\C1=C\C(=O)\C=C/[C@]1(C)[C@H]4C(=O)C[C@@]23C
InChI InChI=1S/C21H26O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-15,18,22,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1 Y Key:XOFYZVNMUHMLCC-ZPOLXVRWSA-N Y
NY (what is this?)  (verify)

Micrograph of fatty liver, as may be seen due to long-term prednisone use. Trichrome stain.

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases (such as moderate allergic reactions), some autoimmune diseases, and (at higher doses) some types of cancer, but it has significant adverse effects.

Medical uses

Prednisone is used for many different indications including: asthma, COPD, CIDP, rheumatic disorders, allergic disorders, ulcerative colitis and Crohn's disease, adrenocortical insufficiency, hypercalcemia due to cancer, thyroiditis, laryngitis, severe tuberculosis, urticaria (hives), lipid pneumonitis, pericarditis, multiple sclerosis, nephrotic syndrome, to relieve the effects of Shingles, lupus, myasthenia gravis, poison oak exposure, Meniere's disease, and as part of a drug regimen to prevent rejection after organ transplant.

Prednisone has also been used in the treatment of migraine headaches and cluster headaches and for severe aphthous ulcer. Prednisone is used as an antitumor drug. It is important in the treatment of acute lymphoblastic leukemia, non-Hodgkin lymphomas, Hodgkin's lymphoma, multiple myeloma, and other hormone-sensitive tumors, in combination with other anticancer drugs.

Prednisone is also used for the treatment of the Herxheimer reaction, which is common during the treatment of syphilis, and to delay the onset of symptoms of Duchenne muscular dystrophy and also for uveitis. The mechanism for the delay of symptoms is unknown. Because it suppresses the adrenal glands, it is also sometimes used in the treatment of congenital adrenal hyperplasia. Prednisone is also used to treat sarcoidosis.

Prednisone can also be used in the treatment of decompensated heart failure to potentiate renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large dose 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, inducing a potent diuresis.

Side effects

Short-term side effects, as with all glucocorticoids, include high blood glucose levels (especially in patients with diabetes mellitus or on other medications that increase blood glucose, such as tacrolimus) and mineralocorticoid effects such as fluid retention. 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, osteoporosis, glaucoma and cataracts, type II diabetes mellitus, and depression upon dose reduction or cessation.

Major

• Increased blood sugar for diabetics
• Difficulty controlling emotion
• Difficulty in maintaining train of thought
• Weight gain
• Immunosuppression
• Facial swelling. Severe.
• Depression, mania, psychosis, or other psychiatric symptoms
• Unusual fatigue or weakness
• Mental confusion / indecisiveness
• Memory and attention dysfunction (Steroid dementia syndrome)
• 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

Minor

• Nervousness
• Acne
• Skin rash
• Appetite gain
• Hyperactivity
• Increased thirst
• Frequent urination
• Diarrhea
• Reduced intestinal flora
• Leg pain/cramps
• Sensitive teeth

Dependency

Adrenal suppression will begin to occur if prednisone is taken for longer than seven days. Eventually, this may cause the body to temporarily lose the ability to manufacture natural corticosteroids (especially cortisol), which results in dependence on prednisone. For this reason, prednisone should not be abruptly stopped if taken for more than seven days; instead, the dosage should be gradually reduced. This weaning process may be over a few days, if the course of prednisone was short, but may take weeks or months if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addison 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.

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 prednisolone (or equivalent) daily for more than 1 week
• been given repeat doses in the evening;
• received more than 3 weeks' treatment
• recently received repeated courses (particularly if taken for longer than 3 weeks)
• taken a short course within 1 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 and who have received treatment for 3 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 has no substantial biological effects until converted via hepatic metabolism to prednisolone.

Industry

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).

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.

Prednisone and prednisolone were introduced in 1955 by Schering and Upjohn, under the brand names Meticorten and Delta-Cortef, respectively. These prescription medicines are now available from a number of manufacturers as generic drugs.

See also

• Chloroprednisone

External links

• National Inventors Hall of Fame induction of Arthur Nobile
• U.S. National Library of Medicine: Drug Information Portal - Prednisone
• The National Center for Biotechnology Information: Prednisone