Anyone's who's benefited from corticosteriods-a cortisone injection,say,or predisone therapy,can  thank those women with RA who reported an improvement in their symptoms in pregnancy. That observation led to the discovery of cortisol and cortisone,powerful hormones secreated by the adrenal cortes,the outer portion of the adrenal glands,by American Dr. Phillip Hench and two researchers. (They shared the 1950 Nobel Prize for their work ). Their findings led the development of corticosteriods,among the most potent anti-inflammatory drugs available. In the body,cortisol and cortisone perform various "housekeeping tasks";they play an important role in maintaining the body's salt and water balance,exert regulatory control over carbohydrate,fat,and protein metabolism,and control routine inflammation from cuts,bruises,and other minor injuries. They're a key part of the body's stress management system:
 
Prednisone is an oral, synthetic (man-made) corticosteroid used for suppressing the immune system and inflammation. It has effects similar to other corticosteroids such as triamcinolone (Kenacort), methylprednisolone (Medrol), prednisolone (Prelone) and dexamethasone (Decadron). These synthetic corticosteroids mimic the action of cortisol (hydrocortisone), the naturally-occurring corticosteroid produced in the body by the adrenal glands. Corticosteroids have many effects on the body, but they most often are used for their potent anti-inflammatory effects, particularly in those conditions in which the immune system plays an important role.
 
Such conditions include arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. Prednisone is inactive in the body and, in order to be effective, first must be converted to prednisolone by enzymes in the liver. Therefore, prednisone may not work as effectively in people with liver disease whose ability to convert prednisone to prednisolone is impaired
 
Predisone is a prescription medication available in generic form and available in  tablets of 2.5, 5, 10, 20, and 50 mg. Oral solution or syrup of 5mg/5ml Store at room temperature 20-25°C (68-77°F), and keep away from moisture. Prednisone is used in the management of inflammatory conditions or diseases in which the immune system plays an important role. Since prednisone is used in so many conditions, only the most common or established uses are mentioned here.
 
Prednisone most often is used for treating several types of arthritis, ulcerative colitis, Crohns disease, systemic lupus, allergic reactions, asthma and severe psoriasis. It also is used for treating leukemias, lymphomas, idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. Corticosteroids, including prednisone, are commonly used to suppress the immune system and prevent the body from rejecting transplanted organs. Prednisone is used as replacement therapy in patients whose adrenal glands are unable to produce sufficient amounts of cortisol.
 
The initial dose of prednisone varies depending on the condition being treated and the age of the patient. The starting dose may be from 5 to 60 mg per day and often is adjusted based on the response of the condition being treated. Corticosteroids typically do not produce immediate effects and must be used for several days before maximal effects are seen. It may take much longer before conditions respond to treatment. Prolonged therapy with prednisone causes the adrenal glands to atrophy and stop producing cortisol. When prednisone is discontinued after a period of prolonged therapy, the dose of prednisone must be tapered (lowered gradually) to allow the adrenal glands time to recover. It is recommended that prednisone be taken with food.  Prednisone may interact with estrogens and phenytoin (Dilantin). Estrogens may reduce the action of enzymes in the liver that break down (eliminate) the active form of prednisone, prednisolone. As a result, the levels of prednisolone in the body may increase and lead to more frequent side effects.
 
Phenytoin increases the activity of enzymes in the liver that break down (eliminate) prednisone and thereby may reduce the effectiveness of prednisone. Thus, if phenytoin is being taken, an increased dose of prednisone may be required. Corticosteroids cross the placenta into the fetus. Compared to other corticosteroids, however, prednisone is less likely to cross the placenta. Chronic use of corticosteroids during the first trimester of pregnancy may cause cleft palate.  Corticosteroids are secreted in breast milk and can cause side effects in the nursing infant. Prednisone is less likely than other corticosteroids to be secreted in breast milk, but it may still pose a risk to the infant.
 
Side effects of prednisone and other corticosteroids range from mild annoyances to serious, irreversible damage, and they occur more frequently with higher doses and more prolonged treatment. Side effects include retention of sodium (salt) and fluid, weight gain, high blood pressure, loss of potassium, headache and muscle weakness. Prednisone MAY cause  puffiness of the face (moon face), growth of facial hair, thinning and easy bruising of the skin, impaired wound healing, glaucoma, cataracts, ulcers in the stomach and duodenum, worsening of diabetes, irregular menses, rounding of the upper back (buffalo hump), obesity, retardation of growth in children, convulsions, and psychiatric disturbances. The psychiatric disturbances include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior.
 
Prednisone suppresses the immune system and, therefore, increases the frequency or severity of infections and decreases the effectiveness of vaccines and antibiotics. Prednisone may cause osteoporosis that results in fractures of bones. Patients taking long-term prednisone often receive supplements of calcium and vitamin D to counteract the effects on bones. Calcium and vitamin D probably are not enough, however, and treatment with bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) may be necessary. Calcitonin (Miacalcin) also is effective. The development of osteoporosis and the need for treatment can be monitored using bone density scans.
 
The major reason that prednisone is tapered, rather than simply discontinued, is that prednisone when taken for an extended period of time, can suppress the ability of the adrenal glands to produce natural cortisone. This is because the adrenal glands can shrink (atrophy) when chronically exposed to prednisone. When our bodies can't make natural cortisone, it can lead to low blood pressure, nausea, vomiting, dizziness, and abdominal pain. This is called adrenal insufficiency. Slow tapering of prednisone minimizes the risk of adrenal insufficiency. Some people also develop muscle and/or joint aching (called steroid withdrawal symptoms) when prednisone is tapered too rapidly or discontinued suddenly.

Corticosteriods are the most powerful anti-inflammatory drugs we have. Were it not for their side effects we would use them much more freely. They are essentil in the treatment of some forms of arthritis,such as systemic lupus erythematosus and polymyalgia rheumatica,where the decision to use them is taken with full knowledge of the risks invoved (patients react more favourable to these medications). They are also widely used,over the short term or in low doses in which the risk of side effects is minimized,to supplement the main treatment in several other conditions.
 
Rheumatoid arthritis is a good example of such a condition. Problems with corticosteriods are of two types-those arising from using doses higher than the amount the body normally makes each day ( about 7.5 mg ),and those arising from the sudden withdrawal of the medication. The likelihood,and severity,of both are directly related to the size of the daily dose and the length of time it is given. When the dose of predisone ( or another similar synthetic corticosteriod ) exceeds 7.5 milligrams a day for more the a few weeks or months,signs of hypercortisonism begin to develop. Cushing's syndrome,a disease state where the adrenal glands produce cortisol in excess and develops hypercortisonism is identical.
 
Fully developed,hypercortisonism may include any or all of the following features : Increased appetite and weight gain,especially on the trunk and face. A chubby face is typical of someone on high-dose,long-term predisone. Easy brusing and skin fragility of the arms and legs,especially in older people. Cataract development. Mood changes. Mild euphoria is common,but depression may occur. Insomnia is frequent. High blood pressure. Extra insulin required by diabetics because of higher blood sugars,and pre-diabetics becoming overtly diabetic. Stomach ulcers,if the patient is taking NSAIDs at the same time. Stunting of growth in children.
 
Osteonecrosis is is a specific type of dead bone,the kind that results when an area of bone loses its blood supply. If this happens near a joint-and the hip is a favorite target-the area of dead bone may collapse-ending up in surgery and a total hip replacement. Cortisone-like drugs have been seen for a long time responsible for osteonecrosis,although this is hard to prove. Fortunately, osteonecrosis from predisone is very rare.
 
Crohn's disease and Lupus patients use corticosteriod more,and it may be responsible. for osteonecrosis. in patient's who develop it. There is no question that the long term use of predisone in SLE increases the risk of hardening of the arteries and,in particular,coronary artery disease. These condition increase the risk of stroke and heart attack, sub -stantially there is some debate as to whether or not predisone has the same effect in RA
 
Osteoprorosis; Bone is a living tissue. Old bone is continually being broken down,in patches. This process is followed almost immediately by the laying down of new bone by bone-forming cells. The new processes of breakdown and repair exceeds repair,bone mass (solidity ) is reduced. Thuis is called osteoporosis. Between 10 and 20 % of all patients with RA,who are on long-term corticosteriods,will experience crush fractures of one or more vertebrae in the backbone. The risk of hip fracture in these patients is 50 %.
 
This risk of fracture can be estimated in any patient,on corticosteriods or not,by measuring bone mineral density (DEXA-dual energy X-ray absorptiometry ). Ordinary x-ray won't do-up to half of bone bass must be lost before they will detect the loss. Bone breakdown continues at a constant rate throughout life. The rate of bone repair,slows down in older people. It also slows in those who are physically inactive,in postmenopausal women with the drop in estrogen production,and in those who get inadequate supplies of calcium and vitamin D. Often,many of these factors are combined.
 
Corticosteriods magnify problems in bone repair. They can cause osteoporosis in anyone,young or old,but the effect is obvious in post-menopausal women (who already exhibit many of the osteoporosis risk factors ). They do this quite quickly,particularily within the first 6 to 12 months of treatment.
 
Corticosteriods affects several elements in bone repair. The amount of calcium available for new bone formation is reduced. They both slow dietary calcium absorption in the intestine and speed its removal from blood by the kidney. They stimulate the bone cells that promote bone breakdown and inhibit the bone cells that promote bone growth.  What this means is that every patient who is started on predisone for anything, but a very short period should also be atarted on an anti-osteoporosis program.
 
If the patient is a post-menopausal woman,replacement estrogen should be seriously considered. Raloxifene is an alternative to estrogen,although it doesn't help menopausal symptoms like hot-flashes It does resemble estrogen in its beneficial effects on bone,yet if there is a fear of uterus or breast cancer,it does not affect the lining of the uterus or breast tissue. A regular program of aerobic physical activity should be designed with the assistance of a physiotherapist, keeping the problems imposed by arthritis in mind.
 
A daily intake of at least 1,000 milligrams should be achieved. One cup of milk will provide 300 milligrams,a cup of yogurt about 400 milligrams. Calcium-containing antacid tablets are another inexpensive souce. A low dose (800 or 900 units ) of vitamin D daily is desirable. Vitamin D is essential to normal bone development. People who are elderly or housebound are very often vitamin D deficient,and have a increased risk of fracture.
 
If it is likely that prednisone will be needed for more than a few weeks,a bisphosphonate can be used to slow bone breakdown. Etidronate,alendronate and pamidronate are bisphosphonates. They have been proved effective in both the prevention and the treatment of osteoporosis. Your physician will decide what is best for you. Regrettably,it is not always possible to avoid corticosteriods. Your doctor will use the lowest dose necessary to maintain efficacy with the shortest possible period in mind.

 

Osteoporosis is characterized by a decrease in bone mass and a deterioration in skeletal microarchitecture, which lead to increased fragility and susceptibility to fractures. In treating established osteoporosis, the objective is to prevent further skeletal deterioration, and to increase bone mass and/or improve bone microarchitecture to reduce the risk of vertebral and/or peripheral fractures.

 

One of the major determinants of skeletal weakness is bone loss that occurs after menopause. The bone loss is a consequence of an increased osteoclastic resorption that is only partially compensated by a moderate rise in the rate of bone formation by osteoblasts. Estrogens calcitonin,and early-generation bisphosphonates were considered effective and well-tolerated agents for maintaining bone mineral density (BMD) of trabecular and cortical bone at premenopausal levels by counteracting the exacerbated activity of osteoclasts induced by the sharp postmenopausal decrease in circulating endogenous estrogens. However, primary prevention of osteoporosis initiated in the immediate postmenopause is not yet considered a public health priority by many, including specialists dealing with bone metabolic disorders, primary care physicians, and the general population. Subsequently, caregivers often face complicated situations with women seeking treatment for the first time at later stages of the disease, namely, after the diagnosis of osteoporosis has already been made on the basis of random radiographs, densitometry, measurements, or, even worse, a clinical fracture.
 
None of the available medications has unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Furthermore, some of these agents are jeopardized by either potential severe toxicity or prohibitive cost, discouraging their widespread or prolonged use. Therefore, new medications are developed with the goal of meeting a better risk-to-benefit (efficacy vs tolerance) ratio in comparison with available medications. As cortisone and pharmaceuticals made in the laboratory to mimic cortisone's effects were used to fight RA as well as other coditions like asthma, lupus, serious drawbacks soon became apparent the unmistakable relief from pain and suffering wrought by large doses of these medications for extended periods of time inflicts a range of serious side effects including diabetes, dangerously high blood pressure,weight gain,thinning of bones (opsteoporosis) to the point where they fracture easily,infections and depression. It was soon evident that a balance had to be struck between the real benefits and the real dangers of these hormones. 

 

Over the intervening years a debate has continued over the use of glucocorticoids. When should they be administered,how much,and for how long ? Do they really slow down the progression of damage in the joints ? Pharmaceutical companies have created synetic forms of these hormones,such as the commonly used predisone,four times as potent as cortisone,and dexamethasone,thirty times more potent. As the debate goes on in medical journals and at conferences,in their day-to-day practise most physicians use cort-predisone,to calm down the pain,swelling,and inflammation in order to improve "quality of life" Because of the potentially devastating effects of cortisone there are general guidlines for its use. When NSAIDs are not able to control symptoms,and DMARDs like methotrexate are given but have not yet taken effect,low doses of glucocorticoid tablets can halt the symptoms in the interim. This is called bridge therapy. Sometimes when neither the combination of NSAIDs or DMARDs is effective,physicians add low doses of glucocorticoids to the mix..

 

 Ideally,one uses the lowest effective dose for the shortest possible time. Sometimes, severe complications of RA require much higher doses. Glucocorticoids also are injected directly into very swollen,painful joints giving relief for several weeks, without wide-ranging side-effects. Research published in 1999 offered some encouraging news, People taking 5 milligrams of the synthetic glucocorticoid predisolone for two years showed a sustained improvement of disease symptoms,and had no significant bone loss. Recent studies also have revealed some of the "unknowns" why glucicirticoids have good anti-inflammatory effects. E.g.,-When cortisone and its synthetic forms like predisone or predisonisolone come in contact with cells,that meeting turns on certain cells so that they make anti-inflammatory proteins,and it turns off other genes that are making inflammatory substance.

 

There were several reasons why these valid observations were not heeded. Treatment guidelines by authoritative bodies were not available. The Physicians Desk Reference of the day did not (and still does not) provide guidance regarding dosage. Physicians were guided by their own experience and ideas and frequently used high doses of glucocorticoids and continued to administer high doses. In most cases, side effects dominated any beneficial effects. This practice resulted in a loss of confidence in glucocorticoids in both physicians and patients.
 
Forty to fifty years ago it was thought that the effect of glucocorticoids was as a potent anti-inflammatory agent similar to aspirin but with more side effects. As pharmaceutical efforts were made to develop a safe glucocorticoid substitute, the term NSAID (nonsteroidal anti-inflammatory drug) was coined. A succession of NSAIDs were developed that were thought to act like steroids with fewer side effects. The NSAIDs dominated the market for more than 25 years.

 

Prednisone has the same COX-2 inhibiting effects as the NSAIDs. In addition, it has many more effects resulting in clinical improvement and bone damage sparing. A clinical example is provided in a study examining cytokine production by CD4 and CD8 lymphocytes before and after 1 year of treatment with methotrexate and prednisone (5 to 10 mg/day). There was a decrease in gamma-interferon and interleukin (IL)-l production and an increase in IL-4 production. Prednisone was responsible for part of this effect.