Synthetic steroids

Prednisilone

In general, serious toxicity with prednisilone starts at 7.5 mg/day.  Moreover, the need for high doses of 1 mg/kg/day in severe autoimmune activity is now being questioned, since much lower doses seem as effective. Pulse methylprednisolone, 500 mg/day, during three consecutive days, is a potent therapy for severe flares (with few side effects).

Medrol (prednisilone) comes in 2, 4, 8, 16, 24 and 32 mg tablets.  Medrol is also injectable at: 20, 40, and 80 mg/ml.  Medrol can be prescribed at various daily doses or as alternate days.  

GC doses can be clustered: low doses are ≤7.5 mg of prednisone-equivalent; medium doses are 7.5-30 mg; high doses are 30-100 mg prednisone-equivalent per day; very high doses >100 mg; when doses are >250 mg of prednisone-equivalent per day for few days, usually no more than 5 days, it is called pulse therapy.

The typical Medrol dosepak is 4 mg tablets given over 6 days in decreasing dosages. 

• Day 1: 2 tablets before breakfast, 1 tablet after lunch, 1 tablet after dinner, 2 tablets at bedtime;
• Day 2: 1 tablet before breakfast, 1 tablet after lunch, 1 tablet after dinner, 2 tablets at bedtime;
• Day 3: 1 tablet before breakfast, 1 tablet after lunch, 1 tablet after dinner, 1 tablet at bedtime;
• Day 4: 1 tablet before breakfast, 1 tablet after lunch, 1 tablet at bedtime;
• Day 5: 1 tablet before breakfast, 1 tablet at bedtime;
• Day 6: 1 tablet before breakfast.

Prednisone and other anti-inflammatory steroids are very different from testosterone and other sex steroids (but people often feel better).  

Dexamethasone (within 18 hours) induces increase in endocytic activity, which favors the scavenging of antigen from the external milieu, decreasing antigen concentration and availability, and simultaneously inhibiting the capacity to stimulate T cells.

Prednisone suppresses immune response, and is medically used when immunity attacks healthy cells (friendly fire).  Steroids are used in asthma, MS, poison ivy, polymyalgia rheumatica, inflamed nerves, rheumatoid arthritis, lupus and many other diseases.

Dexamethasone, a synthetic GC, is a multi-ring structure with an added fluorine.  Fluorine increases drug potency by slowing metabolism and also increases the affinity of dexamethasone for its receptor.

Just as aspirin suppresses prostaglandins everywhere, anti-inflammatory steroids reduce immune response in every organ, beginning with inhibiting movement of white blood cells through capillary walls to attack infections and less surveillance of any fungi or other chronic infection that is being kept in check. 

It is important to be aware that steroids have many effects and to protect against the negative.  Otherwise, like Eleanor Roosevelt, prolonged overuse can cause death (from overwhelming TB, parasite infection and/or adrenal failure).  As a doctor, trained in the 1960s, I always feared steroids.  (Now, I know why: the president's wife.)

Many are infected with TB without knowing.  With a robust immune system, one generally confines live TB to the lungs. But with enough prednisone for long enough, then immune surveillance of the live TB is suppressed, TB germs multiply, and they can spread and kill. 

Before you start on an oral steroid, skin test for TB, and treat with isoniazid or other anti-tubercular if your skin test is positive for as long as you take the steroid.  

Strongyloides is a common intestinal parasite.  This nematode fastens to the distal colon, and its reproduction and spreading is kept in check by our immunity.  Giardia lamblia and Entamoeba histolytica are common protozoans.  Their effects vary from no symptoms as carrier to severe GI disease with malabsorption in giardiasis, or amoebic colitis.

Do albendazole or herbal treatments for intestinal parasites when beginning steroids before attempting to kill systemic parasites. 

Praziquantel is the treatment of choice for systemic helminths.  Prazquantel gets everywhere and even crosses the BBB.  Take steroids first to inhibit any further inflammatory damage from 'friendly fire' (to the nervous system) triggered by their dead bodies, their stressed biofilm or their eggs (that have hooks).  

Helminth worms use suckers to adhere to the wall of the blood vessel, where they can live for up to 30 years.  If the flukes have invaded the CNS, loss of balance or coordination may result, then steroids are given as well in order to reduce the inflammatory response.  Invasion of our CNS is too close for comfort, and must be taken seriously.

Unappealing as parasitic infestations are, mostly these infections go unnoticed.  It is normal to live a long time with a worm or other parasite.  Symptoms often lead to a surgery (on knee, ankle, elbow or low back) or hernia repair.  

Taking steroids also reduces immunity that keeps live viruses under active suppression.  With a live virus vaccine (mumps, rubella, oral polio, yellow fever) or an active herpes infection, steroids are deferred until one month after the vaccine or until the infection has cleared.  Theoretically, one would also defer any steroids because of a bacterial problem, like acute diverticulitis or root canal tooth.

The GCs produced by the body are called cortisone and hydrocortisone and they help to control metabolism (the chemical reactions that convert fuel from food into energy). During the day, when active, there are more GCs made. During the night, or sleep, there are less GCs produced.

The body's normal production of cortisone is about 5-10 mg/day, cortisol rhythm has much diurnal variation, it peaks around 5 AM.  The secretion of cortisone is controlled by a feedback loop to the pituitary, which secretes ACTH to stimulate cortisone.  

GCs make you feel better (about yourself).  They provide a 'sense of well-being'.  In some people with large doses of GC can result in becoming enthusiastically over-active, along with difficulty sleeping.

When one feels threatened, the adrenal glands can increase secretion 1,000X.

When taking enough steroids for long enough, then the pituitary gets so suppressed that when you stop, the pituitary has lost its ability to make ACTH, so when your body is stressed (by an infection), the adrenals can't make "stress amounts" of cortisone and death ensues.

Use of high-dose steroids for more than a week begins to produce suppression of the adrenal glands because the exogenous GCs lower CNS hypothalamic cortico-tropin releasing and pituitary adrenocorticotropic (ACTH) hormones.  

Prolonged taking of steroids at supra-physiologic doses causes suppression.  The adrenal glands (and their circuitry) literally atrophy (undergo apoptosis and shrink like inactive muscles).  Full robust recovery can take months.

GCs cause immune suppression, and the therapeutic part of this effect is mainly decreases in the function and numbers of both B and T lymphocytes.

GCs act in part by inducing the synthesis of IkBa, a protein that traps and thereby inactivates NF-kb (an activator of cytokine genes and a mediator of the proinflammatory action of tumor necrosis factor). Pulsed GCs may impair cytokine generation.

GCs also have direct effect upon cell membranes. In very high doses, GCs dissolve in cell membranes, thereby altering their physicochemical properties and the activities of membrane-associated proteins, which may explain why only high doses are effective in treating acute exacerbations of immunologically-mediated diseases.

GCs inhibit NF-kb (enhancer of activated B cells). Inhibition of NF-kb blunts the capacity of the immune system to mount a response. GCs suppress cell-mediated immunity by inhibiting genes that code for the cytokines Il-1, 2, 3, 4, 5, 6, 8 and IFN-γ, the most important of which is IL-2.  Less cytokine production reduces T cells.

GCs not only reduce T cell proliferation, but also lead to GC-induced apoptosis. The effect is more prominent in immature T cells still inside in the thymus, but peripheral T cells are affected as well.

GCs also suppress humoral immunity.  GCs cause B cells to express less IL-2 and IL-2 receptors, which diminishes both B cell clone expansion and antibody synthesis. Less IL-2 also causes less T lymphocyte activation.

Since GCs  are steroids, they regulate transcription; but GCs also lessen  Fc receptors on macrophages, which decreases phagocytosis.