Use Corticosteroids On Your Canine With Caution
Depending on the situation, these drugs can save lives, or threaten them.
by Randy Kidd, DVM, PhD
Corticosteroids are perhaps the most enigmatic of all the drugs in the western medicine man’s arsenal. It has been said by many practitioners that they are the most used and most abused of all our medicines. Corticosteroids are a necessary component of a healthy physiology and they can be life saving ... or they can cause multiple adverse side effects that can be devastating to a dog’s health and well-being. Since this class of biochemicals affects nearly all cells of the body, their beneficial effects can be widespread – and their adverse effects may be totally debilitating and long-lasting.
So who are these guys that can seemingly wear both white and black hats at the same time?
What they are
Naturally occurring corticosteroids are a class of steroid hormones that are produced in the cortex (thus the “cortico” prefix) of the adrenal gland. The adrenal medulla (inner part) manufactures epinephrine and norepinephrine, the hormones responsible for the “fight or flight” reaction, among other functions. Corticosteroids are made from the same steroidal chemical base that also produces the male and female sex hormones and the androgenic steroids made famous by athletes who want to enhance their muscle mass. However, the corticosteroids are slightly different from the androgenic and sex hormones in their chemical structure, and they are very different in the ways they affect the body.
Corticosteroids are further divided into two major classes of compounds: mineralocorticoids and glucocorticoids.
Mineralocorticoids are a vital component of the body’s hormonal balancing system, even though they make up only a small portion of the overall mix of the corticosteroids in the body. Mineralocorticoids function in the kidney (in the distal tubules) where they stimulate the exchange of sodium and potassium – increasing renal excretion of potassium and increasing resorption of sodium, which in turn helps maintain the body’s water balance by increasing resorption of water.
The principle steroid with mineralocorticoid activity is aldosterone. Cortisol, the major “natural” glucocorticoid in dogs (and other non-rodent species) has weak mineralocorticoid activity. But in the natural state, cortisol’s mineralocorticoid activity is of some importance because, in the healthy animal, there is so much more cortisol secreted than aldosterone.
The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. The vast majority of glucocorticoid activity in most mammals is from cortisol, also known as hydrocortisone.
Since synthetic glucocorticoids are used extensively in veterinary therapy, this article will focus on them.
Activities of glucocorticoids
Glucocorticoids (especially cortisol, the predominant natural glucocorticoid) stimulate several processes that collectively serve to increase and maintain natural conversion of glucose. These effects include:
• Stimulation of gluconeogenesis, the synthesis of glucose from other sources such as amino acids (protein building blocks) and lipids (fats). Glucocorticoids stimulate the enzymes that enhance this process, especially in the liver.
• Mobilization of amino acids from tissues, generating a substrate for gluconeo-genesis.
• Inhibition of glucose uptake in muscle and fatty tissue, thus conserving glucose.
• Stimulation of fat breakdown, releasing fatty acids, which provides energy to various tissues and adds more substrate for gluconeogenesis.
Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. These are the primary medicinal uses of the glucocorticoids and will be discussed more fully below.
Glucocorticoids also have multiple effects on fetal development, including their role in promoting maturation of the lung and production of the surfactant necessary for lung function immediately after birth.
Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism (Cushing’s disease) have effects on many systems. Just a few of the examples include inhibition of bone formation, suppression of calcium absorption, and delayed wound healing. Note that these effects suggest that there probably are many physiologic roles for the glucocorticoids that we are not yet fully aware of. Also note that these effects can occur from drug administration, and most of them are ultimately detrimental to health and healing.
Insufficient production of cortisol is called Addison’s disease (or hypoadreno-corticism). This disease may be caused by autoimmune destruction of the adrenal cortex or as the result of infectious disease and is often accompanied by an aldosterone deficiency. Aldosterone deficiency can be acutely life threatening, causing severe electrolyte imbalance and loss of normal cardiac function. Other signs of Addison’s disease include weakness and lethargy, diarrhea, and cardiovascular disease.
Control of cortisol secretion
Cortisol and other glucocorticoids are se-creted in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. The secretion of ACTH is in turn under the control of the brain’s hypothalamic peptide, corticotrophin-releasing hormone (CRH), creating a classic hypothalamic-pituitary-adrenal axis of control over the ultimate secretion of the glucocorticoids. It is important to recognize that, in the natural state, the brain (hypothalamus) is the primary controlling organ, and whenever the animal is stressed, there will be increased production of cortisol.
Any form of glucocorticoid (whether drug-induced or endogenous – from stress, for example) exerts a negative feedback on this axis and shuts down further secretion of the glucocorticoids. The negative feedback mechanism is medically important because after shutdown, the axis may take several days to gear up again to a normally functioning level.
Effects on inflammation and immune function
From the medical perspective and certainly from the holistic perspective, the most important thing to realize about the very potent anti-inflammatory and immunosuppressive properties of the glucocorticoids is that there is absolutely no way to separate these two properties.
Whenever the glucocorticoids are administered (or produced naturally), the result will be a combination of anti-inflammatory and immunosuppressive activities. Thus, using glucocorticoids is always a balancing act; the multiple actions of glucocorticoids simultaneously allow for beneficial and adverse effects.
The anti-inflammatory activity of gluco-corticoids is primarily directed toward inhibiting the production of arachidonic acid, which in turn inhibits the production of inflammation-causing prostaglandins and leukotrienes. Nonsteroidal anti-inflammatory drugs (NSAIDS) also inhibit prostaglandins (by inhibiting a later enzyme in the cascade, cyclooxygenase), but not leukotrienes.
The immunologic activity of the glucocorticoids is directed primarily toward the cellular component of the immune system: monocyte phagocytic function and cytokine production. Some lymphocytes may be destroyed by the glucocorticoids, particularly neoplastic (tumor-inducing) and activated lymphocytes. These effects can be either beneficial (e.g., treating immune-mediated conditions or some lymphocytic cancers) or detrimental (e.g., impairing the body’s defenses against fungal, viral, and bacterial infections).
In what may be an overlapping function (anti-inflammatory and immunosuppressive), glucocorticoids produce the classic “stress leukogram,” a white blood cell (WBC) picture of increased mature neutrophils, decreased lymphocytes and eosinophils, and variable increases in monocytes.
Pharmacologic uses of the glucocorticoids
Glucocorticoids are commercially available in a variety of forms for either systemic (oral tablets or liquids and injectables) or topical use, and the relative potency and duration of action of these products varies widely.
If we assume the potency of cortisone (the natural glucocorticoid produced by the dog’s adrenal) to be “1,” relative potencies of commercial products may be 5-6 times as potent (prednisone, prednisolone, methylprednisolone, triamcinolone), and even as much as 40 times as potent (dexa-methasone and betamethasone).
We can also categorize commercially available glucocorticoid products based on the length of time they suppress the hypothalamic-pituitary-adrenal axis. On average, short-acting glucocorticoids (hydrocortisone and cortisone, the naturally-produced glucocorticoids) suppress the hypothalamic-pituitary-adrenal axis less than 12 hours; the suppressive activity of long-acting glucocorticoids (dexamethasone and betamethasone) lasts more than 48 hours, and in many cases, the exact duration in dogs is not known. Intermediate-acting products (prednisone, prednisolone, methylprednisolone, and triamcinolone) fall somewhere in between.
Commercial products have variable mineralocorticoid activities when compared to cortisone or hydrocortisone. Prednisone and prednisolone, for example, have about half the mineralocorticoid activity of the natural glucocorticoids, and most other synthetic products have almost none.
Some synthetic glucocorticoid compounds require conversion to an active metabolite. For example, prednisone requires conversion in the liver to prednisolone to become active. Because this conversion is necessary, prednisolone is a better choice for topical application, but since the conversion is rapid and nearly complete, the two drugs are interchangeable for systemic use.
Finally, the biologic half-lives of the glucocorticoids are different (prolonged) from their plasma half-lives, which are responsible for the variability of duration (from short-acting to intermediate to long-acting).
This is because the biologic effects of the glucocorticoids are largely due to alterations in genetic regulation of protein production, and these alterations create a longer time of activity.
Note that glucocorticoid amounts naturally fluctuate in the body throughout the day. Therapeutic protocols should take this diurnal variation into account and, where necessary, prescribe amounts of the drug that would correspond to these daily variations.
Also note that all cases where glucocorticoid therapy has been prolonged (for more than a few days), there is the possibility that the hypothalamus-pituitary-adrenal axis has been shut down by the negative feedback mechanism. These cases, then, require a gradual reduction from the therapeutic levels rather than abrupt cessation. The time and method of “weaning” depends on the glucocorticoid used and the duration of its use. Check with your veterinarian for the correct protocol.
There are many natural alternatives to the glucocorticoids, substances that have anti-inflammatory activity and/or that enhance a balance of the immune system’s function.
• Herbs – There are many herbal remedies that are anti-inflammatory, enhance the immune system, prevent pain, and are specifically directed toward a body system, balancing it in response to inflammation or pain.
Of special interest here is meadowsweet, the original source of aspirin (the old botanical name for meadowsweet, Spirea, is how aspirin got its name). The term salicylate (the “active” ingredient in aspirin) comes from the Latin name for willow, Salix. The herbs that contain salicylate include meadowsweet, wintergreen, the bark of aspen and cottonwood, birch, black cohosh, and willow.
In addition, there are several herbs – examples include licorice, wild yam, yucca, sarsaparilla, and fenugreek – that contain steroidal saponins that have a chemical structure very similar to cortisone. These steroidal saponins have direct anti-inflammatory, cortisone-like effects, and in addition, some of them inhibit an enzyme in the liver that breaks down natural cortisone, thus making it available longer.
Herbal steroids typically do not create an atrophic effect on the adrenals, and in fact are often used to aid in the weaning process from therapeutic glucocorticoid levels.
• Acupuncture has been shown to be beneficial to the immune system and for prevention of inflammation. In addition, acupuncture alleviates pain of arthritis and may promote healing.
• Homeopathy works by enhancing the vital force, an unmeasurable component of the healthy body that has been likened to the immune system.
• The contribution of a low-stress lifestyle to health is also unmeasurable, but undoubtedly valuable. Remember that the body constantly produces glucocorticoids, and whenever there is an excess production, there is the potential for disease. Excess glucocorticoids are produced with excess stress; think about the “Active Dog, Tiny Apartment Syndrome,” a dog left home alone for extended periods (away from the healthy “pack” and forced to abnormally control elimination patterns), constant noise pollution, lack of exercise and open air walks – all these are potential stressors.
In my opinion, the best anti-stressor in the world is to let your dog be a dog; let him reunite with his true inner nature and with a natural and healthy outer environment.
Putting it all together
Okay. So we have the facts before us, and here’s a summary:
• There are both natural and synthetic glucocorticoids, and the synthetically produced products have a wide range of duration and potency.
• Glucocorticoids are a necessary hormone for body maintenance, and therapeutic doses can be beneficial – and harmful.
• Glucocorticoids affect all cells in the body. Their activities are thus far-ranging.
• There is no way to separate the glucocorticoids’ anti-inflammatory activity from their immunosuppressive activity.
• Veterinarians have a variety of products available to them, and each of these products has its niche in the therapeutic toolkit.
• Many diseases respond favorably to glucocorticoid therapy.
• There are many adverse side effects that may come along with glucocorticoid therapy.
• Whenever glucocorticoids are used for prolonged periods, the patient needs to be gradually weaned off them.
• There are some natural options available – options that are likely not as potent, but almost certainly not as potentially harmful.
Now comes the most difficult part. Knowing the advantages and disadvantages of the glucocorticoids, how and when do I choose to use them for my dog? Unfortunately, there’s no good answer. Once again, regrettably, we have to fall back on the old truism, “It all depends. On the individual dog. On the particular case as it is presented. And on the family situation.”
Here’s my take: I would never hesitate to use massive doses of short-acting glucocorticoids in an emergency: anaphylaxis, immune-mediated system collapse, acute trauma, nerve damage. I know that even these applications are now being questioned – because we don’t really have scientific proof that they work for dogs – but the time I spent in an emergency clinic where I used glucocorticoids to effectively treat hundreds of “shocky” animals demonstrated to me their effectiveness.
However, I would think long and hard before I ever used glucocorticoids for dermatitis or chronic immune-mediated diseases. I’d think in terms of the alternative medicines first here – combining both anti-inflammatory and immune system balancing methods – and I would hope these would be potent enough to be curative.
On the other hand, I am not comfortable demanding that we stick with the alternatives no matter what. I think there may come a time with some patients when we do them more harm than good, trying to make the alternatives work. Sometimes a quick regime of short-acting glucocorticoids is just enough to give the animal’s immune system a chance to recover enough to gear up on its own.
For an arthritic animal I’d think even longer and harder about ever using the glucocorticoids. I’ve simply had too much success with acupuncture (along with chondroprotective agents and herbs), and the glucocorticoid side effects (demineralization of bone, weakening of the ligaments and tendons, the possibility for infection), which all seem to work against everything we are trying to accomplish. Furthermore, the glucocorticoids have no pain-relieving activity, and pain is one of the key components of arthritis.
In all cases, I think it is imperative that we (to use a currently popular metaphor) have an exit strategy. Decide beforehand what your exit protocol will be – how long before you think of using alternative tactics, how will you judge results, and most of all, if and when you do decide to quit, what you will use for a “weaning off” protocol.
Finally, I think there may be a place for glucocorticoid therapy for the end-stage animal, for treating any of the diseases where we might commonly use them. It seems to me that in these cases, the advantages may outweigh the disadvantages.
Glucocorticoids are often an inexpensive way to stimulate the metabolism; they may alleviate inflammation; and they oftentimes create a “feel-good” attitude in a previously depressed dog.
Further, in these cases we won’t have to worry about long-term effects, nor will we likely be confronted with the necessity of gradually weaning the animal from the therapy.
-Dr. Randy Kidd earned his DVM degree from Ohio State University and his Ph.D. in Pathology/Clinical Pathology from Kansas State University. A past president of the American Holistic Veterinary Medical Association, he’s author of "Dr. Kidd’s Guide to Herbal Dog Care" and "Dr. Kidd’s Guide to Herbal Cat Care" (see "Resources").