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MIND OVER MEDS - know when drugs are necessary

Chapter 7 Steroids


The story of cortisone is synonymous with Dr. Philip Showalter Hench, of the Mayo Clinic in Rochester, Minnesota. In 1949, Hench shared startling images of patients with RA; all had recovered with synthetic cortisone. His discovery was hailed as a genuine miracle cure. The following year, Hench and his associate, Edward Kendall, received a Nobel Prize for "discoveries relating to the hormones of the adrenal cortex, their structures and biological effects."

As the most powerful anti-inflammatory agent yet discovered, cortisone transformed the practice of rheumatology almost overnight. It also revolutionized ophthalmology, gastroenterology, respiratory medicine, dermatology, and nephrology, and facilitated two remarkable postwar therapeutic developments: organ transplantation and treatment of childhood cancers.

Cortisone and its derivatives, now collectively known as steroids (or corticosteroids), reman among the top ten most widely used prescription and OTC drugs. They remain the most powerful anti-inflammatory agents known, and their significance in general medicine is beyond dispute. It is not surprising that steroids are included in the World Health Organization's Model List of Essential Medicines.

Given practically any disease of unknown cause for which there is no effective treatment, physicians will often put patients on a trial of cortisone to see what happens.


Hormone produced by the adrenal cortex consists of four canon rings linked to form what chemists call the steroid nucleus. Variations on this molecular theme result in drugs with greater or lesser anti-inflammatory potency and more or less of the undesirable effects of salt and water retention.

In 1955, prednisone was introduced into clinical medicine and the first synthetic steroid dug, three years later, triamcinolone was patented. Prednisone is about 5 times stronger than cortisone but has the same salt-and water-retaining properties. Triamcinolone is as powerful as prednisone but has less propensity for salt and water retention. When triamcinolone is dissolved in acetone, the resultant triamcinolone acetone (Trianex, Triesence, Triderm) is very potent and, as a fat-soluble compound, is easily absorbed through the skin, making it the preferred topical steroid for dermatitis and psoriasis. Intramuscular injection of triamcinolone is sometimes used to control allergic asthma, sever contact dermatitis, seasonal allergic rhinitis ( hay fever), and transfusion and drug hypersensitivity reactions (serum sickness). In 2014, the FDA allowed OTC sale of triamcinolone acetonide in nasal spray from under the brand name Nasacort.

Triamcinolone joint infections (Kenalog) for osteoarthritis and RA offer rapid pain relief, usually within 24 to 48 hours. Improvement lasts 6~12 weeks on average, and injections can be done safely 2~3 times a year. (In my experience, their efficacy lessens over time.)


Although inflammation can be troublesome, it is actually the cornerstone of our healing system - the body's way of getting more nourishment and more immune activity to the area that is injured or under attack by germs or toxins . The body regulates inflammation carefully: too little creates susceptibility to infection; too much causes tissue damage and increases risks of allergy and autoimmunity. The adrenal glands and the hypothalamus and pituitary produce very potent hormones that regulate the inflammatory response as well as general metabolism, bone and muscle health, and heart, liver, and kidney function.

Steroids bind tightly to glucocorticoid receptors present in virtually all cells. This interaction then regulates gene expression in the cell nucleus. The most important effects of steroids result from these genomic mechanisms. They occur at all dosages, even very small ones, and they happen relatively slowly --- it may take up to 18 hours for steroids to take genomic effect.

But at higher doses, non-genomic effects come into play rapidly --- over seconds or minutes --- resulting from direct interactions with biological membranes. These interactions influence nerve function in the brain, affecting hormone production, behavior, and cognition. This is an important distinction, because the relative potencies of various steroids are completely different in terms of producing non-genomic versus genomic effects.


Steroids can be lifesaving in case of allergic (anaphylactic) shock and other severe allergic reactions, in the treatment of autoimmune diseases, in case of brain swelling, in cancers of the blood and lymphatic system, and in transplant medicine to prevent rejection of donor organs. In these instances, their worth as immunosuppressant and anti-inflammatory agent is undisputed. But steroids are now used for a great many other conditions, some of them far from serious. It is not a good idea to use such powerful drugs for routine complaints. Most people who use steroids do not understand how they work and how dangerous they can be.


Between 1997 and 2014, the FDA received reports of 90 serious neurologic events, some fatal, rerated to epidural injection of steroids --- a procedure commonly performed to manage neck and back pain.

Inhaled steroids, widely used for management of asthma, have fewer adverse effects than oral steroids, but they can promote fungal infection of the mouth and throat (thrush). Rarely, prolonged use of inhaled steroids in high dosage will cause the same systemic toxicity seen with long-term oral steroid therapy.

Topical steroids can have local, or rarely, systemic side effects. Young children and elderly are more susceptible, because they tend to have thinner skin.

One other concern: because steroids suppress symptoms of disease rather than treating root causes, long-term use may strengthen disease patterns and encourage their spread to other sides. Perhaps the most noteworthy fact about steroids is that they are pleiotropic, meaning that they have multiple effects on diverse biological functions. People take them to alleviate symptoms caused by misdirected inflammation, but they also suppress immunity, increasing susceptibility to infection and retarding wound healing. Over time they regularly cause adverse effects in many systems, from stomach irritation to loss of bone density. Sudden discontinuance of steroid usually results in immediate return of symptom, often worse than before.

Chapter 8 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

They can be miraculously effective at relieving pain, lowering fever, and reducing swelling associated with inflammation. OTC forms are so familiar that most people consider them totally benign and take them frequently or even regularly with little awareness of their risks.

Saliciylic acid, the precursor of aspirin, is a constituent of willow bark, a folk remedy used for centuries in diverse parts of the world. Hippocrates prescribed willow bark tea for headache 2,400 years ago. Aspirin was synthesized in 1897. Today it is one of the most widely used medications in the world. In the 1960s, second NSAID was introduced: indomethacin (Indocin), a prescription medication still used today. Currently, there are at least 20 prescription-only formulations of NSAIDs.


MSAIDS includes a large number of pain-and fever-reducing drugs. Notable anti-inflammatory medications NOT in this class are prednisone and acetaminophen (Tylenol). Prednisone is a steroid; acetaminophen is an OTC drug that reduces pain and fever by a different mechanism.

MSAIDs fall into two categories, selective and non-selective. All NSAIDS acts at the level of cell by inhibiting an enzyme called COX (cyclooxygenase). There are two forms of this enzyme:

Cox-1 is produced constantly in the tissues --- produce prostaglandins

Cox-2 is elicited mainly by inflammation --- produce prostaglandins

Both are involved in making prostaglandins, It is prostaglandins that directly cause pain, fever, and more inflammation. Most NSAIDs are non-selective in that they block both forms of the COX enzyme.

Suppression of COX-1 increases the risk of gastrointestinal ulceration and bleeding, the main adverse effects of these medications. COX-2 inhibitors were developed to reduce those problems. Celcoxib (Celebrex), a prescription NSAID, is now the only selective NSAID still available. Two other selective NSAIDs were removed from the market in 2004 and 2005 due to the increased risk of heart attack and stroke.

NSAIDs can be particularly problematic when used daily for chronic pain. Inflammation is the body's normal response to injury and leads to swelling, pain and sometimes heat and redness. Inflammatory response is beneficial:

it lets us know that we have been injured and that we need to protect the affected body part.

It promotes healing by bringing more blood, nutrients, and immune activity to an injured site.

NSAIDs can decrease the inflammatory response after trauma to bones, joints, muscles, or tendons, rapidly reducing pain and swelling. When left untreated, serious injuries can develop into chronic pain syndromes due to compensations by other posy parts to protect the injured part and to changes in the brain.

Other types of inflammation and pain syndromes that occur in the odd can result from daily "wear and tear," inactivity or over-activity, stress, and chronic illness. Because NSAIDs do not treat the root causes of chronic pain syndromes they may, over time, intensify or prolong the problem by allowing people to continue the activities that have caused it.


Despite being highly effective at reducing a cur and chronic pain, fever, and inflammation, all NSAIDs come with significant risks. The adverse reactions caused by them impact the stomach, intestines, heart, longs, blood vessels, and blood cells. The most significant and common adverse effects occur in the GI tract. The real potential for harm comes with daily use, generally for more than 2 weeks.

When NSAIDs get into the bloodstream and block the COX enzymes, synthesis of prostaglandins decreases. These hormone-like substances protect the stomach lining from acid and other irritants. Over time, deficiency of prostaglandins increases the possibility of gastric bleeding, ulceration, and perforation, any of which can occur in the absence of warning symptoms. Thousands of people die each year from episodes of NSAID-related GI bleeding, many of them had no awareness of the harm.

The decrease in prostaglandins can also damage the small and large intestines, especially in the setting of ulcerative colitis and Crohn's disease.

NSAIDs also affect our blood cells, particularly platelets. Aspirin acts in a unique way: it blocks platelets from clumping together to form clots for the entire lit of the platelet, which is 8 ~12 days. Ibuprofen and dither NSAIDs exert this effect for a much shorter time. In the case of a heart attack, platelet blocking is desirable; in other instances --- such as an upcoming surgery, intestinal bleeding, or a low platelet count to begin with --- it is potentially dangerous.

Aspirin is routinely given to patients who are having a heart attack, and low daily doses of it has been shown to help prevent both heart attacks and strokes. Regular use of NSAIDs other than aspirin can increase blood pressure, worsen heart failure. Naproxen (Aleve) appears to increase heat attack risk least and diclofenac (Voltaren) most.

NSAIDS also impact the kidneys, which need prostaglandin produced by the COX-2 enzyme to maintain the blood flow that keeps them healthy. Because all the NSAIDs block this enzyme and decrease renal blood flow, those with kidney disease should not take them. Even in the absence of kidney disease, those who take diuretics ("water pills") for heart failure or hypertension shod be careful,

Drug Interactions

The major category of drugs that can interact with NSAIDs is blood thinners. When taken with any blood thinner, especially wafering (Coumadin), NSAIDs will increase the risk of GI bleeding. Alcohol intake on its won increases this risk; together with regular use of NSAIDs, alcohol multiplies it. Long-term use of corticosteroids, such as prednisone, can cause to mach ulcers; combined with NSAIDs, the risk is amplified.

Chapter 12 Opioids and the treatment of Chronic Pain


For moderate to severe acute pain, opioids are the drugs of choice. Two natural constituents of opium - cosine and morphine - have been around a long time. Codeine is a weak analgesic, often combined with aspirin or acetaminophen, and also used as a cough suppressant. Morphine is a major analgesic medication; like other opioids it is much more potent when administered parenterally - that is, by injection into a muscle or vein. Over the years, chemists have tinkered with these molecules to produce dozens of semisynthetic and synthetic analogs, often in a vain attempt to separate the analgesic properties from the addictive ones. Heroin was released to the world in 1898 as a safe and effective cough suppressant and pain reliever with none of morphine's risk for dependence, which by then was well know, and there have even many similar claims made for new opioids ever since. Recently, pharmaceutical manufactures made available long-acting forms of morphine (like MS Contin) and other opioids, such as fentanyl (Duragesic), hydromorphone (Dilaudid), and cxycodone (OxyContin).

Opioid drugs work by activating the same brain receptors that bind opioids made within the body. These natural or endogenous opioids include endorphins, which affect mood and pain perception and can be released by many triggers, including exercise and acupuncture. It just happens that molecules made by the opium poppy bind to those same receptors.

For acute pain that resists NSAIDs and acetaminophen opioids are very effective. They also work well for others. Many experts now agree that the risks associated with use of these drugs are likely to outweigh the benefits when they are used long term for most types of non-cancer pain including headache, back, and neck pain. For chronic pain that is episodic, such as migraine, fibromyalgia, and neuropathy, acetaminophen and NSAIDs are preferable to opioids.

The Problems with Opioids

Opioids overdose can cause fatal depression of respiration by direct action of the brain center that controls breathing. This is unlikely in patients taking them regularly because tolerance to this effect develops rapidly. It is more likely when opioids are combined with sedative drugs. The combination of opioids and benzodiazephines ("benzos") is especially dangerous, quadrupling the risk of overdose. Most common are nausea and vomiting, itching, seating, dizziness, drowsiness, and constipation. In the elderly, dizziness can increase the risk of falls. Constipation can be severe. Some people on ling-term opioid treatment experience an odd intensification of sensitivity (hyperalgesia), making the lightness touch unbearable and the pain actually worse.

In end-of-life care --- for example, of people with end-stage cancer who are experiencing constant pain --- opioid analgesia may be a necessity, but the cognitive effects of the rugs, sometimes allied "mental clouding," can be distressing for those who wish to remain lucid through the dying process and be able to communicate with loved ones.

Of course, the overriding concern about long-term use of opioids is addiction and its destructive effects on individual lives and on society. Regular use of any opioid analgesic can lead to tolerance (the need for higher doses to maintain a desired effect), physical dependence, and addiction. Physical dependence, marked by prominent withdrawal symptoms when an opioid is discontinued, is common but not the same as an addiction disorder, which is much more serious. An estimated 5% of those who stay on opioids for mores than a year develop addiction disorder. People who experience euphoria from opioids, especially when they first receive them by injection are more at risk. Addiction disorder represents derangement of the brains reward system. It is characterized not only by physical dependence but by obsessive focus on the drug, behavior problems, impaired social functioning, and loss of productivity.

OxyContin abuse is notorious; the drug is so popular in rural America that it has become known as "hillbilly heroin." By 2011, many of the clinicians involved in promoting increased opioid use were publicly acknowledging that there were significant problems with reliance on these drugs for long-term management of chronic pain. In response to the rapid rise in the misuse and abuse of prescription opioids, a number of states began to restrict their availability. The Federal government took action as well, subjecting manufactures to greater scrutiny, insisting on better formulations, and requiring education of doctors about safe prescribing.

The experience of pain includes both the primary sensation of it and the brains interpretation of that sensation. Local anesthetics like procaine (Novocain) block the former; opioids act in the brain to modify interpretation of pain signals. With opioid-induced analgesia, a patient may report that "the pain is still there, but it doesn't bother me" or "it is as if the pain is happening to someone else." Under hypnosis people often make the same kinds of statements.

Biostimulation is an umbrella term for newer therapies to reduce pain that direct electrical, magnetic, light, and sound stimulation to areas of the body. One example is transcutaneous electrical nerve stimulation (TENS), which can relieve musculoskeletal pain; TENS devices for home use are available. Also available are brain stimulation devices that deliver electromagnetic energy to shift blood flow and reduce excitability of specific areas of the brain involved in chronic pain syndrome. At the present time most can be accessed only in medic settings, but people will soon be able to get devices for home use (such as transcranial direct-current stimulators, or TDCS).

Cognitive behavioral therapy (CBT) can help chronic pain patients identify and change patterns of thought that contribute to the problem.

Nutrients often in need of repletion include vitamin D, magnesium, omega-3 fatty acids, and CoQ10. An anti-inflammatory diet can reduce the need for medication. In addition to emphasizing plant-based foods, the diet includes anti-inflammatory herbs and spices, such as turmeric (Curcuma long) and ginger (Zingiber officiale).

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