Corticosteroids: Miracle Drugs with Caveats

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Representational ImageFile/ GK

With America’s entry into the World War II in December 1941, rumors were rampant that the Nazis were secretly importing bovine adrenal glands from Argentina via submarine to produce extracts for military use. It was long known that animals with surgically removed adrenal glands (adrenalectomized animals) would quickly succumb when exposed to even minimal stress, based on the work of Addison and Brown-Sequard in the 1880s.

It seemed natural to postulate that adrenal extracts could protect against stress. The fear surfaced that Luftwaffe pilots were being given such a drug to allow them to tolerate low oxygen levels (hypoxia ) and fly at altitudes of 40,000 feet or more. Although these rumors were undoubtedly untrue, the specter of a steroid-enhanced enemy grabbed the attention of the US government and impending war influenced the US Government to set up a Research Council in 1941.

A committee of 14 chemists was assembled, including Kendall and the task was defined. Remarkably, the number one priority was the isolation and production of Cortin (compound E). Besides, the development of anti-malarials for potential tropical warfare and Penicillin as an antibiotic to combat infections in soldiers was on number two and three of the list. Hefty money was pumped into adrenal hormone research and the resultant partnering with industry led to isolation and purification of the compound E (Cortin).

On September 21, 1948, Mrs G. (Patient crippled with debilitating Rheumatoid Arthritis ) received her first of twice daily intramuscular injections of 50 mg of compound E at the hands of Dr Charles H. Slocumb, the hospital service junior rheumatologist at Mayo's Clinic . On Day 3 after receiving the shots , she had progressive improvement with her pain and stiffness and by Day 4 she visited other patients to show off her progress. Crippled with her illness she never had felt better in her life before this . A miracle happened and we have all been witnessing the magic of this compound and related analogues since then .This was the dawn of the Cortisone era .

This discovery of cortisone by Philip Hench and Edward Kendall along with the Polish chemist Tadeus Riechstein, received the Nobel Prize in medicine and physiology in 1950. At the same time, chemists at drug companies have manipulated cortisone like a Tinker Toy, adding, deleting or substituting a piece here or there to create new and ever-more-useful structures. Ever since cortisone, a succession of closely related synthetic analogues have remained among the most widely prescribed medications in the world.

Steroids and My journey in medical Career

The long journey from resident to physician and then a practicing cardiologist is butterfly’s experience of metamorphosis and this professional change- encapsulated within medical education research by the more nuanced term ‘transition’- is complex. It is full of challenges, not the least of which is fully accepting the mantle of new status. This role shift involves a great deal of stress and embarking upon this never-ending journey we come across situations where at times we feel helpless when we stare in the face of incurable diseases such as cancer, genetic disorders, HIV , cardiomyopathies amongst others. Not being able to cure a disease, despite being the flagbearer of medicine yet giving all our efforts to the same is one of the most difficult parts of being a doctor. And during many such situations, we use corticosteroid drugs in one or some other form as part of either curative or palliative regimens. I hardly remember any medical specialty/subspecialty where steroids are not used. The remarkable ability of corticosteroids to reduce inflammation has kept them the prime treatment for many serious disorders, including severe asthma, flare-ups of rheumatoid arthritis and lupus, leukemia, ulcerative colitis, dermatological practice and certain eye diseases; and successful solid organ transplant (kidney , Liver and Heart transplant) accomplishments would not have been possible without corticosteroids.

Medicine is a science with many probabilities and possibilities. Human body is not a lab and does not produce the same result always. Diseases vary in their cause and complication. Evidence based medicine at times needs to be refined by experiences. As residents, we have witnessed the miracle of these drugs at innumerable times: the timely administration of steroids in head and spine trauma, brain inflammation, severe life threatening allergic reactions( anaphylactic shock) and many other emergency situations have literally saved lives. In my cardiology practice, I have found use of steroids in limited but nevertheless difficult and important situations in the management of certain cardiac diseases . To mention a few of these disorders are Rheumatic Fever (usually affecting school going children), amyloidosis , sarcoidosis , post pericardiotomy syndrome and many others.

Steroids and the Covid Era

The COVID19 pandemic is a classic of humanity vs. nature. This upstart from the animal kingdom finds a way somewhere in China to jump the barrier into a human host. From there, it begins infecting people by the thousands, then the millions. It is an enigmatic foe, sometimes killing, other times causing no symptoms at all. Humans in skyscrapers and laboratories and mansions are racing against time for treatments and even a cure — yet we still have only a shadow of understanding about the nature of the thing we’re up against.

In an unexpected sign of hope amid the expanding pandemic, an inexpensive and commonly available drug reduced deaths in patients with severe COVID19, the illness caused by the coronavirus. And the saga in search of a drug capable of changing the natural history of the coronavirus disease 19 (COVID-19) experienced a new chapter: dexamethasone emerged and undoubtedly reduced the mortality in hospitalized patients. However, before its emergence, other treatments like Hydroxychloroquine, Remdesivir, Azithromycin , Ivermectin and many others arrived with the promise of miraculous achievements but stayed behind, remaining only adverse effects and lack of medications access for clinical conditions that would truly benefit from their use. Amongst all these molecules , Dexamethasone stood the testament . Thanks to Kindell and others for their discovery of the molecule in 1950 and the rescue of humanity in the 2020s.

The Dark side

Sir William Osler once said, “The person who takes medicine must recover twice, once from the disease and once from the medicine.” The wonder drugs are not always so wonderful. As with any powerful remedy, corticosteroids come with a downside: side effects that can sometimes be as serious as the ailments they are intended to treat.

Steroids are widely misused by doctors, quacks and practitioners of alternative medicine because they produce quick responses to treatment.

People sometimes demand a “quick fix” not just for illness, but also bodybuilding and sports prowess. A “magic bullet” of steroids being readily available gives the sense of artificial well-being, the Steroid Euphoria. Whenever events such as the Asian Games or Olympics occur, steroids are in the news because there is widespread misuse to enhance performance. American film director Nicholas Ray( 1956) - portrayed a movie on cortisone discovery and aftermath.

‘Bigger Than Life’ in which a seriously ill schoolteacher becomes dependent on a "miracle" drug that begins to affect his sanity. Ray posed the question of whether the domestic bliss of the 1950s was a farce and full of fissures and implying that steroids exposed and exacerbated a less-than-idyllic.

My tribute to steroids as’ Preemie parent ‘

Maternal experience of a premature childbirth is configured as a period of crisis, an event that is often experienced as disappointing and dramatic. Faced with the birth of a premature child, the woman mostly becomes a fragile mother, disoriented and particularly vulnerable, dominated by anxiety of death and feelings of guilt. A great contribution to the overcoming of this agonizing and painful experience of the woman and survival of neonate is with the miraculous discovery of role of betamethasone ( a steroid analogue ) by Liggins and Howie in 1972 ,twenty five years after inception of corticosteroids ,for the prevention of primary complication of preterm birth and a leading cause of neonatal death and disability, the Respiratory Distress Syndrome. Since then myriads of premature infant deaths have been prevented by accelerating the maturation of fetal lungs.

As a parent I too have gone through these difficult and harrowing times and am grateful for the opportunity at life of antenatal corticosteroids given to my preemie daughter, my little angel Ayzal (meaning gift of Allah). I thank God every day for my eagerness to hear that first cry , a gift from heaven to cherish love.

The First Cry

The incarnation of Happiness,

Offered as a blessing.

It is the solitude of pain,

That is unbearable to gain,

Like a soothing music,

It heals the hearts.

It is the fusion of love of two entities, That gives the love an identity!

Dr Showkat Hussain Shah is Consultant Cardiologist at GMC Anantnag

Disclaimer: The views and opinions expressed in this article are the personal opinions of the author.

The facts, analysis, assumptions and perspective appearing in the article do not reflect the views of GK.

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