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Hey guys, this is the 3rd entry of my Pharmacology Blogpost. This time I’m going to talk about the most phenomenal drug that has been discovered so far, which is the “Steroids”. As a prelude, I bet many are still perplexed about steroids. Does it bring harm? Does it bring good? If it is so bad why so many people are taking it? I bet you'll be surprised knowing that steroids have been saving so many lives, even right now. There are two types of steroids, endogenous and exogenous. Before we talk about the exogenous steroids (synthetic steroids), let’s understand about the endogenous steroids (natural steroids).

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Adrenal cortex, which is the part of adrenal gland secretes glucocorticoids, which is the other name of the infamous steroid. The release of this hormone is highly dependent on the pituitary gland in our brain. This pituitary gland controls the production of steroid via the action of ACTH, or Adenocorticotrophic Hormone. Apart from the glucocorticoids, the adrenal cortex too secretes mineralocorticoid (a hormone that is important in salt and water retention, which I described in my previous pharmacology blog post, have a look in case you’ve missed it), and hormones with estrogenic or androgenic activity. In humans, the main glucocorticoid is Cortisol.

How does our natural Cortisol works?

Most of the effect of cortisol is widely based on the glucocorticoid receptors in our body. They have various effects because they influence the function of most cells in the body. The major metabolic effect of cortisol is due to the direct actions of this hormones in the cells.

• Permissive effects. There is this special effect of cortisol which is known as the “permissive effects” that somehow affects the other hormones if steroids are low in our body. For example, catecholamines affects the vessels and bronchial smooth muscle. The effect of this catecholamines without the presence of steroid is diminished.

• Physiological effects. Cortisol exerts its metabolic effects on carbohydrate, protein, and fat metabolism. They stimulate gluconeogenesis (the conversion of protein to glucose) and glycogen synthesis in the fasting state. Cortisol increase serum glucose level, stimulates insulin release and activates lipolysis. This action leads to the increase release of fatty acids and glycerol into the circulation. The net results of these actions are mostly prominent in the fasting state. This is the reason why human’s blood glucose level, especially in diabetic patients, can be very high despite fasting for hours.

A patient can come and complain to the doctor about his high glucose level tested via a glucometer despite not eating since 6pm the previous day. The gluconeogenesis of the liver is stimulated by cortisol, especially in the fasting state, which caused the high level of blood glucose despite not eating any food for the past half a day! To stop this action, a basal insulin injections should be given at night so that the glucose level will be reduced at night. High glucose level causes many severe hyperglycemic complications such as diabetic retinopathy, nephropathy, neuropathy, and cardiovascular accidents such as stroke and myocardial infarction.

• Catabolic effects. Cortisol stimulates RNA and protein synthesis in the liver, and they have catabolic (or degrading) effects in connective tissue, muscle, peripheral fat, and skin. Hence the increase level of cortisol in our body can actually reduce our muscle mass, weakness, and thinning of the skin. The bones are also affected, thus high cortisol level can lead to osteoporosis (or brittle bone). In children, high level of cortisol causes growth retardation.

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• Anti-inflammatory and immunosuppressive effects. Cortisol has a massive anti-inflammatory effect. They have suppressive effects on inflammatory cytokines, chemokines and other inflammatory mediators. They also exhibit vasoconstrictive effects on the skin, possibly due to the suppression of mast cells. By vasoconstricting the blood vessels in the skin, they can reduce swellings. Large doses of corticosteroid can inhibit antibody production, thus the immunity in an individual can be suppressed if someone takes a lot of steroids.

• Other effects:

• Brain - Low level of cortisol can cause depression and high level of cortisol often produce behavioral problems to an individual: initially insomnia and euphoria, and subsequently causes depression. High level of cortisol may increase intra-cranial pressure.

• Pituitary functions - Steroids too can suppress the pituitary gland’s functions, leading to many many other hormones disturbances such as the ACTH, Growth hormones, thyroid-stimulating hormones and lutenizing hormones. So many effects huh. There’s more.

• Stomach - High cortisol amount has been associated with peptic ulcer disease in the stomach as they suppress the immune response and causes Helicobacter pylori (a bacteria that is the culprit in peptic ulcer) to be wild.

• Fat distributions - They too promote fat redistribution to the body and the main fat dump are the facial, nuchal, visceral and supraclavicular regions. They antagonize the effects of vitamin D, causing poor calcium absorption.

• Fetal lungs – They exhibit important effects on the development of fetal lungs including the pulmonary surface-active material required for air breathing (surfactant). Hence, steroids are given to pregnant lady if they are expected to deliver the baby before term, to promote fetal lung growth.

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Commonly used Corticosteroids:

Short-Medium Acting:
• Hydrocortisone, Cortisone, Prednisone, Prednisolone, Methylprednisolone
Intermediate Acting
• Triamcinolone, Paramethasone, Fluprednisolone
Long-Acting
• Betamethasone, Dexamethasone

So in which conditions that we can use these corticosteroids?

• Addison’s disease

• Addison’s disease is a condition when there is cortisol deficiency from the adrenal cortex. The symptoms are weakness, fatigue, weight loss, hypotension, hyperpigmentation, and inability to maintain glucose level during fasting. In this disease, about 20-30mg of hydrocortisone must be given daily and higher dose should be given during stressful periods as there’s a condition called Addisonian Crisis that can happen during these periods.

• Congenital Adrenal Hyperplasia
  • This group of disorder is characterized by specific defects in the cortisol synthesis and this will encourage compensatory increase in ACTH release from the pituitary gland. This gland becomes hyperplastic (increase in cell number) and causes more androgenic based hormones to be release. Remember I’ve mentioned that the adrenal cortex secretes androgenic based hormones too. High amount of androgens lead to virilization (increase in hair growth and masculine like symptoms). Oral hydrocortisone 12-18mg/m2/d is given in two unequally divided doses. More doses should be given in the morning as cortisol is physiologically high in the morning and at its lowest around 6pm. Fludrocortisone, 0.05-0.2mg/d should be given with added salt to maintain normal blood pressure, plasma renin activity and electrolytes. Fludrocortisone is a synthetic mineralocorticoid that helps in retaining water and salt.

• Cushing’s syndrome.
  This disease happens when there is increase in corticosteroid in the body, whether it comes from inside or outside (exogenously). I have explained about what does high cortisol level causes in the mechanism of action of glucocorticoids earlier, and thus the symptoms are as such. Truncal obesity, skin thinning, purple striae, easy bruising, infections, osteoporosis and even mental disorders, diabetes and hypertension. One of the management of this condition is via removing the adrenal glands so that they could not produce excessive cortisols. After removing those organs, the patient needs glucocorticoid supplementation in long term maintenance.

• For Diagnostic purposes.
  In Cushing’s syndrome, the cause of increase in cortisol level can be either from an increase in ACTH (pituitary’s fault) or the adrenal cortex itself. Hence, we need to know whether this Cushing’s syndrome is ACTH related or not. In order to do so, a very potent steroid such as the Dexamethasone can be given in small quantities to determine the cause. If you guys are interested, you guys can search the Dexamethasone Suppression Test and Synacthen Test online.

• Lung Maturation.
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As I’ve said earlier, lung maturation is assisted by the presence of cortisol. Treatment of pregnant mother with large doses of Betamethasone is given to reduce the incidence of respiratory distress syndrome in infants delivered prematurely. This drug is the best choice because it is easily transferred across the placenta to the fetus

• Some other non-adrenal disorders that might need corticosteroid
  • Allergic reactions
  • Eye diseases such as allergic conjunctivitis and acute uveitis
  • Gastrointestinal diseases such as inflammatory bowel disease
  • Hematologic disorders such as leukemia and lymphoma
  • Systemic inflammation
  • Infection such as sepsis
  • Bone and Joint inflammations such as in arthritis
  • Neurological disorder such as cerebral edema
  • Organ transplants
  • Pulmonary diseases such as in bronchial asthma
  • Renal disorders such as in nephritis syndrome
  • Skin diseases such as in eczema, dermatoses
  • Thyroid diseases such as in subacute thyroiditis

What are the complications of steroid use?

Yes, there are so many benefits of steroid use. That’s why they are called as the “wonder drugs” as there are plenty of diseases that can be managed using steroids. However, there are many undesirable effects of glucocorticoids that we should watch out.

1. Metabolic effects
   • Iatrogenic Cushing’s Syndrome
   • Acne, Insomnia and increase in appetite
   • Continuous protein breakdown (gluconeogenesis) to produce glucose causing an increase in insulin need which results in weight gain. Eventually diabetes and osteoporosis can develop.
   • Immunosuppression can lead to recurrent infections

2. Other complications
   • Peptic Ulcer
   • Acute Psychosis
   • Hypomania
   • Cataracts
   • Glaucoma
   • Growth retardation in children

3. Adrenal Suppression
   • When corticosteroids are given in more than 2 weeks, this condition may occur. Exogenous corticosteroid will suppress ACTH release, and this leads to reduction in adrenal cortisol production. Less endogenous cortisol and more exogenous corticosteroids. The symptoms which I have mentioned earlier includes the anorexia, nausea, vomiting, weight loss, fever, joint, muscle pain and postural hypotension.

Steroids for muscle building?

Steroids are often abused among athletes. I’m pretty sure many of those athletes need to be the best among the best, cream of the crop. Thus, they need to use a type of supplementation that can boost their performance. Dr Harrison Pope, director of the biological psychiatry laboratory at the McLean Hospital in Belmont, USA said that “In particular, they are highly effective for building upper-body strength. And they work incredibly well,” . Anabolic Steroids are mostly synthetic substance that is similar to the testosterone, a male sex hormone.

Why do they want to use it?

These testosterones increase muscle strength. A study done by Rogerstone and collegues (2007) explained about the effects of this performance-enhancing drugs. Testosterones increases bench press strength and cycling performance. The same study also shows that this drug increases body size, bicep girth and quadriceps circumference. Some other studies showed that testosterones improves lean body mass and increases muscle mass. So somehow this drug can be used as a shortcut for body builders to achieve their ideal body morphology in a nick of time.

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Already thinking of using testosterones/steroids to boost your sports performance? Think again.

These exogenous steroids-testosterone for athlete’s performance brings many side effects such as those I have mentioned earlier. Apart from those steroid side effects, they too develop excessive testosterones side effects such as prominent breasts, baldness, shrunken testicles, infertility, impotence, liver abnormalities, tumours, depression, hypertension, and drug dependence. Manly but no so manly huh?

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In short, steroids are wonderful. God has created them for huge reasons. They are the cure to so many illnesses in this world. For me, they have way more medical uses than the antibiotics though I should not compare but… this is just to show how steroid plays a major role in the world of medicine. However, there is a plethora of severe side effects that comes along with it. Hence, only those who really need it should take it. Alright, that's all for today's blogpost. I hope you guys do learn something from this. Till next time :)

References

1. Katzung et al. Basic & Clinical Pharmacology .Singapore: McGrawHill, 2012. Print
2. 11 facts about steroids. Retrieved on April 13, 2018, from https://www.dosomething.org/us/facts/11-facts-about-steroids
3. What are the benefits of steroids for athletes?. Tommas Linnaeus. Livestrong. Retrieved on April 13, 2018, from https://www.livestrong.com/article/104856-benefits-steroids-athletes/
4. Athletes trading steroids for hormones. Kay Lazar. Boston.com. Retrieved on April 13, 2018, from http://archive.boston.com/sports/baseball/articles/2009/07/31/how_steroids_work_and_why_athletes_are_trading_them_for_manmade_growth_hormones/
5. Performance-enhancing drugs: Know the risks. Mayo Clinic Staff. Mayo Clinic. Retrieved on April 13, 2018, from https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/performance-enhancing-drugs/art-20046134