INTRODUCTION:

Steroids are a man-made version of chemicals, known as hormones, that are made naturally in the human body. Steroids are designed to act like these hormones to reduce inflammation. They’re also known as corticosteroids, and are different to anabolic steroids used by bodybuilders and athletes. Steroids won’t cure your condition, but they’re very good at reducing inflammation and will ease symptoms such as swelling, pain and stiffness. Usually, inflammation is the body’s natural reaction to infection or bacteria. Your immune system produces extra fluid to fight infections or bacteria, which causes swelling, redness and heat in the affected area. You might have noticed this if you have had a cut or wound on your skin.^1,2,3

In some conditions, such as rheumatoid arthritis, the immune system produces inflammation in the joints or other parts of the body by mistake, which can cause permanent damage if left untreated.

Steroids can be used to reduce this immune reaction. Corticosteroids and their biologically active synthetic Derivatives differ in their metabolic and Electrolyte-regulating activities. The endocrine system, and the nervous system. In addition, Corticosteroids endow the organism with the capacity to Resist such stressful circumstances as noxious stimuli and Environmental changes. Corticosteroids are important therapeutic agents used to Treat allergic and inflammatory disorders or to suppress Undesirable or inappropriate immune system actions. The Term corticosteroid is used clinically to describe agent with glucocorticoid activity.^5,6

PHYSIOLOGICAL EFFECT:

As the primary endogenous glucocorticoid, cortisol has A variety of physiologic effects in humans. These effects Are pleiotropic and pedestrian, and affect nearly every or- Gan and metabolic process in the body. Pharmacologic use Of corticosteroids is commonly to suppress or prevent signs And symptoms of allergic responses or inflammation, or to Suppress an inappropriate or unwanted immune responseless commonly, hydrocortisone is used for physiologic Replacement of cortisol when the hypothalamic-pituitary- Adrenal axis is present or circulating cortisol is deficient Due to a primary adrenal condition or due to a secondary Failure of the pituitary or hypothalamus, which results in Deficits of adrenocorticotrophic hormone or corticotrophin- Releasing hormone. Corticosteroid effects on inflammation and immune Function are described below. In addition, these agents Affect carbohydrate, protein, and lipid metabolism, which Results in gluconeogenesis, protein catabolism, and fatty Acid mobilization, along with multiple other effects. Corticosteroids also affect bone and calcium metabolism, Cardiovascular homeostasis, central nervous system function, and a variety of endocrine effects. 2 There also are effects on cardiovascular function and fluid and electrolyte balance that are attributed both to glucocorticoid and miner-alocorticoid activity. With pharmacologic dosing of corticosteroids, these effects are significant and often undesirable, which results in physiologic consequences that are described in the adverse drug reactions and side effects section.

Although corticosteroids are used primarily for their anti-inflammatory effects, they also are associated with beneficial effects on the 2-adrenergic receptor.5 Corticosteroids are associated with upregulation of 2-adrenergic receptor function as well as acting to reverse downregulation of these receptors associated with chronic 2-adren-ergic therapies. Plausible mechanisms for this effect at the 2-adrenergic receptor are to increase coupling of re-captors to G proteins, which increases adenyl cyclase, and to also increase the synthesis of new receptors.³

EFFECT OF ANAESTHESIA AND SURGERY:

Plasma cortisol levels typically increase from two-to-ten-folds following induction of anesthesia, during surgery, and in postoperative period. The maximum ACTH and cortisol levels are reached in the early postoperative period, especially following anesthesia reversal and endotracheal extubation (30 min after extubation). As with other types of stress, the episodic release of cortisol remains intact, but the amplitude of this episodic release is increased. The increase in the plasma cortisol concentration may in part be due to bar receptors and spinal reflexes that signal the hypothalamus of tissue injury associated with surgery.

Other factors that activate HPA axis to release cortisol include proinflammatory mediators released by damaged tissues and presence of postoperative pain. Plasma cortisol concentrations typically return to normal levels within 24 hrs postoperatively but may remain elevated as long as 72 hrs, depending on severity of the surgical trauma. Return of the plasma concentration to normal following surgery is initially characterized by increased plasma concentration of ACTH and cortisol (in the first 24 hrs) followed by a second phase (48–72 hrs) in which plasma ACTH concentrations are low and increased plasma cortisol concentrations are presumably independent of HP system.

In addition to surgical trauma, choice of anesthetic drugs and techniques may influence the HPA response. For example, large doses of opioid may attenuate the cortisol response to surgical stimulation. Volatile anesthetics provide less suppression to this stress-induced endocrine response. Etomidate is unique among drugs administered to induce anesthesia with respect to its ability to inhibit cortisol synthesis (selectively inhibits adrenal 11 beta hydroxylase, the enzyme that converts 11 deoxy cortisol to cortisol) even in the absence of surgical stimulation. Some medications other than glucocorticoids may suppress HPA function and place patients at the risk of developing adrenal insufficiency. Progestational agents such as medroxyprogesterone and megestrol have glucocorticoid activity. Enzyme inducers such as rifampin and carbamazepine enhance the clearance of some synthetic glucocorticoids. Inhibitors of cortisol synthesis include ketoconazole, aminoglutethimide, and etomidate.⁴

IMPORTANT INDICATION OF STEROID IN ANAESTHETIC PRACTICE:

Perioperative Steroid Replacement Therapy. Corticos Teroid supplementation should be provided for patient Being treated with steroids either for hypocortisolism or for other diseases. This is based on the concern that these Patients are more prone to cardiovascular collapse as release of additional endogenous cortisol in response to surgical Stress is not likely. Some patients may display suppression. Of pituitary-adrenal axis with atrophy of adrenal cortex from Long continued therapy with steroid drugs. Steroid administration is necessary in perioperative Period in patients treated for hypoadrenocorticism or in Patients with suppression of HPA axis owing to previous or Present steroid intake. The increase in circulating cor- Tisone levels from normal of 25mg/day to up to 300mg/day in severe surgical stress isone of the important components of stress response of our body. In the perioperative period Due to adrenal suppression, there can be increased vascular Permeability, inadequate vasomotor response, decrease in Cardiac output, and decrease in systemic vascular resistance and left ventricular stroke volume index which can lead to Severe hypotension and cardiovascular collapse, respiratory Depression, hyponatremia, hypoglycemia, hypercalcemia, And hemoconcentration. The specific duration and dose of steroid that can Produce HPA suppression is controversial. The recovery time of normal HPA axis varies from 2–5 days to 9–12 months After discontinuation of steroid therapy. But the ability to Respond to stress returns by 2 months. Traditionally it was believed that the degree of HPA sup- Pression and adrenal atrophy in patients receiving exogenous Glucocorticoids was related to duration and dose of therapy. In patients taking steroids for less than 3 weeks Suppression of HPA axis is rarely clinically insignificant. Conversely, any patient who has received the equivalent of 15mg/day of prednisolone for more than 3 weeks should Be suspected of having HPA suppression. However Recent studies have found poor correlation between HPA Axis function and the cumulative dose or the duration of Therapy. Because of considerable interindividual Variability in the degree and duration of adrenal suppression, it is difficult to accurately predict which patients will Develop adrenal insufficiency when glucocorticoid treatment Is discontinued. Thus, the need to evaluate HPA is a frequent Consideration. Under perioperative conditions adrenal glands secrete 116–185mg of cortisol daily. If plasma cortisol is measured During acute stress, a value of more than 25μg/dL assuredly and more than 15μg/dL probably indicates normal pituitary- Adrenal responsiveness. The intactness of the HPA axis and need for steroid may Be assessed by provocative tests which measure the plasma Cortisol response to administration of ACTH, CRH, lysine, vasopressin, metyrapone, and insulin-induced hypoglycemia. The gold standard for assessment of HPA function is the insulin tolerance test, but short synacthen test is cheaper and less unpleasant^1,7

Tests for Adequacy of HPA Axis:

(1) IV Regular Insulin 0.1–0.15U/kg results in rapi Lowering of blood sugar level within 10–20 min to less Than 2.2mmol/lt which triggers the release of ACTH. From pituitary and cortisol from adrenal cortex. This Indicates the adequacy of HPA axis function.^8,9

(2) 30 Min ACTH Test is the most consistent and Accurate diagnostic tool for preoperative evaluation of HPA axis function. Synthetic ACTH (cosyntropin) In a dose of 250μg is administered IV and a blood Sample for plasma cortisol is collected 30 mins later. Plasma cortisol concentration more than 500nmol/lt (18-20μg/dL) defines adequate adrenal function. This test is recommended as a preoperative screening test for evaluation of HPA integrity integrity.^8,9

(3) Short Synatchen Test: 250μg of ACTH is given and Cortisol is disease measured at 0 and 30 mins. Addi-Son’s is excluded if second cortisol is >500 nmol/L And >200nmol/L greater than baseline. If this does Not exclude Addison’s, an ACT level should be Measured.^8,9

STEROID AND THEIR APPLICATION:

Analgesic Adjuncts Analgesic effect of steroid is suspected to be mediated by Anti-inflammatory and immune suppressive effect. It Anti-inflammatory action results in decreased production of various inflammatory mediators that play a major role in amplifying and maintenance of pain perception. Some Studies have demonstrated the analgesic effect of local Spinal and systemic corticosteroids in combination with Bupivacaine. Dexamethasone microspheres have been Found to prolong the block duration in animal and human Studies, and adding methylprednisolone to local anesthetic Increases the duration of axillary brachial block. Movafegh et al. compared addition of 8 mg dex Amethasone to 34 mL of 1.5% lidocaine to that of 1.5% Of lidocaine. They concluded that the duration of sensory and motor blockade was Significantly longer in the dexamethasone than in the control Group. Paracetamol, NSAIDs, and glucocorticoids have a ceiling of analgesic effect, not being sufficient as monotherapy After extensive surgery. As glucocorticoids act on the Prostaglandin system differently than NSAIDs and have Other anti-inflammatory effects, there may be better analgesia When glucocorticoids are added to NSAIDs. Adverse effects with a single dose of dexamethasone are Probably extremely rare and minor in nature, and previous Studies have demonstrated that short-term use of dexamethasone was safe. ^[1,10]

CONCLUSION:

It can be said that these corticosteroids play an important role in the management of affected wounds Oral mucosa and skin. Steroids won’t cure your condition, but they are very good at reducing inflammation and will ease symptoms such as swelling, pain and stiffness. Corticosteroid therapy can be life-saving in serious and severe medical conditions. Importance of steroid in medical Emergencies cannot be ignored.

REFERENCE:

1. Safiya Shaikh, Himanshu Verma, Nirmal Yadav, Mirinda Jauhari, and Jyothi Bullangowda, A review article on “Applications of Steroid in Clinical Practice” SRMS IMS, Bhojipura, Bareilly 243202, India and KIMS, Hubli 580029, India

2. Dennis M Williams PharmD BCPS AE-C an Article on “Clinical Pharmacology of Corticosteroids”

3. Jatan Sanghavi, Amita Aditya A review article on “Applications of Corticosteroids in Dentistry” Departments of Orthodontics and Dentofacial Orthopedics and Oral Medicine and Radiology, Sinhgad Dental College and Hospital, Pune, Maharashtra, India

4. Application of steroids in Clinical Practice: “Effect of Anaesthesia and Surgery” on https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.hindawi.com/journals/isrn/2012/985495/%23:~:text%3DThe%2520effects%2520of%2520corticosteroids%2520are,the%2520endocrine%2520system%252C%2520and%2520the&ved=2ahUKEwjGldDm2-HuAhVBeX0KHWMGDsUQFjABegQICBAE&usg=AOvVaw0xNuWKvfJnmrL_MVWOFNcH&cshid=1613042662224

5. L. L. Bruton, J. S. Lazo, and K. L. Parker, Goodman and Gilman’S the Pharmacological Basis of Therapeutics, 11th edition, 2006.

6. Text book of Human Anatomy by Gray’s, 68th edition.

7. G. Nicholson, J. M. Burrin, and G. M. Hall, “Peri-operative steroid supplementation,” Anaesthesia, vol. 53, no. 11, pp. 1091–1104, 1998.

8. L. L. Bruton, J. S. Lazo, and K. L. Parker, Goodman and Gilman’S the Pharmacological Basis of Therapeutics, 11th edition, 2006.

9. Braunwald et al., Harrison’s Principles of Internal Medicine by Kasper, 17th edition.

10. H. Mirzai, I. Tekin, and H. Alincak, “Perioperative use of corticosteroid and bupivacaine combination in lumbar disc surgery: a randomized controlled trial,” Spine, vol. 27, no. 4, pp. 343–346, 2002.

Received on 08.03.2021 Modified on 12.10.2021

Asian J. Res. Pharm. Sci. 2022; 12(1):8-10.

DOI: 10.52711/2231-5659.2022.00002