INTRODUCTION:

Physiological effects:

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 secondary failure of the pituitary or hypothalamus, which results in deficits of adreno-corticotrophic hormone or corticotrophin Releasing hormone? Corticosteroids effects on inflammation and immune function are described below.

In addition, these agents affect carbohydrates, 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. There also are effects on cardiovascular function and fluid electrolyte balance that are attributed both to gluco-corticoids and miner-alocorticoid activity. With pharmacologic dosing of corticosteroids, these effects are significants and often undesirable, which results in physiologic consequences that are described in the adverse drug reactions and side-effects section.

Although cortico-steroids are used primarily for their anti-inflammatory effects, they also associated with beneficial effects on the 2-adrenergic receptors. Cortico-steroids are associated with upregulation of 2-adrenergic receptor function as well as acting to reverse down regulation of these receptors associated with chronic 2-adrenergic therapies. Plausible mechanisms for this effects at the 2-arenergic receptor are to increases coupling of re-captors to G proteins, which increases adenyl cyclase, and to also increase the synthesis of new receptors¹

Effects of Anaesthesia and surgery:

Plasma cortisol levels typically increase from two-ten-folds following induction of anesthesia, during surgery, and in posto-perative 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 factor that activate HPA axis to release cortisol include pro-inflammatory 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 of the surgical trauma. Return of the 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 concentration 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 gluco-corticoid. Inhibitors of cortisol synthesis include ketoconazole, aminoglutethimide and etomidate.²

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 or 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 cortisone levels from normal of 25mg/day to upto 300mg/day in serve surgical stress is one of the important components of stress response 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 serve 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 suppression and adrenal atrophy in patients receiving exogenous.

Glucocoticoids 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 comulative 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 periperative conditions adrenal glands secretes 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.³

Tests for Adequacy of HPA axis:

1. IV Regular insulin 0.1-0.15 U/kg results in lowering of blood sugar level within 10-20 min to less. Than 2.2 mmol/lt which triggers the release of ACTH. From pituitary and cortisol from adrenal cortex. This indicates the adequacy of HPA axis function^7,8

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 (18-20 µg/dL) defines adequate adrenal function. This test is recommended as a preoperative screening test for evaluation of HPA integrity.⁴

3. Short Synatchen Test: 250µg of ACTH is given and cortisol is disease measured at 0 and 30 mins. AddiSon’s is excluded if second cortisol is > 500 nmol/L and > 200 nmol/L greater than baseline.if this does not exclude Addison’s an ACT level should be measured.⁶

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 cortico-steroid in combination with bupivacaine, dexamethasone microsphere have been found to prolong the block duration in animal and human studies. And adding methylprednisolone to local anesthetic increases the duration of axilliary brachial block. Movafegh et al. compared addition of 8 mg Amethasone to 34mL of 1.5% lidocaine to that of 1.5% of lidocaine.⁷ They concluded that the duration of sensory and motor blockade was significantly longer in the dexamethasone than in control group. Paracetamol, NSAIDs, and glucocorticoids have a ceiling of analgesic effect, not being sufficient as monotherapy after extensive surgery. As gluco-corticoids act on the prostaglandin system differently than NSAIDs, 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 rarer and minor in nature, and previous studies have demonstrate that short term use of dexamethasone was safe.⁸

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 serve medical conditions. Importance of steroid in medical emergencies cannot be ignored.

REFERENCE:

1. Safiya Shaikh, Himanshu Verma, Nirmal Yadav, Mirinda Jauhari and Jyothi Buliangowdia, A review article on “Application of Steroid in Clinical practice” Published by Hindawi, Volume-2012; DOI:10.5402/2012/985495.

2. Article on Clinical Pharmacology of Corticosteroids by Dennis. M. Williams, by Respiratory Care, DOI: 10.4187/ respcare.06314.

3. Article on “Application of corticosteroid in dentistry” by Jatan Sanghavi, Amita Aditya Published by Journal of Dental and Allied Sciences, 04(1): 19-24, DOI: 10.4103/2277-4696.167533.

4. Aricle on “The Pharmacological Basis of Therapeutics” by L.L. Brunton, J.S. Lazo, K.L. Parker, published by BMJ publishing group, DOI: 10.1136/oem.2007.033902.

5. Textbook of “Human Anatomy by Gray’s 68^th edition.

6. Article on “Peri-operative steroid supplementation” by G.Nicholson, J.M Burrin, G.M.Hall, DOI:10.1046/j.1365-2044.1988.00578.x.

7. Article on “Harrisone’s Principles of Internal Medicines” by Barry R. Masters, DOI: 10.1007/s00417-012-1940-9.

8. Article on “Perioperative use of corticosteroid and bupivacaine combination in lumbar disc surgery: a randomized controlled trials”, by Muhammad Waqas, Hussain Shallwani, Muhammad S. Shanim, Khabir Ahmad, Published by Surgical Neurology International on 05 April-17.

Received on 12.07.2021 Modified on 03.08.2021

Asian J. Research Chem. 2021; 14(6):448-450.

DOI: 10.52711/0974-4150.2021.00078