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[Music] a very good evening to everyone i'm dr nisha kaka and on behalf of netflix i welcome you all for yet another interesting session by dr ganpathi bantwal a renowned endocrinologist so first of all i'll go over and begin with a brief introduction about sir and the topic in the under the discussion today uh dr ganpathi bhantav also after completing his mbbs and md from mysore medical college in bangalore he uh did his dnb and dm in endocrinology from pgi chandigarh he is currently professor and head of endocrinology department at st john's medical college and hospital in bangalore apart from being a distinguished clinician he also has a prolific research experience in his career having published several papers in both international and national reputative journals the topic he is going to elucidate today is about glucocorticoids as we all know the use of glucocorticoids is like a double-edged sword significant benefit can be expected if they're used discriminately and for the right condition proper dosage and for a limited period of time however inappropriate dose duration or abrupt withdrawal after a prolonged period of uh administration can result in debilitating side effects they're often touted as magical life-saving drugs and they're used rampantly across all medical specialties therefore the knowledge about this uh the proper usage is very very important for all healthcare professionals that is why today we have dr ganpathi bantwal so for his expert and insightful view on managing and minimizing the side effects of glucocorticoids well welcome please stay today thank you first of all uh thanks for inviting me to speak on this topic as you rightly told uh glucocorticoids are used rampantly uh by all of them starting from uh i mean everybody so starting from the siddha guys to or homeopaths or who are they are writing but we should be very clear about the side effects of that it does have benefits no doubt in that but then they do have side effects since the discovery in the 1940s they have played an integral role in the management of many inflammatory and immunological conditions it's used as a replacement therapy adrenal insufficiency here we are using as physiological dose so and this we call it as a replacement dose and of course in supraphysiological dose for the management of various dermatological ophthalmologic rheumatologic pulmonary hematologic and gi disorders in endocrine practice where you we use it in for establishing the diagnosis and cause of pushing syndrome so here what we do is we do methazone suppression test so whenever we have any hormones in excess we do a suppression test and that's what we do in pushing syndrome so when if first thing we see is do they have evidence of hypercortisolism and if it is there does it get suppressed so and that's how we come to know by doing the overnight dexamethasone suppression test and of course as a replacement therapy for adrenal insufficiency using physiological replacement dose and for congenital lateral hyperplasia for which the dose and the schedule may not be physiological so what do you mean by that so here what happens is we tend to give a higher dose in the night and the reason being we want to suppress the acth levels and that's the reason we would like to give so normal circumstances we don't give glucocorticoids in the night because we want to mimic the physiology so we have a maximum amount of cortisol in the morning and as the day goes by it comes down and if you see the diurnal rhythm also it's like that you find that your am cortisol is more and the pm cortisol is less so we want to maintain that and if you try to interchange that that is giving a higher dose in the night the patients are at high risk for developing hypothalamus pituitary adrenal axis suppression we also use it in patients with hypopituitarism so that we use this drug for treatment for a replacement so pharmacological uh usually supraphysiological dose as i told you is used in the various conditions so why are we concerned about this is we know a lot of side effects especially osteoporosis and fracture hpa axis suppression hyperglycemia and diabetes cardiovascular disease and dyslipidemia dermatologic and gastrointestinal events psychiatric disturbance and immunosuppression so this is the structure of the glucocorticoid so we call this the cyclopentanol per height of phenanthrene structure so the basic glucocorticoid structure and the chemical modification which are circled that can be introduced to increase glucocorticoid or membrane activity [Music] so you make a changes in these the circled one the function changes so that's what we are going to learn so these are lipophilic so glucocorticoids the glucocorticoid receptors are present in cytosolic but then they are not active because they are acted upon they come in contact with what is known as the heat shock protein now once the glucocorticoid receptors enter the cell then you find that the hsp is displaced the gluco body code now bind to the receptor enter into the nucleus so where they act on the regulatory enzymes so glu and they bring about uh they act on bind the responsive element which are present [Music] in the regulatory regions of the glucocorticoid target genes so the function as either trans activation or trans repression modulating the expression of target genes so that's how they bring about the effects so this is how the structure is so you have cortisol inactivated into cortisone redness on redness alone methamphetamine dexamethasone triams alone you have fluorocortisone so there are many options while prescribing the glucocorticoids common ones is redness alone methyl prednisolone dexamethasone high dose pulsed glucocorticoid therapy may be required in clinical emergencies or severe uncontrolled disease where we use iv methyl fatty salon or even sometimes we use dexamethasone so dexamethasone has been used in different encephalopathy dexamethasone hydros is used in multiple myeloma therapy for five days they use this so they may be required in case of central nervous system emergencies or its enhanced cns penetration [Music] coming to the pharmacokinetics so most of the cortisol in serum is bound to proteins primarily the cbg or cardiff cardio steroid binding global in an albumin in addition much of the biologically available cortisol may be bound to erythrocytes because they have little or no affinity for cbg synthetic steroids other than prednisone either bind weakly to albumin or circulate as free steroid so the plasma disappearance half-life of the synthetic glucocorticoids are generally longer than that of cortisol cortisol has a half-life of around 80 minutes now why is this important is now when you're using the hydrocortisone in patients with type 1 diabetes you get brittle diabetes because life is 80 the action veins off so you find that the glucose goes up and down up and down so that's the reason in patients with type 1 diabetes we tell use prednisone because it has a more smoother action than hydrocortisone given the choice if you find that they are brittle a number of factors that influence both the therapeutic and adverse effects of glucocorticoids like the biological potency pharmacokinetic properties of the glucocorticoid daily dose timing of the dose as i told you intra individual differences in steroid metabolism and the duration of treatment now i put this slide you know why many people ask uh we are using prednisone redness alone methyl condition on dexamethasone why are we using methyl production though if you see potency wise uh actually the glucocorticoid potency is highest for dexamethasone and it is just five times the cortisol with methamphetamine why is that so you can see the affinity to the receptor is maximum for methylpenicillin 1190 compared to dexamethasone 710 and this is a reason why without salon has a very important effect [Music] and the other thing here i just put it is to know the equivalent dose so 20 milligram of hydrocortisone is equivalent to 5 milligram of redness alone or vice alone or on the cortical and four milligram of methyl penicillin and 0.75 milligram of dexamethasone sorry [Music] so this is the slide sorry for that so you can see here 1190 times for methyl penis alone compared to that of dexamethasone now coming to the prednisolon metabolism may influence side effects so the disappearance curves of dry sheated prednisone in five patients who did not develop side effects while taking prednisone and in eight patients who did so you can see uh the red one this one with no side effects because you can see the concentration had come down compared to those so the patients who developed side effects clear technolon from the circulation more slowly the blue one is that how does this t dot gets inactivated so you have the 11 beta hsd type 1 which converts inactivate inactive horizontal cortisol it's expressed in many glucocortical target tissue the type 2 that's the most important one which converts cortisol to cortisone is found mainly in the mental cortical target tissue that is kidney colon salivary glands and in the placenta in which it protects the cell from cortisol activation of the corticosteroid type 1 receptor of the mineral corticoid so what does it mean if the cortisol is in excess cortisol that's an active one it can bind to the mineral particle receptor so normally what happens fluid cortisone or the middle aquatic or gets or the aldosterone goes and binds to the cortical receptors so when you have cortisol in excess it gets bound to the middle cortical receptor also and bringing about the mental cortical action that's the reason you get patients having hypokalemia etc so that effect is because of the melanocorticoid action and the hypertension also [Music] so once it gets inactivated by the type 1 11 beta hst then they don't bind to the middle according and only the aldosterone goes and binds to the middle particular receptor glucocorticoids that are fluorinated at the six alpha or nine alpha position that is dexamethasone flutter cortisone beta methyl zone or methylated at the sixth alpha position that is metal penicillin or methyl oxazoline at position uh the fluoza card are protected from oxidation inactivation by the type 2 enzyme so prednisolone 3d stone rather is more effectively oxidized by 11 beta hst type 2 than is cortisol explains why retinitis on has less salt retaining activity [Music] many glucocorticoids are both substrates for peak glycoprotein mediated efflux from cells and induces a p glycopathy production so there's a gene known as a mdr-1 gene polymorphism of this may influence the therapeutic response to steroids polymorphism in the glucocorticoid receptor gene may increase or decrease sensitivity to glucocorticoids and thus affect the response to both endogenous and exogenous agents this is just a slide to show that what are the interactions which can happen so suppose you are using an anti-cannibal scent like caramel zapping phenomenon [Music] phenytoin they reduce the glucocorticoid exposure and efficacy it will persist for some weeks following this continuation of the and the conversation so you require those alteration when you actually use this coming to anticoagulants like warfarin they may so what is the effect may in this anticoagulant effect of varcharin and increase the risk of gi bleeding so you have to be very cautious so monitor the inr closely significant alteration in warfarin dose will likely to be required within three to seven days of glucocorticoid initiation what about antifungals like ketoconazole interconnell they increase the glucocorticoid exposure and toxicity so the side effects worsens when you actually use this you may have to reduce the dose of these drugs the glucocorticoids anti-diabetic agents glucocorticoid initiation this is very common worsens glucose i mean hyperglycemia antibiotics macrolides like claritamycin they behave like antifungals they increase the glucocorticoid exposure and toxicity we may require to down tighten the dose similarly antivirals like attach indian away return away they also act like uh the antifungals and for that matter clarithromycin so you required to down titled the dose so that dexamethasone male levels may increase the dexamethasone may increase the levels of indian american sacrifice so toxicity may happen so we have to monitor for this coming to anti-infectives efferverance develop in the family scene so they metabolize these drugs so the glucocorticoid exposure and efficacy comes down may persist for weeks following this combination of anti-infective so you require close monitoring what about diuretics uh they produce more potassium wasting so as i told you glucocorticoids in excess can act on the middle of body cavity receptor produce hypertension and hyperkalemia so it converses in the hypokalemias you have to monitor so many patients may come with proximal muscle weakness when you use these drugs because there is hypokalemia uncommonly very rarely you may find that they may even present with something like a periodic paralysis type because it's so low potassium and also and one of the most important thing is when you use these drugs like methyl penicillin you have to be very careful it can produce sometimes arrhythmias also got to be very careful live vaccine immunization with live actions while taking immunosuppressive glucocorticoid dose that is 40 milligram per day of renaissance or equivalent for more than seven days may increase the risk of both generalized and life-threatening infection so postpone live actions for at least three months after high dose glucocorticoid therapies discontinued this was a question commonly asked during the four week times when they were on steroids nsaids may increase the risk of gi ulcers when given concomitantly with glucocorticoids so what you have to do try giving them with a ppi in these type of patients so what are the common clinical uses of corticosteroids systemic so we use it for severe access surveilation of asthma copd allergic rhinitis aerobic dermatitis urticaria angioedema anaphylaxis cycloid etc in dermatology pempigas acute severe contact dermatitis endocrinology already told you gastroenterology ulcerative colitis crohn's autoimmune [Music] hepatitis hematology lymphoma leukemia hemolytic anemia itp rheumatology rheumatoid arthritis sle polymyositis polyarteritis ua it is keratoconjunctivitis in ophthalmology and others like multiple sclerosis post transplantation nephrotic syndrome cerebellary chronic hepatitis [Music] so how does it bring about these effects so anti-inflammatory inhibits inflammation by blocking the action of inflammatory mediators we call it as trans repression or by inducing anti-inflammatory mediators trans activation immunosuppressive suppresses delayed hypersensitivity reaction by directly affecting t lymphocytes antiproliferating inhibition of dna synthesis and epidermal cell turnover was a constrictive inhibition action of histamine and other vasoconstrictive mediators uh well this has already been told to you i will not go much into that just to tell you the duration of action of dexamethasone is 36 to 72 hours related glucocorticoid activity is 30 for dexamethasone and betamethasone protocortisone has glucocorticoid activity of 10 to 15 but then you can see the male aquatic activity 125 to 150 hydrocortisone we take as one cortisone redness on redness alone is around point eight methylprednisolone milder body product with this mineral a minimal dexa and betamethasone are very negligible menlo corticott activity but then duration of action is the one which is very important [Music] so interactions which i already told you so i will not go much into that this is just uh the same thing what i told you in a different form [Music] now coming to the side effects of short-term and long-term steroid use short-term gi intolerance increased predisposition to infection delayed wound healing increased appetite so this is one reason people put on weight fluid and sodium retention mood changes weakness insomnia amenorrhea acne long term musculoskeletal growth retardation osteoporosis myopathy a vascular necrosis of bone very important hpa axis separation you must know this withdrawal syndrome adrenal crisis can happen cataracts glaucoma with ophthalmological involvement gastritis peptic ulcers pancreatitis intestinal perforation can happen then metabolic hyperglycemia pushing oil features hyperkalemia hyperlipidemia cutaneous hirsutism atrophy hyperpigmentation acne and nervous system more than personality changes psychosis pseudohuman cerebri for most glucocorticoid related adverse events a threshold dose or treatment duration has not been established we don't know what is the threshold dose or the side effects okay now let me go into the osteoporosis fractures in osteonecrosis they stimulate osteoclastic activity initially first six to 12 months of therapy followed by a decrease in bone formation by suppressing osteoblastic activity in the bone marrow decreasing osteoblast function and lifespan and it promotes the osteo apoptosis of osteoblast and osteocytes and that's how they produce osteoporosis a meta-analysis of more than 80 studies in adults found that the use of more than five milligram per day of fitness loan was associated with significant reductions in bmd and an increase in fracture risk within three to six months of treatment initiation this fracture risk was independent of patients age gender and underlying disease so this loss of bone marrow density in patients who are taking glucocorticoid occurs primarily in the first six months of therapy and then it slows down after one year so you can see in the first three months of therapy the risk of fracture increases by as much as 75 percent before a significant decrease in bmd happens so fracture that can spread dominantly in regions with high amount of cancerous bone spine and proximal femur [Music] what about osteonecrosis so we also call it as a vascular necrosis or we call it something like that keratin so austenitis develops in nine to forty percent of adult patients receiving long term global body part therapy i told you this is like the curated i mean coronary artery disease of the heart no similarly this is the coronary artery disease of the bones it can act as a result of systemic therapy or via intra-articular injections as well as in the absence of glucocorticoid induced osteoporosis uh usually happens with higher dose and prolonged treatment but it can occur with low doses or even short term cortical exposures we have had patients who develop with replacement doses of hydrocortisone also what are the risk factors excessive alcohol intake hypercoagulable states sickle cell disease radiation exposure and hiv infections so you can see here the probability is the 10 year probabilities of a hip fracture or a major osteoporotic fracture by age according to those of glucocorticoids so when you use a very small dose say less than 2.5 the risk is very little for all ages for high dose that is more than 7.5 you can see it increases at all ages plus 25 [Music] at 40 50 60 70s and plus 10 at 80 and 90 and overall there's a plus 20. what about major osteoporotic fracture at low dose minus 2 i mean at 2.5 milligrams of penicillin it's very minimal but high dose does a 15 increase risk so this is the most important thing hp access separation so the duration of glucocorticoid therapy and doses of glucocorticoid therap treatment are not reliable predictors which patients will develop adulenes suppression it has happened even after exposure to even five days duration of high dose glucocorticoid it can even happen with inhaled topical and intraocular glucocorticoids long acting formulations naturally produce higher risk timing i told you this is very important don't give it in the night if at all you want to give it give it in the morning alternate day therapy theoretically less suppressive because you are giving some time for the recovery of the hp access but then there is no solid clinical evidence to support this how does uh i mean what are the symptoms adrenal suppression they feel mentalized nausea vomiting diarrhea abdominal pain headache usually in the morning fever anorexia weight loss myalgia arthralgia these are the most important thing poor linear growth in children who are weight gain in children and crisis when it's been suffered so when you give exogenous the endogenous gets suppressed and you stop the drug suddenly they become very all the symptoms so you may develop hypertension lethargy hyponatremia seizures and coma so this happens following abrupt discontinuation of glucocorticoid therapy you don't have any evidence-based guidelines for tapering glucocorticoids but then it should be a gradual tapering of the glucocorticoid yeah what are the other side effects usually appearance and weight gain so especially you find that truncal obesity facial adipose tissue moon faces and the dorsal cervical adipose tissue so in a survey of two thousand one hundred patients long-term glucocorticoid uses that is a mean prednisone equivalent which was around 16 plus or minus 14 milligrams for more than 60 days 70 percent had weight gain happens within the first two months both those in duration dependent higher in younger patients with a higher bmi and higher caloric intake this rate increases linearly with those so less than 5 mg 4.3 percent 5 to 7.5 15 percent 25 with those more than 7.5 coming to hyperglycemia and diabetes the effects of glucocorticoid administration on glucose levels are observed within hours of glucose steroid exposure and they are dose dependent so what happens is predominantly post prandtl increase compared to fasting blood glucose coming to cataracts and glaucoma once again this is also those dependent one common mcq which is always asked is they produce posterior subcapsular cataract which is more visually significant and require early treatment the time until onset is at least one year with doses more than 10 milligram per day of oral patients alone uh although posterior subcapsular cataracts are seen in patients treated system systemically or even occasionally in those receiving inhaled corticosteroids they can also happen secondary to local treatment like topical eye drops periocular or intravitreal administration glaucoma more serious complication systemic corticosteroids can painlessly increase intraocular pressure leading to visual loss field loss optic disc cupping optic nerve atrophy once the systemic therapy is discontinued the elevation in interocular pressure often resolves within a few weeks but the damage to the optic nerve is often permanent ocular hypertension and glaucomatous visual field defects have been reported using systemic steroids especially with the family or personal history of open-angle glaucoma so these are the patients who are at iris you are a person or family history of open-angle glaucoma diabetes is another risk factor high myopia or connective tissue disease particularly rheumatoid arthritis so you have a screen when you use them please the other condition is central serious choreo retinopathy [Music] this type of korean retinopathy is associated with formation of sub retinal fluid in the macular region which leads to separation of retina from its underlying photoreceptors so the present with a central blur vision and reduced visual equity so you have to be very cautious how do you treat downtight at the dose or stop it temporarily coming to cuterious adverse humans skin thinning fragility padpura red stripe usually reversible or the striae are permanent uh they interfere with the natural wound healing by inhibiting leukocyte and macrophage infiltration decreasing collagen synthesis and wound maturation [Music] reducing keratinocyte growth factor expression of skin injury how do you prevent that so you could use epidermal growth factor tgf beta pdgf or tetrachlorodeca oxygen what about cardiovascular diseases and dyslipidemia patients on these drugs have a higher cbd risk including hypertension hyperglycemia obesity especially the dose is more than 7.5 milligram in a large retrospective study case control study found glucocor current usage of glucocorticoid significantly increased risk of heart failure a twofold increase at 20 percent higher risk of isd but not ischemic stroke of transit ischemic attack and this risk was greater with higher dose with current versus past use for dyslipidemia there is conflicting results so i told you before more than 7.5 higher risk hypertension and heart failure worsen because of sodium and fluid retention and this happens immediately after cordicosteroid therapy uh people have also found mi heart failure in some studies even tia and stroke with this use coming to the gi events so increased risk of gastritis ulcer formation with perforation hemorrhage dyspepsia abdominal distension and esophageal ulceration but a large meta-analysis uh of control randomized control trials a fail to show a significant association between glucocorticoid use in peptic ulcers recent evidence such as the risk of peptic ulcer disease due to corticosteroid alone is low but increases significantly when you use it in combination with nsids acute pancreatitis also has been reported myopathy these are not a very common side effect so when they are on high-dose steroids you find that they have a proximal muscle weakness this is because of the catabolic effect of glucocorticoids and air of course weeks to months dose is more than 10 milligram and higher the dose more the weakness [Music] symptoms improve within three to four weeks of those reductions usually result after discontinuation of glucocorticoid you do good exercise both resistant and endurance exercise they help to attenuate glucocorticoid induced muscle atrophy [Music] another important thing critical illness myopathy especially if you're using large doses of iv glucocorticoids and neuromuscular blocking agents they are characterized by severe diffuse proximal and distal weakness that develop over several days usually reversible but may lead to prolonged icu admissions increased length of hospital stay severe necrotizing myopathy and sometimes increased mortality so treatment directed towards this continuation of glucocorticoid therapy on reductions of those as soon as possible as well as aggressive management of underlying comorbid conditions what about psychiatric and cognitive uh disturbances a lot of them happen like memory impairment agitation anxiety fear hypomania insomnia irritability lethargy psychosis it can happen even on the first day also forget one week it can happen in the first day dosed and duration dependent a family history of depression or alcoholism has been reported as a risk factor uh those who develop psychiatric manifestation of short poses report mania euphoria on long term depressive symptoms sleep disturbances and unpleasant dream especially if you use it in the evening hours so many times even when you use it as a replacement therapy the evening dose can produce that and many times we may have to cut down the evening dose a decline in declarative and working memory has been reported with glucocorticoid therapy once again these are all dose dependent frequently occurred during the first few weeks of therapy and they also found a partial loss of some explicit memory especially doses of 5 to 40 milligram for at least one year so the psychosis happens with higher dose low albumin levels is predictive when you develop psychosis in some patients you may give antipsychotic therapy dose reduction some people have tried lithium in this type of patients as you know it's an immunosuppressive thing you have to be cautious uh so a meta-analysis of 71 trials involving more than 2000 patients overall rate of infectious complications higher 60 higher versus control but not so when the dose was less than 10 mg or a cumulative dose less than 700 milligram the other factors include underlying disorder patients age concomitant use of immunosuppressive or biological therapies very high levels patients susceptible to invasive fungal and viral infection like aspergillus nuclear mycosis this is especially true in bone marrow transplant recipients early recognition is in fact difficult because they mask the symptoms of fever etc so they are not manifest signs and symptoms as clearly as non-users children very important so when you use this inadvertently or for a long time growth and puberty gets affected final height may be compromised so in a study of cystic fibrosis patients whom they followed up for nine approximately 10 years they found that height was affected in these type of patients uh then children can also have vertebral fractures they're often asymptomatic even when moderate or severe especially it's located in the mid thoracic and at the thoracolumba junction now coming to practical recommendation for monitoring prevention and management so you require a thorough history and physical examination to assess for risk factors or pre-existing conditions that may potentially be exacerbated by glucocorticoid therapies right such as diabetes dyslexia cardiovascular disease gi disorders affective disorders of osteoporosis so this is what you do height weight bmi bp cbc glucose lipids bmd annual height measurement use tracks bone health uh look into the once again looked into the bmd z scores you will check into that uh look for dyslipidemia hyperglycemia eye examination so general guidelines initiate only if there is published evidence of objective therapeutic benefit use only after specific therapies fail [Music] identify a specific therapeutic objective use objective criteria of response administer sufficient glucocorticoid for a sufficient time to achieve the desired response administer glucocorticoid for no longer than that is necessary to achieve the desired response terminate if you don't get a benefit or if complications arise or if maximum benefit has not been achieved use the lowest dose try to use it as a single dose in the morning consider intermittent or alternate dose if possible [Music] use glucocorticoids pairing agents like uh whenever possible like omalizumab in severe asthma azata hyperincyclophosphate vasculitis methotrexate in rheumatoid arthritis [Music] so this is very important carry a steroid treatment car so we always give to our patients because many times when they go to the hospital with some fever etc first question they ask why are you taking you should not take this it will produce a lot of problem so if you show that card they know okay this patient requires glucocorticoids for survival [Music] avoid contact with persons having infections such as shingles chicken pox measles not discontinued look glucagon therapy abruptly unless advised to do so by the physician healthy lifestyle balanced diet adequate calcium intake smoking cessation reduction in alcohol consumption regular physical activity and monitor for signs and symptoms of adverse events so how do you screen so when you screen for hydraulic insufficiency or hpa axis suppression if the patient has received systemic corticosteroids for more than two consecutive weeks or more than three cumulative weeks in the last six months patients and symptoms weakness fatigue mellitus which i took told you poor weight gain headaches especially in the morning hypoglycemia hypertension how do you screen early morning cortisol levels you must measure no oral glucocorticoids in the evening and morning prior to the test they must be completed by 8 am so we tell get a morning cortisol [Music] if the morning cortisol is normal but the patient has symptoms of adrenal insufficiency you can do a low dose active stimulation test and that is a one microgram synaptic test samples taken at 0 30 minutes and 60 minutes peak cortisol is less than 500 nanomoles or 20 you can say 20 micrograms per deciliter then the patient has that or early morning cortisol level less than three millimoles or the rather three micrograms per deciliter once again is suggestive of possible adrenal insufficiency what are the recommendations for management so suppose you find them your hydrocortisone injections 100 milligrams per meter square body surface area im or iv stat with saline volume expansion then i give 25 milligrams per meter square sixth hourly for surgery hydrocortisone injection 50 to 100 milligram per meter square pre-op and then 25 milligrams per meter square sixth hourly illness or fever double the dose and if the patient is having vomiting then you give injectables physiological doses around 8 to 10 milligrams per meter square body surface area educate the family about stress steroid dosing emergency medical contact recommendation for management of adult sufficiency in adults so you can give actually say if it's a minor one just a 25 milligram injectables you can use just before the surgery and then they take the usual dose for moderate surgeries 25 milligram six hourly you can give severe fifty two hundred milligrams per day you can give critical illness fifty two hundred milligrams six hourly you could give it how do you taper so suppose somebody is on hydrocortisone uh say he's on pretty salon you come to the minimal dose which is five milligram what we do is they will be on the minimal dose which is five and then we reduce it to half a tablet that is it comes to two point five don't have two point five in the tablets then we switched from 2.5 mg say two to four weeks we switched them to hydrocortisone 2.5 milligram of redness alone is equivalent to around 10 to 12 milligrams of hydrocortisone so we split them i give them five milligram or 7.5 milligram and another 5 milligram say for 4 weeks reduce it 5 and 2.5 then we give 2.5 2.5 2.5 once a day two point five alternate days so gradually over a period of time three to six months with down tight rate so when you are on a single dose you could actually measure the cortisol levels the next day and see whether the cortisol has started becoming detectable the moment you find that the cortisol has become detectable that means to say this hpa axis is recovering whether the patient has become completely normal you can do a act stimulation test and if it crosses more than 500 animals or 20 micrograms per deciliter that the patient has recovered it's almost similar to that for even children [Music] this was one protocol by samuels we don't follow this protocol uh what about glucocorticoid induced osteoporosis so what you can do is uh all of them you must tell them to take calcium vitamin d this is mandatory 1000 to 1200 milligrams of calcium vitamin d you must give them daily which is 1000 to 2000 iu per day or you can give 60k once a month or even months in 15 days is also fine when the patient is on this and if the duration of therapy is more than three months it's better we start them and they do and the dose of glucocorticoids are more than 7.5 mg more than three months it's better we start the monument allendronate residonate zolindronite in some patients we could also use uh terry paratide and we have also used denozu map in this type of patients uh glucose treatment so glucocorticoid induced the targets remain the same we want the a1c to be less than seven percent so glucocorticoids worsen the insulin resistance so use metformin but then metformin alone may not be sufficient especially when you are using higher dose so then you can if the patient is on only marginal increases in the postpartum glucose you could use a dpp fourier meters but if you find that the dose is high say use 40 milligram of redness alone then you can use an nps in the morning because the glucocorticoid or nph acts the exactly the same way as how apprentice alone so when you spread my salon the glucose starts increasing free lunch it takes post lunch the action is there up to around 12 to 1 a.m in the night and morning there is no glucocorticoid at all and that's why you find that the fasting glucose is always normal when you use these type of drugs and the peak happens to three hours late after lunch so that's the reason we give an nph in the morning and the nph will act exactly the same way how glucocorticoid will act so to conclude glucocorticoids are used to treat a variety of inflammatory and autoimmune disorders prolonged use is associated with serious adverse events patients should be advised regarding the side effects and the ways to minimize them they should be advised to carry a steroid alert card with them should be told to identify ideal suppression and how to treat monitor for side effects especially growth effects osteoporosis and hyperglycemia thank you for patient hearing thank you sir for a wonderful detail session uh we're open to questions uh you're free to post your questions or in fact with uh qrays and requests um meanwhile i have a question for a lot of times uh iv steroids are added in neurological conditions like multiples and they're considered superior steroids because of less gastrointestinal side effects and higher potency what is your opinion on that because there's a lot of papers that say there is no real benefit of iv glucocorticoids over oral uh glucocorticoids do you think especially in neurological conditions uh they are superior to oral steroids yes they are superior to oral glucocorticoids that's the reason i put that slide methyl prednisone without any doubt is very important now i'll give you another example for example in thyroid associated of almond protein iv steroids methyl penicillin without any doubt is better than the oral steroids similarly in multiple sclerosis also short-term steroids they're very effective so they are beneficial uh compared to that of all the steroids okay for hyperpituitarism which one is better prednisone okay so the answer is if the patient cannot afford it then pregnancy alone is fine see we require to give what is known as a physiological replacement and the physiological replacement is is actually hydrocortisol now how do you give that so normally we give around see the dose varies between 15 to 25 milligrams so we divide them into three doses what we do is we give them around 20 milligram 10 milligram in the morning the moment it gets up milligram 12 to 1 o'clock and another 5 milligram at around 6 o'clock roughly we give three doses so that by around one o'clock two o'clock when you have the least level of corticoid it matches the physiology so that's how we actually do the uh thing so that is better but then as i told you some patients may not feel that well especially if they are a diabetic and all so then we may have to change it to this alone but once again uh if you want a further fine tune it you could give an additional 2.5 mg at around say nine o'clock if the patient says no i'm feeling very uncomfortable the moment i get up that's because the effect of the steroid at six o'clock in the night has gone so another minimal dose 2.5 of hydrocortisone can also be given [Music] see if there is a necessity to use uh steroids we have to give but then as you rightly told high myopia they are at risk for glaucoma but then if there is a necessity we may have to use it because because the short term we require to use it so i will continue to use because so then we can give a high dose steroid for few days and then just stop it so like that we can actually give it so in our hospital sometimes uh say for asthma we give methyl fitness alone also so our uh pulmonologists give methyl penicillin infusions for 2-3 days so that it becomes better so that's also been right so you can actually give oh can we give hydrocortisone in uh ccf with pulmonary edema you have to be a little bit cautious when you use this because it has a fluid retaining property so you have to be cautious but then if the patient is definitely requiring it you use it now for example if the patient is having addison's disease and his developer pulmonary edema we have to use because hydrocortisone is required for survival for him without that they'll die culminating will treat with a diabetic or something more than that we can use so when is it required you must use it by the pros and cons patience where you must require you should uh say i told addison's they're required for survival you just use it like that [Music] if you want for the anti-inflammatory effects hydrocortisone is fine you can also use dexamethasone not an issue that's also fine because in our this one they use what you call dexamethasone also so the pulmonolist use it so that's fine both are equally good okay so uh yeah so don't use high uh what you call high potency one like low beta solve you can use uh lower ones i mean the weaker ones like mommy zone so these things can be used see now there are many people who develop atopic eczemas initially you may require a slightly higher dose but then they all become better and after that just apply over those lesions only so don't apply the whole body so the moment your whole body uses such a large surface area it all gets absorbed if you just put some concentrated one over that active lesions only they actually do very well so you actually have to see that or you can use a lesser potency one like momento zone etcetera okay so thank you sir uh dr surya prakash is asking does hybrid dose of redness alone and hydrocortisone can be given one in morning [Music] if you give it in the morning so don't give fitness alone in the night you are producing hpa axis suppression so that you have to remember now when do we use this type of a regimen now this type of a regimen rarely we use it in patients with congenital electrical hyperplasia so there what happens is we want to bring down the levels of uh ac th because that's a driving force there so then we use steroids three times and a very very small dose of prednisone in the evening so but that is not really good because we found that though they say it's been usa now when you use this small dose of kidney salon the dose of hydrocortisone actually comes down but still we found that especially in children it was having a growth suppressive effects though the dose was so small and overall if you compare the dose was actually less in when you use this combination still the growth suppressing potency was there so that's the reason i'm not in favor actually of this type of a regimen and when you use hydrocodone it's more physiological and not only that it has the least side effect now why is it important is i told you that the half-life is around 80 minutes and after that you find that you're giving some time for a little bit of recovery also so that's the reason suppose you use a drug like dexamethasone 36 hours non-stop action you've completely suppressed it so there's no question of recovery if suppose you used it for a short term here what happens you give time for recovery the side effects are lesser so suppose somebody develops pushing features so he was on small dose of separateness you change into hydrocortisone these symptoms start becoming lesser if the patient was on dexamethasone change them to hydrocortisone so all the side effects can be lessened with hydrocortisone because you are giving some time for recovery also [Music] any more questions i think all the questions are different and we can end the session [Music] topic yes thank you thank you to everyone who joined and participated in this session hope you all had a very informative and an enjoyable you
Managing and Minimizing the side effects of Glucocorticoids
The term “glucocorticoids” (GCs) represents both naturally secreted hormones by adrenal cortex and anti-inflammatory and immunosuppressive agents. Systemic glucocorticoids are an essential therapy for a range of conditions, but their multiple side effects can produce significant morbidity for patients. Cushing’s syndrome, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, osteoporosis, psychiatric disturbances, and immunosuppression are among the most important side effects which are significantly noticeable at high doses for prolonged periods. Dr. Ganapathi Bantwal, Professor & Head of Dept. of Endocrinology helps us understand these crucial parameters to effectively manage glucocorticoid side effects.
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