Glucocorticosteroids Colour Notes 2024 PDF

Dr. L. Harmse [email protected] Purpose  Explore glucocorticosteroids as potent anti-inflammatory agents  Understand their effects on normal physiology  Relate normal effects to ADR profile  Apply this knowledge to develop a safe therapeutic approach...

Dr. L. Harmse [email protected] Purpose  Explore glucocorticosteroids as potent anti-inflammatory agents  Understand their effects on normal physiology  Relate normal effects to ADR profile  Apply this knowledge to develop a safe therapeutic approach Consider: The effects of glucocorticosteroids on the HPA axis. ADVERSE EFFECTS Harm ADRENAL SUPPRESSION The dose needs to be tapered when the treatment is stopped. DOSE TAPERING Benefit Always keep in mind that glucocorticosteroids can bestow a lot of benefits to the patient But they can also harm patients. therefore glucocorticoid steroids are a true representation of a double edged sword. It is our job to balance the harmfuland the beneficial effects.  Objectives  Understand the role of glucocorticosteroids in disease management  Describe the relative POTENCIES of the glucocorticosteroids  Describe their effects on gene expression  Know and explain the effects on normal physiology  Describe effects on HPA axis ( Adrenal suppression/crisis)  Describe the effects of glucocorticosteroids on the immune system  List and explain the causes of the adverse effects  Understand the role of glucocorticosteroids in the management of asthma and other diseases The main therapeutic uses of exogenous glucocorticosteroids are related to their effects on the immune Overview of therapeutic uses system. Immune system Glucocorticosteroids are used in diseases with underlying inflammation, because glucocorticosteroids possess excellent anti-inflammatory efects. diseases such as inflammatory bowel disease (IBS) and asthma respond well to glucocorticosteroids. Anti-inflammatory effects Immunosuppressive effects Glucocorticosteroids also cause immunosuppression. Consequently patients with allergic reactions, patients being prepped for organ transplantation, and patients on treatment for cancer/ autoimmune Inflammatory bowel Allergic reactions diseases/rheumatic disorders/ skin disorders, respond well to the immunosuppressive effects of disease glucocorticosteroids. Organ transplantation Inflammation Cancer –haematological Glucocorticosteroids are also used in other conditions, including: Asthma Autoimmune diseases Adrenal insufficiency Premature neonates ( glucocorticosteroids stimulate the synthesis of surfactant this helps the Rheumatic disorders lungs of premature babies to mature and thereby reduce respiratory distress) Skin disorders Multiple Sclerosis ( glucocorticosteroids are used during exacerbations and for management of Other uses the disease) Renal disease (glucocorticosteroids are used in renal diseases with an autoimmune component) Adrenal insufficiency Premature neonates – lungs  reduces respiratory distress Multiple sclerosis Renal disease  How do glucocorticosteroids function to suppress the immune system? Firstly we need to understand that the body produces cortisol and other endogenous Introduction to GS function glucocorticosteroids (e.g. corticosterone). Therefore glucocorticosteroid medications mimic the action of cortisol.  Endogenous & exogenous glucocorticosteroids On a normal day the body produces approximately 10 to 20 mg of glucocorticosteroids. However, under stressful conditions the body can produce between 20 to 300 mg of  Normal : 10-20 mg/day Stressed: 20-300 mg/day glucocorticosteroids per day.  Treatment - not curative Note: glucocorticosteroid use is not a curative treatment ! But it is useful for the long-term management of a number of chronic conditions.  Mechanism of action: The mechanism of action of glucocorticosteroids is complex, but briefly this is what happens: 1. Glucocorticosteroids bind to a cytoplasmic glucocorticoid receptor  BINDS Cytoplasmic glucocorticoid receptor 2. Binding to this receptor affects gene expression via specialised molecules called glucocorticoid response elements (GRE’s). These molecules are found on promoter regions  Affect gene expression of genes and they facilitate transcription of a large number of genes. 3. Glucocorticosteroids can either induce or inhibit gene expression.  Via glucocorticoid response elements (GRE’s)  Either induce or inhibit gene expression Here we will look at the simplified explanation of the mechanism of action of glucocorticosteroids. Mechanism of action 1. A glucocorticosteroid is transported in the bloodstream by glucocorticoid binding globulin. 2. The glucocorticosteroid molecule is lipid soluble and thus easily crosses the cell membrane and enters into the cytoplasm of the cell. 3. The glucocorticoid receptor is trapped inside the cytoplasm by three proteins: HSP70 (heat shock protein 70), HSP90 (heat shock protein 90) and IP(immunophillin). These three proteins trap the glucocorticoid S : glucocorticosteroid receptor in the cytoplasm of the cell and prevent it from randomly migrating to the nucleus. GR : receptor 4. Once the glucocorticosteroid binds to the glucocorticoid receptor the receptor undergoes a confirmational change. HSP: heat shock protein 5. This confirmational change releases the heat shock proteins (HSP70 &HSP90) and immunophilin (IP) IP: immunophillin from the glucocorticoid receptor. 6. Two glucocorticosteroid-glucocorticoid receptor complexes join together to form a dimer. GRE: glucocorticoid response 7. This dimer readily crosses the nuclear membrane to bind to glucocorticoid response elements (GRE’s) element on the DNA. 8. Glucocorticoid response elements (GREs) are specific genetic sequences found in the promoter regions CBG: glucocorticoid binding of genes. The glucocorticosteroid-glucocorticoid receptor complex has a high affinity for it. globulin 9. Once bound, it enables the binding of RNA polymerase to the gene locus and transcription of a specific gene then takes place. 10. Once transcription of the gene is complete, the mRNA is processed to mature mRNA and transported out of the nucleus and into the cytoplasm where protein synthesis takes place. 11. The newly synthesised protein then changes the specific function of the cell where it was synthesised.  Let’s explore how glucocorticosteroids are able to reduce inflammation. Glucocorticosteroids and gene transcription Panel A 1. Once cells of the immune system are activated, transcription factors that promote the synthesis of immune mediators are transported into the nucleus. 2. Examples of these transcription factors are the molecules AP1 and NF-kB. 3. The transcription factors bind to response elements on the DNA and cause the synthesis of mRNA. 4. The mRNA is translated into protein cytokines that are mediators of the inflammatory process. Panel B 1. Glucocorticosteroid-glucocorticoid receptor complexes will enter the nucleus. 2. Once inside the nucleus the glucocorticosteroid-glucocorticoid receptor (GCS-GR) complex will bind to (Annexin I) the transcription factors, preventing them from interacting with the DNA and causing the synthesis of mRNA required for inflammatory mediator production. 3. Therefore the glucocorticosteroid suppresses mRNA formation. 4. Consequently fewer protein cytokines are made. Transcription 5. This ultimately results in less inflammation. AP1 factors NF-ĸB Panel C AP1 1. Glucocorticosteroids bind to glucocorticoid response elements on the DNA. NF-ĸB 2. This facilitates the transcription of mRNA and increases the synthesis of lipoprotein-1which in turn inhibits the enzyme phospholipase A2. So we can see how inflammation is suppressed in two ways 1) by decreasing the synthesis of inflammatory cytokines and 2) by increasing the synthesis of lipocortin-1 or annexin-1 that directly inhibits phospholipase A2. This slide lists a few of the genes that are affected by glucocorticosteroids. We can divide these genes into those whose transcription is stimulated and those whose transcription is inhibited. Genes whose transcription is stimulated by GCSs : Examples of affected genes 1. Lipocortin-1 or Annexin-1 which is an important anti-inflammatory agent. The normal function of glucocorticosteroids is to always ensure that there is enough energy available for the heart and the brain to function. 2. In times of stress glucocorticosteroids will stimulate the transcription of genes that are responsible for Transcription stimulation Transcription inhibition making glucose. Therefore we have an increase in the synthesis of enzymes involved in the gluconeogenic pathway, which is the pathway responsible for making glucose from various precursor molecules. Cytokines: Lipocortin (annexin-1) Genes whose transcription is inhibited by GCSs : IL-1, IL-2, TNF-α, 1. Pro-inflammatory cytokines (IL-1, IL-2, TNF-alpha, gamma-Interferon, IL-6). All of which are important Gluconeogenic pathway mediators of the inflammatory response. γ-interferon, IL-6 2. Phospholipase A2. In addition to annexin-1 inhibiting phospholipase A2 activity, GCSs also suppress the synthesis of phospholipase A2. enzymes Phospholipase A2 3. IL-2 receptor. GCSs inhibit the synthesis of the IL-2 receptor. 4. Cyclooxygenase-2 enzyme. GCSs inhibit the synthesis of the COX-2 enzyme that is responsible for the Interleukin-2 receptor formation of prostaglandins during the inflammatory response. Cyclooxygenase-2  An important aspect of GCS therapy is the effect that exogenous GCSs have on the hypothalamic-pituitary- Hypothalamic-pituitary-adrenal axis adrenal axis (HPA-axis). Let us explore why this is important. stress trauma diurnal rhythms 1. Under normal conditions, stress, trauma and diurnal rhythms all act on the hypothalamus, to cause the secretion of corticotropin releasing hormone (CRH). 2. CRH acts on the anterior pituitary gland to cause the synthesis and secretion of ACTH. Hypothalamus 3. ACTH is released into the bloodstream and acts on the adrenal cortex to cause the formation of cortisol (the bodies endogenous glucocorticoid). 4. Should you provide the patient with exogenous glucocorticosteroids it is going to stimulate a negative CRH feedback inhibition system which will have a negative effect on the anterior pituitary gland as well as the hypothalamus. Effectively it shuts down the HPA axis. TNF-, IL-2 5. On the other hand, glucocorticosteroid levels will also have a negative effect on the immune system. IL-1, IL-6 Anterior pituitary gland 6. Components of the immune system such as TNF – alpha, IL – 2, IL – 1, IL – 6 and various other cytokines also act on the hypothalamus and the anterior pituitary gland to help maintain this axis. 7. If we were to suppress the secretion of all of these cytokines by administering glucocorticosteroids, it is Immune system ACTH Negative going to have a negative effect on the HPA axis. feedback Why is all of this important? This is important because when we are giving a patient exogenous glucocorticosteroids it is going to cause Adrenal cortex Negative feedback in this system. Therefore we will no longer get synthesis of endogenous cortisol, which will no longer be accumulated and stored in the adrenal cortex. Thus whenever a patient on continuous GCS therapy requires additional cortisol to help them cope with a stressful situation, no cortisol is available for them. this Glucocorticoids leads to an adrenal crisis. GCSs can induce an acute adrenal crisis. This is caused by adrenal insufficiency Which means that there is a lack of production of indigenous GCSs. this can happen when GCSs are used for more than 14 days. When GCSs use is CS induced Acute Adrenal crisis stopped, it is important to employee dose tapering over a couple of days. why? It needs to happen over a couple of days to allow the HPA axis to resume normal functioning. therefore GCSs are not stopped cold turkey, that are rather tapered over a couple of days. If a patient has been on GCSs for extended time periods, it will take longer to wean  Cause: adrenal insufficiency (CS use > 14 days) NB! them off the GCS and get the HPA axis to function normally.  NB! Dose tapering – when use exceed 14 days When GCSs are used the synthesis of endogenous cortisol is inhibited. Therefore there is no reserve in the adrenal glands for the patients when they are experiencing stress. Therefore when a patient on GCS is exposed to normal  Suppression of HPA axis by exogenous GS stressful conditions, surgery, trauma or an infection there is no reserve of cortisol that can be released for the patient to cope with the specific stress. so in these patients if there is a known stressor one needs to increase the dose of  Triggers: stress, surgery, trauma, infection exogenous GCS to help them cope with the stressful situation. The symptoms of an acute adrenal crisis can be mild (which includes myalgia, malaise, anorexia and weakness) or  Symptoms severe and life-threatening (which includes vomiting, fever, hypotension and shock).  Mild : myalgias, malaise, anorexia, weakness The management of an acute adrenal crisis is parenteral hydrocortisone. Hydrocortisone contains mineralocorticoid  Severe: vomiting, fever, hypotension, shock activity. This will aid patience in times of stress And helps them to rebalance their fluid status. In patients receiving GCS it is important to try and preserve the HPA axis. This can be done by alternate day dosing or  Management: parenteral hydrocortisone by giving them their dose early in the morning.  Preserve HPA axis – alternate day dosing or morning dose Physiological responses and adverse effects The adverse effects of GCS are closely related to the normal physiological responses to cortisol. Inflammatory response Susceptibility to infections 1. Both the inflammatory response and the immune response are suppressed. this leads to increased susceptibility to opportunistic infections and cancer. It is important to remember not to give patients Immunological response Cancer immunisations when they are on GCS therapy Because the immune response will be suppressed. 2. They are also complex effects on metabolism. Liver glycogen deposition, gluconeogenesis and Liver glycogen deposition glucose output from the liver is increased. However, glucose utilisation is decreased. Altogether this Gluconeogenesis Diabetes ; fat deposition predisposes the patient to diabetes And abnormal fat deposition. 3. There is increased protein and bone catabolism. This is because the glucose is synthesised from the Glucose output from liver breakdown of proteins. this result in muscle wasting, growth suppression and osteoporosis/ Glucose utilization Muscle wasting osteonecrosis. 4. GCSs can cross the blood brain barrier, and thus has an effect on the mood of patience on GCS Growth suppression therapy. Patients can have symptoms like psychosis, aggression and depression. Protein catabolism Osteoporosis / osteonecrosis 5. Gastric acid and Pepen secretion is increased. This can lead to the formation of gastric ulcers, Bone catabolism especially if the patients are also taking NSADs. Mood Psychosis / aggression 6. In the kidney, Na+ reabsorption an K+/H+ excretion is increased. This causes sodium and water retention which leads to hypertension and oedema, as well as hypokalaemia which leads to muscle Gastric acid and pepsin Gastric ulceration weakness. Na+ reabsorption Na+ and H2O retention  K+ /H+ excretion Hypertension & Oedoema HypokalaemiaMuscle weakness Patients on prolonged GCS therapy develop symptoms associated with Cushing’s syndrome. These E Euphoria, aggression, Intracranial are also known as cushingoid features. Smood depression changes hypertension - Buffalo hump Cataracts apnormal fatdeposition Hypertension Moon face, red cheeks Truncal fat deposition. Thinning of skin Necrosis of femoral head Muscle wasting * Other effects include : Easy bruising Osteoporosis Renal calculi Hyperglycaemia Negative nitrogen balance Poor wound healing Immunosuppression Increased appetite Obesity  How can we mitigate the severity of the adverse drug reactions and still benefit from GCS therapy? Factors affecting severity of adverse drug reactions The route of administration is critical. drugs that are administered by the parenteral and oral roots are more prone to having serious and permanent adverse effect. Therefore if these routes of administration can be  Route of administration avoided we can mitigate some of the serious long-term adverse effects of GCS therapy. if we can administer GCS drugs to specific sites where they are needed ( eg. In asthma to the lungs and in rheumatoid arthritis to  parenteral specific joints that require the GCS) we can mitigate the serious long-term generalised adverse effects.  oral If IV or oral administration of GCS drugs Are required then the duration and the dose must be carefully  site specific  lungs, skin, intra-articular injections titrated. Generally we want the shortest duration and the lowest dose. However they awesome conditions where a high dose for a short duration may be more beneficial. Where possible do alternate day dosing for oral therapy. This not only protects the HPA Axis but also decreases the severity of adverse effects.  Duration and dose of therapy  shortest & lowest Be cognizant of mineralocorticoid activity, especially in elderly patients as it causes uncalled for increases in  NB! alternate day dosing for oral therapy blood pressure as well as retainment of fluid causing oedema.  Mineralocorticoid activity In recent years drug formulations of GCS have improved. There are three drugs, budesonide,fluticasone and ciclesonide that are inactivated by first pass liver metabolism. Up to 99% percent of these drugs are  Drug formulation – first pass effect (Metabolism) metabolised once it is absorbed from the GIT. This makes these drugs more amenable to long-term treatment and these agents have a particular place in the management of asthma. Therefore, in inhaled formulations budesonide, fluticasone, ciclesonide they do not cause serious long-term adverse effects. 95-99% liver metabolized  inactivated One of the most common uses of synthetic GCS drugs is for their anti-inflammatory effect. (GCS drugs have a profound effect on inflammation). Anti-inflammatory effect 1. Whenever cell membranes are damaged phospholipids A2 is activated. glucocorticosteroids 2. Activated phospholipase A2 releases a arachidonic acid from the damaged cell membrane. 3. Arachidonic acid is converted to prostaglandins by the help of the cyclooxygenase enzymes and to Cell membrane leukotrienes by the help of the lipoxygenase enzymes. 4. Both prostaglandins and leukotrienes are important inflammatory mediators. Phospholipase A2 lipocortin 5. GCSs in tern stimulate the synthesis of Annexin-1 which is a direct inhibitor of phospholipase A2. Therefore it prevents the downstream formation of inflammatory mediators. (annexin-1) Phosholipase A2 Arachidonic acid cyclooxygenase lipoxygenase prostaglandins leukotrienes Inflammatory mediators  Apart from suppression of inflammation, GCS drugs also affect other components of the immune system causing a state of immune suppression. GCS drugs have an effect on lymphocytes, monocytes, basophils and endothelial cells. 1. As previously seen, lymphocytes are suppressed and numerous cytokines that are important in the Effects on the propagation of the immune response are inhibited. 2. GCS drugs affect monocytes by suppressing the synthesis and secretion of various cytokines, prostaglandins & leukotrienes, as well as Fc and C3 receptors (which are important for immune system propagation of the immune response) 3. GCS drugs affect basophils by inhibiting the release of histamine and leukotrienes. 4. Endothelial cells are important in localising the inflammatory response, because these cells Decrease secrete adhesion molecules, cytokines and arachidonic acid metabolites to do so. GCS drugs suppress all these molecules. Inflammatory and The overall effect of GCS therapy is decreased inflammatory and immune responses. Immune responses Glucocorticosteroids are not contraindicated for use in children but their use requires careful consideration in terms of the long-term adverse effects. GCSs when used irresponsibly in children can lead to serious effects as listed below. Growth retardation Adverse effects in children: Delayed sexual development Catabolic effect on bone Long term systemic treatment Iatrogenic Cushing syndrome Development of diabetes Increased susceptibility to cataracts  Growth retardation Increased absorption through skin — it is important to remember that the absorption of GCSs through the skin of children and neonate is increased which can cause serious systemic adverse effects, thus it must be  Delayed sexual development used with caution and outmost care.  Catabolic effect on bone  Iatrogenic Cushing syndrome  Development of diabetes  Increased susceptibility to cataracts  Increased absorption through skin  The effects of GCS on bone requires special consideration. Effects on Bone Osteoporosis is one of the main problems faced with long-term use of GCS therapy.  Osteoporosis The mechanism of osteoporosis due to GCS therapy is as follows: 1. Gonadal steroid synthesis is inhibited with long-term GCS use.  Mechanisms of osteoporosis 2. This causes a decreased absorption of calcium from the GIT and at the same time causes increased parathyroid hormone levels.  Inhibition of gonadal steroid synthesis 3. As a result there is an overall suppression of osteoplast activity and bone and this causes the formation of osteoporosis after approximately three months use of GCS therapy.  Decreased absorption of Ca2+ from GIT Osteonecrosis is another problem associated with prolonged use of GCS therapy and needs to be addressed. Increase PTH What this is, is an aseptic necrosis of joints and can occur with both high-dose short-term use as well as long-term use. Osteonecrosis presents as shoulder, knee or hip pain and is directly related to atrophy of  Suppress osteoblast activity these specific joints. The prognosis is poor and patients usually require shoulder, hip or knee replacement.  Osteonecrosis  Aseptic necrosis of joints  Presents as shoulder, knee, hip pain  High dose short and long term use It is very important to be aware of steroid rage. GCS therapy has profound effects on the mood of Steroid rage patients and aggression and psychosis is common. depression has also been described in patients having long-term GCS therapy. However despite this fact, GCS therapy is not contraindicated and Behavioral changes patients who are suffering from psychiatric illness.  common aggression/ psychosis  not CI in psychiatric illness  The topical use of GCSs requires special consideration. Topical use: effects on skin When GCS is applied to the skin it causes damage to the collagen, which is broken down to provide amino acids  catabolic effect damages collagen for glucose synthesis. As a result in skin we get numerous adverse effects, atrophy being one of the most important ones, the formation of stretch marks (striae), acneiform eruptions, perioral dermatitis, fungal and  atrophy, striae, acneiform eruptions, perioral dermatitis, bacterial infections, hypo-pigmentation, rosacea. fungal and bacterial infections, hypo-pigmentation, rosacea GCSs can penetrate the skin and cause systemic adverse drug reactions especially in children. Therefore it  Penetrate skin and cause systemic ADRs esp children should be used with caution in both neonates and children. It is important to know the potency of topical GCSs. Nb!! Topical glucocorticosteroids (Know potency) Most potent (Group IV): clobetasol Most potent : (Group IV) Very potent (Group III): Beclomethasone, betamethasone, mometasone, fluticasone, triamcinolone clobetasol Moderately potent (Group II) Betamethasone (1⁄2 strength of what it is in group 3) Weakly potent (Group I) Hydrocortisone. ( hydrocortisone is a weekly potent GCS and constitutes group 1.). Very potent (Group III) Only group 1 GCS topical preparations are available for over-the-counter use. Beclomethasone, betamethasone, mometasone, fluticasone, triamcinolone Moderately potent (Group II) Betamethasone (½ strength) Weakly potent (Group I) Hydrocortisone Here are some examples of adverse effects of glucocorticosteroids when used on skin. 1. Perioral dermatitis 2. Acneiform eruptions 3. Atrophy of the skin (note the seriousness of the lesions that can form when GCSs are used for a long period of time) 4. Rosacea is a common occurrence in babies and neonates. We need to use GCS with utmost care in skin conditions. They should be used for the shortest period possible so that they do not have any serious long-term adverse effects.  The use of GCS in asthma is of great importance. Glucocorticoid use in asthma Inhaled GCSs make up an important portion of the asthma management regime. Note: beclomethasone is no longer used frequently since it does have some systemic adverse effects. Inhaled glucocorticoids Budesonide, Fluticasone and Ciclesonide are the preferred drugs since they have a 95% first-pass metabolism and a low incidence of systemic adverse effects.  Beclomethasone  Budesonide When is systemic GCSs are indicated we can use: Prednisone, Prednisolone, Methylprednisolone Preferred use and Hydrocortisone to manage the asthma. However these drugs have systemic adverse effect and  Fluticasone  Ciclesonide 95% First pass metabolism therefore treatment is as short as possible so that patients can be returned to their use of inhaled GCS. Note: Systemic glucocorticoids Prednisone (inactive) is converted to prednisolone (active)  Prednisone in the liver  Prednisolone Systemic adverse effects  Methylprednisolone  Hydrocortisone Inhaled GCSs have a unique set of adverse effects. One of the most important effects is the effect that it has on the local immune system. Oropharyngeal candidiasis is very very common impatience using inhaled glucocorticosteroids. However there is a very simple way to prevent this and Adverse effects of inhaled glucocorticoids that is by instructing patients to rinse their mouth after using their inhaler so that the GCS does not stick to the oral cavity. Common: The vocal cords are also affected and we see this as hoarseness, dysphonia and cough.  Oropharyngeal candidiasis  Treat with nystatin, clotrimazole, fluconazole Note: Budesonide, Ciclesonide & Fluticasone have a very low incidence of systemic adverse effects but in rare cases these effects can still be seen. So we always need to  Vocal cords: hoarseness , dysphonia, cough be on the lookout for: Cataracts, Growth retardation in children, Osteoporosis, Easy bruising, Thinning of skin and HPA and adrenal suppression. NB! Very low incidence with budesonide & fluticasone These adverse effects are very rare in patients taking inhaled GCS but they can  Cataracts occur in a very low percentage of patients.  Growth retardation in children  Osteoporosis  Easy bruising  Thinning of skin  HPA and adrenal suppression  Available preparations The available preparations of glucocorticosteroids For systemic use Can be classified as short-acting, intermediate-acting, and long-acting. We very rarely use mineralocorticoids, they are only used in Anti- Sodium- Dosage Forms exceptional circumstances when patients are not synthesising any adrenal cortisol. inflammatory retaining potency We also need to consider the anti-inflammatory potency, sodium retaining potency and the dosage forms of available preparations. Short-acting hydrocortisone 1 1 oral, injectable, tp Hydrocortisone and Cortizone are the short acting molecules. Both of them have an anti-inflammatory cortisone 0.8 0.8 oral, injectable, tp potency close to 1 & both have a sodium retaining potency close to1. The dosage forms for both of these agents are oral, injectable and topical. Intermediate-acting The intermediate acting agents listed alongside have a much higher anti-inflammatory potency and a very prednisone 4 0.3 oral low sodium retaining potency. prednisolone 5 0.3 oral, injectable, tp Please take note that GCS drugs used in nasal sprays (e.g. triamcinolone) are prone to causing methylprednisolone 5 0 oral, injectable, tp nosebleeds. triamcinolone 5 0 tp, nasal spray The long acting agents listed alongside have an even greater anti-inflammatory potency and no sodium retaining potency. Long-acting betamethasone 25 0 oral, injectable, tp dexamethasone 30 0 injectable Mineralocorticoids fludrocortisone 10 250 oral, injectable, tp Therapeutic considerations  Potent anti-inflammatory drugs  Not curative ↓  Long term use requires : *find the best  Repeated re- evaluation of payance for (i) dose (ii) route of administration ↑ the patient !  adverse effect vs therapeutic effect  Osteoporosis management (> 3 months): When patients are taking glucorticosteroids for longer than three months their bone density needs to be monitored. It is also very important to give these patients calcium and vitamin D Monitor bone density  give calcium & Vit D supplements. supplementation Consider replacement of gonadal steroids  The longer a patient is treated with GCS, the longer it will take for their HPA axis to return to NB in long term ES use > normal. - When patients are on GCS therapy immunisation needs to be delayed as the GCS therapy will cause an improper or decreased response to the vaccine and can also activate the pathogen in live  Dose tapering vaccines.  Longer than 2 weeks  Longer treatment periods = longer dose tapering  CS and immunization?  If oral /IV high dose monitor:  blood glucose,  blood pressure  fluid status Resources:  Available online resources: Wits Health Sciences Library