Systemic glucocorticoids
? Potent immunosuppressive and anti-inflammatory agents
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? Knowledge of basic pharmacology - essential to maximize theirefficacy and safety as therapeutic agents
? Major naturally occurring glucocorticoid ? Cortisol (hydrocortisone)
? Synthesized from cholesterol by the adrenal cortex
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? Normally, <5% of circulating cortisol is unbound the activetherapeutic form
? Remainder - inactive
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Mechanism of glucocorticoids action
? Passive diffusion of the glucocorticoids through the cell membrane
? F/b binding to soluble receptor proteins in the cytoplasm
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? The hormone-receptor complex then moves to the nucleus? Regulates the transcription of its target genes
Cellular effects of glucocorticoids
? Affect the replication and movement of cells
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? Induce monocytopenia, eosinopenia, and lymphocytopenia? Lymphocytopenia - a redistribution of cells - migration from the
circulation to other lymphoid tissues
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? Increase in circulating PMN leukocytes - movement of cells from thebone marrow, diminished rate of removal from circulation and
possibly inhibition of neutrophil apoptosis
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? Macrophage functions, including phagocytosis, antigen processing
and cell killing - decreased by cortisol
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? This affects immediate and delayed hypersensitivity? Granulomatous infectious diseases (e.g. tuberculosis) - prone to
exacerbation/ relapse during prolonged glucocorticoid therapy
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? Antibody-forming cells, B lymphocytes and plasma cells - relativelyresistant to effects of glucocorticoids
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Short courses of glucocorticoidsHave been used for
? Severe dermatitis
? Contact dermatitis
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? Atopic dermatitis? Photodermatitis
? Exfoliative dermatitis & Erythrodermas
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Fundamental principles of glucocorticoids therapy? Before glucocorticoids therapy with is begun - the benefit
? Alternative/ adjunctive therapies (azathioprine, cyclophosphamide)
? Especially if long term treatment
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? Coexisting illnesses such as diabetes, hypertension and osteoporosisneed consideration
Diet during glucocorticoids therapy
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? Low in calories, fat and sodium? High in protein, potassium and calcium as tolerated
? Also consider associated comorbidities
? Protein intake - to reduce steroid-induced nitrogen/ muscle wasting
? Minimize alcohol, coffee and nicotine/ smoking
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? Encourage exercise? Basic preventative measures ? to be followed
Potential adverse effects
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? A plethora of variety of side effects, when used in high
(supraphysiological) doses and in long term regimens
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? Short courses (2?3 weeks) of GCs relatively safeSide effects due to mineralocorticoids action
? Hypernatraemia and water retention
? Hypertension and weight gain
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? Hypokalaemia, hypocalcaemiaSide effects due to glucocorticoids action
? Hyperglycaemia, development of diabetes
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? Deterioration of diabetic control? Dyslipidaemia ? hypertriglyceridaemia, hypercholesterolaemia
? Increased appetite, weight gain
? Menstrual irregularities
? Cushingoid features (lipodystrophy) ? moon face, `buffalo hump',
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central obesity (thin limbs, plump trunk)
Cutaneous side effects
? Purpura, bruising, striae, dermal and epidermal atrophy,
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telangiectasia
? `Steroid acne', rosacealike syndrome
? Impaired wound healing
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? Hirsutism? Fat atrophy with injected GCs
? Cutaneous infections ? staphylococcal and herpetic
? Hyperhidrosis
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? Osteoporosis.?Osteonecrosis (avascular necrosis).
? Growth impairment in children.
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? Gastrointestinal
?Peptic ulceration.
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?Bowel perforation (particular risk with active diverticulitis andrecent bowel anastomosis).
?Pancreatitis.
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?Fatty liver.
?Gastrooesophageal reflux.
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?Candidiasis.? Psychiatric - occur in approximately 6% of patients
?Psychosis.
?Euphoria, depression, agitation.
?Suicidal ideation.
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?Insomnia, nightmares.?Irritability, mood lability.
? Ocular
?Ocular hypertension and glaucoma.
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?Cataracts ? posterior subcapsular.?Central serous chorioretinopathy.
?Ocular infections, including herpes simplex.
? Neuromuscular
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? Muscle weakness (proximal myopathy).?Intracranial hypertension (pseudotumor cerebri).
?Spinal epidural lipomatosis.
? Infections
?Tuberculosis reactivation.
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?Opportunistic infections (consider Pneumocystis jiroveci pneumoniaprophylaxis)
? Prior to initiating GC therapy
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? The patient and family members provided adequate counselling? Information about the potential adverse effects
? A steroid treatment card - to be provided
Dosage regimens
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? Oral administration - Depends on:?Clinical diagnosis
?Severity
?Presence of other factors
? Prednisolone (or equivalent) at a starting dose of up to 1 mg/kg bw/d,
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ideally given as a single morning dose
? Less likely to cause adverse effects
? Less likely to result in HPA axis suppression
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Pulse therapy
? Oral
? IV Pulse therapy (DCP, DP, methylprednisolone)
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? Administration of supra-pharmacologic doses of drugs in anintermittent manner - "pulse therapy"
? In pemphigus, pulse therapy refers to intravenous (IV) infusion of high
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doses of steroids for quicker, better efficacy and to decrease the side
effects of long-term steroids
? Feduska et al. first used pulse therapy in 1972 for reversal of renal
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allograft rejection
? In India, JS Pasricha & Ramji Gupta, 1984
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Oral minipulse therapy (OMP)? Corticosteroids therapy i.e., dexamethasone/betamethasone
? On 2 consecutive days in a week
? Can be continued for up to 3-6 months
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? MC Indications ? vitiligo, alopecia areataDCP / DP Pulse therapy
? DCP
? DP
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? Methylprednisolone - also used? Most common indication - Pemphigus
Medications
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? Dexamethasone (100 mg) ? economic option
? or methylprednisolone (20-30 mg/kg)
? With cyclophosphamide 500 mg on 2nd day of pulse
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Steps of pulse therapy
Phases of pulse therapy
Modifications
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? Dexamethasoneazathioprine pulse (DAP):
? Cyclophosphamide is replaced by daily oral azathioprine.
? No bolus dose of azathioprine is given during the pulse
? DAP is recommended for unmarried patients
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? Who have not completed their family (Cyclophosphamide not given-gonadal failure at a cumulative dose of 30 g and 12 g in women and
men)
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Common side effects
? Mood and behavior alteration, hyperactivity, psychosis, disorientation
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and sleep disturbances - 10% patients? Hyperglycemia, hypokalemia
? Infections
? Hiccups, facial flushing, diarrhea, weakness,
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? Generalized swelling, myalgia? Arrhythmias and shock