SEMINAR PRESENTATION

TOPIC:PREVENTION & MANAGEMENT OF SIDE EFFECTS OF SYSTEMIC STEROIDS

MODERATOR:DR VIJAY PALIWAL

INTRODUCTION

• Glucocorticoids play vital role in maintenance & regulation of immune and circulatory functions

• Extensively used to treat many inflammatory and autoimmune disorders.

• Anti inflammatory effects of corticosteroids cannot however be separated from their metabolic effects

Adrenals

Kidney

Posterior Pituitary Gland

Hypothalamus

AnteriorPituitary Gland

ACTH

Stress Circadian

rhythm

CRH

(-)

Glucocorticoids, Catecholamines, etc..

Glucocorticoids, Catecholamines, etc..

Muscle: Net loss of aminoAcids (glucose)

Liver: Deamination of

proteins into amino acids,

gluconeogenesis (glucose)

Fat Cells: Free fatty

acid mobilization

Heart rate: Increased

Immune system: altered

Hypothalamopituitary adrenal (HPA) axis: Negative Feedback

Classification of Corticosteroids

ADVERSE EFFECTSCLASSIFIED AS :1. Dose-dependent2. Duration-dependent

Short term Long term

Dose-dependent

• Hyperglycemia• Hyperlipidemia • Peptic ulcer disease• Psychosis

Duration-dependent

• Hypertension • Cushingoid changes• Growth impairment• Osteoporosis • Osteonecrosis • Opportunistic infections

Adverse effects

Psychiatric•Sleep disturbance/activation•Mood disturbance•Psychosis

Skin/soft tissue•Cushingoid appearance•Abdominal striae•Acne•Hirsutism•Oedema

Neurologic•Neuropathy•Pseudomotor cerebri

Cardiovascular•Hypertension

• Occur with prolonged use of high doses• Cushing’s disease MSK

•Osteoporosis•Asceptic necrosis of bone•Myopathy

Endocrine•Diabetes mellitus•Adrenal cortex suppression Immunologic•Lymphocytopenia•Immunosuppression•False-negative skin test

Opthalmic•Cataract•Narrow-angle glaucoma

Developmental•Growth retardation

• The risk of side effects depends on the Dose

– low dose (< 10 mg/day of prednisone)– medium dose (10-20 mg/day)– high dose (> 20 mg/day)

Type of steroid – long-acting – short-acting

Length of treatment: (Long-term treatment > 3 months)

Other medical problems

FOLLOW UP PROTOCOL

EXAMINATION• At 1 mth – then after

every 2-3 mthBlood pressure,wtHt & wt plotted on

growth curve(in children)

Thorough h/o at each visit for adverse effects

• At least every 6 mth initially then annually

Opthalmological examination

LABORATORY• At 1 mth – then after

every 3-4 mth K level FBS TGL

• Near time of cessation of long term CS therapy

8-9 am cortisol level

ADVERSE EFFECTS

• METABOLIC EFFECTS• HYPERGLYCAEMIA• Mechanism:GC-increased hepatic glucose/glycogen

production,gluconeogenesis through protein catabolism,induces IR decrease glucose entry into cell

• A/D Effects: increased appetite & wt gain• Therapy Effect:Especially with high CS dose• Additional risk factor:Family or personal history of DM,obesity,

patients with underlying impaired glucose tolerance or subclinical diabetes

• Prevention:Dietary measures(low in saturated fat & calories), Regular monitoring of blood glucose levels & Hb A1C during therapy is important

• Diagnosis: Fasting glucose level

• Management: Proper diet Insulin Oral hypoglycaemics,insulin sensitizers

• Treatment involves reduction in glucocorticoid dose• If steroid is stopped - hyperglycemia may fully reverse over many

months. • When hyperglycemia is persistent (mostly during the day with N to

minimally elevated fasting glucose levels) - drugs are prescribed blood glucose levels < 250 mg/dL - addition of insulin-sensitizing drugs

(thiazolidinediones, metformin) and/or insulin secretagogues blood glucose levels > 250 mg/dL especially if pt is symptomatic then

insulin therapy should be considered.

• HYPERTENSION• Mechanism:MC Effect-Na retention also due to GC induced

vasoconstriction• A/d Effect:CHF,excessive wt gain,hypokalemia• Therapy Effect:CS with high MC effect,therapy over 1 yr,pulse CS• Additional risk factor:Prior hypertension,elderly patient• Prevention:Na restriction,choose CS with low MC effect• Diagnosis: Monitor bp• Management: 1. Na restriction.2. Treatment is not different from all hypertensive patients, although in

some patients, blocking MC receptors with spironolactone may be more effective than using other antihypertensives.

3. Thiazides can also be prescribed

• HYPERLIPIDEMIA• Mechanism:GC Effect-catabolic state,initiated by elevated

lipoprotein lipase• A/d Effect:hypertriglyceridemia• Therapy Effect:high CS dose• Additional risk factor:caloric/saturated fat excesses,

personal/family history of hyperlipidemai,DM,hypothyroidism• Prevention:low calorie,low saturated fat diet• Diagnosis: triglycerides level• Management: Gemfibrozil,statins

• CUSHINGOID CHANGES• Mechanism:Altered fat distribution,result of overall fat

catabolism• A/d Effect:moon facies.truncal obesity,buffalo hump• Therapy Effect:CS for atleast 2-3 months• Additional risk factor:Excessive caloric intake due to increased

appetite• Prevention:Dietary measures,exercise

• Diagnosis: Low ACTH level Low cortisol level No response to cosyntropin stimulation test Higher than normal fasting glucose Low blood potassium level Low bone density as measured by dual x-ray

absorptiometry (DEXA) High cholesterol particularly high TG & low HDL

HPA AXIS EFFECTS• Mechanism:Reduced GC & MC reserves• A/D Effects:Steroid withdrawl syndrome Addisonian crisis• Therapy Effects:Steroid taken>3weeks,evening dose,long

half life followed by abrupt cessation• Additional risk factors:Major surgery,trauma,illness,severe

gastroenteritis with fluid & electrolyte loss• Prevention:Appropriate CS tapering• Diagnosis: By History of patient• Management: Raise CS dose then taper much more slowly

• Pathophysiology: Corticosteroid administration results in a negative feedback effect via glucocorticoid receptors in anterior hypothalamus which in turn suppresses production of CRH & ACTH

• Prolonged suppression of ACTH levels leads to atrophy of adrenal cortex & secondary adrenal insufficiency.

• Therapeutic glucocorticoid administration is M/C cause of secondary AI

• Chronic administration of exogenous glucocorticoids induces atrophy of pituitary corticotroph cells.

• Clinically relevant if exogenous steroid therapy is withdrawn too rapidly.

• C/F: anorexia, nausea, emesis, weight loss, fatigue, myalgias, arthralgias, headache, abdominal pain, lethargy, postural hypotension, fever & skin desquamation

Clinical manifestations of adrenal insufficiency

Strategies to prevent steroid induced HPA axis suppression:

• Acute adrenal insufficiency is a feared complication • No good predictive marker to anticipate acute AI • Clinical evaluation remains key element in its diagnosis. • If AI is suspected,HPA suppression can be assessed with dynamic

tests.• During stress situation, steroid administration is then recommended

depending on the severity of the stress.• Long-term steroids should be tapered gradually to allow the adrenal

glands to resume cortisol production.• The first step is reduction from pharmacological to physiological doses. • This depends on the disease activity and the level of control with

steroids.• The next step is to taper from physiological dose to complete

withdrawal and this depends on the degree of HPA suppression.

• In short term treatments (< 10 days) irrespective of dosage or type of steroid cessation of therapy should be abrupt shortening total length of therapy & diminishing S/Es

• In intermediate term treatments (10-30 days) glucocorticoid should be withdrawn over a period of 2 weeks with dose reduction every 4 days

• In long term treatments some principles for dose reduction should be observed prior to medication withdrawal:

(a) switch to short or intermediate-acting glucocortcoids(b) reduce no. of doses aiming at once-a-day dosing in morning(c) gradual glucocortcoid dose reduction (e.g. for doses of prednisolone

above 20 mg, the reduction should be no more than 25% every 4 days; for doses between 10-20 mg the reduction should be no more than 2.5 mg every 7 days and for doses < 10 mg the reduction should be no more than 2.5 mg every 15 days).

Strategies for management of established HPA axis suppression• In the end of the protocol for dose reduction HPA axis testing can

be performed with morning dosage of serum cortisol.

– Levels greater than 10 mcg/dL indicate adequate recovery of the axis and allow glucocorticoid withdrawal.

– Levels less than 5 mcg/dL indicate suppressed axis and need of dose reduction with an additional waiting period of 2-4 weeks before cessation.

– Cortisol concentration kept between 5 and 10 mcg/dL requires ACTH stimulation test to ensure adrenal recovery& adequate endogenous cortisol production in the face of stressful situations.

A suggested algorithm for withdrawal from chronic steroid therapy. Physiologic doses

of glucocorticoid are equivalent to prednisone 5 to 7.5 mg/d or hydrocortisone 15 to 20 mg/d.

ADRENAL CRISES• Most crises were due to glucocorticoid dose reduction or lack of

stress-related dose adjustment• Occurs more often in patients older than > 60 years. PREVENTION• Patients should add 5–10 mg hydrocortisone to their normal

regimen shortly before strenuous activities• More severe physical stress such as fever requires doubling of daily

doses until recovery. • In vomiting/diarrhoea drug should be administered parenterally. • For major surgery, trauma and diseases that require monitoring in

intensive care pt should receive iv infusions of 100–150 mg hydrocortisone in 5% glucose per 24 h.

• Results of some studies advocate lower doses (25–75 mg/ 24 h) for minor / moderate surgical stress.

• MANAGEMENT • Immediate iv administration of 100 mg hydrocortisone

followed by 100–200 mg in 24 h and continuous infusion of larger volumes of physiological saline solution (initially 1 L/h) under continuous cardiac monitoring.

• In case of newly diagnosed (or suspected) adrenal crises treatment must not be delayed by diagnostic work-up.

• Baseline blood samples for ascertainment of cortisol and ACTH should be drawn immediately before hydrocortisone administration

RENAL SYSTEM - Fluid and electrolyte balance• Associated with sodium & water retention• Potassium loss occurs & hypokalaemic alkalosis may develop.

PREVENTION• The blood pressure should be checked at each outpatient visit &

antihypertensive treatment may be necessary. • Corticosteroids should be used with extreme caution in patients

with limited cardiac reserve as cardiac failure can develop.

MANAGEMENT • Recommend a low salt diet• Diet rich in K (most fruits, vegetables, especially broccoli and

carrots, fish & poultry)• Occasionally K supplements are required.• If a thiazide diuretic is chosen as the antihypertensive agent the

serum potassium should be carefully monitored. • Thiazides also have a beneficial effect on osteoporosis by reducing

calcium loss in the urine.

STEROIDS AND BONE• Comparison of normal cycle

of bone remodeling (upper panel) with an abnormal one caused by steroid excess (lower panel)

• Decreased number of osteoblasts & their premature apoptosis as well as incomplete repair of bone in latter.

• Newly formed bone is in light tan.

PATHOPHYSIOLOGY

RISK FACTORS

• Under 15 years & over 50 years• Gender• Post-menopausal /amenorrhoeic

women• Slim build• Limited mobility• Medications:increase risk of

osteoporosis include thyroxine &heparin

• Dose & duration of steroid use• Underlying medical conditions

which independently could lead to bone loss such as RA

PREVENTION

• Undertake weight bearing exercise (such as brisk walking)

• Stop smoking & alcohol intake• Avoidance of activities such as heavy

lifting, high-impact aerobics & contact sports

• Adequate dietary intake (e.g. 3-4 dairy serves each day) or calcium tablets up to a daily intake of 1500mg elemental calcium per day

• Vitamin D in various forms including monthly colecalciferol 50,000 units (1.25 mg)

• Oestrogen i.e. hormone replacement tablets in females that have had early menopause

• DOC - Bisphosphonates (alendronate, etidronate, zolidronic acid) are prescribed for patients at higher risk of fracture.

Initial laboratory assessment forglucocorticoid-induced osteoporosis.

PREVENTION• Aim - commence therapies before bone loss occurs. • Studies have demonstrated that bone loss occurs early • Within first 3 to 6 months• Bone loss that has occurred is usually never fully regained

even after steroids are discontinued• Bisphosphonates(alendronate, cyclical etidronate &

risedronate) our recommended first-line therapy for the prevention & treatment of GIOP.

• At both lumbar spine & femoral neck

Treatment sequence for prevention & management of steroid induced osteoporosis

Treatment of steroid induced osteoporosis

AVASCULAR NECROSIS(Osteonecrosis)

• AVN : manifested by pain and limitation of motion in one or more joints.

PATHOPHYSIOLOGY• intraosseous lipocyte hypertrophy & apoptosis of osteoblast-

intraosseous hypertension-compression of blood vessels - bone ischemia and necrosis.

• increased lipids -cause fat emboli which occlude blood vessels

• fatigue fractures occur which cannot mend.

PREVENTION & MANAGEMENT• Early detection is imp because early intervention may prevent progression

to degenerative joint disease requiring joint replacement. • 20 % of pts with AVN have N x-rays & bone scan shows only non-specific

changes • MRI : most sensitive techniques • Patients should be regularly questioned about pain and limitation of

motion of joints • The magnetic resonance T2 weighted image shows a double ring sign

representing a central low intensity area of fat necrosis surrounded by an increased signal of vascular proliferation; this is pathognomonic for osteonecrosis

• If imaging shows AVN an orthopedic surgeon skilled in early intervention with core decompression may be able to halt progression of disease

• Patients with AVN have an increased risk that other joints will be affected. • The progression of AVN to destructive joint disease may require joint

replacement surgery

Growth suppression

• Steroids inhibit linear growth. • Reduce growth hormone production and direct inhibitory effect on

bone and connective tissue. • Growth suppression is more likely if steroids are given for > 6 mths.• Administration of deflazacort (oxazoline derivative of

prednisolone), an alternative form of prednisolone, appears to have fewer effects on growth & steroid-induced osteoporosis but is not being commonly used.

STEROID INDUCED MYOPATHY

• Direct catabolic effect on skeletal muscle via effects on intermediary metabolism that provide amino acids as a substrate for gluconeogenesis

• May be related to: decreased protein synthesis increased protein degradation alterations in carbohydrate metabolism mitochondrial alterations electrolyte disturbances decreased sarcolemmal excitability

• Interfere with insulin-like growth factor-I (IGF-I) signaling - leading to increased myocyte apoptosis

• Glucocorticoid-induced suppression of Akt1 ultimately results in increased amounts of ubiquitin-ligase atrogin-1 (MAFbx) that targets muscle proteins for degradation

• Local growth factors production plays a crucial role in glucocorticoid-induced muscle atrophy.

• Glucocorticoids can cause muscle atrophy by altering the muscle production of IGF-I and myostatin, two growth factors exhibiting opposite effects on muscle mass development.

• Decrease in IGF-I together with increase in myostatin both induced by glucocorticoids inhibit satellite cells activation as well as myoblast proliferation and differentiation.

• In mature muscle fibers, these growth factor changes cause downregulation of protein synthesis and stimulation of protein degradation.

Alterations in protein breakdown signaling induced by glucocorticoids. Stimulatory effects on protein breakdown results from different mechanisms. First, glucocorticoids (GC) stimulate several proteolytic systems by activating transcription factor FOXO. Secondly, stimulation of

GSK3β may also be involved in the stimulatory effects of glucocorticoids on protein breakdown.

• RISK INCREASES : Flourinated steroids ( triamcinolone, dexamethasone, bethametasone) Chronic use of steroids ( prednisolone > 30mg/day )

• Presentation : 1. ACUTE 2.CHRONIC(CLASSIC)

ACUTE• Associated with high dose iv.

glucocorticoid use• Present as: acute quadriplegia • Muscle stretch reflexes typically are

normal.• Sensory examination should be normal.• Lab: Most pts have high levels of serum

CK as well as associated myoglobinuria.EMG may be abnormal

• Biopsy – distinctive loss of thin filaments by EM. Shows focal & diffuse necrosis of all fiber types, without predilection for type II fibers.

• Rx- drug withdrawal, supportive care rehabilitation

• Prognosis - recovery is slow

CHRONIC• Proximal muscle weakness associated

with cushingoid appearance • Facial & sphincter muscles - spared.• Myalgias become a prominent feature • Pelvic girdle muscles are affected more

severely and earlier than are pectoral girdle muscles.

• Muscle bulk N but muscle atrophy can occur.

• Muscle stretch reflexes typically N• Sensory examination should be N• Lab. - serum levels of CK typically are

within the reference range. Creatinine excretion in the urine increases dramatically & can precede clinical appearance of myopathy by several days.EMG & NCS are N.Myoglobinuria & rhabdomyolysis are absent

• Biopsy – preferential atrophy of type – II muscle fibers

• Rx – drug withdrawal

PREVENTION AND TREATMENT• PREVENTION:Exercise, caution with steroid tapering after high dose

• Rehabilitation Program• Physical Therapy• Aerobic exercises and resistance training • Range-of-motion exercises (either passive, active-assisted or active depending on degree of

weakness) and stretching exercises should be performed to prevent joint contractures. • Bed mobility, balance activities, transfer training & gait training should be included to

address decreased mobility.

• Occupational Therapy• Focus on maximizing patient's ability to independently perform activities of daily living. • Training include use of assistive devices to enhance the patient's performance of self-care

tasks• Balanced forearm orthosis to allow positioning of the upper arm in a manner that permits

more independent feeding• In cases of myopathy caused by long-term corticosteroid use, decreasing dose to < 30 mg/d

threshold may result in resolution of muscle weakness. • In patients in whom myopathy has resulted from a short course of high-dose corticosteroid

use, partial or complete recovery has been reported following the discontinuation of steroid administration

• Other experimental treatment include: IGF-I Branched -chain amino acids(leucine) Glutamine Creatine Taurine Androgens such as testosterone and DHEA

• Various medications like K supplements, phenytoin, vitamin E & anabolic steroids have been tried as potential treatments

• Treatment recommendations for steroid myopathy are a decrease in dose of steroid to below a threshold level or the discontinuation of steroid

• Alternate-day dosing could also be considered.

• Another recommendation is that currently administered steroid be exchanged for one that is not fluorinated

Steroid induced Ocular complications

IT INCLUDES:

• Conjunctival necrosis• Corneal stromal calcification• Delayed corneal wound healing• Glaucoma:POAG

– Ocular hypertension– Open angle– Optic nerve cupping– VF loss

• Cataract(Posterior subcapsular cataract)• Retinal/choroidal emboli• Central serous chorioretinopathy• Decreased resistance to infection

Pathophysiology: Mechanisms involved in cataract formation include :

increased glucose levels due to an increased gluconeogenesis inhibition of Na + /K + -ATPase inhibition of glucose-6-phosphate-dehydrogenase inhibition of RNA synthesis covalent binding of steroids to lens proteins.

• Glucocorticoid-induced morphological & functional changes in trabecular meshwork (TM) are considered to be main mechanisms leading to increased intraocular pressure

• Glaucoma is seen mainly with topical- high dose inhaled or oral steroids and much less commonly with systemic steroids.

• It was found that dexamethasone treatment causes specific upregulation of the TIGR/MYOC gene(Trabecular Meshwork Inducible Glucocorticoid Response (TIGR) gene ) in the human TM cells but not in other cells.

• Mutations in this gene lead to impaired secretion of the protein resulting in misfolding and accumulation of aggregates inside the cells.

• Children are at greatest risk since they can develop cataracts with lower doses & shorter treatment durations than adults

• Cataracts may be seen as early as within 6 mths of treatment & even in children on alternate day therapy.

• Glucocorticoid induced glaucoma is usually observed within a few weeks after initiation of steroid therapy.

• May also be seen years after cessation of steroid therapy hence monitoring should continue even after steroids are stopped.

Strategies to prevent development of steroid induced ocular complications: • Ophthalmologic examinations are recommended every 6 months

for pts on long-term systemic glucocorticoid therapy. • Progression of cataract may still occur despite decreasing dose but

discontinuing it may occasionally deter further cataract formation or reverse lens opacification.

Strategies for treatment of established ocular complications: • Cataracts often are small but can affect visual acuity significantly

requiring surgical intervention. • Stopping treatment will halt the progress of cataract but will usually

not reverse the changes already present.

GASTROINTESTINAL COMPLICATIONSPathophysiology:

increase gastric acid secretionreduce gastric mucusgastrin and parietal cell hyperplasiadelay the healing of ulcers

Adverse effects includeGastritisPeptic ulcers Upper gastrointestinal bleedingOral candidiasisAcute pancreatitis - is another major complication especially

in children.

Prevention• minimized by administration of oral steroid with food• use of antacids - including H2 receptor antagonists or PPI

Treatment of established gastrointestinal complications: • Any symptoms suggestive of PUD should be promptly investigated

with gastroduodenoscopy & appropriate treatment started in consultation with gastroenterologist

EFFECT ON IMMUNE SYSTEM

Anti-inflammatory actions of corticosteroidsCorticosteroid inhibitory effect

Main pathogens of concern in Steroid- induced immunodeficiency

• Due to immunosuppression masking of infection symptoms may occur preventing early clinical recognition.

• Any live virus vaccine should not be given to children • HIV positive children may be considered for Pneumocystis jeroveci

prophylaxis.PREVENTIVE MEASURES• Alternate-morning therapy and doses of < 10 mg/d of prednisone

equivalent may significantly reduce the chance of opportunistic infection.

• History of TB contact should be obtained prior to beginning therapy

• Baseline chest radiograph & Mantoux test should be done. • Infection prevention can be improved by general measures like

frequent hand washing, avoiding exposure to infectious cases and use of appropriate vaccines.

Strategies for treatment of established immune suppression: • There should be no abrupt stoppage of steroid - this will

almost certainly lead to acute AI.• Safe course is - lower dose of steroid to a level which should

no longer suppress the host’s defences and yet which is adequate to prevent the development of acute glucocorticoids withdrawl.

• This level is approx. one and one-half to two times a physiologic maintenance dose of cortisol

• Appropriate cultures should be obtained but until the results are known a broad spectrum antibiotic should be given.

NEUROLOGICAL MANIFESTATIONS OF STEROID

• Steroid-induced psychosis represents spectrum of psychological changes -can occur at any time during treatment.

• Mild-to-moderate symptoms include – Agitation Anxiety Insomnia Irritability Restlessness

• Severe symptoms include – Mania Depression Psychosis

• Often develop after 4 days of corticosteroid therapy although can occur late in therapy or after treatment ends

• Act at steroid specific receptors and suppress filtering by hippocampus - irrelevant stimuli

• Suppressed hypothalamus pituitary axis & enhanced dopamine neurotransmission

• Depression via a reduction in serotonin levels.• First-line treatment- to taper /discontinue steroid• If this is not possible because of comorbid disease or severe

psychosis consider adding low-dose atypical antipsychotics in pts with manic / hypomanic symptoms.

• Second-line treatment Consider mood stabilizers such as lithium or valproic acid in pts with normal RFT

Corticosteroid-induced psychosis: Adjunctive treatment studies

DERMATOLOGICAL SIDE EFFECTS

CATEGORY• Wound healing &

related changes

• Pilosebaceous unit

MECHANISM• Decrease collagen,ground sub,dec re-

epithelization & angiogenesisA/E:Non-healing wounds ,ulcer, striae

atrophy,telangiectasis

• Androgenicity,P.ovaleA/E:steroid acne&rosacea

CATEGORY• Vascular

• Cutaneous inf.

• Hair effects

• Others

MECHANISM• Catabolic effect on vascular smooth muscleA/E:purpura

• A/E:Staphylococcal,herpes

• A/E:Telogen effluvium,hirsutism

• A/E:Acanthosis nigricans

Atrophy and striae induced by topical steroids

Tinea incognito. Signs of dermatophyte infection are partly suppressed bytreatment with a potent topical steroid

Stretch marks Skin thinning

HAEMATOLOGICAL EFFECTS

• Polycythaemia a feature of Cushing’s syndrome but does not appear to be a feature of corticosteroid therapy.

• Promotes blood coagulation and alters the patient’s response to anticoagulants

• Hence frequent checks on the extent of anticoagulation are

necessary especially if the steroid dose is varying. 

REPRODUCTIVE SYSTEM• Men can experience longer

erections / higher frequency of erections yet a decrease in sperm production- resulting in sterility.

• Men might also find that they are impotent

• According to Concepts of Chemical Dependency, prostate cancer has been found in rare instances.

• In females- interruption of their menstrual cycle

• Can develop infertility issues • Both sexes might experience

changes in sex drive, either an increase in desire or a loss of desire.

STEROIDS AND PREGNANCY• CATEGORY – C DRUG• Cataracts , cyclopia, interventricular septal defect, gastroschisis,

cleft lip, hydrocephalus, coarctation of aorta,clubfoot ,LBW,IUGR stillbirth has been reported

• For maternal disease, derivatives of cortisone and prednisone are suggested since they are more readily inactivated by placenta as opposed to dexamethasone & betamethasone which are more likely to reach the fetus in the active state.

• As with any medication use of steroid must be weighed against severity of maternal disease.

A note on steroid side effects….Dermatologic and soft tissue

Skin thinning and purpura, easy bruising, Cushingoid appearance, alopecia, acne, hirsutism, striae, hypertrichosis

Ocular Posterior subcapsular cataract, elevated intraocular pressure/glaucoma, exophthalmos

Cardiovascular Hypertension, dyslipidemia, premature atherosclerotic disease, arrhythmias with pulse infusions

Gastrointestinal Gastritis, peptic ulcer disease, pancreatitis, steatohepatitis, visceral perforation

Renal Hypokalemia, fluid volume shifts

Genitourinary and reproductive

Amenorrhea/infertility, intrauterine growth retardation

Bone/muscle Osteoporosis, avascular necrosis, myopathy

Neuropsychiatric Euphoria, dysphoria/depression, insomnia/akathisia, psychosis, pseudo tumor cerebri

Endocrine Diabetes, HPA axis insufficiency

ID Heightened risk of typical infections, opportunistic infections, herpes zosterS. Monrad

CONCLUSION

• The appropriate anticipation of these side-effects with timely implementation of evidence-based guidelines has the potential significantly to prevent, minimize and treat common and disabling complications of glucocorticoid therapy.

• When steroids are prescribed measures should be taken to minimise their side effects.

• Clearly chance of significant side effects increases with dose & duration of treatment and so minimum dose necessary to control disease should be given

THANK YOU