2. SteroidsSteroids
Steroids are fast catching up with antibiotics
as the most abused class of drugs today
High doses of corticosteroids and
other immunosuppressive agents may cause AIDS
3. IntroductionIntroduction
• The adrenal produces various classes of
hormones, each of which aid in dealing with the
stress faced by animals and people almost daily
• At least two of these groups –
Glucocorticoids and Mineralocorticoids
are necessary for life
• Corticosteroids or corticoids refer to natural
gluco- and mineralo-corticoids and their
synthetic analogues
4. ContentsContents
History and BiosynthesisHistory and Biosynthesis
Mechanism of actionMechanism of action
Physiological and Pharmacological actionsPhysiological and Pharmacological actions
Pharmacokinetics and preparationsPharmacokinetics and preparations
Uses – therapeutic and diagnosticUses – therapeutic and diagnostic
Dosage schedule and withdrawalDosage schedule and withdrawal
Adverse reactions and contraindicationsAdverse reactions and contraindications
Precautions during therapyPrecautions during therapy
ContraindicationsContraindications
6. AnatomyAnatomy
An inner medulla,An inner medulla, is a sourceis a source
of catecholamine – adrenalineof catecholamine – adrenaline
and nor-adrenalineand nor-adrenaline
Chromaffin cell is the principalChromaffin cell is the principal
cell typecell type
Medulla is richly innervated byMedulla is richly innervated by
sympathetic fibres and issympathetic fibres and is
considered as extension ofconsidered as extension of
sympathetic nervous systemsympathetic nervous system
Medulla develops fromMedulla develops from
ectoderm (neural crest)ectoderm (neural crest)
An outer cortex,An outer cortex, whichwhich
secretes several classes ofsecretes several classes of
steroid hormones includingsteroid hormones including
GlucocorticoidsGlucocorticoids andand
MineralocorticoidsMineralocorticoids
Three different concentricThree different concentric
zones of cells that differ inzones of cells that differ in
major steroid hormones theymajor steroid hormones they
secretesecrete
Cortex develops fromCortex develops from
mesodermmesoderm
7. Adrenal CortexAdrenal Cortex
The adrenal cortex is a factory of steroid hormonesThe adrenal cortex is a factory of steroid hormones
10 – 30 different steroids are synthesized from this10 – 30 different steroids are synthesized from this
tissue, but two classes are of importancetissue, but two classes are of importance
Steroid ClassSteroid Class PrototypePrototype Physiological effectPhysiological effect
MineralocorticoidMineralocorticoid Aldosterone (z. glomerulosa)Aldosterone (z. glomerulosa) Na, K and waterNa, K and water
homeostasishomeostasis
GlucocorticoidGlucocorticoid Hydrocortisone or cortisol (z. fasciculata)Hydrocortisone or cortisol (z. fasciculata)
CorticosteroneCorticosterone
Glucose and manyGlucose and many
other homeostasisother homeostasis
Adrenal cortex also produces sex steroids – Androgens,
Dehydroepiandrosterone (DHEA) – z. reticularis
8. BiosynthesisBiosynthesis
Synthesized from cholesterolSynthesized from cholesterol
through a series of enzyme-through a series of enzyme-
mediated transformationsmediated transformations
ACTHACTH stimulates adrenalstimulates adrenal
steroid synthesissteroid synthesis
Aldosterone synthesis is notAldosterone synthesis is not
stimulated by ACTH but bystimulated by ACTH but by
angiotensin II, although ACTHangiotensin II, although ACTH
does stimulate synthesis ofdoes stimulate synthesis of
aldosterone precursorsaldosterone precursors
Circulating Potassium exerts aCirculating Potassium exerts a
permissive effect onpermissive effect on
angiotensin II stimulation; highangiotensin II stimulation; high
potassium enhances and lowpotassium enhances and low
potassium diminishespotassium diminishes
11. Regulation of SynthesisRegulation of Synthesis
• Synthesized and
released under
influence of ACTH - Ant.
Pituitary (HPA axis)
• Regulated by CRH
from hypothalamus
and by feedback
levels of blood
concentrations
12. 1.1. Control by circadianControl by circadian
rhythm (Diurnalrhythm (Diurnal
rhythm) – morningrhythm) – morning
riserise
2.2. Stress:Stress:
hypoglycaemia,hypoglycaemia,
physical stress etc.physical stress etc.
Regulation of Synthesis - OthersRegulation of Synthesis - Others
14. Glucocorticoids - MOAGlucocorticoids - MOA
Not stored:Not stored:
rate of synthesis = rate of releaserate of synthesis = rate of release
Synthesize rhythmically and controlled bySynthesize rhythmically and controlled by
irregular pulses of ACTH, influenced by light andirregular pulses of ACTH, influenced by light and
major pulses occur early in the morning andmajor pulses occur early in the morning and
after mealsafter meals
Glucocorticoids act via their receptors located inGlucocorticoids act via their receptors located in
nucleus (GR)nucleus (GR)
GRs are widely distributed and located almost inGRs are widely distributed and located almost in
all cells of the bodyall cells of the body
They are made up of almost 800 amino acidsThey are made up of almost 800 amino acids
15. Glucocorticoids - MOAGlucocorticoids - MOA
GR receptors are located in the cytoplasmGR receptors are located in the cytoplasm
One GR receptor has a DNA binding domain and aOne GR receptor has a DNA binding domain and a
ligand binding domain along with stabilizing proteinsligand binding domain along with stabilizing proteins
(HSP 90 and HSP 70)(HSP 90 and HSP 70)
This receptor is incapable of activating transcriptionThis receptor is incapable of activating transcription
Binding of free steroid molecule to GR forms an unstableBinding of free steroid molecule to GR forms an unstable
compoundcompound
Therefore HSP and other proteins get dissociatedTherefore HSP and other proteins get dissociated
The S+GR complex enters the nucleus and binds toThe S+GR complex enters the nucleus and binds to
Glucocorticoids response element (GRE) on gene andGlucocorticoids response element (GRE) on gene and
regulate transcription by RNA polymerase II and othersregulate transcription by RNA polymerase II and others
The resulting mRNA is transported to cytoplasm forThe resulting mRNA is transported to cytoplasm for
production of protein and bring about final responseproduction of protein and bring about final response
17. ActionsActions
Numerous and widespread actions:Numerous and widespread actions:
Carbohydrate, lipid and protein metabolismCarbohydrate, lipid and protein metabolism
Fluid and electrolyte balanceFluid and electrolyte balance
Normal functioning of CVS, immune system, kidneys, skeletal muscles and nervous systemNormal functioning of CVS, immune system, kidneys, skeletal muscles and nervous system
Provides resistance to stress and noxious stimuli and environmental changesProvides resistance to stress and noxious stimuli and environmental changes
Permits and facilitates the actions of other hormonesPermits and facilitates the actions of other hormones
Direct ActionsDirect Actions
Permissive ActionsPermissive Actions
• Lipolytic effects
• Effect on BP
• Effect on bronchial muscles
• (e.g.,sympathomimetic amine)
18. Actions of Corticosteroids -Actions of Corticosteroids -
MineralocorticoidMineralocorticoid
Aldosterone is the prototype of mineralocorticoid effectsAldosterone is the prototype of mineralocorticoid effects
Acts on the distal tubule to enhance absorption of Na+Acts on the distal tubule to enhance absorption of Na+
Increase excretion of K+ and HIncrease excretion of K+ and H
Similar effects occur in colon, sweat gland and salivarySimilar effects occur in colon, sweat gland and salivary
glandgland
Deficiency of mineralocorticoid action leads toDeficiency of mineralocorticoid action leads to ––
dilutional hyponatraemia, hyperkalamia, acidosis,dilutional hyponatraemia, hyperkalamia, acidosis,
massive loss of Na+ and decreased EFC volumemassive loss of Na+ and decreased EFC volume
(essential for survival)(essential for survival)
Hyperaldosterinism:Hyperaldosterinism: Positive Na+ balance, expansion ofPositive Na+ balance, expansion of
ECF, increased plasma Na, hypokalaemia, alkalosis andECF, increased plasma Na, hypokalaemia, alkalosis and
progressive rise in BP – hypertension, myocardialprogressive rise in BP – hypertension, myocardial
fibrosis etc.fibrosis etc.
19. Glucocorticoid actions -Glucocorticoid actions -
Carbohydrate & protein metabolismCarbohydrate & protein metabolism
Profound effect on carbohydrate and protein metabolismProfound effect on carbohydrate and protein metabolism
– aimed at protecting glucose dependent tissues (brain– aimed at protecting glucose dependent tissues (brain
and heart)and heart)
Promotes glycogen deposition in liver and stimulate it toPromotes glycogen deposition in liver and stimulate it to
form glucose from amino acids – gluconeogenesisform glucose from amino acids – gluconeogenesis
In peripheral tissues decreases utilization of glucose,In peripheral tissues decreases utilization of glucose,
increase protein breakdown and activate lipolysis – formincrease protein breakdown and activate lipolysis – form
amino acids and glycerol for gluconeogenesisamino acids and glycerol for gluconeogenesis
All these results in -All these results in -
Diabetes like stat resistant to insulin – increased glucose releaseDiabetes like stat resistant to insulin – increased glucose release
from liver + decreased peripheral glucose utilizationfrom liver + decreased peripheral glucose utilization
Negative Nitrogen balance (catabolic effect) – amino acid usedNegative Nitrogen balance (catabolic effect) – amino acid used
up in gluconeogenesis – increased urea productionup in gluconeogenesis – increased urea production
Mobilization of amino acids – muscles, thinning of bone and skinMobilization of amino acids – muscles, thinning of bone and skin
20. Actions:Actions: Carbohydrate and protein metabolismCarbohydrate and protein metabolism
GluconeogenesisGluconeogenesis
Peripheral actionsPeripheral actions (mobilize AA & glucose and(mobilize AA & glucose and
glycogen)glycogen)
Hepatic actionsHepatic actions
Peripheral utilization of glucosePeripheral utilization of glucose
Glycogen deposition in liverGlycogen deposition in liver
(activation of hepatic glycogen synthase)(activation of hepatic glycogen synthase)
Negative nitrogen balance & hyperglycaemia
21. Fat MetabolismFat Metabolism
Redistribution of fats in different areas of theRedistribution of fats in different areas of the
bodybody
Due to permissive facilitation of effects of otherDue to permissive facilitation of effects of other
agents – GH, glucagons, Adr, thyroxine andagents – GH, glucagons, Adr, thyroxine and
insulininsulin
Deposition of fats in face, neck and shoulder – moonDeposition of fats in face, neck and shoulder – moon
face/buffalo humpface/buffalo hump
Glucocorticoids facilitated hormone sensitive lipolysisGlucocorticoids facilitated hormone sensitive lipolysis
action of GH and Adr. + Glucocorticoids mediatedaction of GH and Adr. + Glucocorticoids mediated
increased insulin = net result is insulin mediatedincreased insulin = net result is insulin mediated
lipogenesis and fat depositionlipogenesis and fat deposition
Peripheral adipocytes are less sensitive to insulin, butPeripheral adipocytes are less sensitive to insulin, but
in face and neck predominant action – fat depositionin face and neck predominant action – fat deposition
22. Actions of GlucocorticoidsActions of Glucocorticoids
Water excretion:Water excretion:
Glucocorticoids play important role in maintaining normal GFR - inGlucocorticoids play important role in maintaining normal GFR - in
adrenal insufficiency capacity to excrete water is lost – water intoxicationadrenal insufficiency capacity to excrete water is lost – water intoxication
Calcium Balance:Calcium Balance:
Decrease absorption of Ca++ in GIT and increased excretion – calciumDecrease absorption of Ca++ in GIT and increased excretion – calcium
depletion -depletion - osteoporosisosteoporosis
Skeletal muscle:Skeletal muscle:
Normal muscular activity needs Glucocorticoids at its optimum levelNormal muscular activity needs Glucocorticoids at its optimum level
Excess level leads to muscular weakness and wastingExcess level leads to muscular weakness and wasting
Muscular weakness occurs in both Hypocorticism (due to hypodynamicMuscular weakness occurs in both Hypocorticism (due to hypodynamic
circulation) and hypercorticism – due to hypokalaemiacirculation) and hypercorticism – due to hypokalaemia
CNS:CNS:
Euphoria – in pharmacological dosesEuphoria – in pharmacological doses
Addison's disease – apathy, depression and psychosisAddison's disease – apathy, depression and psychosis
High doses – induce seizureHigh doses – induce seizure
23. Actions of GlucocorticoidsActions of Glucocorticoids
CVS:CVS: Permissive role on pressor effect with Adr and angiotensinPermissive role on pressor effect with Adr and angiotensin
Maintain tone of arterioles and myocardial contractilityMaintain tone of arterioles and myocardial contractility
Adrenal insufficiency leads to low cardiac output and arteriolar dilatationAdrenal insufficiency leads to low cardiac output and arteriolar dilatation
and poor response to adrenalineand poor response to adrenaline
Cardiovascular collapse – along with mineralocorticoidsCardiovascular collapse – along with mineralocorticoids
Blood and lymphoid tissues:Blood and lymphoid tissues:
Destruction of lymphoid tissue – modest in normal personsDestruction of lymphoid tissue – modest in normal persons
In presence of malignancy of lymphatic cells – lytic actions areIn presence of malignancy of lymphatic cells – lytic actions are
significant (apoptosis) – used in lymphomassignificant (apoptosis) – used in lymphomas (Basis of Use)(Basis of Use)
Minor effects on haemoglobin and RBCs – protect against haemolysis ofMinor effects on haemoglobin and RBCs – protect against haemolysis of
RBCs –RBCs – Increase in number of RBCsIncrease in number of RBCs
Decreases the numbers of circulating lymphocytes, monocytes,Decreases the numbers of circulating lymphocytes, monocytes,
eosinophils and basophils but increases Polymorphseosinophils and basophils but increases Polymorphs
24. Glucocorticoids – anti-inflammatoryGlucocorticoids – anti-inflammatory
and immunosuppressive effectsand immunosuppressive effects
Suppress inflammatory response to all noxious stimuli:Suppress inflammatory response to all noxious stimuli:
Pathogens, chemical,physical and immune mediatedPathogens, chemical,physical and immune mediated
stimuli, hypersensitivitystimuli, hypersensitivity
Underlying cause of disease is not correctedUnderlying cause of disease is not corrected
Reduction in cardinal signs of inflammationReduction in cardinal signs of inflammation
Anti-inflammatory effects are non—specific and coversAnti-inflammatory effects are non—specific and covers
all components of inflammation:all components of inflammation:
Effects on concentration, distribution and functions of peripheralEffects on concentration, distribution and functions of peripheral
leukocytes – increased neutrophils & their activityleukocytes – increased neutrophils & their activity
In macrophages: reduction of arachidonic acid metabolitesIn macrophages: reduction of arachidonic acid metabolites
(mediators) like PG, LT and PAF synthesis that results from(mediators) like PG, LT and PAF synthesis that results from
activation of phospholipase A2activation of phospholipase A2
Basis of exogenous use of most clinical usesBasis of exogenous use of most clinical uses
25. Glucorticoids - Multiple
Mechanisms
Recruitment of WBC & monocyte - macrophage intoRecruitment of WBC & monocyte - macrophage into
affected area & elaboration of chemotactic substancesaffected area & elaboration of chemotactic substances
Lipocortin: decreased production of PG, LT and PAFLipocortin: decreased production of PG, LT and PAF
Negative regulation of COX 2: inducible PGNegative regulation of COX 2: inducible PG
productionproduction
Negative regulation of genes in cytokines ofNegative regulation of genes in cytokines of
macrophages, endothelial cells and lymphocytes:macrophages, endothelial cells and lymphocytes:
production of IL (1, 2, 3, 6), TNFproduction of IL (1, 2, 3, 6), TNFαα, GM-CSF etc. –, GM-CSF etc. –
fibroblast proliferation and T-lymphocyte function –fibroblast proliferation and T-lymphocyte function –
interference with chemotaxisinterference with chemotaxis
26. Contd.Contd.
In endothelial cells-Endothelial leucocyte adhesionIn endothelial cells-Endothelial leucocyte adhesion
moleculemolecule (ELAM)(ELAM) and otherand other CAMCAM are inhibited –are inhibited –
adhesion and localization of leucocytes interferedadhesion and localization of leucocytes interfered
Release of histamine from basophils is inhibitedRelease of histamine from basophils is inhibited
Decreased production ofDecreased production of collagenasecollagenase – prevention of– prevention of
tissue destructiontissue destruction
Decreased functioning ofDecreased functioning of osteoblastsosteoblasts and increasedand increased
activity ofactivity of osteoclasticosteoclastic activity -activity - osteoporosisosteoporosis
Decreased IgG productionDecreased IgG production
Decreased generation of induced nitric oxideDecreased generation of induced nitric oxide
28. Immunosuppressive & anti-allergicImmunosuppressive & anti-allergic
actionsactions
Suppresses all types of hypersensitivity &Suppresses all types of hypersensitivity &
allergic phenomenonallergic phenomenon
At High dose: Interfere with all steps ofAt High dose: Interfere with all steps of
immunological responseimmunological response
Causes greater suppression of CMI (graftCauses greater suppression of CMI (graft
rejection & delayed hypersensitivity)rejection & delayed hypersensitivity)
Transplant rejection: antigen expression fromTransplant rejection: antigen expression from
grafted tissues, delay revascularization,grafted tissues, delay revascularization,
sensitisation of T lymphocytes etc.sensitisation of T lymphocytes etc.
30. Glucocorticoids - PharmacokineticsGlucocorticoids - Pharmacokinetics
Therapeutically given by various routes – orally, IM, IV,Therapeutically given by various routes – orally, IM, IV,
topicallytopically
Hydrocortisone undergoes high first pass metabolismHydrocortisone undergoes high first pass metabolism
Oral bioavailability of synthetic corticoids is highOral bioavailability of synthetic corticoids is high
Both, endogenous and therapeutically administered GCBoth, endogenous and therapeutically administered GC
are bound to Corticosteroid Binding Globulin (CBG)are bound to Corticosteroid Binding Globulin (CBG)
Synthetic steroids have to undergo reduction in liver toSynthetic steroids have to undergo reduction in liver to
active compoundsactive compounds
Metabolized in liver and excreted in urineMetabolized in liver and excreted in urine
Exogenously administered hydrocortisone has t1/2 of 1.5Exogenously administered hydrocortisone has t1/2 of 1.5
HrsHrs
31. Steroid PreparationsSteroid Preparations
An ideal GC should have noAn ideal GC should have no
mineralocorticoid activitymineralocorticoid activity
Structural changes to the basic cortisolStructural changes to the basic cortisol
molecule resulted in a number ofmolecule resulted in a number of
compounds withcompounds with
Minimal mineralocorticoid activityMinimal mineralocorticoid activity
Greater potencyGreater potency
Longer duration of actionLonger duration of action
37. Therapeutic usesTherapeutic uses
A number of diverse disease states respond toA number of diverse disease states respond to
GCsGCs
Physiologic doses of Corticosteroids are usedPhysiologic doses of Corticosteroids are used
for replacement therapy in primary andfor replacement therapy in primary and
secondary adrenal insufficiency such assecondary adrenal insufficiency such as
Addison`s diseaseAddison`s disease
Supraphysiologic doses are used for their anti-Supraphysiologic doses are used for their anti-
inflammatory effects in arthritis, asthma andinflammatory effects in arthritis, asthma and
inflammatory bowel diseaseinflammatory bowel disease
In organ transplant patients and those withIn organ transplant patients and those with
autoimmune disorders corticosteroids are usedautoimmune disorders corticosteroids are used
for their immunosuppressive effectsfor their immunosuppressive effects
38. Replacement TherapyReplacement Therapy
Adrenal insufficiency – acute/chronicAdrenal insufficiency – acute/chronic
Abrupt withdrawal of steroid therapyAbrupt withdrawal of steroid therapy
Chronic infections – TuberculosisChronic infections – Tuberculosis
Autoimmune adrenal diseaseAutoimmune adrenal disease
Surgery, Hemorrhage and AIDSSurgery, Hemorrhage and AIDS
Congenital adrenal hyperplasiaCongenital adrenal hyperplasia
Congenital disorder due to deficiency of 21-Congenital disorder due to deficiency of 21-
hydroxylse enzyme – no cortisol but ACTH –hydroxylse enzyme – no cortisol but ACTH –
increased androgen productionincreased androgen production
CAH
39. Replacement TherapyReplacement Therapy
Acute adrenal insufficiencyAcute adrenal insufficiency
IV replacement of sodium chloride and fluidIV replacement of sodium chloride and fluid
IV hydrocortisone 100 mg stat followed by100 mgIV hydrocortisone 100 mg stat followed by100 mg
every 8 Hrs – maximal daily rate of secretionevery 8 Hrs – maximal daily rate of secretion
(alternatively, dexamethasone can be used)(alternatively, dexamethasone can be used)
Chronic adrenal insufficiencyChronic adrenal insufficiency
HydrocortisoneHydrocortisone
Prednisolone or dexamethasone – long actingPrednisolone or dexamethasone – long acting
Fludrocortisone for mineralocorticoid effectsFludrocortisone for mineralocorticoid effects
Congenital adrenal hyperplasiaCongenital adrenal hyperplasia
Hydrocortisone 0.6 mg/kg in divided doses – toHydrocortisone 0.6 mg/kg in divided doses – to
maintain feedback suppressionmaintain feedback suppression
40. Anti-inflammatory UsesAnti-inflammatory Uses
For suppression of inflammatory components inFor suppression of inflammatory components in
––
Rheumatoid arthritis – as adjuvant with NSAIDs inRheumatoid arthritis – as adjuvant with NSAIDs in
severe casessevere cases
Osteoarthritis – NSAIDs, intra-articular injectionOsteoarthritis – NSAIDs, intra-articular injection
Rheumatic fever – severe cases with carditis andRheumatic fever – severe cases with carditis and
CHFCHF
Gout – NSAID failed cases and colchicine failedGout – NSAID failed cases and colchicine failed
cases – intra-articular injectioncases – intra-articular injection
Vasculitic disorders: Polyarteritis nodosaVasculitic disorders: Polyarteritis nodosa
42. Autoimmune diseasesAutoimmune diseases
Autoimmune haemolytic anaemiaAutoimmune haemolytic anaemia
Idiopathic thrombocytopenic purpuraIdiopathic thrombocytopenic purpura
Active chronic hepatitis, alcoholic hepatitisActive chronic hepatitis, alcoholic hepatitis
(Prednisolone 1-2 mg/kg/day given till(Prednisolone 1-2 mg/kg/day given till
remission followed by gradual withdrawalremission followed by gradual withdrawal
or low dose maintenance)or low dose maintenance)
ITP
43. Renal diseasesRenal diseases
Nephrotic syndrome in childrenNephrotic syndrome in children
Renal disease secondary to SLERenal disease secondary to SLE
Renal sarcoidosisRenal sarcoidosis
Glomerulonephritis – membranous typeGlomerulonephritis – membranous type
(Life saving importance – usually given in(Life saving importance – usually given in
large doses followed by tapering tolarge doses followed by tapering to
maintenance dose)maintenance dose)
SLE
44. Organ TransplantOrgan Transplant
Combined with otherCombined with other
immunosuppressants – cyclosporin,immunosuppressants – cyclosporin,
azathioprineazathioprine
For prolonged use:For prolonged use:
Prednisolone or methylprednisolone arePrednisolone or methylprednisolone are
usedused
Intermediate duration of actionIntermediate duration of action
Can be easily taperedCan be easily tapered
Can be converted to an alternate regimeCan be converted to an alternate regime
45. Allergic DisordersAllergic Disorders
Exhibit a delayed response in allergies (1-2 hrsExhibit a delayed response in allergies (1-2 hrs
even in IV injection)even in IV injection)
In anaphylaxis, angioneurotic oedema andIn anaphylaxis, angioneurotic oedema and
serum sickness etc. – adrenaline is the choiceserum sickness etc. – adrenaline is the choice
Seasonal allergies, bee sting, drug allergies –Seasonal allergies, bee sting, drug allergies –
Allergic reactions can be suppressed byAllergic reactions can be suppressed by
corticosteroids as supplementscorticosteroids as supplements
Intranasal administration in allergic rhinitis -Intranasal administration in allergic rhinitis -
budesonide and flunisolidebudesonide and flunisolide
46. Bronchial AsthmaBronchial Asthma
The increased recognition of the immunological andThe increased recognition of the immunological and
inflammatory nature of Bronchial asthma has led to theinflammatory nature of Bronchial asthma has led to the
use of corticosteroidsuse of corticosteroids
In severe asthma attacksIn severe asthma attacks
IV hydrocortisone MethylprednisoloneIV hydrocortisone Methylprednisolone
Oral prednisoloneOral prednisolone
Acute attacks:Acute attacks:
*Inhaled beclmethasone, budesonide, flunisolide*Inhaled beclmethasone, budesonide, flunisolide
alone or combined with beta-2 agonists/ipratropiumalone or combined with beta-2 agonists/ipratropium
*Oral steroids*Oral steroids
47. Infectious DiseasesInfectious Diseases
Indicated only in severe infective diseasesIndicated only in severe infective diseases
to tide over crisis or prebent complictionsto tide over crisis or prebent complictions
AIDS and pneumocystis carinii pneumoniaAIDS and pneumocystis carinii pneumonia
In haemophilus influenza meningitis to reduceIn haemophilus influenza meningitis to reduce
neurological complicationsneurological complications
Tubercular meningitisTubercular meningitis
Lepra reactionLepra reaction
ScepticaemiaScepticaemia
Lepra reaction
48. Ocular DiseasesOcular Diseases
Important drug therapy for suppressingImportant drug therapy for suppressing
inflammation in eye and preservation of sightinflammation in eye and preservation of sight
Topical instillations are used for conditions of theTopical instillations are used for conditions of the
anterior chamber – allergic conjunctivitis, iritis,anterior chamber – allergic conjunctivitis, iritis,
iridocyclitis and keratitis etc.iridocyclitis and keratitis etc.
Systemic steroids for the posterior chamberSystemic steroids for the posterior chamber
Dexamethasone topical 0.1%Dexamethasone topical 0.1%
Prednisolone oralPrednisolone oral
Contraindicated in viral, fulminant bacterialContraindicated in viral, fulminant bacterial
infections, fungal infections and injuriesinfections, fungal infections and injuries
49. Skin DiseasesSkin Diseases
The largest application of steroid therapyThe largest application of steroid therapy
Topical forms are widely used in manyTopical forms are widely used in many
eczematous skin diseaseseczematous skin diseases
Systemic therapy are also required andSystemic therapy are also required and
may be life saving inmay be life saving in
Pemphigus vulgarisPemphigus vulgaris
Exfoliative dermatitisExfoliative dermatitis
Stevens-Johnson syndromeStevens-Johnson syndrome
Pemphigus
vulgaris
50. GITGIT
Inflammatory conditions of intestine likeInflammatory conditions of intestine like
Ulcerative colitisUlcerative colitis
Crohn`s diseaseCrohn`s disease
Coeliac diseaseCoeliac disease
(oral therapy or retention enema with hydrocortisone)(oral therapy or retention enema with hydrocortisone)
May mask the major complications likeMay mask the major complications like
perforation and peritonitisperforation and peritonitis
51. MalignancyMalignancy
Essential for combined chemotherapy ofEssential for combined chemotherapy of
Acute lymphatic leukemiaAcute lymphatic leukemia
Hodgkin's and other lymphomasHodgkin's and other lymphomas
Hormone responsive breast carcinomaHormone responsive breast carcinoma
Symptomatic relief in other advanceSymptomatic relief in other advance
malignancies by improving appetite andmalignancies by improving appetite and
controlling secondary hypercalcaemiacontrolling secondary hypercalcaemia
Hodgkin`s
lymphoma
52. Cerebral OedemaCerebral Oedema
Cerebral oedema due to tumorsCerebral oedema due to tumors
(neoplasms)(neoplasms)
Traumatic and poststroke oedema (?)Traumatic and poststroke oedema (?)
(Dexamethasone or betamethasone is(Dexamethasone or betamethasone is
preferred because no Na+ retainingpreferred because no Na+ retaining
activity)activity)
Other CNS conditions - spinal chord injury,Other CNS conditions - spinal chord injury,
Bell`s palsy and neurocysticercosisBell`s palsy and neurocysticercosis
(Oral Prednisolone is the preferred drug)(Oral Prednisolone is the preferred drug)
53. Other UsesOther Uses
Antiemetic – with ondansetronAntiemetic – with ondansetron
Acute mountain sicknessAcute mountain sickness
Aspiration pneumonia, pulmonary oedemaAspiration pneumonia, pulmonary oedema
from drowningfrom drowning
Hyperthyroidism – thyroid stormHyperthyroidism – thyroid storm
54. Adverse EffectsAdverse Effects
Two types:Two types:
From abrupt withdrawalFrom abrupt withdrawal
Chronic therapeutic use of high doseChronic therapeutic use of high dose
WithdrawalWithdrawal
Flare up of underlying diseaseFlare up of underlying disease
Suppression of HPA axis and acute adrenalSuppression of HPA axis and acute adrenal
insufficiencyinsufficiency
Increased ICT and papilloedemaIncreased ICT and papilloedema
56. Other Important Adverse EffectsOther Important Adverse Effects
Fluid and Electrolyte Disturbance – Na and waterFluid and Electrolyte Disturbance – Na and water
retentionretention
Precipitation of Diabetes mellitus – hyperglycemiaPrecipitation of Diabetes mellitus – hyperglycemia
Increased susceptibility to infections – immune responseIncreased susceptibility to infections – immune response
suppressionsuppression
Peptic ulceration – bleeding & perforationPeptic ulceration – bleeding & perforation
Osteoporosis – flat spongy bonesOsteoporosis – flat spongy bones
Osteonecrosis – avascular necrosis of head of femur,Osteonecrosis – avascular necrosis of head of femur,
humorous etc.humorous etc.
Myopathy – weakness of musclesMyopathy – weakness of muscles
Cataract – posterior sub capsularCataract – posterior sub capsular
Glaucoma – prolonged topical therapyGlaucoma – prolonged topical therapy
Growth retardation – in childrenGrowth retardation – in children
57. ContraindicationsContraindications
Say no to any drug formulation combined withSay no to any drug formulation combined with
steroidssteroids
Remember that STEROIDS are life saving drugsRemember that STEROIDS are life saving drugs
Note the following conditions where u have to beNote the following conditions where u have to be
extremely cautious:extremely cautious:
Peptic ulcerPeptic ulcer
Hypertension and Diabetes mellitusHypertension and Diabetes mellitus
Viral and fungal infectionsViral and fungal infections
Tuberculosis and other diseasesTuberculosis and other diseases
OsteoporosisOsteoporosis
Epilepsy and psychosisEpilepsy and psychosis
CHF and renal failureCHF and renal failure
58. Choosing a SteroidChoosing a Steroid
Benefit/risk ratio is a major considerationBenefit/risk ratio is a major consideration
Drugs with primary glucocorticoid activityDrugs with primary glucocorticoid activity
are usedare used
Minimal dose to achieve the desiredMinimal dose to achieve the desired
effects is choseneffects is chosen
Topical or local therapy is preferredTopical or local therapy is preferred
whenever possiblewhenever possible
59. Choosing a Steroid – contd.Choosing a Steroid – contd.
• Once daily dosing is usuallyOnce daily dosing is usually
preferred for oral glucocorticoidspreferred for oral glucocorticoids
• Large steroid doses areLarge steroid doses are
administered in divided doses toadministered in divided doses to
reduce local GIT effectsreduce local GIT effects
• In order to mimic the normal diurnalIn order to mimic the normal diurnal
cycle and reduce the risk ofcycle and reduce the risk of
adrenal suppression, GCs shouldadrenal suppression, GCs should
be given in the morning betweenbe given in the morning between
6-10 AM6-10 AM
• Alternate day therapy allows theAlternate day therapy allows the
HPA axis to recover on off daysHPA axis to recover on off days
Single
dose
Steroid
60. Withdrawal of Steroid TherapyWithdrawal of Steroid Therapy
Taper the dose to reduce GC dose by 2.5-5 mg ofTaper the dose to reduce GC dose by 2.5-5 mg of
prednisolone equivalent dailyprednisolone equivalent daily
Once the GC dose is reduced to 5 mg of prednisoloneOnce the GC dose is reduced to 5 mg of prednisolone
equivalent, the patient may be switched to a shorterequivalent, the patient may be switched to a shorter
acting agent for further taperingacting agent for further tapering
Intermediate acting corticosteroids allow for more flexibleIntermediate acting corticosteroids allow for more flexible
dosing scheduledosing schedule
Have potent glucocorticoid effectsHave potent glucocorticoid effects
Causes lesser suppression of HPA axisCauses lesser suppression of HPA axis
Causes less GIT irritationCauses less GIT irritation
Preferred for oral therapyPreferred for oral therapy
Prednisolone, methylprednisolone and triacinolone have a halfPrednisolone, methylprednisolone and triacinolone have a half
life of 12-36 Hrs, are available in a number of dosage formslife of 12-36 Hrs, are available in a number of dosage forms
61. Adrenocorticosteroid InhibitorsAdrenocorticosteroid Inhibitors
Metyrapone:Metyrapone: 11 beta-hydroxylase11 beta-hydroxylase enzyme inhibitor –enzyme inhibitor –
used in Cushing`s syndrome and test of pituitaryused in Cushing`s syndrome and test of pituitary
efficiencyefficiency
Aminoglutethemide:Aminoglutethemide: Stops conversion of cholesterol toStops conversion of cholesterol to
pregnelonepregnelone (Medical adrenalectomy)(Medical adrenalectomy) – Breast cancers– Breast cancers
Mifepristone:Mifepristone: Progesterone antagonistProgesterone antagonist
Spironolactone:Spironolactone: Aldosterone antagonistAldosterone antagonist
Ketoconazole:Ketoconazole: Inhibits synthesis of all hormones inInhibits synthesis of all hormones in
testes and adrenal cortex – used in Cushing`stestes and adrenal cortex – used in Cushing`s
syndrome and also in hirsutism in femalesyndrome and also in hirsutism in female
62. Must Know!Must Know!
Biosynthesis and Regulation ofBiosynthesis and Regulation of
CorticosteroidsCorticosteroids
Mechanism of action of CorticosteroidsMechanism of action of Corticosteroids
Name of commonly used GlucocorticoidsName of commonly used Glucocorticoids
Anti-inflammatory andAnti-inflammatory and
immunosuppressive actions ofimmunosuppressive actions of
GlucocorticoidsGlucocorticoids
Important Adverse effects ofImportant Adverse effects of
CorticosteroidsCorticosteroids
Therapeutic uses of CorticosteroidsTherapeutic uses of Corticosteroids
Addison’s disease is named after Dr. Thomas Addison – adrenal insufficiency. It was described by Harvey Cushing in 1932.[2][3] - also called hyperadrenocorticism or hypercorticism)
Bring about a series of reactions to form steroids. Corticoids are 21 carbon compounds having cyclopentanoperhydrophenanthrene nucleus
In absence lipolytic hormones hydrocortisone does not cause lipolysis
Adrenaline and noradrenaline do not cause lipolysis in absence of glucocorticoids
Principal action is to enhance Na+ reabsorption in distal tubule
Glucocorticoids have dose related important effects in carbohydrate, protein, fat metabolism but these effects are also responsible for some its serious adverse effects. Because of release of glucose in blood insulin is released in peripheral tissues and inhibit uptake of glucose by muscles
An enzyme that inhibits the activity of phospholipase A2. Lipocortins are activated by glucocorticoids.
Decrease movement of neutrophils from blood vessels and increased activity of neutrophils and macrophages by altering the gene transcription of CAM and cytokines
Decrease movement of neutrophils from blood vessels and increased activity of neutrophils and macrophages by altering the gene transcription of CAM and cytokines
DOCA – only mineralocorticoid activity, used occasionally in addison`s disease for replacement therapy Sub lingual route 2.5 to 5 mg)
Bell's palsy or idiopathic facial paralysis[1]is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side. Several conditions can cause a facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no