Corticosteroids ppt

7/23/2019 Corticosteroids ppt

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CorticosteroidsCorticosteroids

Department of PharmacologyDepartment of PharmacologyNEIGRIHMS, ShillongNEIGRIHMS, Shillong


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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


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IntroductionIntroduction

The adrenal produces variousclasses of hormones, each of whichaid in dealing with the stress faced by

animals and people almost dailyAt least two of these groupsGlucocorticoids and

Mineralocorticoidsare necessary for lifeCorticosteroids or corticoids referto naturalgluco- and mineralo-corticoids and

their


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ContentsContents

History and iosynthesisHistory and iosynthesis Mechanism of actionMechanism of action Physiological and Pharmacological actionsPhysiological and Pharmacological actions

Pharmaco!inetics and preparationsPharmaco!inetics and preparations "ses # therapeutic and diagnostic"ses # therapeutic and diagnostic Dosage schedule and $ithdra$alDosage schedule and $ithdra$al

%d&erse reactions and contraindications%d&erse reactions and contraindications Precautions during therapyPrecautions during therapy ContraindicationsContraindications


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HistoryHistory

'()) # %ddison*s disease'()) # %ddison*s disease

'()+ # %drenal glands essential for life'()+ # %drenal glands essential for life

'-. # Corte/ 0 medulla'-. # Corte/ 0 medulla

'-1 # Cushing2s syndrome'-1 # Cushing2s syndrome ')1 # %ldosterone')1 # %ldosterone


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%natomy%natomy

An inner medulla,An inner medulla,is ais asource of catecholamine #source of catecholamine #adrenaline and nor3adrenalineadrenaline and nor3adrenaline

Chromaffin cell is the principalChromaffin cell is the principalcell typecell type

Medulla is richly inner&ated 4yMedulla is richly inner&ated 4ysympathetic fi4res and issympathetic fi4res and isconsidered as e/tension ofconsidered as e/tension ofsympathetic ner&ous systemsympathetic ner&ous system

Medulla de&elops fromMedulla de&elops from

ectoderm 5neural crest6ectoderm 5neural crest6

An outer cortex,An outer cortex,$hich$hichsecretes se&eral classes ofsecretes se&eral classes of

steroid hormones includingsteroid hormones includingGlucocorticoidsGlucocorticoids andandMineralocorticoidsMineralocorticoids

7hree different concentric7hree different concentric8ones of cells that differ in8ones of cells that differ inma9or steroid hormones theyma9or steroid hormones they

secretesecrete Corte/ de&elops fromCorte/ de&elops from

mesodermmesoderm


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%drenal Corte/%drenal Corte/

7he adrenal corte/ is a factory of steroid hormones7he adrenal corte/ is a factory of steroid hormones

'. # -. different steroids are synthesi8ed from this'. # -. different steroids are synthesi8ed from this

tissue, 4ut t$o classes are of importancetissue, 4ut t$o classes are of importance

Steroid ClassSteroid Class PrototypePrototype Physiological effectPhysiological effect

MineralocorticoidMineralocorticoid %ldosterone 58: glomerulosa6%ldosterone 58: glomerulosa6 Na, ; and $aterNa, ; and $aterhomeostasishomeostasis

GlucocorticoidGlucocorticoid Hydrocortisone or cortisol 58: fasciculata6Hydrocortisone or cortisol 58: fasciculata6

CorticosteroneCorticosterone

Glucose and manyGlucose and many

other homeostasisother homeostasis

%drenal corte/ also produces se/ steroids # %ndrogens,

Dehydroepiandrosterone 5DHE%6 # 8: reticularis


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iosynthesisiosynthesis

Synthesi8ed from cholesterolSynthesi8ed from cholesterolthrough a series of en8yme3through a series of en8yme3mediated transformationsmediated transformations

%C7H%C7H stimulates adrenalstimulates adrenalsteroid synthesissteroid synthesis

%ldosterone synthesis is not%ldosterone synthesis is notstimulated 4y %C7H 4ut 4ystimulated 4y %C7H 4ut 4yangiotensin II, although %C7Hangiotensin II, although %C7Hdoes stimulate synthesis ofdoes stimulate synthesis ofaldosterone precursorsaldosterone precursors

Circulating Potassium e/erts aCirculating Potassium e/erts apermissi&e effect onpermissi&e effect onangiotensin II stimulation< highangiotensin II stimulation< highpotassium enhances and lo$potassium enhances and lo$potassium diminishespotassium diminishes


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Steroid iosynthesis 3 contd:Steroid iosynthesis 3 contd:


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asal Secretionasal Secretion

GroupGroup HormoneHormone DailyDaily

GlucocorticoidsGlucocorticoids CortisolCortisol

CorticosteroneCorticosterone

5 !" mg5 !" mg

# 5 mg# 5 mg

MineralocorticoidsMineralocorticoids AldosteroneAldosterone

$$% deo&ycorticosterone$$% deo&ycorticosterone

5 $5" mcg5 $5" mcg

'race'race

Se& HormonesSe& Hormones

AndrogenAndrogen

(rogestogen(rogestogen)estrogen)estrogen

DH*ADH*A

(rogesterone(rogesterone)estradiol)estradiol

$5 !" mg$5 !" mg

"+, "+- mg"+, "+- mg'race'race


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Regulation of SynthesisRegulation of Synthesis

=Synthesi8ed and

released under

influence of %C7H 3 %nt:

Pituitary 5HP% a/is6

= Regulated 4y CRH

from hypothalamus

and 4y feed4ac!

le&els of 4loodconcentrations


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':': Control 4y circadianControl 4y circadian

rhythm 5Diurnalrhythm 5Diurnal

rhythm6 # morningrhythm6 # morning

riserise1:1: Stress>Stress>

hypoglycaemia,hypoglycaemia,

physical stress etc:physical stress etc:

Regulation of Synthesis 3 ?thersRegulation of Synthesis 3 ?thers


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Diurnal &ariation of CortisolDiurnal &ariation of Cortisol


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Glucocorticoids 3 M?%Glucocorticoids 3 M?%

Not stored>Not stored> rate of synthesis @ rate of releaserate of synthesis @ rate of release

Synthesi8e rhythmically and controlled 4ySynthesi8e rhythmically and controlled 4y

irregular pulses of %C7H, influenced 4y light andirregular pulses of %C7H, influenced 4y light andma9or pulses occur early in the morning andma9or pulses occur early in the morning andafter mealsafter meals

Glucocorticoids act &ia their receptors located inGlucocorticoids act &ia their receptors located innucleus 5GR6nucleus 5GR6

GRs are $idely distri4uted and located almost inGRs are $idely distri4uted and located almost inall cells of the 4odyall cells of the 4ody

7hey are made up of almost (.. amino acids7hey are made up of almost (.. amino acids


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GR receptors are located in the cytoplasmGR receptors are located in the cytoplasm ?ne GR receptor has a DN% 4inding domain and a?ne GR receptor has a DN% 4inding domain and a

ligand 4inding domain along $ith sta4ili8ing proteinsligand 4inding domain along $ith sta4ili8ing proteins5HSP . and HSP A.65HSP . and HSP A.6

7his receptor is incapa4le of acti&ating transcription7his receptor is incapa4le of acti&ating transcription inding of free steroid molecule to GR forms an unsta4leinding of free steroid molecule to GR forms an unsta4le

compoundcompound 7herefore HSP and other proteins get dissociated7herefore HSP and other proteins get dissociated 7he SBGR comple/ enters the nucleus and 4inds to7he SBGR comple/ enters the nucleus and 4inds to

Glucocorticoids response element 5GRE6 on gene andGlucocorticoids response element 5GRE6 on gene andregulate transcription 4y RN% polymerase II and othersregulate transcription 4y RN% polymerase II and others

7he resulting mRN% is transported to cytoplasm for7he resulting mRN% is transported to cytoplasm forproduction of protein and 4ring a4out final responseproduction of protein and 4ring a4out final response


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%ctions%ctions

umerous and widespread actions!umerous and widespread actions! Car4ohydrate, lipid and protein meta4olismCar4ohydrate, lipid and protein meta4olism luid and electrolyte 4alanceluid and electrolyte 4alance Normal functioning of CS, immune system, !idneys, s!eletal muscles and ner&ous systemNormal functioning of CS, immune system, !idneys, s!eletal muscles and ner&ous system Pro&ides resistance to stress and no/ious stimuli and en&ironmental changesPro&ides resistance to stress and no/ious stimuli and en&ironmental changes Permits and facilitates the actions of other hormonesPermits and facilitates the actions of other hormones

Direct %ctionsDirect %ctions

Permissi&e %ctionsPermissi&e %ctions= .ipolytic effects

= *ffect on /(= *ffect on bronchial muscles= (e.g.,sympathomimetic amine)


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%ctions of Corticosteroids 3%ctions of Corticosteroids 3

MineralocorticoidMineralocorticoid %ldosterone is the prototype of mineralocorticoid effects%ldosterone is the prototype of mineralocorticoid effects %cts on the distal tu4ule to enhance a4sorption of NaB%cts on the distal tu4ule to enhance a4sorption of NaB Increase e/cretion of ;B and HIncrease e/cretion of ;B and H Similar effects occur in colon, s$eat gland and sali&arySimilar effects occur in colon, s$eat gland and sali&ary

glandgland Deficiency of mineralocorticoid action leads toDeficiency of mineralocorticoid action leads to##

dilutional hyponatraemia, hyper!alamia, acidosis,dilutional hyponatraemia, hyper!alamia, acidosis,massi&e loss of NaB and decreased EC &olumemassi&e loss of NaB and decreased EC &olume5essential for sur&i&al65essential for sur&i&al6

Hyperaldosterinism>Hyperaldosterinism> Positi&e NaB 4alance, e/pansion ofPositi&e NaB 4alance, e/pansion ofEC, increased plasma Na, hypo!alaemia, al!alosis andEC, increased plasma Na, hypo!alaemia, al!alosis andprogressi&e rise in P # hypertension, myocardialprogressi&e rise in P # hypertension, myocardialfi4rosis etc:fi4rosis etc:


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Glucocorticoid actions 3Glucocorticoid actions 3

Car4ohydrate protein meta4olismCar4ohydrate protein meta4olism Profound effect on car4ohydrate and protein meta4olismProfound effect on car4ohydrate and protein meta4olism

# aimed at protecting glucose dependent tissues 54rain# aimed at protecting glucose dependent tissues 54rainand heart6and heart6

Promotes glycogen deposition in li&er and stimulate it toPromotes glycogen deposition in li&er and stimulate it to

form glucose from amino acids # gluconeogenesisform glucose from amino acids # gluconeogenesis In peripheral tissues decreases utili8ation of glucose,In peripheral tissues decreases utili8ation of glucose,increase protein 4rea!do$n and acti&ate lipolysis # formincrease protein 4rea!do$n and acti&ate lipolysis # formamino acids and glycerol for gluconeogenesisamino acids and glycerol for gluconeogenesis

%ll these results in 3%ll these results in 3

Dia4etes li!e stat resistant to insulin # increased glucose releaseDia4etes li!e stat resistant to insulin # increased glucose releasefrom li&er B decreased peripheral glucose utili8ationfrom li&er B decreased peripheral glucose utili8ation Negati&e Nitrogen 4alance 5cata4olic effect6 # amino acid usedNegati&e Nitrogen 4alance 5cata4olic effect6 # amino acid used

up in gluconeogenesis # increased urea productionup in gluconeogenesis # increased urea production Mo4ili8ation of amino acids # muscles, thinning of 4one and s!inMo4ili8ation of amino acids # muscles, thinning of 4one and s!in


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Actions0Actions0Carbohydrate and protein metabolismCarbohydrate and protein metabolism

GluconeogenesisGluconeogenesis Peripheral actionsPeripheral actions 5mo4ili8e %% glucose and glycogen65mo4ili8e %% glucose and glycogen6

Hepatic actionsHepatic actions

Peripheral utili8ation of glucosePeripheral utili8ation of glucose

Glycogen deposition in li&erGlycogen deposition in li&er5acti&ation of hepatic glycogen synthase65acti&ation of hepatic glycogen synthase6

1egative nitrogen balance 2 hyperglycaemia


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at Meta4olismat Meta4olism

Redistri4ution of fats in different areas of theRedistri4ution of fats in different areas of the4ody4ody

Due to permissi&e facilitation of effects of otherDue to permissi&e facilitation of effects of otheragents # GH, glucagons, %dr, thyro/ine andagents # GH, glucagons, %dr, thyro/ine andinsulininsulin Deposition of fats in face, nec! and shoulder # moonDeposition of fats in face, nec! and shoulder # moon

faceF4uffalo humpfaceF4uffalo hump Glucocorticoids facilitated hormone sensiti&e lipolysisGlucocorticoids facilitated hormone sensiti&e lipolysis

action of GH and %dr: B Glucocorticoids mediatedaction of GH and %dr: B Glucocorticoids mediatedincreased insulin @ net result is insulin mediatedincreased insulin @ net result is insulin mediatedlipogenesis and fat depositionlipogenesis and fat deposition

Peripheral adipocytes are less sensiti&e to insulin, 4utPeripheral adipocytes are less sensiti&e to insulin, 4utin face and nec! predominant action # fat depositionin face and nec! predominant action # fat deposition


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%ctions of Glucocorticoids%ctions of Glucocorticoids

ater e/cretion>ater e/cretion> Glucocorticoids play important role in maintaining normal GR 3 inGlucocorticoids play important role in maintaining normal GR 3 in

adrenal insufficiency capacity to e/crete $ater is lost # $ater into/icationadrenal insufficiency capacity to e/crete $ater is lost # $ater into/ication Calcium alance>Calcium alance>

Decrease a4sorption of CaBB in GI7 and increased e/cretion # calciumDecrease a4sorption of CaBB in GI7 and increased e/cretion # calcium

depletion 3depletion 3 osteoporosisosteoporosis S!eletal muscle>S!eletal muscle> Normal muscular acti&ity needs Glucocorticoids at its optimum le&elNormal muscular acti&ity needs Glucocorticoids at its optimum le&el E/cess le&el leads to muscular $ea!ness and $astingE/cess le&el leads to muscular $ea!ness and $asting Muscular $ea!ness occurs in 4oth Hypocorticism 5due to hypodynamicMuscular $ea!ness occurs in 4oth Hypocorticism 5due to hypodynamic

circulation6 and hypercorticism # due to hypo!alaemiacirculation6 and hypercorticism # due to hypo!alaemia

CNS>CNS> Euphoria # in pharmacological dosesEuphoria # in pharmacological doses %ddisons disease # apathy, depression and psychosis%ddisons disease # apathy, depression and psychosis High doses # induce sei8ureHigh doses # induce sei8ure


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%ctions of Glucocorticoids%ctions of Glucocorticoids

C3S0C3S0Permissi&e role on pressor effect $ith %dr and angiotensinPermissi&e role on pressor effect $ith %dr and angiotensin Maintain tone of arterioles and myocardial contractilityMaintain tone of arterioles and myocardial contractility %drenal insufficiency leads to lo$ cardiac output and arteriolar dilatation%drenal insufficiency leads to lo$ cardiac output and arteriolar dilatation

and poor response to adrenalineand poor response to adrenaline Cardio&ascular collapse # along $ith mineralocorticoidsCardio&ascular collapse # along $ith mineralocorticoids

lood and lymphoid tissues>lood 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 aresignificant 5apoptosis6 # used in lymphomassignificant 5apoptosis6 # used in lymphomas 4/asis of se64/asis of se6

Minor effects on haemoglo4in and RCs # protect against haemolysis ofMinor effects on haemoglo4in and RCs # protect against haemolysis ofRCs #RCs # Increase in num4er of RCsIncrease in num4er of RCs

Decreases the num4ers of circulating lymphocytes, monocytes,Decreases the num4ers of circulating lymphocytes, monocytes,eosinophils and 4asophils 4ut increases Polymorphseosinophils and 4asophils 4ut increases Polymorphs


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Glucocorticoids # anti3inflammatoryGlucocorticoids # anti3inflammatory

and immunosuppressi&e effectsand immunosuppressi&e effects Suppress inflammatory response to all no/ious stimuli>Suppress inflammatory response to all no/ious stimuli>

Pathogens, chemical,physical and immune mediatedPathogens, chemical,physical and immune mediatedstimuli, hypersensiti&itystimuli, hypersensiti&ity

"nderlying cause of disease is not corrected"nderlying cause of disease is not corrected

Reduction in cardinal signs of inflammationReduction in cardinal signs of inflammation %nti3inflammatory effects are nonspecific and co&ers%nti3inflammatory effects are nonspecific and co&ers

all components of inflammation>all components of inflammation> Effects on concentration, distri4ution and functions of peripheralEffects on concentration, distri4ution and functions of peripheral

leu!ocytes # increased neutrophils their acti&ityleu!ocytes # increased neutrophils their acti&ity In macrophages> reduction of arachidonic acid meta4olitesIn macrophages> reduction of arachidonic acid meta4olites

5mediators6 li!e PG, J7 and P% synthesis that results from5mediators6 li!e PG, J7 and P% synthesis that results fromacti&ation of phospholipase %1acti&ation of phospholipase %1

asis of e/ogenous use of most clinical usesasis of e/ogenous use of most clinical uses


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Glucorticoids 3 Multiple

Mechanisms Recruitment ofRecruitment of C C monocytemonocyte33 macrophage intomacrophage into

affected area ela4oration of chemotactic su4stancesaffected area ela4oration of chemotactic su4stances

JipocortinJipocortin> decreased production of PG, J7 and P%> decreased production of PG, J7 and P%

Negati&e regulation of C?K 1> induci4le PGNegati&e regulation of C?K 1> induci4le PGproductionproduction

Negati&e regulation of genes in cyto!ines ofNegati&e regulation of genes in cyto!ines of

macrophages, endothelial cells and lymphocytes>macrophages, endothelial cells and lymphocytes>

production of IJ 5', 1, -, +6, 7Nproduction of IJ 5', 1, -, +6, 7NLL, GM3CS etc: #, GM3CS etc: #fi4ro4last proliferation and 73lymphocyte function #fi4ro4last proliferation and 73lymphocyte function #

interference $ith chemota/isinterference $ith chemota/is


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Contd:Contd:

In endothelial cells3Endothelial leucocyte adhesionIn endothelial cells3Endothelial leucocyte adhesion

moleculemolecule 5EJ%M65EJ%M6and otherand other C%MC%M are inhi4ited #are inhi4ited #

adhesion and locali8ation of leucocytes interferedadhesion and locali8ation of leucocytes interfered

Release of histamine from 4asophils is inhi4itedRelease of histamine from 4asophils is inhi4ited

Decreased production ofDecreased production of collagenasecollagenase# pre&ention of# pre&ention of

tissue destructiontissue destruction

Decreased functioning ofDecreased functioning of osteo4lastsosteo4lasts and increasedand increased

acti&ity ofacti&ity of osteoclasticosteoclasticacti&ity 3acti&ity 3 osteoporosisosteoporosis

Decreased IgG productionDecreased IgG production

Decreased generation of induced nitric o/ideDecreased generation of induced nitric o/ide


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(hospholipids

Arachidonic acids

lipo&ygenase Cycyloo&ygenase

.eu7otriene(rostaglandins8

'hrombo&ane

(rostacyclins

(hospholipase A#

.ipocortin

Corticosteroids

(A9 by lipocortin


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Immunosuppressi&e anti3allergicImmunosuppressi&e anti3allergic

actionsactions Suppresses all types of hypersensiti&ity Suppresses all types of hypersensiti&ity

allergic phenomenonallergic phenomenon

%t High dose> Interfere $ith all steps of%t High dose> Interfere $ith all steps of

immunological responseimmunological response Causes greater suppression of CMI 5graftCauses greater suppression of CMI 5graft

re9ection delayed hypersensiti&ity6re9ection delayed hypersensiti&ity6

7ransplant re9ection> antigen e/pression from7ransplant re9ection> antigen e/pression fromgrafted tissues, delay re&asculari8ation,grafted tissues, delay re&asculari8ation,

sensitisation of 7 lymphocytes etc:sensitisation of 7 lymphocytes etc:


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Glucocorticoids # %nti3inflammatoryGlucocorticoids # %nti3inflammatory

and Immunosuppressi&e effectsand Immunosuppressi&e effects


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Glucocorticoids 3 Pharmaco!ineticsGlucocorticoids 3 Pharmaco!inetics

7herapeutically gi&en 4y &arious routes # orally, IM, I,7herapeutically gi&en 4y &arious routes # orally, IM, I,topicallytopically

Hydrocortisone undergoes high first pass meta4olismHydrocortisone undergoes high first pass meta4olism ?ral 4ioa&aila4ility of synthetic corticoids is high?ral 4ioa&aila4ility of synthetic corticoids is high oth, endogenous and therapeutically administered GCoth, endogenous and therapeutically administered GC

are 4ound to Corticosteroid inding Glo4ulin 5CG6are 4ound to Corticosteroid inding Glo4ulin 5CG6 Synthetic steroids ha&e to undergo reduction in li&er toSynthetic steroids ha&e to undergo reduction in li&er to

acti&e compoundsacti&e compounds

Meta4oli8ed in li&er and e/creted in urineMeta4oli8ed in li&er and e/creted in urine E/ogenously administered hydrocortisone has t'F1 of ':)E/ogenously administered hydrocortisone has t'F1 of ':)

HrsHrs


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Steroid PreparationsSteroid Preparations

%n ideal GC should ha&e no%n ideal GC should ha&e no

mineralocorticoid acti&itymineralocorticoid acti&ity

Structural changes to the 4asic cortisolStructural changes to the 4asic cortisol

molecule resulted in a num4er ofmolecule resulted in a num4er of

compounds $ithcompounds $ith Minimal mineralocorticoid acti&ityMinimal mineralocorticoid acti&ity

Greater potencyGreater potency

Jonger duration of actionJonger duration of action


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Important agentsImportant agents

In9ecta4le>In9ecta4le>etamethasone De/amethasoneetamethasone De/amethasone

Prednisolone MethylprednisolonePrednisolone Methylprednisolone

Hydrocortisone 7riamcinoloneHydrocortisone 7riamcinolone ?ral>?ral>

etamethasone ludricortisoneetamethasone ludricortisonePrednisolone PrednisonePrednisolone Prednisone

MethylprednisoloneMethylprednisolone 7opical>7opical>

etamethasone Clo4etasoletamethasone Clo4etasol

lucinolone Mometasonelucinolone Mometasone

Inhalation>Inhalation>eclomethasone udesonideeclomethasone udesonide

lunisolodelunisolode


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Chemical StructuresChemical Structures

Pharmaceutical steroids are usually o4tained fromcholic acid 5o4tained from cattle6 or sapogenins found

in plants of Jiliacaceae


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Cyclopentanoperhydrop

henanthrenes!eletonRings are la4eled as %,

, C and D:

Natural steroids ha&e

t$o methyls

Num4ering of each position

essentially follo$s a uniform

pattern e/cept for the

methyls:


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Relati&e %cti&ityRelati&e %cti&ity

CompoundCompound DurationDuration GCGC MCMC *:uivalent*:uivalentdose 4mg6dose 4mg6

HydrocortisoneHydrocortisone S%S% '' '' 1.1.

PrednisolonePrednisolone I%I% OO .:(.:( ))

MethylMethyl

PrednisolonePrednisolone

I%I% )) .:).:) OO

7riamcinolone7riamcinolone I%I% )) .. OO

De/amethasoneDe/amethasone J%J% 1)1) .. .:A).:A)

etmethasoneetmethasone J%J% 1)1) .. .:A).:A)

%ldosterone%ldosterone MCMC .:-.:- ).. 3 -...).. 3 -... N"N"

Deso/ycortisoneDeso/ycortisone

acetate 5D?C%6acetate 5D?C%6MCMC .. '..'.. 1:) 5S:1:) 5S:

lingual6lingual6


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Corticosteroids 3 ClinicalCorticosteroids 3 Clinical

PharmacologyPharmacology


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7herapeutic uses7herapeutic uses

% num4er of di&erse disease states respond to% num4er of di&erse disease states respond toGCsGCs

Physiologic doses of Corticosteroids are used forPhysiologic doses of Corticosteroids are used forreplacement therapy in primary and secondaryreplacement therapy in primary and secondary

adrenal insufficiency such as %ddison*s diseaseadrenal insufficiency such as %ddison*s disease Supraphysiologic doses are used for their anti3Supraphysiologic doses are used for their anti3

inflammatory effects in arthritis, asthma andinflammatory effects in arthritis, asthma andinflammatory 4o$el diseaseinflammatory 4o$el disease

In organ transplant patients and those $ithIn organ transplant patients and those $ithautoimmune disorders corticosteroids are usedautoimmune disorders corticosteroids are usedfor their immunosuppressi&e effectsfor their immunosuppressi&e effects


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Replacement 7herapyReplacement 7herapy

%drenal insufficiency # acuteFchronic%drenal insufficiency # acuteFchronic%4rupt $ithdra$al of steroid therapy%4rupt $ithdra$al of steroid therapy Chronic infections # 7u4erculosisChronic infections # 7u4erculosis%utoimmune adrenal disease%utoimmune adrenal disease Surgery, Hemorrhage and %IDSSurgery, Hemorrhage and %IDS

Congenital adrenal hyperplasiaCongenital adrenal hyperplasia

Congenital disorder due to deficiency of 1'3Congenital disorder due to deficiency of 1'3hydro/ylse en8yme # no cortisol 4ut %C7H #hydro/ylse en8yme # no cortisol 4ut %C7H #increased androgen productionincreased androgen production

C%H


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Replacement 7herapyReplacement 7herapy

%cute adrenal insufficiency%cute adrenal insufficiency I replacement of sodium chloride and fluidI replacement of sodium chloride and fluid I hydrocortisone '.. mg stat follo$ed 4y'.. mgI hydrocortisone '.. mg stat follo$ed 4y'.. mg

e&ery ( Hrs # ma/imal daily rate of secretione&ery ( Hrs # ma/imal daily rate of secretion

5alternati&ely, de/amethasone can 4e used65alternati&ely, de/amethasone can 4e used6 Chronic adrenal insufficiencyChronic adrenal insufficiency

HydrocortisoneHydrocortisone Prednisolone or de/amethasone # long actingPrednisolone or de/amethasone # long acting

ludrocortisone for mineralocorticoid effectsludrocortisone for mineralocorticoid effects Congenital adrenal hyperplasiaCongenital adrenal hyperplasia

Hydrocortisone .:+ mgF!g in di&ided doses # toHydrocortisone .:+ mgF!g in di&ided doses # tomaintain feed4ac! suppressionmaintain feed4ac! suppression


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%nti3inflammatory "ses%nti3inflammatory "ses

or suppression of inflammatory components inor suppression of inflammatory components in

## Rheumatoid arthritis # as ad9u&ant $ith NS%IDs inRheumatoid arthritis # as ad9u&ant $ith NS%IDs in

se&ere casesse&ere cases ?steoarthritis # NS%IDs, intra3articular in9ection?steoarthritis # NS%IDs, intra3articular in9ection

Rheumatic fe&er # se&ere cases $ith carditis andRheumatic fe&er # se&ere cases $ith carditis and

CHCH

Gout # NS%ID failed cases and colchicine failedGout # NS%ID failed cases and colchicine failedcases # intra3articular in9ectioncases # intra3articular in9ection

asculitic disorders> Polyarteritis nodosaasculitic disorders> Polyarteritis nodosa


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Intra3articular SteroidsIntra3articular Steroids

Can 4e used in inflammatory

Non3inflammatory diseases= ;nee 9oint= Shoulder 9oint= 7ennis el4o$= Carpal tunnel syndrome


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%utoimmune diseases%utoimmune diseases

%utoimmune haemolytic anaemia%utoimmune haemolytic anaemia Idiopathic throm4ocytopenic purpuraIdiopathic throm4ocytopenic purpura

%cti&e chronic hepatitis, alcoholic hepatitis%cti&e chronic hepatitis, alcoholic hepatitis

5Prednisolone '31 mgF!gFday gi&en till5Prednisolone '31 mgF!gFday gi&en tillremission follo$ed 4y gradual $ithdra$alremission follo$ed 4y gradual $ithdra$al

or lo$ dose maintenance6or lo$ dose maintenance6

I7P


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Renal diseasesRenal diseases

Nephrotic syndrome in childrenNephrotic syndrome in children

Renal disease secondary to SJERenal disease secondary to SJE Renal sarcoidosisRenal sarcoidosis

Glomerulonephritis # mem4ranous typeGlomerulonephritis # mem4ranous type

5Jife sa&ing importance # usually gi&en in5Jife sa&ing importance # usually gi&en inlarge doses follo$ed 4y tapering tolarge doses follo$ed 4y tapering to

maintenance dose6maintenance dose6

SJE


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?rgan 7ransplant?rgan 7ransplant

Com4ined $ith other immunosuppressantsCom4ined $ith other immunosuppressants

# cyclosporin, a8athioprine# cyclosporin, a8athioprine

or prolonged use>or prolonged use>

Prednisolone or methylprednisolone arePrednisolone or methylprednisolone are

usedused Intermediate duration of actionIntermediate duration of action

Can 4e easily taperedCan 4e easily tapered

Can 4e con&erted to an alternate regimeCan 4e con&erted to an alternate regime


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%llergic Disorders%llergic Disorders

E/hi4it a delayed response in allergies 5'31 hrsE/hi4it a delayed response in allergies 5'31 hrs

e&en in I in9ection6e&en in I in9ection6

In anaphyla/is, angioneurotic oedema andIn anaphyla/is, angioneurotic oedema and

serum sic!ness etc: # adrenaline is the choiceserum sic!ness etc: # adrenaline is the choice Seasonal allergies, 4ee sting, drug allergies #Seasonal allergies, 4ee sting, drug allergies #

%llergic reactions can 4e suppressed 4y%llergic reactions can 4e suppressed 4y

corticosteroids as supplementscorticosteroids as supplements

Intranasal administration in allergic rhinitis 3Intranasal administration in allergic rhinitis 3

4udesonide and flunisolide4udesonide and flunisolide


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ronchial %sthmaronchial %sthma

7he increased recognition of the immunological and7he increased recognition of the immunological andinflammatory nature of ronchial asthma has led to theinflammatory nature of ronchial asthma has led to theuse of corticosteroidsuse of corticosteroids

In se&ere asthma attac!sIn se&ere asthma attac!s

I hydrocortisone MethylprednisoloneI hydrocortisone Methylprednisolone ?ral prednisolone?ral prednisolone

%cute attac!s>%cute attac!s>

Inhaled 4eclmethasone, 4udesonide, flunisolideInhaled 4eclmethasone, 4udesonide, flunisolide

alone or com4ined $ith 4eta31 agonistsFipratropiumalone or com4ined $ith 4eta31 agonistsFipratropium ?ral steroids?ral steroids


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Infectious DiseasesInfectious Diseases

Indicated only in se&ere infecti&e diseasesIndicated only in se&ere infecti&e diseases

to tide o&er crisis or pre4ent complictionsto tide o&er crisis or pre4ent complictions%IDS and pneumocystis carinii pneumonia%IDS and pneumocystis carinii pneumonia

In haemophilus influen8a meningitis to reduceIn haemophilus influen8a meningitis to reduce

neurological complicationsneurological complications

7u4ercular meningitis7u4ercular meningitis

Jepra reactionJepra reaction ScepticaemiaScepticaemia

Jepra reaction


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?cular Diseases?cular Diseases

Important drug therapy for suppressingImportant drug therapy for suppressinginflammation in eye and preser&ation of sightinflammation in eye and preser&ation of sight

7opical instillations are used for conditions of the7opical instillations are used for conditions of the

anterior cham4er # allergic con9uncti&itis, iritis,anterior cham4er # allergic con9uncti&itis, iritis,iridocyclitis and !eratitis etc:iridocyclitis and !eratitis etc: Systemic steroids for the posterior cham4erSystemic steroids for the posterior cham4er De/amethasone topical .:'QDe/amethasone topical .:'Q

Prednisolone oralPrednisolone oral Contraindicated in &iral, fulminant 4acterialContraindicated in &iral, fulminant 4acterial

infections, fungal infections and in9uriesinfections, fungal infections and in9uries


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S!in DiseasesS!in Diseases

7he largest application of steroid therapy7he largest application of steroid therapy 7opical forms are $idely used in many7opical forms are $idely used in many

ec8ematous s!in diseasesec8ematous s!in diseases Systemic therapy are also reuired andSystemic therapy are also reuired and

may 4e life sa&ing inmay 4e life sa&ing in Pemphigus &ulgarisPemphigus &ulgaris E/foliati&e dermatitisE/foliati&e dermatitis Ste&ens3ohnson syndromeSte&ens3ohnson syndrome

Pemphigus&ulgaris


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GI7GI7

Inflammatory conditions of intestine li!eInflammatory conditions of intestine li!e "lcerati&e colitis"lcerati&e colitis Crohn*s diseaseCrohn*s disease

Coeliac diseaseCoeliac disease

5oral therapy or retention enema $ith hydrocortisone65oral therapy or retention enema $ith hydrocortisone6

May mas! the ma9or complications li!eMay mas! the ma9or complications li!e

perforation and peritonitisperforation and peritonitis


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MalignancyMalignancy

Essential for com4ined chemotherapy ofEssential for com4ined chemotherapy of%cute lymphatic leu!emia%cute lymphatic leu!emia Hodg!ins and other lymphomasHodg!ins and other lymphomas Hormone responsi&e 4reast carcinomaHormone responsi&e 4reast carcinoma

Symptomatic relief in other ad&anceSymptomatic relief in other ad&ancemalignancies 4y impro&ing appetite andmalignancies 4y impro&ing appetite andcontrolling secondary hypercalcaemiacontrolling secondary hypercalcaemia

Hodg!in*s

lymphoma


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Cere4ral ?edemaCere4ral ?edema

Cere4ral oedema due to tumorsCere4ral oedema due to tumors5neoplasms65neoplasms6

7raumatic and poststro!e oedema 5T67raumatic and poststro!e oedema 5T6

5De/amethasone or 4etamethasone is5De/amethasone or 4etamethasone ispreferred 4ecause no NaB retainingpreferred 4ecause no NaB retainingacti&ity6acti&ity6

?ther CNS conditions 3 spinal chord in9ury,?ther CNS conditions 3 spinal chord in9ury,ell*s palsy and neurocysticercosisell*s palsy and neurocysticercosis

5?ral Prednisolone is the preferred drug65?ral Prednisolone is the preferred drug6


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?ther "ses?ther "ses

%ntiemetic # $ith ondansetron%ntiemetic # $ith ondansetron%cute mountain sic!ness%cute mountain sic!ness%spiration pneumonia, pulmonary oedema%spiration pneumonia, pulmonary oedema

from dro$ningfrom dro$ning Hyperthyroidism # thyroid stormHyperthyroidism # thyroid storm


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%d&erse Effects%d&erse Effects

7$o types>7$o types> rom a4rupt $ithdra$alrom a4rupt $ithdra$al

Chronic therapeutic use of high doseChronic therapeutic use of high dose

ithdra$alithdra$al lare up of underlying diseaselare up of underlying disease

Suppression of HP% a/is and acute adrenalSuppression of HP% a/is and acute adrenal

insufficiencyinsufficiency Increased IC7 and papilloedemaIncreased IC7 and papilloedema


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%d&erse Effects%d&erse Effects

Cushing*s ha4itus


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?ther Important %d&erse Effects?ther Important %d&erse Effects

luid and Electrolyte Distur4ance # Na and $ater retentionluid and Electrolyte Distur4ance # Na and $ater retention Precipitation of Dia4etes mellitus # hyperglycemiaPrecipitation of Dia4etes mellitus # hyperglycemia Increased suscepti4ility to infections # immune responseIncreased suscepti4ility to infections # immune response

suppressionsuppression

Peptic ulceration # 4leeding perforationPeptic ulceration # 4leeding perforation ?steoporosis # flat spongy 4ones?steoporosis # flat spongy 4ones ?steonecrosis # a&ascular necrosis of head of femur,?steonecrosis # a&ascular necrosis of head of femur,

humorous etc:humorous etc: Myopathy # $ea!ness of musclesMyopathy # $ea!ness of muscles

Cataract # posterior su4 capsularCataract # posterior su4 capsular Glaucoma # prolonged topical therapyGlaucoma # prolonged topical therapy Gro$th retardation # in childrenGro$th retardation # in children


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ContraindicationsContraindications

Say no to any drug formulation com4ined $ithSay no to any drug formulation com4ined $ithsteroidssteroids

Remem4er that S7ER?IDS are life sa&ing drugsRemem4er that S7ER?IDS are life sa&ing drugs Note the follo$ing conditions $here u ha&e to 4eNote the follo$ing conditions $here u ha&e to 4e

e/tremely cautious>e/tremely cautious> Peptic ulcerPeptic ulcer Hypertension and Dia4etes mellitusHypertension and Dia4etes mellitus iral and fungal infectionsiral and fungal infections

7u4erculosis and other diseases7u4erculosis and other diseases ?steoporosis?steoporosis Epilepsy and psychosisEpilepsy and psychosis CH and renal failureCH and renal failure


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Choosing a SteroidChoosing a Steroid

enefitFris! ratio is a ma9or considerationenefitFris! ratio is a ma9or consideration

Drugs $ith primary glucocorticoid acti&ityDrugs $ith primary glucocorticoid acti&ity

are usedare used

Minimal dose to achie&e the desiredMinimal dose to achie&e the desired

effects is choseneffects is chosen

7opical or local therapy is preferred7opical or local therapy is preferred

$hene&er possi4le$hene&er possi4le


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Choosing a Steroid # contd:Choosing a Steroid # contd:

=?nce daily dosing is usually?nce daily dosing is usually

preferred for oral glucocorticoidspreferred for oral glucocorticoids=Jarge steroid doses areJarge steroid doses are

administered in di&ided doses toadministered in di&ided doses to

reduce local GI7 effectsreduce local GI7 effects=In order to mimic the normal diurnalIn order to mimic the normal diurnal

cycle and reduce the ris! ofcycle and reduce the ris! ofadrenal suppression, GCs shouldadrenal suppression, GCs should

4e gi&en in the morning 4et$een4e gi&en in the morning 4et$een

+3'. %M+3'. %M=%lternate day therapy allo$s the%lternate day therapy allo$s the

HP% a/is to reco&er on off daysHP% a/is to reco&er on off days

Single

dose

Steroid


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ithdra$al of Steroid 7herapyithdra$al of Steroid 7herapy

7aper the dose to reduce GC dose 4y 1:)3) mg of7aper the dose to reduce GC dose 4y 1:)3) mg ofprednisolone eui&alent dailyprednisolone eui&alent daily

?nce the GC dose is reduced to ) mg of prednisolone?nce the GC dose is reduced to ) mg of prednisoloneeui&alent, the patient may 4e s$itched to a shortereui&alent, the patient may 4e s$itched to a shorter

acting agent for further taperingacting agent for further tapering Intermediate acting corticosteroids allo$ for more fle/i4leIntermediate acting corticosteroids allo$ for more fle/i4le

dosing scheduledosing schedule Ha&e potent glucocorticoid effectsHa&e potent glucocorticoid effects Causes lesser suppression of HP% a/isCauses lesser suppression of HP% a/is Causes less GI7 irritationCauses less GI7 irritation Preferred for oral therapyPreferred for oral therapy Prednisolone, methylprednisolone and triacinolone ha&e a halfPrednisolone, methylprednisolone and triacinolone ha&e a half

life of '13-+ Hrs, are a&aila4le in a num4er of dosage formslife of '13-+ Hrs, are a&aila4le in a num4er of dosage forms


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%drenocorticosteroid Inhi4itors%drenocorticosteroid Inhi4itors

Metyrapone>Metyrapone>'' 4eta3hydro/ylase'' 4eta3hydro/ylaseen8yme inhi4itor # useden8yme inhi4itor # usedin Cushing*s syndrome and test of pituitary efficiencyin Cushing*s syndrome and test of pituitary efficiency

%minoglutethemide>%minoglutethemide>Stops con&ersion of cholesterol toStops con&ersion of cholesterol topregnelonepregnelone 5Medical adrenalectomy65Medical adrenalectomy6# reast cancers# reast cancers

Mifepristone>Mifepristone>Progesterone antagonistProgesterone antagonist

Spironolactone>Spironolactone>%ldosterone antagonist%ldosterone antagonist

;etocona8ole>;etocona8ole>Inhi4its synthesis of all hormones in testesInhi4its synthesis of all hormones in testesand adrenal corte/ # used in Cushing*s syndrome andand adrenal corte/ # used in Cushing*s syndrome andalso in hirsutism in femalealso in hirsutism in female


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Must ;no$UMust ;no$U

iosynthesis and Regulation ofiosynthesis and Regulation ofCorticosteroidsCorticosteroids

Mechanism of action of CorticosteroidsMechanism of action of Corticosteroids

Name of commonly used GlucocorticoidsName of commonly used Glucocorticoids%nti3inflammatory and immunosuppressi&e%nti3inflammatory and immunosuppressi&e

actions of Glucocorticoidsactions of Glucocorticoids

Important %d&erse effects of CorticosteroidsImportant %d&erse effects of Corticosteroids 7herapeutic uses of Corticosteroids7herapeutic uses of Corticosteroids


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7han! Vou7han! Vou

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