LIFE BEFORE DISCOVERY OF STEROIDS

CLINICAL USE OF STEROIDS BY DrBALBIR part-1

1855 THOMAS ADDISON STUDIED SYMPTOMS OF ADRENAL GLAND DESTRUCTION

1856 BROWN SEQUARD ESTABLISHED ADRENAL GLAND WAS NECESSARY FOR LIFE

ADRENAL GLANDS NECESSARY FOR LIFE

STROIDS FROM VARIOUS PARTS OF ADRENAL GLAND

ZONA GLOMERULOSA-ALDOSTERON, DEOXYCOTICOSTERON MINERALOCORTCOIDS ZONA FASICULATA-CORTISONE, HYDROCORTISOLEGLUCOCORTICOIDS ZONA ARATICULARISDEHYDROEPIANDROSTERONE,ANDROSTENEIDIONEANDROGEN TRACES OF ESTROGEN AND PROGESTRONE

ADRENAL CORTICAL HARMONES STEROIDS

PURE ENDOGENOUS STEROIDS ARE LIPID AND ORGANIC SOLVENT SOLUBLE STEROIDS CONJUGATED WITH SULFURIC ACID OR GLUCRONIC ACID ARE WATER SOLUBLE.

DAILY SECRETION OF STEROIDS

HYDROCORTISONE-8-25mg/day
ALDOSTERONE-0.05-0.2mg/day

COTICOSTERONE-2-4 mg/day
DEHYDROEPIANDROSTERONE-15-30mg/day ANDRSTENEDIONE-1-10mg/day LEVEL OF ACTH IN BLOOD DETERMINES LEVEL OFGLUCOCORTICOIDS LEVEL OF ADH DETERMINES LEVEL OF MINERALOCORTICOIDS

STEROIDS IN BLOOD ARE IN FREE AND COMBINED FORMS PHARMACOLOGICAL EFFECTS ARE DUE TO FREE FORM. STEROIDS BIND WITH CBG (CORTISOL BINDING PROTEIN ) STEROIDS ARE METABOLISED IN LIVER AFTER CONJUGATION AND EXCRETED IN URINE STEROID+CBG_LIVER CONJUGATION- EXCRETION THROUGH KIDNEY

STEROIDS IN BLOOD

ADRENAL GLANDS IN FOETUS

FOETUS ADRENAL GLAND BIGGER THAN KIDNEY AT BIRTH ADRENAL GLAND IS 1/3 THE SIZE OF KIDNEY ADULT ADRENAL GLAND 5-15gm ONLY

DROCORTISONE ,COTICOSTERONE,,DESOXYCORTISONE,DEHYDROCORTIS ALDOSTERONE ARE BIOLOGICALLY ACTIVE SECRETED BY ADRENAL GLAND

1943 ACTH WAS SHOWN TO BE RESPONSIBLE FOR ADRENAL GLAND STRUCTURAL AND FUNCTIONAL INTEGRITY

STRESS

NORMAL ADRENAL GLAND

LIFE RETURNS TO NORMAL

STRESS

HENCH USED CORTISONE IN RELIEF OF RHEUMATOID ARTHRITIS NOBLE PRIZE WINNERS IN MEDICINE FOR STEROIDS

STEROID SYNTHESISING TEAM IN THE LAB

STEROIDS THE AMRIT CHURNED OUT OT OF SEA

LIFE AFTER DISCOVERY OF STEROIDS

STEROID THE DOUBLE EDGED SWORD

STRUCTRE OF GLUCOCORTICOIDS

STRUCTURE OF MINERALOCORTICOIDS

CHOLESTROL RAW MATERIAL FOR ENDOGENOUS STEROIDS

EFFECT OF CORTICO STEROIDS

GLUCOCORTIC Approximate OIDS equivalent dose(mg) Short acting Cortisone Hydrcortisone Internmediate acting Prednisone Prednisolone Triamcinolone Methyl prednisolone Long acting Dexamethasone 0.75 Betamethasone 0.6-0.75 Glucocorticoid 5 5 4 4 25 20

Relative anti inflamatory potency

Relative Half life mineralocorticoid Plasma potency (min)

Biological (hour)

0.8 1

2 2

30 80-118

8-12 8-12

4 4 5 5

1 1 0 0

60 115-212 200+ 78-188

18-36 18-36 18-36 18-36

20-30 20-30 Equivalencies

0 0Half life Potencies and

110-210 300 Half life

36-54 36-54

ANTI ANABOLIC EFFECT-STOPS COMBINATION OF AMINOACIDS INTO THE PROTEIN IN THE PERIPHERAL TISSUE. NEOGLUCOGENESIS TAKES PLACE IN THE LIVER(liver proteins being converted to glucose). Level of aminoacids as well as glucagone rise on chronic administration of STEROIDS. REDISTRIBUTION OF FATS FROM PERIPHERY TO NECK SUPRACLAVICULAR AREA AND FACE

METABOLIC EFFECTS OF STEROIDS

SODIUM RETENTION AND POTASSIUM LOSS BETAMETHASONE ,DEXAMETHASONE AND TRIAMCINOLONE CAUSE LOSS OF SODIUM CALCIUM-STOP ABSORPTION OF CALCIUM FROM GUTS DUE TO ANTAGONISTIC EFFECT ON VIT D DEVELOPMENT OF CARTILAGE IS REDUCED, DECREASES LINEAR GROWTH, SEVERE OSTEOPROSIS

ELECTROLYTES & STEROIDS

HYDROCORTISONE IS ESSENTIAL FOR EXCRETING A WATER LOAD ORGANISM WITH DAMAGED ADRENAL GLAND DIE OF WATER INTOXICATION

NEUTROPHILS INCREASE IN NUMBER IN BLOOD LYMPHOCYTES AND EOSINOPHILS DECREASE IN NUMBER IN BLOOD DUE TO REDISTRIBUTION. THEREIS NO LYSIS OF LYMPHOCYTES IN NORMAL PERSON IN LYMPHOBLASTIC LEUKEMIA THEREIS DECREASE IN LYMPHOCYTES DUE TO RAPID DESTRUCTION BY CORTICOSTEROIDS

BLOOD AND COTICOSTEROIDS

POSIVE IONOTROPIC EFFECT ON HEART

POTENTIATES PRESSOR EFFECT OF ADRENALIN AND NORADRENALIN ON BLOOD VESSELS

CARDIOVASCULAR SYSTEM

INCREASE IN BASAL NOCTURNAL GASTRIC ACID SECRETION

GASTRIC EROSION

ANTI INFLAMATORY EFFECT IF FIBROSIS HAS TAKEN PLACE NO EFFECT EFFECTS ARE DELYED EARLY EFFECTS ARE
EARLY EFFECTS ARE REDUCED EDEMA,CAPILLARY DILATATION,PHAGOCYTE MIGRATION AND PHAGOCYTOSIS ARE REDUCED

REDUCED

FIBROBLASTIC PROLIFERATION. DEPOSITION OF COLLEGEN CICATRIZATION ARE REDUCED. FIBRIN ONCE FORMED CAN NOT BE DISSOLVED BY CORTICOSTEROIDS

MECHANISM OF ANTI INFLAMATORY EFFECT

REDUCE THE TRANSFER OF NEUTROPHILS AND MACROPHAGES TO THE SITE OF INFLAMATION INHIBT THE EFFECT OF MIGRATION INHIBITORY FACTOR(MIF) RESPONSIBLE FOR KEEPING NEUTROPHILS CLUMPED TOGATHER AT THE AFFECTED AREA INHIBIT THE PRODUCTION OF PLASMINOGEN ACTIVATOR BY NEUTROPHILS RESULTING IN LESS PRODUCTION OF PLASMIN HELPFUL IN ENTERY OF NEUTROPHILS IN AFFECTED AREA. INHIBIT ENZYME PHOSPHOLIPASE-A2 STOPING CHEMOTAXIS FOR MIGRATION OF NEUTROPHILS

GLUCOCORTICOIDSPHOSPHOLIPASE A2--PHOSPHOLIPIDS

ARCHIDIONIC ACID PROSTAGLANDINS

LEUKOTRIENS

CHEMOTAXIS INHIBITION BY GLUCOCORTICOIDS

50% OF STEROID GIVEN BY INTRA ARTICULAR INJECTION IS ABSORPED INTO SYSTEMIC CIRCULATION

MODERATE DOSE OF GLUCO CORTICOIDS DESTROY T LYMPHOCYTES, CELLULAR IMMUNITY IS REDUCED. HUMURAL IMMUNITY IS NOT AFFECTED. REJECTION OF TRANSPLANTED PART IS REDUCED. VERY HIGH DOSES OF STEROIDS REDUCE GLOBULIN PRODUCTUON

ANTI ALLERGY AND IMMUNOSUPRESSIVE ROLE OF GLUCOCORTICODS

ANTI INFLAMATORY EFFECT IN ALL THESE CASES

STEROIDS PRODUCE

STEROIDS PRODUCE ANTIINFLAMATORY IN ALL THESE CASES

LONG USE OF GLUCOCORTICOIDS

SUPRESSION OF HYPOTHALMO-HYPOPHYSIAL -ADRENAL AXIS

SUPRESSION OF HYPOTHALMO HYPOPHYSIAL ADRENAL AXIS

NORMAL DOSE OF STEROIDS HAVE NO SIDE EFFECTS HIGH DOSE OF STEROIDS PRODUCE SUPRESSION OF HHA AXIS WITHIN 1WEEK- IN 1YEAR IT MAY BE TOTALLY KNOCKED OUT INTERMEDIATE DOSES OF STEROIDS SHOULD BE GIVEN ON ALTERNATE DAY IN EMERGENCY TREATMENT HIGH DOSE SHOULD BE GIVEN IN MORNING IF FOR LONG TIME GIVE ON ALTERNATE DAY LONG ACTING STEROIDS FOR SUBSTITUTION THERAPY SHOULD BE GIVEN IN THE NIGHT

STRESS MANAGEMENT IN INSUFFICIENT ADRENALCORTICOSTEROIDS

MINOR STRESS-DIARRHEA,G/E,FIBRILLATION ,LACERATION SEVERE EXERCISE,MINORSURGERY100mgHYDRCORTISONE IN DAY MAJOR STRESS-LAPROTOMY-400mg HYDROCORTISONE DAILY. DECREASING DOSE BY HALF NEXT DAY TILL MINIMAL DOSE IS REACHED. WITHDRAWL OF DOSE SHOULD BE ACCORDING TO SEVERITY OF DISEASE SYMPTOMS. IFTAPERING OF DOSE IS VERY FAST WITHDRAWL SYMPTOMS CAN OCCUR-FEVER ,MYALGIA,MALAISE, AND ARTHRALGIA.

IN PREGNANCY USE ONLY PREDNISOLONE DO NOT USE DEXAMETHASONE & BETA MTHASONE AS THEY PASS INTO BABY

ADVERSE REACTIONS OF STEROIDS

TOXIC EFFECTS OF STEROIDS ARE RELATED TO INDIVIDUAL SUSCEPTIBILITY, DOSAGE AND DURATION SINGLE HIGH DOSE HOWEVER LARGE IS HARMLESS SHORT TERM SMALL TO MODERATE DOSE THERAPY IS SAFE DO NOT HESITATE OF HIGH DOSE IN EMERGENCY

ADVERSE REACTIONS

ULCERS IN GASTRIC MUCOSA DUE TO PROLONGED SMALL DOSE OR HIGH DOSE

ADVERSE EFFECTS OF STEROIDS ON GIT

Proximal myopathy Triamcinolone is notorious for this effect

Adverse effects of Steroids on CNS

LOCAL GLUCOCORTICOID THERAPY.

ON PROLONGED USE IN CHILDREN

HYPERTENSION SALT & WATER RETENSION HYPOKALEMIA ALKALOSIS DEXAMETHASONE,BETAMETHASONE, TRIAMCINOLONE DO NOT CAUSE THESE EFFECTS

SIDE EFFECTS OF STERIODS ON CVS

IN DIABETICS KETOACIDOSIS, NON KETOTIC HYPERGLYCEMIC HYPEROSMOLAR COMA HYPERLIPIDEMIA BUFFALO HUMP DISTRIBUTION OF FATS, MOON FACED AND CENTRAL OBESITY

METABOLIC EFFECTS OF STEROIDS

PINK FLORID STRIAE FRIABLE SKIN

ECHYMOSIS

DEXAMETHASONE & BETAMETHASONE CAUSE THESE BOTH CONDIT CAPILLARY FRAGILITY

SAFE STEROIDS FOR GROWING CHILDREN CORTISONE-50mg/squaremeter Prednisolone Doublle dose Betamethasone-Dexamethasone thrice bigger dose canbe given

STEROIDS CAN FLAREUP TUBERCULOSIS

Glucocorticoids increase clearance of salicylates. Abrupt stoppage of Glucocorticoids can result in toxicity of salicylates if they are given togather Barbiturates,Phenytoin and Rifampicin increase the degradation of corticosteroids

Interaction with various drugs

Use of steroids systemic use CortisoneAcetate-Tab 25mg Dose50mg

to400mg/Daily Inj.Cortisone25mg/ml 2. Tab Hydrocortisone 1Tab 10mg Inj. Hydrocortisone hemisuccinate-100mg vial I/V OR Retention enema100mg in 120ml water Prednisolone Tab 5mg Dose 10-100mg/day. Prednisone-Tab5mg Dose10-100mg/day. Prednisolone Acetate Suspention for I/m I/A Petriarticular Methyl prednisolone tab4mgDose8-80mg/day Inj.Methylprednisolone40mg vialDosev40mg -120mg/day Tab Triamcilone dose4-48mg/day Inj.Triamcilon5-40mg I/mor I/A ONLY

MILD-HYDROCORTISONE 1-2.5% MODERATE CLOBETASONE BUTYRATE 0.05% POTENT BETAMETHASONE VALERATE 0.1%HYDRCORTISONEBUTYRATE 0.1% VERY POTENT CLOBETASONE PROPIONATE-0.05% FLUCINOLONE ACITONIDE 0.025%

Topical stroids

THERAPEUTIC USE OF GLUCOCORTICOIDS

SUBSTITUTION THERAPY & PHARMACOLOGICAL THERAPY

SUBSTITUTION THERAPY
ONLY USED IN ADDISONS DISEASE AND HYPOPITUTRISM TREATED WITH MINERALOCORTICOIDS

(1) INTENSIVE SHORT TERM THERAPY (2)PROLONGED HIGH DOSE THERAPY (3)LOW DOSE CHRONIC PALLIATIVE THERAPY (4) CHRONIC SUPRESSION OF PITUTARY ACTH (5) TOPICAL APPLICATION (6) INTRA ARTICULAR AND INTRA TENDINOUS USE

PHARMACOLOGICAL THERAPY

TO SAVE LIFE AND REDUCE MORBIDITY IN POTENTIALLY LETHAL CONDITIONS WHERE INFLAMATORY OR METABOLIC RESPONSE OF THE BODY THREATENS LIFE ITSELF

INTENSIVE SHORT TERM THERAPY

ANAPHYLECTIC SHOCK STATUS ASTHMATICUS CIRCULATORY COLLAPSE ACUTE NECROTIC VASCULITIS WATER INTOXICATION CENTRAL HYPERTHERMIA ACUTE HYPERCALCEMIA

LETHAL CONDITIONS WHERE STEROIDS ARE LIFE SAVING

Gluco corticoids take several hours to produce effect

Status asthmaticus & glucocorticoids

Circulatory collapse

Single massive dose of long acting steroids

Thanks Blessed are those who are healthy