Steroid therapy

1. SYSTEMIC STEROID
THERAPY
Dr. Samia Farhin
Intern doctor (Batch: Tm-09)
Department of Medicine
Tairunnessa Memorial Medical College & Hospital

2. INTRODUCTION
 Steroids are fast catching up with antibiotics as the most
extensively used class of drugs today to treat many
inflammatory and autoimmune disorders.
 The adrenal produces various classes of hormones, each of
which aid in dealing with the stress faced by animals and
people almost daily.
 These hormones affect almost all body organs and are
extremely important in maintaining homeostasis when
secreted in normal amounts.
 Disease results from inadequate or excessive secretion.

3.  Exogenous steroids are used as drugs in a variety of
disorders. Their use must be closely monitored,
because they have profound therapeutic and adverse
effects.
 To understand the effects of steroids used as drugs, it
is necessary to understand the physiologic effects and
other characteristics of the endogenous hormones.

4. SECRETION OF ENDOGENOUS STEROID
 Corticosteroid secretion is controlled by the
hypothalamus,the anterior pituitary,and adrenal cortex (the
hypothalamic–pituitary–adrenal,or HPA axis).
 Various stimuli (eg, low plasma levels of corticosteroids; pain;
anxiety; trauma; illness; anesthesia) activate the system.
 The mechanism by which the hypothalamus and anterior
pituitary “learn” that no more corticosteroids are needed is
called a negative feedback mechanism.

6. TYPES OF ENDOGENOUS
CORTICOSTEROIDS
The adrenal cortex produces approximately 30
steroid hormones, which are divided into –
1.Glucocorticoids :-
a)Cortisol,
b)Corticosterone
c)Cortisone
2.Mineralocorticoids :-
a)Aldosterone
3.Adrenal sex hormones.
a)Male (androgens)
b)Female (estrogens and progesterone)
Chemically, all corticosteroids are derived from cholesterol and
have similar chemical structures.

7. BASAL SECRETION
Group Hormone Daily
Glucocorticoids:- Cortisol
Corticosterone
5-30 mg
2-5 mg
Mineralocorticoids:- Aldosterone
11-Deoxycorticosterone
5-150 mcg
Trace
Sex Hormone:-
Androgen
Progestogen
Oestrogen
DHEA
Progesterone
Oestradiol
5-30 mg
0.4-0.8 mg
Trace

8. DIURNAL VARIATION
Glucocorticoids are secreted cyclically, with the
largest amount being produced in the early morning and the
smallest amount during the evening hours (in people with a
normal day–night schedule).

9. MECHANISM OF ACTION OF
GLUCOCORTICOIDS
 Endogenous & exogenous (drug molecules) steroids are
act at the cellular level by binding to glucocorticoid
receptors in target tissues.
 Then they diffuse through the cell membranes of target
cells.
 Inside the cell, they bind with receptors in intracellular
cytoplasm.

10. ‘’CONTINUED’’
 The drug–receptor complex then moves to the cell
nucleus, where it interacts with DNA to stimulate or
suppress gene transcription.
 Glucocorticoids increase or decrease transcription
of many genes to alter the synthesis of proteins that
regulate their many physiologic effects (eg,
enzymes, transport proteins, structural proteins).

11. Overall, corticosteroids have multiple mechanisms
of action and effects including the following:-
 Inhibiting arachidonic acid metabolism.
 Strengthening or stabilizing biologic membranes.
 Inhibiting the production of interleukin-1, tumor
necrosis factor, and other cytokines.
 Impairing phagocytosis.
 Inhibiting tissue repair
 Impairing lymphocytes

13. A)Numerous & widespread actions :-
1.Carbohydrate metabolism :-
a)↑Formation of glucose (gluconeogenesis)
b)↓Cellular use of glucose
c) Both the ↑production and ↓use of glucose promote higher
levels of glucose in the blood (hyperglycemia).
2.Protein metabolism :-
a)↑Breakdown of protein into amino acids (catabolic
effect).
b)↑rate of amino acid transport to the liver and conversion to
Glucose.
c)↓Rate of new protein formation from dietary and other amino
acids (antianabolic effect).
ACTIONS OF GLUCORTICOIDS ON BODY
SYSTEMS

14. ‘’CONTINUED’’
3.Lipid Metabolism:-
a)↑Breakdown of adipose tissue into fatty acids
b)↑Oxidation of fatty acids within body cells
4. Inflammatory and Immune Responses:-
a)↓Inflammatory response
b)↓Immune response.

16. 5.Cardiovascular System:-
a)Regulate arterial blood pressure by modifying vascular
smooth muscle tone,by modifying myocardial contractility, and
by stimulating renal mineralocorticoid and glucocorticoid
receptors.
b)↑The response of vascular smooth muscle to the
pressor effects of catecholamines and other vasoconstrictive
agents.

17. ‘’CONTINUED’’
6.Nervous System:-
a)Physiologic amounts help to maintain normal
nerve excitability.
b)Pharmacologic amounts ↓nerve excitability,
slow activity in the cerebral cortex, and alter brain
wave pattern.

18. 7.Musculoskeletal System;-
a)Maintain muscle strength when present in
physiologic amounts but cause muscle atrophy (from
protein breakdown) when present in excessive amounts.
b)↓Bone formation and growth and ↑bone breakdown.
c)↓Intestinal absorption and ↑renal excretion of
calcium.These effects contribute to bone demineralization
(osteoporosis) in adults and to ↓linear growth in children.

19. 8.Respiratory System:-
a)Help to maintain and restore responsiveness to the
bronchodilating effects of endogenous catecholamines,such as
epinephrine.
b)Stabilize mast cells and other cells to inhibit the
release of bronchoconstrictive and inflammatory substances,
such as histamine.
9.Gastrointestinal System :-
a)↓Viscosity of gastric mucus.
This effect may ↓protective properties of the mucus and
contribute to the development of peptic ulcer disease.

20. EMERGENCY HORMONE
In any type of stress; like trauma,
infection, surgical operations; increase ACTH secretion,
which within minutes greatly increase serum cortisol level.
This cortisol cause rapid mobilization of fat &
amino acids from stores, making them available for energy
& synthesis of other compounds including glucose & new
proteins.
That’s why cortisol is called Emergency
Hormone.

21. MECHANISM OF ACTION OF
MINERALOCORTICOIDS
Aldosterone secretion is
regulated by followings-
1.ACTH from pituitary
gland
2.Renin-Angiotensin
system
3.K+ concentration of the
extracellular fluid
4.Quantity of body Na+.

22. EFFECTS OF MINERALOCORTICOIDS ON
BODY SYSTEM
A)Renal effect :-
1.Increased tubular reabsorption of Na+
2.Enhanced tubular excretion of K+
3.Increased tubular secretion of H+
4.Increased extracellular fluid volume
B)Circulatory effect :-
1.Hypersecretion of aldosterone increase blood volume & cardiac
output leading to moderate to severe hypertension
2.In absence of aldosterone,decrease ECF volume leading to
decrease plasma volume,circulatory shock develops rapidly.

23. ‘’CONTINUED’’
C)Effects on sweat glands, salivary glands & intestinal
absorption :-
1.Increase reabsorption of NaCl & the secretion of K+ by
the ducts.
2.Enhances sodium absorption by the intestines,
especially in the colon, which prevents loss of sodium in the
stools.

24. LIFE SAVING HORMONE
Aldosterone is called Life Saving
Hormone; because-
There is a fixed equilibrium between Na+ &
K+; that maintain Na-K+ pump. This equilibrium is
maintained by aldosterone.
In its absence or decreased concentration, a person may
die from circulatory shock due to hyponatraemia &/or
from serious cardiac toxicity including weakness of
contraction & arrhythmia due to hyperkalaemia.

25. MECHANISM OF ACTION OF ANABOLIC
STEROIDS
 Anabolic steroids are membrane permeable and
influence the nucleus of cells by direct action.
 Pharmacodynamic action of anabolic steroids begin
when the exogenous hormone penetrates the
membrane of the target cell and binds to an androgen
receptor located in the cytoplasm of that cell.
 From there, the compound hormone-receptor diffuses
into the nucleus, where it either alters the expression of
genes or activates processes that send signals to other
parts of the cell.

26. EFFECTS OF ANABOLIC STEROIDS ON
BODY SYSTEM
1.Normal maturation in the male
2.Sperm production
3.Increased synthesis of muscle protein
4.Decreased bone resorption

27. EXAMPLES OF SYSTEMIC STEROIDS

28. ACCORDING TO ROUTE, SOME IMPORTANT STEROIDS
#Injectable:
Betamethasone Dexamethasone
Prednisolone Methylprednisolone
Hydrocortisone Triamcinolone
#Oral:-
Betamethasone Fludrocortisone
Prednisolone Prednisone
Methylprednisolone
#Topical:
Betamethasone Clobetasol
Flucinolone Mometasone
#Inhalation:
Beclomethasone Budesonide
Flunisolode

29. INDICATION OF STEROIDS
THERAPY
A)Replacement Therapy :-
1.Acute adrenal insufficiency (Addisonian Crisis)
2.Chronic adrenal insufficiency (Addison’s disease)
3.Congenital adrenal hyperplasia
B)Pharmacotherapy (non-endocrine use):-
a)Pulmonary : 1.Bronchial asthma
2.Aspiration Pneumonia
3.Prevention of foetal RDS

30. ‘’CONTINUED’’
b)Hypersensitivity:-
1.Serum sickness
2.Contact Dermatitis
3.Anaphylaxis
c)Collagen Vascular disease:-
1.Rheumatoid arthritis
2.Osteoarthritis
3.Syetemic lupus erythematosus
d)Cardiovascular System :-
1.Rheumatic fever
e)Autoimmune Disease:-
1.Autoimmune haemolytic Anaemia
2.Idiopathic thrombocytopenic purpura
3.Active chronic hepatitis, alcoholic hepatitis

31. ‘’CONTINUED’’
f)Renal system :-
1.Nephrotic syndrome
2.Glomerulonephritis (membranous type)
3.Renal disease secondary to SLE
4.Renal sarcoidosis
g)Neurological:-
1.Cerebral oedema
2.Meningitis (in children, tuberculosis)
h)Eye diseases:-
1.Optic neuritis
2.Allergic conjunctivitis
3.Iritis, iridocyclitis and keratitis

32. ‘’CONTINUED’’
i) Malignancy:-
Essential for combined chemotherapy of-
1.Acute lymphatic leukemia
2.Hodgkin's and other lymphomas
3.Hormone responsive breast carcinoma
j)Organ Transplant:-
Combined with other immunosuppressants – cyclosporine,
azathioprine; to prevent graft rejection
k)Other use:-
1.Antiemetic – with ondansetron
2.Acute mountain sickness
3.pulmonary oedema from drowning
4.Hyperthyroidism – thyroid storm

33. CHOOSING A STEROID
 Once daily dosing is usually
preferred for oral glucocorticoids.
 Large steroid doses are
administered in divided doses to
reduce local GIT effects
 In order to mimic the normal diurnal
cycle and reduce the risk of adrenal
suppression,GCs should be given in
the morning between 6-10 AM.
 Alternate day therapy allows the
HPA axis to recover on off days

34. ADVERSE EFFECTS OF STEROID
THERAPY
Most patients who are given daily doses of
100mg of hydrocortisone or more or equivalent amount of
synthetic steroid for longer then two weeks; may develop
series of changes-
 Adrenal or pituitary-adrenal axis suppression
 Iatrogenic Cushing syndrome
 Other complications

35. CLASSIFICATION OF ADVERSE EFFECTS
Dose-dependent
Hyperglycemia
• Hyperlipidemia
• Peptic ulcer disease
• Psychosis
Duration-dependent
• Hypertension
• Cushingoid changes
• Growth impairment
• Osteoporosis
• Osteonecrosis
• Opportunistic infections

36. ‘’CONTINUED’’
Long time corticosteroids therapy results two
categories of adverse effects –
a)Due to rapid /sudden withdrawal :-
1.Flare up of underlying disease
2.Acute adrenal suppression
3.Other effects: fever,myalgia,arthalgia & malaise.

37. ‘’CONTINUED’’
b) Due to long term use of corticosteroids:-
1.Fluid & electrolytes disturbance
a)Hypokalaemia
b)Oedema
c)Hypertension
2.Metabolic changes :-
a)Iatrogenic Cushing Syndrome
b)Hypokalaemia with glycosuria
3.Increase susceptibility to infection due to suppression of
immunity.

38. 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
• Aseptic necrosis of
bone
• Myopathy
Endocrine
• Diabetes mellitus
• Adrenal cortex
suppression
Immunologic
• Lymphocytopenia
• Immunosuppression
• False-negative skin
test
Ophthalmic
• Cataract
• Narrow-angle
glaucoma
Developmental
• Growth retardation

39. MANAGEMENT OF ADVERSE EFFECTS
1.Gradual withdrawal of glucocorticoids
2.Treatment of the developed problems :-
a)Treatment of infection by appropriate antibiotics
b)Treatment of hypertension by anti-hypertensive
c)Treatment of fluid & electrolyte imbalance
3.Strict monitoring of the progress of the patient condition
4.Prevention of adverse effect:-
a)Use small dose of anabolic steroid
b)Vitamin D, Ca++ supplement to prevent
osteoporosis.

40. ‘’CONTINUED’’
c).Adrenocorticoids antagonists :-
a)Metyrapone : 11 beta-hydroxylase enzyme
inhibitor– used in Cushing`s syndrome and test of pituitary
efficiency
b)Aminoglutethemide: Stops conversion of
cholesterol to pregnelone (Medical adrenalectomy) –
Breast cancers
c)Mifepristone: Progesterone antagonist
d)Spironolactone: Aldosterone antagonist
e)Ketoconazole : used in Cushing`s syndrome and
hirsutism in female.

41. RISK FACTORS FOR STEROIDS SIDE
EFFECTS
The risk of side effects depends on followings :-
A)Dose :-
 low dose (< 10 mg/day of prednisone)
 medium dose (10-20 mg/day)
 high dose (> 20 mg/day)
B)Type of steroid
 long-acting
 short-acting
C)Length of treatment: (Long-term treatment > 3 months)
D)Other medical problems

42. A CHECKLIST PRIOR TO THE ADMINISTRATION OF
GLUCOCORTICOIDS IN PHARMACOLOGICAL DOSES
1.Presence of tuberculosis or other chronic infection (chest x-
ray, tuberculin test)
2.Evidence of impaired glucose intolerance, history of
gestational diabetes, or strong family history of type 2 diabetes
mellitus in first-degree relative.
3.Evidence of preexisting (or high risk for) osteoporosis (bone
density assessment in organ transplant recipients or
postmenopausal patients)

43. ‘’CONTINUED’’
4.History of peptic ulcer, gastritis, or esophagitis
5.Evidence of hypertension, cardiovascular disease,
or hyperlipidemia (triglyceride level).
6.History of psychological disorders

44. SUPPLEMENTARY MEASURES TO MINIMIZE
UNDESIRABLE METABOLIC EFFECTS OF
GLUCOCORTICOIDS
1.Diet : should take the drug after meal.
2.Monitor caloric intake to prevent weight gain.
3.Diabetic diet if glucose intolerant.
4.Restrict sodium intake to prevent edema and minimize
hypertension.
5.Provide supplementary potassium if necessary.
6.Consider antacid, H2 receptor antagonist, and/or H+,
K+,-ATPase inhibitor therapy

46. FOLLOW UP PROTOCOL
EXAMINATION
a)At 1 month – then after every
2-3 month :-
1.Blood pressure, weight
2.Height & weight plotted on
growth curve(in children)
3.Thorough h/o at each visit
for adverse effects
b)At least every 6 mth initially
then annually:
1.Opthalmological
examination.
LABORATORY
a)At 1 month – then after every 3-4
month :-
1.K+ level
2.FBS
3.TGL
4.X-ray vertebral column
b)Near time of cessation of long
term CS therapy :-
8-9 am cortisol level

47. CONTRAINDICATIONS OF STEROID
THERAPY
1.Peptic ulcer disease
2.Hypertension
3.Congestive Cardiac failure
4.Any active infection
5.Diabetes Mellitus
6.Glaucoma
7.Cushing’s syndrome

48. STEROID WITHDRAWAL
SYNDROME
 Acute adrenal insufficiency results from too
rapid withdrawal of corticosteroids after prolong therapy;
then a characteristics Steroid withdrawal syndrome can
developed.
 Criteria :-
1.Fever
2.Myalgia
3.Arthalgias
4.Malaises
5.Itchy skin nodules
6.Rhinitis
7.Conjunctivits

49. WITHDRAWAL OF STEROID
THERAPY
The longer the duration of therapy, the slower
must be the withdrawal by following steps-
A)Taper the dose to reduce glucocorticoids dose by 2.5-
5 mg of prednisolone equivalent daily :-
1.Patient category:
Any patient who is dosed with glucocorticoids for
longer than 14 day.
2.Steroids required tapering :-
a)Prednisone, prednisolone, methylprednisolone.
b)Triamcinolone

50. ‘’CONTINUED’’
3.Procedure of tapering:
a)Divide each daily dose into a morning and an afternoon
portion.
b)Begin reducing the afternoon dose while maintaining the
morning dose at the same level.
c)Upon reaching 5mg per day, proceed more slowly.
d)Once the dose is reduced to 5 mg of prednisolone equivalent,
the patient may be switched to a shorter acting agent for further
tapering.
e)split the morning dose in half again and continue decreasing
the afternoon dose by ½ mg as symptoms allow.
f)Repeat the process until the dose is reduced to zero.

52. 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 steroid therapy.
When steroids are prescribed, measures should be taken
to minimize 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.

53. THANK YOU