For MBBS/BDS as part of Endocrine pharmacology

2. Corticosteroids:-
Adrenal Gland
Outer (Adrenal Cortex)
(3 layers)
Inner (Adrenal Medulla)
Secretes on sympathetic stimulation
Epinephrine
(Predominantly)
Norepinephrine
Zona glomerulosa
(Mineralocorticoids)
e.g.-Aldosterone
F(x)- Na+ & H20 retention
K+ & H+ excretion
Zona Fasciculata
Zona Reticularis
(Glucocorticoids)
e.g.- cortisol,
Corticosteroids
F(X)- Regulate
carbohydrate & protein
metabolism
Androgens
 Hypersecretion-
Primary
hyperaldosteronism
(Conn’s syndrome)
 Hypersecretion-
Cushing’s syndrome
Hyposecretion- of all the hormone leading
to Addison’s Disease

4. • Biosynthesis:-
• Corticoids (gluco + Mineralo)-21-carbon compounds having a
cyclopentanoperhydro-phenanthrene (steroid) nucleus.
• synthesized in the adrenal cortical cells from cholesterol under the control of
ACTH
 Regulation of
synthesis and
secretion of
corticosteroids

5. Mineralocorticoids
Synthesize from → Zona glomerulosa(Adrenal cortex)
Most important Mineralocorticoids →Aldosterone
Site of Action→ Kidney (DCT & Collecting duct)
Function-Na+ retention by ↑Na+ reabsorption
MOA:- Aldosterone
↓↓
Bind to mineralocorticoids receptor
↓↓
stimulate synthesis of aldosterone induce protein(AIP)
↓
Stimulation of Na+/K+ exchanger in the apical membrane
↓↓
Responsible for action

6. Aldosterone effects
Deficiency state:-
↓Na+ reabsorption →Hyperkalemia & acidosis
Excess:-
Retention of Na+ & water-hypertension & oedema
Hypokalemia
Alkalosis
Synthesize from → Zona Fasciculata (Adrenal cortex)
MOA:-
Glucocorticoids

8. Pharmacological Action:-
CNS:- Mild euphoria
Higher dose→↓seizure threshold (precipitate seizure in epileptic pt.)
CVS:- Glucocorticoids
Hypertension (permissive action)
GIT:- Inhibit-PG’s→↑GA & pepsin secretion→ aggravate Peptic ulcer
Hematopoietic system:-
Destruction of Malignant-T & B cells but little effect on normal cells
↑RBC, platelet & neutrophils
↓ lymphocytes, eosinophils, basophiles
Promote Na+ & water retention
(except synthetic glucocorticoids )
Potentiate effect of catecholamine &
angiotensin-II on smooth muscle
week mineralocorticoid action

9. • Metabolism:-
Carbohydrate metabolism- : through
↓utilization of glucose by peripheral tissues
Stimulate gluconeogenesis from amino acids
Protein metabolism:- (breakdown-protein)
Displace amino acids from protein synthesis(catabolic action)→muscle wasting
Fat metabolism:-
Redistribution of fat from peripheral tissue → central such as
Back of neck & shoulder (buffalo hump)
Abdomen & face (moon face)
Anti-insulin effects (insulin
resistance)→Hyperglycaemia
Centripetal obesity

10. • Anti-inflammatory action:-
Stimulation
Inhibit IL-1,2,6 & TNF-α
Stabilize lysosomal membrane
↓leucocyte migrate to site of injury
Potent
Anti-
inflammatory
action
Immunity:- suppress cell mediated(T-cell) immunity more than humoral
immunity (B-cells)-immunosuppressant
Favors spread of infection→ impaired capacity of defensive cells to kill micro-
organism

11. Interfere healing & scare formation
Inhibit chemotaxis of immune cells
Inhibit the release of IL-2→↓T-cell proliferation
↓Antibody production from β-cells
Calcium metabolism:-
Glucocorticoid
Inhibit calcium
absorption from the gut
↑renal excretion
of calcium
↓Blood Calciumlevel
Promote Osteoclastic action
(bone resorption action)
Inhibits Osteoblastic
action (bone forming
cells)
osteoporosis and pathological fracture of vertebral
bodies

12. • Skeletal muscles:-
Corticosteroids are required for the normal function of skeletal muscles.
Weakness occurs in both hypocorticism and hypercorticism
Prolonged use →muscle wasting and weakness (steroid myopathy)

13. Classification of corticosteroids
Glucocorticoids Mineralocorticoids
Short acting Intermediate
acting
Long acting
 Hydrocortisone
 Prednisolone
 Methyl prednisolone
 Triamcinolone
 Deflazacort
 Dexamethasone
 Betamethasone
Local Acting
 Beclomethasone
 Budesonide
 Fluticasone
 Desoxycorticosterone
acetate (DOCA)
 Fludrocortisone
 Aldosterone
T1/2-<12hr T1/2-12-36hr T1/2->36hr

14. • Individual drugs:-
1. Hydrocortisone (cortisol):- Rapid action + short duration of action
Glucocorticoids + Mineralocorticoids action
Uses:-
Acute adrenal insufficiency
Status asthmaticus
Anaphylactic shock (emergency uses)
ulcerative colitis-Topically and as suspension for enema
2. Prednisolone:-
It is 4 times more potent than hydrocortisone
Has intermediate duration of action
Also process→ mineralocorticoid Action(Na+ & water retention)-higher dose
Uses-used preparation for allergic, inflammatory, autoimmune disorders and in
malignancies.
It causes less HPA axis suppression if given once daily in the morning

15. 3.Prednisone:-
• It is a prodrug, gets converted to prednisolone in liver;
• less efficacious, hence rarely used
4.Methyl-prednisolone:-
• It is used for its anti-inflammatory and immunosuppressant effects; as high-dose pulse
therapy
• in renal transplant, pemphigus vulgaris, etc.
• Routes: Retention enema in ulcerative colitis
5.Triamcinolone:-
• More potent and relatively more toxic than prednisolone.
• It has no mineralocorticoid activity
6. Dexamethasone:-
Very potent and highly selective glucocorticoid.
It is also long-acting causes marked pituitary-adrenal suppression
USES:-inflammatory and allergic conditions like shock & cerebral edema

16. 6.Betamethasone:- Similar to dexamethasone
• USES:- cerebral edema and other states in which fluid retention must be
avoided
7. Beclomethasone:-
They have local action
It is used by inhalation in bronchial asthma, as nasal spray for allergic rhinitis;
as ointment for skin and mucous membrane lesions.
HPA-axis suppression is minimal
8. Budesonide:-more potent than beclomethasone
• 9. Fluticasone:-
• Uses:-
• Asthma & COPD-inhalational route
• Inflammatory bowel disease-orally
• skin and mucous membrane lesions- ointment

17. • Desoxy-corticosterone acetate (DOCA):-
• It has selective mineralocorticoid activity and is used in Addison’s disease as
replacement therapy
• Fludrocortisone:-
• Potent mineralocorticoid activity.
• USES:-
• Addison’s disease:- as a replacement therapy (fludrocortisone + hydrocortisone)
Side effects of corticosteroid therapy:-
• Depends on dosages + duration of therapy
• Less side effect-short period(<2 weeks)
• ↑risk→ prolong use+ ↑dosing

18. Hypothalamic–pituitary–adrenal (HPA) axis suppression:-
Not seen-<1 week therapy with mild-moderate & high doses
Required precautions-during long term therapy
1. Topical use of steroids is preferred
2. Short- or intermediate-acting steroids (e.g. hydrocortisone, prednisolone) should
be preferred
3. If daily dose is high-split the dosing
2/3-dose at Morning
1/3-dose at Evening
4. Try alternate-day steroid therapy in chronic conditions like bronchial asthma,
nephrotic syndrome, systemic lupus erythematosus (SLE), etc
5. Tapering of dose-Withdrawal of steroids after long-term (2 weeks) treatment
should be very slow to allow recovery of normal adrenocortical function.
Minimize the HPA axis suppression

19. • Abrupt stoppage- Glucocorticoid therapy following prolonged use leads to
Flaring up of the underlying disease being treated.
• Withdrawal symptoms- like fever, myalgia, arthralgia, malaise, etc.
Metabolic effects:- Hyperglycaemia, precipitation of diabetes mellitus (DM) or
aggravation of pre-existing diabetes.
Cushing’s habitus:- Abnormal fat distribution causes peculiar features with
moon face, buffalo hump and thin limbs
GIT:- Peptic ulceration sometimes with haemorrhage or perforation.
Salt and water retention: Mineralocorticoid effect may cause oedema,
hypertension and even precipitation of CCF, particularly in patients with primary
hyperaldosteronism.
Rx-minimized by using synthetic steroids like dexamethasone, betamethasone,
etc.
Muscle- hypokalemia leading to muscle weakness and fatiguability.
Long-term steroid therapy –cause steroid myopathy

20. Bone:-
Osteoporosis with pathological fractures of vertebral bodies is common. Ischemic necrosis
of the femoral head can also occur.
Growth retardation in children is more common with dexamethasone and
betamethasone.
Eye:- Glaucoma and cataract may occur on prolonged therapy.
CNS:- Behavioral disturbances like nervousness, insomnia, mood changes can occur
psychosis may be precipitated.
Long-term therapy- steroids leads to immunosuppression, which makes the patient
more vulnerable to various infections like fungal (candidiasis, cryptococcosis), viral
(herpes, viral hepatitis), bacterial (reactivation of latent tuberculosis), etc.
Inhalational steroids- can cause local irritation and fungal infection of upper
respiratory tract, which can be prevented by the use of spacer and by rinsing the mouth
after inhalation.

21. Therapeutic uses of glucocorticoids:-
Endocrinal uses:-
1. Acute adrenal insufficiency:- (Medical emergency)
Rx-
I.V. hydrocortisone and i.v. normal saline with 5% glucose to correct fluid and
electrolyte imbalance. Precipitating causes such as trauma, infection or
hemorrhage should be treated.
2. Chronic adrenal insufficiency:-(Addison’s disease)
Treated with oral hydrocortisone
2/3-moring dose +1/3-evening dose + adequate salt and water.
2. Chronic secondary adrenocortical deficiency
3. Congenital adrenal hyperplasia
4. Maintenance therapy in Cushing syndrome (after surgical removal of
pituitary/adrenal tumor)

22. Non-endocrinal uses:-
• Because of their dramatic symptomatic relief, they are often misused. Non-
endocrinal diseases require
1. In dentistry:-Topical or systemic glucocorticoids are used in:-
• Recurrent aphthous stomatitis
• Chronic ulcerative stomatitis
• Oral pemphigoid
• Erythema multiforme
• Temporomandibular joint pain:- Intra-articular triamcinolone is used.
2. Rheumatoid arthritis:-
Immediate symptomatic relief but no action on progression of the disease.
Intra-articular injection is preferred only if one or two joints are involved.
Use adjunct NSAIDs & DMARDs

23. 3.Osteoarthritis:- rarely used in OA. Intra-articular injection is recommended for
acute episodes.
4. Rheumatic fever:-
They produce more rapid symptomatic relief than aspirin
Prednisolone is given along with aspirin and should be continued until the
erythrocyte sedimentation rate (ESR) comes to normal and then the steroid is
tapered off gradually.
5. Allergic diseases:- such as
Hay fever, Reactions to drugs, Urticaria, serum sickness, Contact dermatitis,
Angioneurotic oedema
Anaphylaxis-(DOC-adrenaline) as corticosteroid are slow onset of action.
Adjuvant I.V.- hydrocortisone+ I.M. Adrenaline
6.Bronchial Asthma-
Moderate to severe asthma-inhaled or systemic glucocorticoids
I.V. hydrocortisone + nebulized β2-agonist and ipratropium bromide

24. • Advantage-
• ↓ mucosal oedema and bronchial hyperirritability
• ↓development of resistance to glucocorticoids
Status asthmatics:-inhalational preparations like beclomethasone, budesonide
or fluticasone because they cause minimal systemic adverse effects.
7.Immunosuppressive therapy:-
Collagen vascular disease- large dose glucocorticoids(steroid with negligible
salt and water retaining property is preferred )
Skin graft-To avoid rejection
Organ transplantation-Glucocorticoids prevent as well as treat graft rejections
Acute immune disease-thrombocytopenia
Renal disease- Glucocorticoids are the first-line drugs in nephrotic syndrome
Chronic demyelinating polyneuropathies- e.g. Guillian barre syndrome

25. Myasthenia gravis
8. Ocular diseases:- used to suppress inflammation in the eye thus they prevent
damage to vision.
Administered- topically, sub conjunctivally, systemically or by retrobulbar
injection, depending upon the condition.
Contraindicated in herpes simplex, keratitis and ocular injuries.
9. Skin diseases:-
They dramatically relieve itching, pain, and inflammation in allergic and other
dermatoses.
To minimize systemic effects, topical steroids are preferred.
Systemic steroid therapy is needed in severe conditions like exfoliative dermatitis,
dermatomyositis, pemphigus, etc. Psoriasis, keloids and hypertrophic scar are
sometimes treated by intralesional injection of steroids.
10.Lung maturation in the foetus- betamethasone is given to mother who is going
to delivered premature baby(12mg i.m. followed by 12mg i.m. next day)
↓incidence of respiratory distress syndrome in infant

26. 11.Cerebral oedema:- oedema is caused by brain tumors, metastatic lesions and
tubercular meningitis. A steroid without salt and water retaining activity (e.g.
dexamethasone) is preferred.
12.Intestinal diseases:- They are used in ulcerative colitis when the patient is not
responding to other forms of treatment. Methylprednisolone can be administered as
retention enema during acute episodes
13.Hypercalcemia:- Hypercalcemia of sarcoidosis, and vitamin D intoxication responds
to prednisolone
Others:-
HIV related disorders e.g. pneumocystis carinii pneumonia, MAC
Lepra reaction & septic shock
Contraindication:-
 Hypertension Epilepsy
Diabetes mellitus Psychosis
Peptic ulcer Congestive cardiac failure
Tuberculosis Renal failure
Herpes simplex keratitis Glaucoma
Osteoporosis

28. • Anabolic Steroids are drug derived from synthetic testosterone, a
natural male hormone that are used to enhance performance
• They are synthetic androgens with greater anabolic(skeletal muscle) and
lesser androgenic activity
• On skeletal muscle testosterone →↑strength + muscle mass when used
with exercise for development of muscle & often misused
• Testosterone- potent anabolic effect, but it cannot be used because of
its strong androgenic effect
• Doping:- “Use of an expedient (substance or method) which is potentially harmful
to athletes’ health and/or capable of enhancing their performance, or the presence
in the athletes body of a prohibited substance or evidence of the use there of or
evidence of the use of a prohibited method”

29. Anabolic Steroids
Drug Anabolic
Androgenic
ratio
Preparation & Dose
Methandienone 3:1 Orally/i.m.
Nandrolone phenyl propionate 3:1 i.m.
Nandrolone decanoate 3:1 25 – 50 mg/3 wk, i.m.
Stanozolol 3:1 2 - 6 mg/day, p.o.
Oxymetholone 3:1 5 – 10 mg/day, p.o.
Ethylestrenol 3:1 5 – 10 mg/day, p.o.
29

30. Mechanism of Action :-
Anabolic steroid increase the body mass & increase the physical
performance by
1.Increasing the incorporation of amino acids into protein
2.Increasing the RNA polymerase activity in skeletal muscles.
3.Antagonizing protein catabolic effects of glucocorticoids
Antagonizing protein catabolic effect of glucocorticoids
Resulted-weight gain

31. 1. Catabolic states- In chronic illness they use to improve appetite &
feeling of wellbeing (as a protein anabolic agents)
2. During recovery from prolonged illness, surgery, burns, trauma or
chronic debilitating diseases.’
3. Short stature
– Athletic performance- misused by athletes. Their use by athletes is
prohibited. They can be detected in the urine by antidoping investigations.
– In postmenopausal and senile osteoporosis - ↓ca++ ion excretion (preferred
drug bisphosphonate)

32. Side effect:-
In Men:-
• Oligozoospermia,infertility – due to inhibition of LH,FSH(Negative feedback)
• Gynaecomastia- due to peripheral conversion of testosterone to estrogen
In women-
 Virilization,
 muscle hypertrophy ,
 acne,
 hirsutism,
 frontal hair thinning,
 deepening of voice ,
 Anovulation

33. Teretogenic effect-
pseudomaphroditism (female uterus)
Children- Impairment of growth due to – premature closer of epiphyses
Toxicity in either sex-
Na+,H20 retention-oedema,
polycythaemia,
cirrhosis of liver.
Cholestatic jaundice-mainly with methyltestosterone
Abuse is sports- due to non-pharmacological use – serious side effect
Contraindication-
Pregnancy
Renal dysfunctions
Patients suffering from migraine, diabetes

34. Thank you