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Pharmacology Surgery Medicine




Substances secreted from the adrenal cortex—

Zona Glomerulosa—Mineralocorticoids (Aldosterone)

Zona Fascicularis—Glucocorticoids (Cortisol)

Zona Reticularis—Adrenal Androgen / Adrenal Sex Steroid


Substances secreted from the adrenal medulla—

Epinephrine and Nor-epinephrine.


      The term corticosteroids means → Mineralocorticosteroids + Glucocorticosteroids

  → Glucocorticoids + Mineralocorticoids


***  steroid nucleus contains CPP (Cyclo-Pentano Perhydro Phenanthrene) ring

***  precursor of steroid is cholesterol (from plasma lipoprotein)

*** steroids are more potent anti-inflammatory than NSAID because they act on top of the pathway of mediators activation (blocks phospholipids).


Major endogenous cortical hormone—






Cortisol (Hydrocortisone)



Adrenal Androgens—

Dehydroxy-epi-andosterone (DHEA)




*** some of the androgens, after entering the adipose tissue are converted into ‘estrone’, a weak oestrogen which produces some oestrogenic effects.


Mechanism of Action of Steroids—they act by a mechanism called steroid induced gene expression. The hormone by lipid diffusion crosses the cell membrane, enters into the cytosol and binds with a cytosolic receptor. This receptor-hormone complex now binds with a pre-determined specific area of a specific DNA which stimulates transcription. As a result there is formation of mRNA and new protein (both structural and enzymatic).


Nature of effect corticosteroids—

1. Physiological effect—it is seen due to endogenous corticosteroids in physiological state and can be reproduced by the synthetic analogue.

2. Pharmacological effect—these are the effects which are seen when heavier doses of corticosteroids are used (not seen in normal physiological state).

Anti-inflammatory, immunosuppressive and osteoporetic action when heavier doses are used but not in physiological state.

3. Permissive effect—some actions of other hormone (ex—vaso-constriction action or lipolysis of nor-adrenalin) are seen, only when some Cortisol is present in the tissue. A minimum or certain amount has to be present in the body for the production of other hormones and normal body function (certain amount of corticosteroids are needed for bronchodilatation).


*** pharmacological and permissive effects are only seen in glucocorticoids but not in mineralocorticoids.

*** in increased dose there is exaggerated physiological function.





These are the principal hormones which—

§    Influences carbohydrate, fat and protein metabolism

§    Are anti-inflammatory (highest anti-inflammatory effects)

§    Oppose the body changes due to stress


Note :- however overlapping of effects between glucocorticoids and mineralocorticoids may occur. Though true mineralocorticoids like aldosterone has no anti-inflammatory effects.


Types of Glucocorticoids—

Short to medium acting—

Hydrocortisone (Cortisol)—natural


Prednisone, Prednisolone—synthetic

Intermediate acting—




Long acting—




Mechanism of Action of Glucocorticoids—this hormone after entering or reaching the cytosol binds with inactive glucocorticoids receptors (GR). This GR is a part of a very big molecule which contains 2 other molecules (ex—HSP-90, HSP-70). This big molecule also contains other protein molecules. When glucocorticoids binds with GR, GR becomes active and is detached from the rest of the complex and moves to highly specific area of DNA with which it binds and as a result transcription of mRNA occurs, new protein (structural and enzymatic) are synthesized by the cell.


Note :-the highly specific part of DNA with which receptor-hormone complex binds is called glucocorticoid responsive element (GRE).


Pharmacological effects of Glucocorticoids—

Cortisol is the major endogenous glucocorticoid in human. (Prednisolone, β-methasone are exogenous glucocorticoids)


1. Metabolic effects—

a.    Carbohydrate metabolism

                    i.   ↑ blood sugar level, ↑ hepatic glycogenesis, ↑ hepatic neo-glucogenesis.

                 ii.   ↓ peripheral utilization of sugar

b.    Fat metabolism—

                    i.   Redistribution of the fat which accumulates in the face (moon face) and shoulder region (buffalo hump). On the other hand, extremities are thin.

                 ii.   The lipolysis by adrenalin is intensified (example of permissive effect). So, more glycerol is available.

c.     Protein metabolism—there is increased protein catabolism which leads to increased amino acid availability.

*** as there is increased availability of amino acid (from protein catabolism) and glycerol (from lipolysis), more substrate are available for gluconeogenesis. Glucocorticoids also ↑ the hepatic uptake of theses substrates.

d.    Electrolyte metabolism—has effects on electrolyte metabolism.

e.     Catabolic effects on organ system—

                    i.   Bones develop osteoporosis (chronic therapy of glucocorticoids makes bones susceptible to fracture)

                 ii.   Lymphoid tissue regress

               iii.   Very heavy dose causes muscle wasting


2. Effects on stress—glucocorticoids oppose the various harmful effects of stress. At the time of stress hypothalamus is first stimulated, subsequently more ACTH is released resulting in more glucocorticoids secretion.


3. Effects on blood cells—the count of lymphocyte, monocytes and eosinophils decreases and count of RBC, neutrophil and platelet increases.


4. Anti-Inflammatory and anti-allergic effects—in pharmacological doses glucocorticoids can cause suppression of inflammation, allergy and lymphocyte mediated immunity.

Glucocorticoids by forming lipocortin inhibits Phospholipase A2, therefore synthesis of eicosanoids like TxA2, leukotriens (LT), prostaglandins (PG) etc are stopped. As a result vasodilatation, leukocyte immigration, chemotaxis, phagocytosis etc decrease causing inhibition of inflammation. (causes vasoconstriction)

Glucocorticoids also oppose capillary permeability, thus transudate or exudate formation reduces.

By their permissive action glucocorticoids intensify vasoconstriction action of catecholamines. Thus reduces the chance of developing septicemic shock.

Glucocorticoids also inhibit fibroblastic activity.


5. Immuno-suppressive or Anti-immune effects—glucocorticoids reduce antibody formation. They block the effects of migration-inhibition factor and macrophage-inhibition factor. They reduce the antigen release from the grafted tissue. The anti-inflammatory functions of glucocorticoids also contribute to the anti-immune effects.

Because of immuno-suppression host-defense becomes weak and normal antigen-antibody reaction is altered.


Note :-

Monocyte releases→ TNF, IL1, Pyrogen. (monocytes are also responsible for phagocytosis)

            IL1 causes→ ↑ Fever, ↑ Neutrophil, ↑ PAF, ↑ PG, ↓ Lymphocytes.

Lymphocytes releases→ IL2.

            IL2 causes→ ↑ CD8 + T cells.

T Lymphocytes releases→ TNFα.

            TNFα causes→ responsible for septicemic shock feature.


6. Other effects—

§    On CNS—causes behavioural changes (particularly in heavier doses). Euphoria is common. They also influence α region of EEG, thus influences sleep.

§    On growth of children—inhibits growth.

§    On foetal lung—glucocorticoids help formation of surfactant in the pulmonary alveoli.

§    On the bones—they produce osteoporosis.

§    Large doses of steroid can stimulate excessive acid and pepsin production.

§    Antagonizes effects of vit-D on Ca+ metabolism.

§    Large doses may rarely raise intracranial pressure.


*** Steroids ↓ vascular permeability so, given in oedema, nephrotic syndrome.

      It ↑ BP so, given in shock.

      ↓ transport and release of chemical mediators.


Pharmacokinetics of Glucocorticoids—

Absorption—in case of oral route natural steroids have incomplete absorption and artificial steroids have better absorption.

In blood stream they bind with CBG (cortisol binding globulin). Any disease changing the CBG in the circulation will change the total amount of steroids.

Metabolism—mainly in the liver by reduction. Metabolites then undergoes conjugation reaction with glucoronic acid and SO4 (glucoronidation and sulphation).


Indications / Uses of Glucocorticoids—

A.  Replacement therapy (Endocrine diseases)—

              i.   Acute adrenal insufficiency. (IV Hydrocortisone)

           ii.   Chronic adrenal insufficiency, ex—Addison’s disease. (Hydrocortisone, Fludrocortisone / DOCA)

         iii.   Congenital adrenal hyperplasia—deficiency of 21-β-hydroxylase.

         iv.   Stimulates foetal lung maturation.

            v.   For diagnosis purpose of certain adrenocortical diseases.


B.  Pharmacotherapy for Non-Endocrine diseases—

              i.   Bronchial Asthma.

           ii.   Sarcoidosis.

         iii.   ITP—Idiopathic Thrombocytopenic Neuritis

         iv.   Arthritides—Rheumatoid Arthritis, Osteoarthritis, Rheumatic Fever, Gout.

            v.   Collagen diseases—SLE (systemic lupus erythromatosus), Polyarteritis Nodosa,

  Dermatositis, Nephrotic Syndrome.


         vi.   Severe Allergic Reactions—Anaphylaxis (drug of choice is Adrenalin) Angioneurotic Oedema,

 Urticaria, Serum Sickness.

       vii.   Autoimmune Diseases—Autoimmune Haemolytic Anaemia, Thrombocytopenia, Active Chronic Hepatitis.

    viii.   Eye Diseases, Optic Neuritis.

          ix.   Skin Diseases

            x.   Intestinal Diseases—Ulcerative Colitis, Crohn’s Disease.

          xi.   Cerebral Oedema—Tumor (space occupying lesion), Stroke, Trauma, Tubercular Meningitis.

       xii.   Angioneurotic oedema.

     xiii.   Malignancy—ALL, Hodgkin’s Disease and other Lymphomas.

     xiv.   Organ Transplantation (prevention of rejection), Skin Auto-Grafting—to suppress immunity.

        xv.   Shock


Routes of administration of Glucocorticoids—

§    Oral

§    IV (Hydrocortisone in acute bronchial asthma)

§    IM (for gynecological problem)

§    Inhalation (Betamethasone in bronchial asthma)

§    Intra-articular (Arthritis)


*** steroids are usually used locally but if not working then used oral or IV (in bronchial asthma inhalation at first but if not working then it is given orally or IV)


Adverse effects of Glucocorticoids—

1.      Cushing Syndrome (after prolong use)

2.      Fragile Skin

3.      Hyperglycemia

4.      Muscle Weakness

5.      Delayed Healing of wound

6.      Peptic Ulcer

7.      Osteoporosis (prolong use, may cause fracture)

8.      Glaucoma, Posterior Subscapular Cataract

9.      Growth Retardation

10.  Psychosis

11.  Cardiovascular Embarrassment

12.  HPA (hypothalamo-pituitary-adrenal) Axis


*** corticosteroids should always be withdrawn slowly at a tapering dose because HPA-axis take time to adjust.


Contraindications of Glucocorticoids—

1.      PUD (Peptic Ulcer Disease)

2.      DM (Diabetes Mellitus)

3.      HTN (Hypertension)

4.      Pregnancy

5.      TB (Tuberculosis)

6.      Osteoporosis

7.      Psychosis

8.      Epinephrine

9.      CCF (Congestive Cardiac Failure)/CHF (Congestive Heart Failure)

10.  Glaucoma


*** steroids ↑ blood sugar and thus not given in DM

*** steroid is catabolic hormone which breaks down protein, carbohydrate and fat. Insulin is anabolic hormone


Inhaled steroids for bronchial asthma—Betamethasone and Dexamethasone.


*** These two are called mega-steroids because—

1.        Very large molecular structure

2.        Very potent

3.        Long duration of action

4.        Very high anti-inflammatory effect (35 times than hydrocortisone)

5.        No salt retaining activity


Advantage of inhaled steroids over systemic steroids—

§    Can be given in low doses but they reach the target tissue in high concentration.

§    Have fewer systemic side effects.


*** corticosteroids are given as life saving drugs in anaphylactic shock. Another life saving drug is adrenalin.

*** life saving drugs are given when vital signs are hampered—↓ BP, ↓ Respiratory rate (bronchospasm)

*** in penicillin induced anaphylactic shock Histamine ↓ BP, adrenalin physiologically antagonizes action of Histamine.


Individual Glucocorticoids—


§    Principal natural Glucocorticoid

§    Can be given orally or IV

§    IV preparation acts in 1-2 hours

§    Suspension form can be given intra-articularly (in arthritis)


§    A synthetic Glucocorticoid with predominant anti-inflammatory action

§    Has very little Na+ retaining action (so, can be used safely in heart failure)

§    Used for many non-adrenal diseases


§    Synthetic Glucocorticoid

§    It is a pro-drug (another pro-drug is Levodopa)

§    It is converted to prednisolone in liver




They are principally concerned with electrolyte (Na+, K+) balance.


Types of Mineralocorticoids—






Mechanism of Action of Mineralocorticoids—the mechanism of action is almost same. The only difference is that mineralocorticoids can bind with the glucocorticoid responsive element of some specific tissue only, like renal tubules, certain brain areas, colon etc.


Why mineralocorticoids is effective in the collecting tubule of kidney, where glucocorticoids do not work?—

There is an enzyme 11-β-hydroxysteroid dehydrogenase which can degrade the glucocorticoids but not mineralocorticoids. This enzyme is present only in aldosterone responsive tissue (ex—renal tubule) where therefore glucocorticoids disappear. As a result of gene expression by aldosterone Na+-K+-ATPase enzyme is produced, thus results in Na+ reabsorption and K+ ejection.


Indications of Mineralocorticoids—

In mineralocorticoids deficiency, like Addison’s disease.


*** Addison’s disease is a disease of all three layers of the adrenal cortex so, Glucocorticoids and Mineralocorticoids both are given for the treatment.



§    Main natural Mineralocorticoid

§    After oral dosing it is rapidly inactivated by hepatic first pass metabolism. (so, not used orally)

§    May be given IM for treatment of acute adrenal insufficiency



§    A synthetic Mineralocorticoid

§    It has great Na+ retaining action

§    Can be given orally

§    Used in the treatment for Addison’s disease (chronic condition)


Antagonists of adreno-cortical agents—

Adreno-cortical antagonists are those drugs that inhibit the synthesis of corticosteroid hormones or block their action.


Glucocorticoids antagonists—

§    Metyrapone (used for diagnosis of adrenal function)

§    Aminoglutethimide (inhibits the steroid synthesis by blocking the first step, cholesterol→ prednisolone)

§    Ketoconazole (an anti-fungal drug, responsible for reducing adrenal cortical hormones, ↑ ACTH production)

§    Mitotane


Mineralocorticoids antagonists—

§    Spironolactone

§    Drospirenone