ADRENCORTCCAL HORMONES

Adenocortical hormones control the metabolism of carbohydrate (CHO), protein, fat and water electrolytes.

Adencortical hormones are classified into:

1. Glucocorticoid       – Cortisone
   • Hydrocortisone (Cortisol)
2. Mineralocorticoid – Aldosterone
   • Desoxycorticosterone
3. Sex Hormone        – Estrogen
   • Androgen

Glucocorticoids

The important glucorticoid secreted in man is hydrocortisone. It posseses some mineralocorticoid activity as well. Cortisone is less potent and is converted to hydrocortisone by liver.

They are classified as

1. Short acting e.g cortisone, hydrocortisone
2. Intermediate acting e.g predinsolone, triamcinolone
3. Long acting e.g dexamethasone, betamethasone)

Dexamethasone and betamethasone have got a high glucorticoid activity while cortisone and hydrocortisone have high mineralocorticoid action. Therapeutic activity in inflammatory disorder is proportional to the glucocorticoid activity.

Actions on CHO metabolism:

• antinsulinic effect
• decreases Peripheral utilization of glucose,
• increases gluconeogenesis
• promote glycogen storage

Protein metabolism:

• Inhibit protein synthesis,
• Increases catabolism

Fat metabolism:

• Interferes with fat storage causing deposits with characteristic distribution (neck, supraclavicular area, and face

Electrolyte and H₂O metabolism

• Sodium and water retention
• Hypokalmia

Suppression of pitutary adenocortical system CNS: Euphoria and stimulation

CVS: Restore vascular reactivity

GIT: Increase gastric acid secretion

Blood: Increase number of RBC, Hypercoagulability

Uric acid: Increased excretion

Calcium metabolism: increased Ca⁺⁺excretion, interfere with Ca⁺⁺ absorption

Antinflammatory: Inhibit exudation, capillary dilatation, migration of phagocyte, fibroblast, inhibit fibrous tissue formation

Antiallergic: through inhibition of antibody production suppress tissue inflammatory response.

Absorption and fate: It has fair absorption, bound to a -globuin (transcortin).And in the liver, cortisone is converted into hydrocortisone.

Therapeutic use

1. Replacement therapy: In Addisons disease and Addisonian crisis
2. Antinflammatory: in conditions like Collagen disease (rheumatoid carditis, arthritis),
3. Hypersensitivity reactions: (Bronchial Asthma, status asthmatic), Blood disease due to circulating antibodies (autoimmune disease), Skin disease (eczema), Eye disease (allergic inflammation of the eye), Nephrotic syndrome, Acute gout.
4. Immunosuppression: In tissue / organ transplantation.

Precautions

• Check weight for fluid retention
• Test urine for sugar
• Follow blood pressure through measurement and check bones by X-rayfor osteoporosis
• Doses should be tapered slowly (Don’t stop abruptly)
• Increase dose in surgery, infection
• Encourage diet rich in K⁺, protein and adequate calcium, low Nacl
• Rule- out infection before initiation of treatment

Side effects:

• Due to prolonged use: Weight gain and edema hypokalmia, hyperglycemia, osteoporosis, psychiatric disturbance, susceptibility to infection (like TB), peptic ulceration, cushing syndrome, retarded growth
• Complication with rapid withdrawal results in adrenacortical insufficiency due to depression of adrenocortical activity

Contraindication:

They are contraindicated in patients with peptic ulcer disease, acute infection like active tuberculosis, diabetes mellitus, psychosis, pregnancy

Mineralocorticoid

Aldosterone

It is the main mineralocorticoid of adrenal cortex. It increases absorption of Na at distal tubule and increases K⁺ excretion. They are not widely used in therapeutics rather its antagonists are of value in cases of edema.

Thyroid and Antithyroid Drugs

They inhibit the function of the thyroid gland and used in hyperthyroidism.

Antithyroid drugs include:

1. Thiourea compounds, e.g. , propylthiouracil, methimazole, carbimazole
2. Ionic inhibitors, e.g. , potassium percholate, potassium thiocyanate
3. Iodide, e.g. , Lugol’s iodine, potassium iodide
4. Radioactive iodine (¹³¹I)

Thiourea Compounds

Inhibit the formation of throid hormone through inhibiting the oxidation of iodide to iodine by peroxidase enzyme and blocking the coupling of iodothryosines to form iodothyronines.

They are contraindicated in pregnant and lactating women.

Toxicities include drug fever, skin rashes, increased size and vascularity of the thyroid gland, and agranulocytosis.

Ionic Inhibitors

Potassium percholate prevents the synthesis of thyroid hormones through inhibition of uptake and concentration of iodide by the gland. It has the risk of aplastic anemia, therefore no longer used in the treatment of hyperthyroidism.

Iodides:

Improve manifestations of hyperthyroidism by decreasing the size and vascularity of the gland so they are required for preoperative preparation of the patient for partial thyroidectomy.

Iodides act through inhibition of the “protease” enzyme which releases T₃ and T₄ from thyroglobulin, and organification.

Radioactive Iodine:

It is used in hyperthyroidism as sodium ¹³¹I orally. It is trapped and concentrated as ordinary iodine, which emits beta rays that act on parenchymal cells of the gland.

It is contraindicated in pregnancy and lactation as it affects thyroid gland in the fetus and the infant. Its important toxicity is hypothyroidism.

Propranolol

This is an important drug which controls the peripheral manifestations of hyperthyroidism (tachycardia, tremor). In addition, it decreases the peripheral conversion of T₄ to T₃.

Thryoid Storm (Crisis)

This is a sudden acute exacerbation of all the symptoms of thyrotoxic which rarely occur after thyroidectomy. Manifestations include hyperpyrexia, gastrointestinal symptoms, dehydration, tachycardia, arrhythmia, restlessness, etc. which may progress to shock and death.

Management: It consists of infusion of intravenous fluids, supportive management, and also administration of propylthiouracil, sodium iodide, hydrocortisone, and propranolol.