Propranolol Hyperthyroidism Dose

Explain why propranolol is used in hyperthyroidism.
Answer:

β-adrenergic blockers:

• Many of the symptoms of hyperthyroidism are sympathetic overactivity as there is increased tissue sensitivity to catecholamines in hyperthyroidism.
• β- adrenergic blockers like propranolol relieve symptoms like palpitation, tremors, nervousness, sweating, and myopathy.
• They also inhibit the peripheral conversion of T₄ to T₃ in higher doses. They only provide symptomatic relief and are used as adjuvants. They are very useful in controlling the symptoms of thyroid storm.

Read And Learn More: Pharmacology Question And Answers

Ionic inhibitors:

• Interfere with the concentration of iodine by the thyroid gland. Thiocyanate and perchlorate inhibit the organification of iodine.
• Food items like cabbage; drugs like sodium nitroprusside and cigarette smoking increase the concentration of thiocyanate in the blood and may result in hypothyroidism.

Drugs That Influence Thyroid Function:

• Amiodarone, an antiarrhythmic drug that contains iodine—can cause hypothyroidism or hyperthyroidism, chemical thyroiditis, and thyrotoxicosis.
• Phenytoin, carbamazepine, phenobarbitone, rifampicin, and protease inhibitors cause microsomal enzyme induction → ↑ ↑ metabolism of  T₃ and T₄
• Cholestyramine and cholestipol bind → ↓ ↓ absorption of thyroid hormones in the gut.
• Proton pump inhibitors, ciprofloxacin, and sucralfate → ↓ ↓ T4 absorption.
• Lithium and amiodarone inhibit the synthesis and release of thyroid hormones.
• Sulfonamides inhibit the coupling reaction.
• Drug-induced hypothyroidism or hyperthyroidism is best treated by stopping the drug.

Corticosteroids

Corticosteroids Overview:

• Corticosteroids are hormones produced in the cortex of the adrenal gland. They are glucocorticoids, mineralocorticoids, and a small amount of androgens.
• Cortisol is the major glucocorticoid, while aldosterone is the major mineralocorticoid. The secretion of the adrenal cortex is under the control of ACTH, secreted by the anterior pituitary and this is in turn regulated by
• CRF and plasma corticosterone levels . This is termed hypothalamic-pituitary-adrenal axis.

Structure and biosynthesis:

The corticosteroids have a cyclopentanoperhydrophenanthrene (steroid) ring. They are synthesized in the adrenal cortex from cholesterol under the influence of ACTH.

In a normal person, every day about 10–20 mg of hydrocortisone (maximum in the early morning) and 0.125 mg of aldosterone are secreted. They are also released in response to stress.

Glucocorticoids

Question 8. Name/list the glucocorticoids. Describe their actions and mechanism of action.
Answer:

Glucocorticoids include:

• Hydrocortisone or cortisol (natural glucocorticoid)
• Prednisolone
• Triamcinolone
• Dexamethasone
• Betamethasone
• Paramethasone

Hydrocortisone has both glucocorticoid and mineralocorticoid activity.

Glucocorticoid Actions:

• Glucocorticoids (GC) influence several systems in the body.
• They enable the body to handle stress. Apart from direct effects, glucocorticoids also have other actions in coordination with other hormones or regulators and are called permissive effects.

1. Metabolic effects: Glucocorticoids have effects on carbohydrate, protein, and fat metabolism.

• Glucocorticoids increase blood glucose levels.
• Increase protein breakdown—are catabolic hormones; they reduce muscle mass.
• Promote lipolysis and fat is mobilized from the extremities and is deposited over the face, neck, and shoulder, described as ‘moon face’, ‘fish mouth’, and ‘buffalo hump’, respectively.

2. Anti-inflammatory and immunosuppressive effects:

• Glucocorticoids have profound anti-inflammatory properties which is the basis for their beneficial effects in several conditions.
• They are also immunosuppressants. Glucocorticoids:
• Suppress the development of inflammatory responses to all types of stimuli like chemical, mechanical, and immunological stimuli.
• Inhibit both early and late manifestations of inflammation. Inhibition of late responses like capillary proliferation, collagen deposition, fibroblastic activity, and scar formation may delay wound healing.
• Inhibit migration and depress the function of the leukocytes and macrophages and inhibit the release of chemical mediators of inflammation. The ability of these cells to respond to antigens is decreased.
• Even a single dose of glucocorticoids decreases the number of WBCs—lymphocytes, monocytes, eosinophils, and basophils decline.
• Induce the synthesis of a protein—lipocortin which inhibits phospholipase A2 thereby decreasing the production of prostaglandins and leukotrienes. GC also suppresses the production of COX-2 in the inflammatory cells.
• Suppress production of cytokines (IL-6 and IL-b) which play a key role in inflammation.

Immunosuppressant effect:

Glucocorticoids suppress cell-mediated immunity, prevent manifestations of allergy and inflammation, and prevent homograft rejection. Large doses also inhibit antibody production.

3. CVS: Glucocorticoids reduce capillary permeability, thereby reducing fluid exudation and maintaining the tone of arterioles. They have a positive inotropic effect on the heart. Prolonged use can cause hypertension.

4. Skeletal muscle: Essential for normal muscular activity.

5. CNS: GC is required for the normal functioning of CNS. Deficiency results in apathy and depression, while large doses result in restlessness, anxiety, and sometimes psychosis. Large doses may increase intracranial pressure.

6. GIT: ↑ Secretion of gastric acid and pepsin in the stomach → may worsen the acid peptic disease.

7. Calcium metabolism: GC inhibit absorption and increase the renal excretion of calcium— they antagonize the effect of vitamin D on calcium absorption.
Bone resorption takes place.

8. Formed elements of blood: Their lymphocytic effect is useful in lymphomas, but they increase the number of platelets and RBCs.

9. Kidney: They are essential for maintaining normal GFR.

10. Fetal lungs: They have a vital role in the development of fetal lungs and stimulate the production of surfactants.

Mineralocorticoid Actions:

Glucocorticoids have a weak mineralocorticoid action but many synthetic glucocorticoids are free of this activity.

Mineralocorticoid Mechanism of Action:

• Glucocorticoids bring about their effects by activating the glucocorticoid receptors which are nuclear receptors but in an inactivated state, they are found in the cytoplasm.
• Corticosteroids enter the cells by simple diffusion, bind to specific receptors present in the cytoplasm, and activate them.
• The drug–receptor complex then moves into the nucleus where it binds to specific sites on DNA (called glucocorticoid response elements or GRE) and induces the synthesis of specific mRNA. Such mRNA regulates the synthesis of new proteins which bring about the hormone effects.

Mineralocorticoid Pharmacokinetics:

Glucocorticoids are well absorbed orally. Biological half-life is longer because of their mechanism of action. They are metabolized by microsomal enzymes in the liver

Relative potency of some corticosteroids: