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endocrine drugs pharmacology
This document discusses the endocrine system and hormones. It focuses on steroid hormones like cortisol and aldosterone that are produced by the adrenal cortex. Cortisol regulates glucose metabolism and has anti-inflammatory effects. Aldosterone controls electrolyte and fluid levels. Long-term high-dose use of glucocorticoids can lead to diabetes, osteoporosis, and infections due to immune suppression. Adrenal crisis is a medical emergency caused by a lack of cortisol and requires immediate treatment with hydrocortisone injections. Abrupt withdrawal from glucocorticoid therapy should be avoided.
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endocrine drugs pharmacology
- 1. Dr. Haji Bahadar Assistantprofessor, KMU-IPMS 1
- 2. The studyof drugs acting on endocrine system of the body. Endocrine system: The endocrine system is the collection of glands that produce hormones that regulate numerous physiological functions of the body such as growth, metabolism, sexual functions etc. 2
- 3. 1. Peptide/ Protein(Range from 3 amino acids to hundreds of amino acids in size. ) 2. Steroid????? 3. Amine (Thyroid hormones and Catecholamines) 4. Eicosanoid (Fatty acid derivatives ,prostaglandins ) 3
- 4. Steroid is anorganic compound having a core structure composed of seventeen carbon atoms, bonded in four "fused" rings. 4
- 5. The water soluble{ amine (epinephrine) and peptide/protein hormones} are secreted by exocytosis, travel freely in the bloodstream, and bind to cell-surface receptors. The lipid soluble hormones { thyroid hormone, steroid hormones } diffuse across cell membranes, travel in the bloodstream bound to transport proteins, and diffuse through the membrane of target cells . 5
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- 7. - On cellsurface Peptides and proteins - In cytoplasm Steroids - In nucleus Thyroid hormones 7
- 8. The adrenal glandsare located above the kidney and are composed of two regions: the cortex and the medulla. The adrenal cortex consists of three anatomic zones: the outer zona glomerulosa, which secretes the aldosterone; the intermediate zona fasciculata, which secretes cortisol; and the inner zona reticularis, which secretes adrenal androgens. The adrenal medulla, lying in the center of the adrenal gland, is functionally related to the sympathetic nervous system and secretes the catecholamines epinephrine and norepinephrine in response to stress. 8
- 9. The adrenal cortexsynthesizes and secretes two steroidal hormones: the glucocorticoids (cortisol) and the mineralocorticoids (aldosterone). Cortisol is involved in the regulation of glucose metabolism along with anti-inflammatory and immunosuppressive properties. Aldosterone is involved in controlling electrolyte and fluid levels. 9
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- 11. SHORT ACTING Plasmat½: 0.5 – 2 hours Biological t½: 8 – 12 hours Cortisol Cortisone Fludrocortisone INTERMEDIATE ACTING Plasma t½: 2 – 5 hours Biological t½: 18 – 36 hours Prednisone Prednisolone LONG ACTING Plasma t½: 3 – 6 hours Biological t½: 36 – 54 hours Dexamethasone Betamethasone Triamcinolone 11
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- 14. All steroidal hormonesenter the cell and bind to receptors present in the cytoplasm. The hormone- receptor complex translocates into the nucleus, and alter the gene expression. 14
- 15. Metabolic effects a) Carbohydratemetabolism ➨ Increased gluconeogenesis (in liver and kidney). ➨ Increased glycogen synthesis and storage (in liver). b) Lipid metabolism ➨ Increased lipolysis, which leads to an increased plasma levels of free fatty acids c)Protein metabolism ➨ Increased protein synthesis in the liver. ➨ Decreased synthesis and increased breakdown of proteins 15
- 16. Gastrointestinal effects: ➨ Increasedproduction of gastric acid and pepsin Anti inflammatory effects: ➨ Inhibition of phospholipase A2 production (through induction of lipocortin the synthesis of lipocortin, an enzyme the acts as an inhibitor of phospholipase A2) ➨ Decreased Transcription ( the first step of gene expression, in which a particular segment of DNA is copied into RNA (especially mRNA) by the enzyme RNA polymerase) of genes coding for cyclooxygenase 2 ➨ Decreased production of interleukins (mainly IL-2). ➨ Inhibition of histamine release from basophils and mast cells. 16
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- 18. ◦ Acute andchronic adrenocortical insufficiency ◦ Addison's disease: it is a disorder that occurs when the body produces insufficient amounts of certain hormones produced by adrenal glands. In Addison's disease, the adrenal glands produce too little cortisol and often insufficient levels of aldosterone as well. ◦ Arthritis (rheumatoid arthritis ◦ Systemic Lupus erythematosus or SLE (an inflammatory autoimmune disease causing scaly red patches on the skin, especially on the face) ◦ Asthma ◦ Acute allergic reaction ◦ As immune suppressant to prevent transplant rejection ◦ Drug reactions ◦ Insect venom allergy 18
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- 20. Short term use ➨Weight gain ➨ Mood changes (hypomania or depression) ➨ Glucose intolerance ➨ Retarded wound healing Long-term effects (months, years) ➨ Diabetes: increased transcription of enzymes that convert amino acids into glucose in liver and kidney cells. ➨ Osteoporosis(a condition in which the bones become brittle and fragile due to demineralization ) ➨ Opportunistic infections 20
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- 22. Adrenal crisisis acute adrenal insufficiency. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment. Hypothalamic–pituitary–adrenal axis (HPA axis): Cortisol production is regulated by the pituitary gland. This is a small gland behind the nose and under the brain. The pituitary gland releases adrenocorticotropic hormone (ACTH). This is a hormone that causes the adrenal glands to release cortisol. 22
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- 24. The adrenalgland The pituitary gland is injured and cannot release ACTH Stopping treatment too suddenly with glucocorticoid medicines such as prednisone or hydrocortisone(abrupt withdrawal ) 24
- 25. Abdominal painor flank pain Confusion, loss of consciousness, or coma Dehydration Dizziness or light-headedness Fatigue, severe weakness Headache High fever Loss of appetite Low blood pressure Nausea, vomiting Rapid heart rate Rapid respiratory rate Slow, sluggish movement Unusual and excessive sweating on face or palms 25
- 26. In adrenalcrisis, a person needs an immediate injection of hydrocortisone through a vein (intravenous) . 26
- 27. A singledose of corticosteroids, even if very large, is virtually without harmful effects. When glucocorticoid therapy is prolonged over periods of weeks or months, with doses exceeding the equivalent of substitution therapy, the incidence of adverse effects is greatly increased. When glucocorticoid therapy is prolonged over periods of weeks or months, then HPA axis is suppressed. Abrupt withdrawal should be avoided, and the drug dose must be gradually reduced(dose tapering). 27
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