Phar m5-6

• Adrenocortical steroids


  • Mineralocorticoids
  • Sex hormones
  • Glucocorticoids
• Adrenocortical steroids release


  1. CRH released from hypothalamus

  2. Stimulates pituitary gland to release ACTH

  3. ACTH causes adrenal cortex to release adrenocortical steroids
• Increased glucocorticoids


  Inhibit further CRH release, decreasing ACTH
• Mineralocorticoids


  Class of corticoids that influence the salt/water balance in body
• Aldosterone


  Promotes Na+ and water reabsorption, and K+ excretion, resulting in increased blood volume and blood pressure
• Aldosterone release


  Stimulated by RAS and ACTH
• Sex hormones


  Affect sexual development and reproduction
• Adrenal cortex secretes a lot of DHEA
• Sex hormones secreted by adrenal cortex have minimal roles, majority produced by ovaries (estrogen) and testes (testosterone)
• Glucocorticoids


  Class of corticoids important for metabolism and immune function
• Cortisol


  Main glucocorticoid, synthesised from cholesterol
• Synthetic corticosteroids


  • Prednisone - suppresses immune system
• Effects of glucocorticoids


  • Metabolic effects
  • Catabolic and anti anabolic effects
  • Anti inflammatory and immunosuppressive effects
  • CNS effects
  • Mineralocorticoids-like action
• Long term adverse effects of glucocorticoids: iatrogenic Cushing syndrome, peptic ulcers
• Glucocorticoids must be stopped slowly, allowing HPA axis to regain function without the exogenous glucocorticoids (if stopped fast, can have adrenal crisis due to rapid glucocorticoid reduction - hypotension, vomiting, fever)
• Clinical indications of glucocorticoids

  • Anti-inflammatory (main)
  • Therapy for disturbed adrenal function
• Adrenal hypofunction


  Chronic adrenocortical insufficiency caused by adrenal gland disorder (primary), pituitary gland disorder (secondary)
• Addison's disease is treated with hydrocortisone and a mineralocorticoid
• Cushing syndrome


  Increase in glucocorticoid secretion due to ACTH-secreting pituitary tumour or adrenal gland tumour
• Treatment for Cushing syndrome: removal of tumour and hydrocortisone therapy (since won't be able to produce cortisol if part of adrenal cortex was removed)
• Therapy unrelated to adrenal function

  • Organ Transplantation
  • Rheumatic disorders
  • Inflammatory diseases
  • Inflammatory dermatoses
  • Inflammatory bowel disease
• Glucocorticoids in organ transplantation


  Given after transplant as immunosuppressive to inhibit rejection by reducing antigen expression from grafted tissue
• Glucocorticoids interfere with generating primary antibody forming cells
• Glucocorticoids are used with other immunosuppressive agents for long term control of rheumatic and inflammatory diseases, but not as first line treatment
• Topical glucocorticoids


  Minimally absorbed but absorption is increased in inflamed skin, may suppress pituitary adrenal axis negative inhibition, can cause Cushing syndrome, restricted growth in kids
• Ulcerative colitis


  Inflammation of GI tract in colon or rectum, treated with topical hydrocortisone to localise effects
• Crohn's disease


  Chronic condition causing inflammation of GI, treated with oral prednisone for moderate-severe, IV administration for severe
• Blood glucose regulation


  • Insulin
  • Oral hypoglycemic agents
• Insulin


  Needed to use glucose as energy source, secreted from pancreatic beta cells, binds to insulin receptors to decrease blood glucose by increasing glucose uptake into cells and stimulating glycogen formation
• Diabetes


  Elevated blood glucose levels
• Gestational diabetes


  Abnormality in blood glucose noted for first time during pregnancy, placenta and placental hormones create insulin resistance, increases risk of diabetes in mom and baby in future
• Type 1 diabetes


  Insulin dependent, pancreatic beta cell destruction leading to insulin deficiency, treated with insulin
• Type 2 diabetes


  Non-insulin dependent, pancreatic beta cell dysfunction leading to insulin resistance, treated starting with metformin
• Insulin types

  • Rapid-acting
  • Short-acting
  • Intermediate acting
  • Long-acting
• Insulin treats type 1 diabetes, diabetic ketoacidosis, and potentially type 2 diabetes when other treatments aren't adequate
• Adverse effect of insulin is hypoglycemia, treated with simple sugar
• Biguanides


  Oral hypoglycemic agents that prevent glucose production in liver, metformin decreases gluconeogenesis and increases glucose uptake
• Biguanides are first line therapy for type 2 diabetes, can be used in combination, and do not cause hypoglycemia
• Insulin secretagogues


  Oral hypoglycemic agents that stimulate pancreatic beta cells to increase insulin secretion, patients must have functional beta cells (only for type 2 diabetes)
• Sulfonylureas


  Insulin secretagogues that inhibit K+ channels on beta cells causing depolarization and increased Ca2+ entry, leading to increased insulin release