Pharmacology of Steroids, glucocorticoids and Mineralocorticoids Flashcards
What is the major glucocorticoid is
cortisol
What is the most important
mineralocorticoid
aldosterone
Different between the glucocorticoid and mineralocorticoid receptor distribution in the body?
- Glucocorticoid receptors are widely distributed throughout the body - mineralocorticoid receptors are confined mainly to excretory organs , such as the kidney, colon, salivary glands and sweat glands.
Explain the effect of glucocorticoid?
1 . Promote normal intermediary metabolism 2. Increase resistance to stress 3. Alter blood cell levels in plasma 4 . Have anti inflammatory action 5 . Affect other systems
Have anti inflammatory action:
Action of therapeutic effects of glucocorticoids are the result of? How?
- The lowering of circulating lymphocytes
- Inhibit the ability of leukocytes and macrophages to respond to mitogens and antigens.
- Glucocorticoids also decrease the production and release of proinflammatory
cytokines . - Inhibit phospholipase A 2 , which blocks the release of arachidonic acid (the precursor
of the prostaglandins and leukotrienes) from membrane bound phospholipid. - Stabilize mast cell and basophil membranes , resulting in decreased histamine
-The decreased production of prostaglandins and leukotrienes is believed to be central to
the anti inflammatory action.
What are Therapeutic uses of the corticosteroids? Explain.
- Replacement therapy for primary adrenocortical insufficiency (Addison disease)
- Replacement therapy for secondary or tertiary adrenocortical insufficiency
3 . Diagnosis of Cushing syndrome - Relief of inflammatory
6 . Treatment of allergy
7 . Acceleration of lung maturation
How CS used in Treatment of allergic?
Corticosteroids are beneficial in the treatment of allergic rhinitis , as well as drug, serum, and transfusion allergic reactions
KEEP in MIND for PHARMACOTHERAPY:
1.[Note: In the treatment of allergic rhinitis and asthma, fluticasone and others) are applied topically to the respiratory tract through inhalation from a metered dose dispenser.
2. This minimizes systemic effects and allows the patient to reduce or eliminate the use
of oral corticosteroids.]
How CS used in Relief of inflammatory symptoms?
- Corticosteroids significantly reduce the manifestations of inflammation
associated with rheumatoid arthritis and inflammatory skin conditions ,
including redness , swelling , heat , and tenderness that may be present at the
site of inflammation. - These agents are also important for maintenance of symptom control in persistent asthma , as well as management of asthma exacerbations and
active inflammatory bowel disease - In noninflammatory disorders such as osteoarthritis , intra articular corticosteroids may be used for treatment of a disease flare.
- Corticosteroids are not curative in these disorders
How CS used in Replacement therapy for primary adrenocortical insufficiency (Addison
disease)?
- Addison disease is caused by adrenal cortex dysfunction (as diagnosed by the
lack of response to ACTH administration). - Hydrocortisone, which is identical to natural cortisol, is given to correct the
deficiency. - Failure to do so results in death .
- The dosage of hydrocortisone is divided so that two thirds of the daily dose is
given in the morning and one third is given in the afternoon. [Note: The goal of
this regimen is to mimic the normal diurnal variation in cortisol levels
Absorption and fate of CS?
- Orally administered corticosteroid preparations are readily absorbed .
- Selected compounds can also be administered intravenously , intramuscularly , intra
articularly topically , or via inhalation or intranasal delivery. - All topical and inhaled glucocorticoids are absorbed to some extent and, therefore, have
the potential to cause hypothalamic pituitary adrenal (HPA) axis suppression
Excretion of CS?
Metabolism and Excretion of CS?
- Corticosteroids are metabolized by the liver microsomal oxidizing enzymes.
- The metabolites are conjugated to glucuronic acid or sulfate , and the
products are excreted by the kidney . - [Note: The half life of corticosteroids may increase substantially in hepatic
dysfunction.]
Adverse effects of CS?
Refer picture in lecture note.
- Adverse effects are often dose related.
- For example, in patients with rheumatoid arthritis, the daily dose of prednisone was the strongest
predictor of occurrence of adverse effects.
- Osteoporosis is the most common adverse effect due to the ability of glucocorticoids to
suppress intestinal Ca 2 + absorption, inhibit bone formation, and decrease sex hormone synthesis.
- Patients are advised to take calcium and vitamin D supplements .
- Bisphosphonates may also be useful in the treatment of glucocorticoid induced osteoporosis.
-The classic Cushing like syndrome (redistribution of body fat, puffy face, hirsutism, and increased
appetite) is observed in excess corticosteroid replacement.
- Cataracts may also occur with long term corticosteroid therapy.
- Hyperglycemia may develop and lead to diabetes mellitus. Diabetic patients should monitor blood
glucose and adjust medications accordingly if taking corticosteroids.
Dosage of CS?
Many factors should be considered in determining the dosage of corticosteroids,
including:
1. glucocorticoid versus mineralocorticoid activity,
2. duration of action,
3. type of preparation,
4. and time of day when the drug is administered.
*When large doses of the hormone are required for more than 2 weeks, suppression of the HPA axis occurs. Alternate day administration of the corticosteroid may prevent this adverse effect by allowing the HPA axis to recover/function on days the hormone is not taken.
Why CS must be tapered down before discontinuation?
- Sudden discontinuation of these drugs can be a serious problem if the patient has suppression of the HPA axis.
- In this case, abrupt removal of corticosteroids causes acute adrenal insufficiency that can be fatal.
- This risk, coupled with the possibility that withdrawal might cause an exacerbation of the disease , means that the dose must be tapered
slowly according to individual tolerance. The patient must be monitored carefully.
