Pharm Block II - Corticosteroids Antiplatelets/Anticoagulants

Question 1

Outline hypothalamic-pituitary-adrenal feedback mechanisms for endogenous corticosteroid release

Answer 1

Hypothalmus releases corticotropin releasing factor (CRF) -> CRF acts on pituitary gland releasing corticotropin or ACTH -> these act on adrenal glands releasing aldosterone and cortisol (12-25mg/d) -> cortisol regulates the hypothalmus by negative feedback

Question 2

Why give corticosteroids in the morning

Answer 2

The levels of cortisol are influenced by sleep cycle. Release peaks in the morning and have a stimulating effect. Exogenous corticosteroid is administered in attempts to mimic natural cycle and is giving in the morning to prevent insomnia.

Question 3

2 types of corticosteroids

Answer 3

1. glucocorticoids (act similar to cortisol, promotes gluconeogenesis)2. mineralcorticoids (similar to aldosterone)

Question 4

Glucocorticoid MOA

Answer 4

Inhibits phosopholipase A2 decreases production of arachidonic acid inhibiting cyclooxgenase (reducing prostaglandins) and lipooxygenase (reducing leukotrienes)

Question 5

Mineralocorticoids MOA

Answer 5

Acts on kidney tubules and collecting ducts to reabsorb Na, bicarb, water, and decreases reabsorption of K

Question 6

physiologic dose of steroid

Answer 6

replacement or maintenance dose. The glucocorticoid dose administered to elicit the same effects as natural cortisol production in the body. mimics the diurnal pattern of normal secretion.

Question 7

Oral steroid dosing - acute

Answer 7

Moderate to high dose for rapid resolution of symptoms (7-14 days, burst therapy)

Question 8

Oral steroid dosing - acute

Answer 8

Minimum dose for shortest duration possible, morning dose preferred, sometimes POD

Question 9

Oral steroid dosing - tapering principles

Answer 9

Less than 14 days with no prior exposure: rapid taper acceptable; long term exposure: slow taper mandatory; short term exposure to high dose with chronic use of low dose: rapid taper to chronic dose okay.

Question 10

short term effects of glucocorticoids

Answer 10

hyperglycemia, elevated WBC count (due to demargination), GI bleed/ulcers, sodium retention (edema, hypertension CHF), hypokalemia, metabolic acidosis, steroid psychosis

Question 11

long term effects of glucocorticoids

Answer 11

HPA axis suppression after 2 wks, cushingoid features, muscle weakness, thinning of skin, osteoporosis, cataracts/glaucoma, decreased immune response, poor wound healing

Question 12

Anticoagulants: MOA

Answer 12

diminishes clotting factor actions; warfarin antagonizes cofactor funcitons of vitamin K resulting in production of clotting factors with diminished activity

Question 13

anticoagulants prototype drug

Answer 13

warfarin (oral), heparin (IV)

Question 14

antiplatelets MOA

Answer 14

inhibits production of thromboxane; aspirin inhibits COX-1 -> inhibiting thromboxane A2 synthesis from arachidonic acid in platelets resulting in suppression of platelet aggregation

Question 15

antiplatelets prototype drug

Answer 15

aspirin