*Steroids

Question 1

Steroid use/misuse

Answer 1

Question 2

STEROID HORMONES

Answer 2

• Sex hormones are a special class of steroids
  that control growth, sexual development and
  behavior
• Steroids passively cross cell membranes and
  bind to intracellular receptors
• Glucocorticoids, released during stress,
  suppress the immune response, increase blood
  glucose, and regulate energy metabolism

Question 3

Adrenal hormones

Answer 3

Question 4

What are glucocorticoids responsible for

Answer 4

Homeostasis regulation

Question 5

What are mineralocorticoids reponsible for

Answer 5

• Fluid and electrolyte balance
• Wound healing

Question 6

What are androgens responsible for

Answer 6

Male sexual characteristics

Question 7

What are progestinsa nd estrogens responsible for

Answer 7

Progestins

• progesterone-like Pregnancy hormone

Estrogens

• Female sexual charateristics
• Pregnancy hormone

Question 8

GLUCOCORTICOID MECHANISM OF ACTION

Answer 8

• Glucocorticoids are endogenous and synthetic anti-
  inflammatory mediators
• As lipids, they can passively diffuse across a cell membrane and bind to/active the cytosolic glucocorticoid receptor
• Once bound, the complex enters the nucleus where it promotes transcription of genes whose products suppress inflammatory pathways
• Steroids also interfere with the activity of pro-inflammatory transcription factors such as NF-kB and activator protein-1 (AP-1)
• Steroids are routinely used in overactive immune responses associated with allergy, asthma, AI disease and sepsis

Question 9

GLUCOCORTICOID-MEDIATED HOMEOSTASIS

Answer 9

• Physiologic and pharmacologic mechanisms of GC action are
  inherently linked since they are mediated by the same receptor
• Accordingly, supraphysiologic exposure to corticoids is
  potentially detrimental to several metabolic, hormonal, and
  immunologic functions

Question 10

HYPOTHALAMUS-PITUITARY-ADRENAL AXIS

(Regulation of Corticosteroid Secretion)

Answer 10

• The HPA axis serves the primary role of managing the body’s response to STRESS
• The end-products of this axis are cortisol, and to some degree, epinephrine, the body’s stress hormones
• In response to stressful stimuli, cortisol is released for several
  hours
• Inflammatory and immune diseases are associated with
  cytokine-mediated activation of the HPA-axis, leading to
  cortisol release as an autoregulatory endo product of the
  cascade, thereby linking immune and neuroendocrine pathways

Question 11

Glucocorticoid physiology

Answer 11

Question 12

ENDOGENOUS ANTIINFLAMMATORY MEDIATION

Answer 12

• Lipocortin (Annexin A-1) is a member of the annexin group of cellular and
  bloodborne proteins which acts as an endogenous protein inhibitor of the
  phospholipase A2 (PLA2) enzyme, COX-2 and leukocyte inflammatory
  pathways at multiple levels
• PLA2 is a primary activation enzyme of the arachidonic acid inflammation
  pathway
• During the inflammatory response, annexin A-1 is mobilized to the cell
  surface where it conversely assumes a dual role: inhibiting the innate
  immune response and promoting the adaptive T-cell response
• Induction of expression of the annexin-A1 gene is the main anti-inflammatory, immunosuppressive mechanism of glucocorticoids

Question 13

GLUCOCORTICOID EFFECTS

Answer 13

Question 14

MMP Role in Biological Processes

Answer 14

Question 15

STEROID TAPERING

Answer 15

• Adrenal cortical atrophy (adrenal crisis) due to HPA axis
  suppression can result within weeks of steroid therapy
  initiation
• Abrupt discontinuation of oral steroid use can result in a
  dramatic HPA axis upregulation due to the suddenly low
  circulating levels
• Symptoms of abrupt withdrawal include
  headache, lethargy, fainting, weight loss,
  hypoglycemia, N&V\
• Tapering the dose down to physiologic levels (equivalent to 5-
  7.5 mg prednisone) allows the body to gradually ramp up
  endogenous production
• Depending on the dose and duration of therapy, tapering may proceed by 2.5-10 mg every 2-7 days
• Rebound inflammation requires a return to the last dose used prior to the final reduction (examquestion)
• Relapse is avoided by continuing therapy slightly beyond
  resolution of inflammation
• Topical ophthalmic steroids should also be tapered

Question 16

STEROID ADMINISTRATION

Answer 16

• Topical
  • Most common route of administration in eye care
• Oral
  
  • Renal function is a key concern
• Inhalation
• Local injection
• Intravenous

Question 17

Prednisone indications

Answer 17

• Corticosteroid-responsive conditions
• Adrenal insufficiency
• MS; acute exacerbation
• Asthma; acute
• Asthma; severe persistent
• Gout; acute
• COPD exacerbation
• Alcoholic hepatitis; acute

Question 18

STEROIDS: GENERAL ADVERSE EFFECTS

Answer 18

Dose & Duration Dependent

• Increased hunger
• Depression
• Muscle fatigue
• Cataracts
• Elevated IOP
• Hair pattern changes
• Easy bruising
• Acne
• Osteoporosis
• Swelling
• Hirsutism
• Xanthomas
• Diabetic complications
• Peptic ulceration
• Hypertension
• Mood changes
• Delayed wound healing
• Adrenal insufficiency
• Growth inhibition in kids
• Immunosuppression
• Cushing’s syndrome
• Hypokalemia

Question 19

Topical opthalmic drug interactions and cautions of prednisone

Answer 19

Topical Ophthalmic Drug Interactions
• Naphazoline, tetrahydrozyline, phenylephrine: additive
hypertensive effects

Cautions
• Diabetes
• Active infection
• Hypertension
• Myasthenia gravis
• Optic neuritis
• Ocular HSV