*Steroids Flashcards
1
Q
Steroid use/misuse
A
2
Q
STEROID HORMONES
A
- Cholesterol backbone
- 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
3
Q
Adrenal hormones
A
4
Q
What are glucocorticoids responsible for
A
Homeostasis regulation
5
Q
What are mineralocorticoids reponsible for
A
- Fluid and electrolyte balance
- Wound healing
6
Q
What are androgens responsible for
A
Male sexual characteristics
7
Q
What are progestinsa nd estrogens responsible for
A
Progestins
- progesterone-like Pregnancy hormone
Estrogens
- Female sexual charateristics
- Pregnancy hormone
8
Q
GLUCOCORTICOID MECHANISM OF ACTION
A
- 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
9
Q
GLUCOCORTICOID-MEDIATED HOMEOSTASIS
A
- 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 (importance of taperig)
10
Q
HYPOTHALAMUS-PITUITARY-ADRENAL AXIS
(Regulation of Corticosteroid Secretion)
A
- 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
11
Q
Glucocorticoid physiology
A
12
Q
ENDOGENOUS ANTIINFLAMMATORY MEDIATION
A
- 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
13
Q
GLUCOCORTICOID EFFECTS
A
14
Q
MMP Role in Biological Processes
A
15
Q
STEROID TAPERING
A
- 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,consider ester-based steroids due to their safety profile
- Some chronic condtions require lifelong low-dose steroid use - corneal transplant, stromal immune corneal disease, chronic uveitis, recalcitrant dry eye disease
16
Q
STEROID ADMINISTRATION
A
- Topical
- Most common route of administration in eye care
- Oral
- Renal function is a key concern
- Inhalation
- Local injection
- Intravenous
17
Q
Prednisone indications
A
- Corticosteroid-responsive conditions
- Adrenal insufficiency
- MS; acute exacerbation
- Asthma; acute
- Asthma; severe persistent
- Gout; acute
- COPD exacerbation
- Alcoholic hepatitis; acute
18
Q
STEROIDS: GENERAL ADVERSE EFFECTS
A
Dose & Duration Dependent
- Increased hunger
- Depression
- Muscle fatigue
- Cataracts
- Elevated IOP
- Hair pattern changes
- Easy bruising
- Acne
- Osteoporosis
- Swelling
- Hirsutism
- glaucoma
- cataracts
- hypokalemia
- Xanthomas
- Diabetic complications
- Peptic ulceration
- Hypertension
- Mood changes
- Delayed wound healing
- Adrenal insufficiency
- Growth inhibition in kids
- Immunosuppression
- Cushing’s syndrome
- Hypokalemia
20
Q
Relative glucocorticoid potency vs mineralocorticoid influence
A
34
Q
Opthalmic steroids
A
NB most potent on list is Durezol (difluprednate)
37
Q
DEXTENZA 0.4mg Dexamethasone (pellet)
A
- Post-op pain and inflammation
- Allergic conjunctivitis
- Removable if necessary via saline irrigation or manual expression
- Designes to deliver tapered dose
- Contains fluorescine for visualization
- Preservative free
38
Q
Topical steroid indications
A
