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Glucocorticoids (starred Info) Flashcards

1
Q

List the 3 types of formulations glucocorticoids can come in

A
  • aqueous
  • alcoholic
  • suspensions
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2
Q

Aqueous glucocorticoids

A
  • double esters (na phosphate or na succinate)
  • IM/IV for large doses
  • emergencies
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3
Q

Alcoholic solution glucocorticoids

A
  • glucorcorti. base w/o a salt
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4
Q

Suspension glucocorticoids

A
  • insoluble esters
  • opaque consistency
  • salts (acetate, diacetate, tebutate, valerate)
  • SQ or IM; no IV
  • slow onset; last for about 2-4wks
  • acetonide and pivalate: very insoluble, slow onset, last for >4 wks
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5
Q

Cortisol (hydrocortisone)

A
  • 1 hr gluco
  • ++ mineralo
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6
Q

Cortisone (prodrug)

A
  • .8 hours gluco
  • ++ Mineralo
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7
Q

Prednisone (prodrug)

A
  • 4 hrs gluco
    • mineralo
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8
Q

Prednisolone

A
  • 4 hrs gluco
    • mineralo
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9
Q

Methyprednisolone

A
  • 5 hrs gluco
    • mineralo
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10
Q

Short acting glucocorticoids (5)

A
  • cortisol
  • cortisone
  • prednisone
  • prednisolone
  • methyprednisolone
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11
Q

Intermediate acting glucocorticoids (2)

A
  • triamcinolone
  • triamcinolone actonide
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12
Q

Triamcinolone

A
  • 5 hrs gluco
  • 0 mineralo
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13
Q

Triamcinolone acetonide

A
  • 35 hrs gluco
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14
Q

Long acting glucocorticoids (3)

A
  • flumethasone
  • dexamethasone
  • betamethasone
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15
Q

Flumethasone

A
  • 15 hrs gluco
  • 0 mineralo
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16
Q

Dexamethasone

A
  • 30 hrs gluco
  • 0 mineralo
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17
Q

Betamethasone

A
  • 30 hrs gluco
  • 0 mineralo
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18
Q

Aldosterone+fludrocortisone=

A

Mineralocorticoid effects

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19
Q

Dexamethasone/ betamethasone/ flumethasone

A

Glucocorticoid effects

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20
Q

Mineralocorticoids

A
  • maintaining electrolyte homeostasis
  • triggers wound healing
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21
Q

Glucocorticoids

A
  • carb, protein, & lipid metabolism
  • role in immune response
  • natural glucocorticoids have some mineralocorticoid activity
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22
Q

Major endogenous glucocorticoid

23
Q

Major mineralocorticoid

A

Aldosterone

24
Q

Pharmacology of glucocorticoids

A
  • binding strength=potency & duration
  • PK of circulating glucocorticoids have little effect on potency or duration
  • activity depends on proteins produced
25
Glucose metabolism
- incr. gluconeogenesis and glyconeogenesis - decre. glucose uptake in periph. Tissues - insulin resistance
26
Protein & lipid metabolism
- decreased protein synth - increased protein catabolism - incre. Lipolysis
27
Anti-inflamm. Effects
- lipocortin prod. - inhibit PL A2 activity ( blocks synthesis of inflamm. Mediators) - affects COX & LOX paths - decrease vasc. Permeability - microcirculation & membrane integrity - stabilize lysosomal enzymes, decr. Histamine form., antagonize toxins and kinins
28
Immunosuppression
- suppress cell-mediated immunity via induce apoptosis in normal lymphoid organs - inhibit clonal expansion of T and B lymph. - decr. IgG & Complement levels - reduce leukocyte accumulation @ inflamm. Site - reduce # circulating eosin, basop, & monoc - inhibit interferon synth - immunosuppressive @ medium to high doses
29
Other important effects
- prednisolone & methylprednisolone: enhance K+ excretion and Na+ retention - incr. renal excretion - decr. Intestinal Ca2+ absorp. - bone healing affected - endocrine suppression of ACTH, GH, TSH
30
Clinical uses of glucocorticoids
- physiological replacement therapy - intensive short term & shock therapy - anti-inflamm. & anti-allergic - immunosupp. For autoimmune diseases - chronic palliative therapy - alternate day therapy
31
Physiological replacement therapy
- adrenalectomized & addisonian K9s and Cats - 0.2-1 mg/kg/day of hydrocortisone - 0.1-0.2 mg/kg/day of prednisolone - moderate stress: 2-5x per day - severe stress: 5-20x per day, until stressful experience gone
32
Intensive short term & shock therapy
- improve survival in hemorrhagic & septic shock - Tx should be started in 4hrs - high dose recomm. - H2O soluble glucocorts - include aggressive H2O therapy & broad-spectrum abx in septic shock
33
Anti-inflamm. & anti-allergic therapy indications
- pruritic dermatoses - allergic pulmonary disease - allergic gastroenteritis
34
Anti-inflamm. & anti-allergic drugs
- most common in SMALL ANIMALS: prednisolone or prednisone - most common in LARGE ANIMALS: dexamethasone (high potency & low cost) - induction: 0.55 mg/kg q12h PO - maintenance: 0.55-2.2 mg/kg q48h PO
35
What drug is ONLY USED IN CATS to TX inflammation and allergic rxns
Prednisolone!!!!!!
36
Induction and Maintenance for immunosuppressive therapy for autoimmune diseases
- Induction: prednisolone 2.2-6.6 mg/kg q12h; dexamethasone 0.33-1.1 mg/kg q12h - maintenance: prednisolone 1.0-2.2 mg/kg, alternate day
37
Autoimmune diseases glucocorticoids are used for
- IMHA - immune mediated thrombocytopenia
38
Important facts to know for using glucocorticoids to treat autoimmune diseases
- use highest recomm. Dose until clinical signs reduce - don’t stop Tx until autoimmune disease is gone for 2-3 mos - create Dx plan that excludes infectious dieases before starting Tx
39
Chronic palliative therapy
- used when NSAIDs aren’t successful @ managing chronic conditions - used for chronic arthritis & K9 hip dysplasia - intermittently used or on alternate-day basis
40
Alternate day therapy
- long term therapy w/ glucocorts or large doses-> HPAA suppression & increases side effects - allows HPAA to recover on off days - change to alternate day use should be gradual to avoid withdrawal
41
Why can prednisolone be used as an alternate day drug and not dexamethasone
- prednisolone has a long DOA & dexamethasone has short DOA - prednisolone has intermediate potency & is easier to taper dose
42
Drugs used to treat acute dermatitis
- hydrocortisone - prednisolone
43
Drugs used to Tx chronic dermatitis
Dexamethasone, betamethasone, triamicinolone
44
Intraarticular admin.
- primarily in horses for jt pain and inflamm. From arthritis and bursitis - triamcinolone acetonide
45
Ophthalmic applic.
- Tx for retinitis, choroiditis, optic neuritis, orbital cellulitis - forms: solutions, ointments, susp. - contraindicated in corneal ulcers
46
Neurological applic.
- Tx for numerous problems (Acute spinal/CNS trauma, acute cervical pain, peripheral neuropathies
47
What disease is a common adverse effect
Cushing’s syndrome
48
Clinical signs of cushing’s
- PU/PD - symmetric, bilat. Alopecia - periph. Myopathy - fat redist. - muscle atrophy - increased infection susc.
49
Adverse effects part 2
- gluconeogenic & insulin antagonistic effects-> onset of diabetes mellitus - long term HPAA-adrenal gl. Atrophy-> iatrogenic secondary hypoadrenocorticism - abrupt stopping-> addisonian-like crisis - glycogen accumulation in hepatocytes (hepatomegaly & hepatopathy) - slow turnover of enterocytes & inhibit. Of protective PG
50
Adverse effects part 3
- reduce collagen synth. - laminits (due to high doses in horses) - suscept. To infect (UTIs) - can be reduced via alternate day regimen
51
HPAA
Hypothalamic-pituitary-adrenal axis
52
Mineralocorticoids affect which layer
Zona glomerulosa
53
Glucocorticoids affect which zones
zona fasiculata & zona reticulariss
54
Epi & norepi. Affect which zone
Medulla

Pharmacology (20 decks)

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