Glucocorticoids (starred Info) Flashcards
List the 3 types of formulations glucocorticoids can come in
- aqueous
- alcoholic
- suspensions
Aqueous glucocorticoids
- double esters (na phosphate or na succinate)
- IM/IV for large doses
- emergencies
Alcoholic solution glucocorticoids
- glucorcorti. base w/o a salt
Suspension glucocorticoids
- 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
Cortisol (hydrocortisone)
- 1 hr gluco
- ++ mineralo
Cortisone (prodrug)
- .8 hours gluco
- ++ Mineralo
Prednisone (prodrug)
- 4 hrs gluco
- mineralo
Prednisolone
- 4 hrs gluco
- mineralo
Methyprednisolone
- 5 hrs gluco
- mineralo
Short acting glucocorticoids (5)
- cortisol
- cortisone
- prednisone
- prednisolone
- methyprednisolone
Intermediate acting glucocorticoids (2)
- triamcinolone
- triamcinolone actonide
Triamcinolone
- 5 hrs gluco
- 0 mineralo
Triamcinolone acetonide
- 35 hrs gluco
Long acting glucocorticoids (3)
- flumethasone
- dexamethasone
- betamethasone
Flumethasone
- 15 hrs gluco
- 0 mineralo
Dexamethasone
- 30 hrs gluco
- 0 mineralo
Betamethasone
- 30 hrs gluco
- 0 mineralo
Aldosterone+fludrocortisone=
Mineralocorticoid effects
Dexamethasone/ betamethasone/ flumethasone
Glucocorticoid effects
Mineralocorticoids
- maintaining electrolyte homeostasis
- triggers wound healing
Glucocorticoids
- carb, protein, & lipid metabolism
- role in immune response
- natural glucocorticoids have some mineralocorticoid activity
Major endogenous glucocorticoid
Cortisol
Major mineralocorticoid
Aldosterone
Pharmacology of glucocorticoids
- binding strength=potency & duration
- PK of circulating glucocorticoids have little effect on potency or duration
- activity depends on proteins produced
Glucose metabolism
- incr. gluconeogenesis and glyconeogenesis
- decre. glucose uptake in periph. Tissues
- insulin resistance
Protein & lipid metabolism
- decreased protein synth
- increased protein catabolism
- incre. Lipolysis
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
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
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
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
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
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
Anti-inflamm. & anti-allergic therapy indications
- pruritic dermatoses
- allergic pulmonary disease
- allergic gastroenteritis
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
What drug is ONLY USED IN CATS to TX inflammation and allergic rxns
Prednisolone!!!!!!
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
Autoimmune diseases glucocorticoids are used for
- IMHA
- immune mediated thrombocytopenia
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
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
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
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
Drugs used to treat acute dermatitis
- hydrocortisone
- prednisolone
Drugs used to Tx chronic dermatitis
Dexamethasone, betamethasone, triamicinolone
Intraarticular admin.
- primarily in horses for jt pain and inflamm. From arthritis and bursitis
- triamcinolone acetonide
Ophthalmic applic.
- Tx for retinitis, choroiditis, optic neuritis, orbital cellulitis
- forms: solutions, ointments, susp.
- contraindicated in corneal ulcers
Neurological applic.
- Tx for numerous problems
(Acute spinal/CNS trauma, acute cervical pain, peripheral neuropathies
What disease is a common adverse effect
Cushing’s syndrome
Clinical signs of cushing’s
- PU/PD
- symmetric, bilat. Alopecia
- periph. Myopathy
- fat redist.
- muscle atrophy
- increased infection susc.
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
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
HPAA
Hypothalamic-pituitary-adrenal axis
Mineralocorticoids affect which layer
Zona glomerulosa
Glucocorticoids affect which zones
zona fasiculata & zona reticulariss
Epi & norepi. Affect which zone
Medulla
