Classes of Glucocorticoid Usage Flashcards
What is the natural function of glucocorticoids? In what 3 ways does it do this?
protects glucose-dependent cerebral function by…
- stimulating the formation of glucose by the liver
- decreasing the peripheral utilization of glucose
- promoting glucose storage as glycogen
How is the natural effect of glucocorticoids observed? Why?
muscle wasting, delayed wound healing, thinning of skin
body is working to protect glucose in important tissues, like the brain and heart
What are the 3 physiological effects of glucocorticoids?
- increase gluconeogenesis from amino acids and glycerol
- decrease protein synthesis
- increase lipolysis to release glycerol from FFAs
What do glucocorticoids do during fasting?
maintains glucose concentrations by increasing the release of glucose by the liver and gluconeogenesis by glycogen synthase
What is the pharmacological effect of glucocorticoids in the near-term fetus? What happens when neonates mature before their adrenal axis?
stimulates the synthesis of surfactant proteins (GR knockouts do not survive long due to lung atelectasis)
neonatal respiratory distress syndrome
What are the 3 major effects of glucocorticoids on energy metabolism?
- antagonize effects of insulin - increase glucose production from amino acids (gluconeogenesis)
- enhance lipolysis - redistributes fat and stimulates appetite to stimulate hyperinsulinemia
- inhibits bone formation - inhibits osteoblast proliferation and the synthesis of bone matrix, stimulates osteoclasts
What cardiorespiratory effect do glucocorticoids have?
direct positive chronotropic and inotropic effects by increasing the number and affinity of β1-adrenergic receptors and α-adrenergic receptors in vascular smooth muscle (hypertension)
How do glucocorticoids affect water and electrolyte balance?
invariably leads to PU/PD by inhibiting ADH release and increases glomerular filtration
What effect do pharmacological doses of glucocorticoids have on the stomach? In what patients should these be used very carefully?
stimulates excessive production of acid and pepsin
- patients under stress
- those already on drugs that contribute to GI damage (NSAIDs)
How do glucocorticoids affect nutrient absorption? Liver function?
facilitates fat absorption and antagonizes the effect of vitamin D and calcium absorption
hepatomegaly and elevated liver enzymes (slowly reversible 1-1.5 months after discontinuation of therapy)
How do glucocorticoids affect the immune system?
- alters concentration, distribution, and function of peripheral leukocytes (apoptosis of normal lymphoid cells)
- inhibits antibody production at high doses of long-term therapy
- inhibits virus-induced IFN synthesis
- inhibits monocyte differentiation into macrophages
What is the purpose of most glucocorticoid therapy? How can clinicians judge the efficacy of treatment?
suppress clinical signs
define specific therapeutic objectives - raise hematocrit, suppress allergic reactions
How are glucocorticoids used for physiologic replacement therapy? What 2 common conditions are treated this way? What medications are used?
use glucocorticoids in amounts like those naturally made (cortisol) in the adrenal gland
- adrenalectomized animals
- Addisons disease
- rarely indicated in large animals
hydrocortisone/cortisone and prednisolone/prednisone**
In what cases may intensive short-term doses of glucocorticoids increase survival? What should this therapy also include?
hemorrhagic and septic shock
- fluid therapy
- broad spectrum antimicrobial for endotoxic shock
In what case is short-term (shock therapy) glucocorticoid usage contraindicated?
chronic sepsis - immunosuppressive effects
What is the main concern for glucocorticoid usage as anti-inflammatory and anti-allergic therapy? For what 3 conditions may they be used?
such diseases are difficult to definitively diagnose and misuse of glucocorticoids is not uncommon
- symptomatic treatment of pruritic dermatoses
- allergic pulmonary disease
- allergic gastroenteritis
What is the preferred glucocorticoid for the treatment of inflammatory and allergies in small animals?
prednisolone or prednisone
What is the main disadvantage to depot glucocorticoid usage for inflammatory and allelrgic therapy? What are 3 common long-acting injectable products work this way?
drug dosage cannot be reduced/stopped once its given, even if it’s incorrect
- prednisolone acetate
- dexamethasone in propylene glycol
- triamcinolone
What are the 2 most common causes of immune dysregulation?
- genetics
- environment - infectious agents, drugs, vaccines, neoplasia
What are 2 common causes of lymphocyte dysfunction? What are common inappropriate responses to immunosuppressive therapy?
- failure of lymphocyte selection
- antibody or self-antigen generation
tissue destruction and clinical disease
What are 4 common inflammatory diseases with an immune-mediated etiology in dogs and cats that can be treated with glucocorticoids? What is the goal to this treatment?
- inflammatory bowel disease (IBD)
- immune-mediated hemolytic anemia (IMHA)
- immune-mediated thrombocytopenia (IMT)
- immune-mediated polyarthritis (IMPA)
induce disease remission by inhibiting inflammation and modulating lymphocyte function while minimizing adverse drug effects
What is the first-line treatment of inflammatory and immune diseases? What 4 immunosuppressants are also used?
glucocorticoids
- cyclosporine
- azathioprine
- chlorambucil
- mycophenolate
How are glucocorticoids used with acute illness caused by immune-mediated disease?
highest immunosuppressive recommended dose until clinical signs decline and taper slowly
When can glucocorticoid usage be discontinued for autoimmune disease? What can be used for incomplete remission?
once disease is in remission for 2-3 months
add other immunosuppressants, like cyclophosphamide (alkylating agent)
What commonly happens with glucocorticoid therapy lasting longer than 2 weeks in dogs?
loss of adrenal functional reserve —> typically takes 2 weeks to normalize cortisol secretion
(more than 2 week treatment is considered chronic therapy)
How does the cellular effect of glucocorticoids compare are anti-inflammatory and immunosuppressive doses?
inhibit phospholipase A2 and the release of pro-inflammatory cytokines
target macrophage function by downregulating Fc receptor expression and decreasing responsiveness to antibody-sensitized cells and antigen processing
How does prednisone compare to prednisolone? How does pharmacokinetics compare in cats?
prednisone is a prodrug that becomes prednisolone
cats achieve higher plasma concentrations when administered oral prednisolone vs. prednisone (may lack enzymes)
What 3 glucocorticoids can be used for immunosuppressive therapy?
- prednisone/prednisolone
- dexamethasone - lacks mineralocorticoid activity
- budesonide - soft corticoid with low absorption and distribution, which allows it to avoid systemic adverse effects but must be administered to the site where its action takes place
At what dose is immunosuppressing effects achieved with glucocorticoids?
high doses —> 2-4 mg/kg, observe patient and change dose accordingly
When is every other day dosage recommended for glucocorticoid immunosuppressive therapy? What is the purpose of this therapy? What types of glucocorticoids cannot be used this way?
intermediate-acting drugs (12-36 hours)
reach immunosuppression while minimizing (but not preventing) adrenal atrophy
long duration activity glucocorticoids
What are 7 possible side effects of immunosuppressive therapy glucocorticoid usage?
- iatrogenic hyperadrenocorticism
- adrenal gland suppression
- GI ulceration and colon perforation
- insulin resistance
- muscle catabolism
- delayed wound healing
- opportunistic infections (esp. urinary)
When are close monitoring and clinical vigilance with glucocorticoid especially important?
- intolerable or life-threatening side effects
- lack any clinically significant response to steroids with 7-14 days of treatment
(alternative immunosuppressive drugs need consideration)
What 4 situations of minor stress may benefit with glucocorticoid supplementation? What severely stressful situation? What drug is used?
- minor surgery
- general anesthesia
- minor illness
- visit to vet
major surgery including adrenalectomy
prednisolone or prednisone (acetate)
What are the effects of the different doses of glucocorticoids?
- ANTI-INFLAMMATORY: 10x physiologic dose
- IMMUNOSUPPRESSIVE: 2x anti-inflammatory dose
- SHOCK: 5-10x immunosuppressive dose
