Glucocorticoids Flashcards
(47 cards)
What is the natural function of glucocorticoids?
The natural function of glucocorticoids is to protect glucose-dependent cerebral functions.
How do glucocorticoids protect glucose-dependent cerebral functions?
- Stimulating the formation of glucose by the liver
- Decreasing the peripheral utilization of glucose
- Promoting its storage as glycogen
The protective functions of glucocorticoids serve to?
These effects protect the glucose dependent tissues, the brain and heart, from starvation
If glucocorticoids do not perform their functions, what happens?
- Muscle wasting
- Delayed wound healing
- Thinning of the skin
List the Physiological roles of glucocorticoids:
- Increase gluconeogenesis
- Decrease protein synthesis
- Increase lipolysis → release of glycerol and free fatty acids
- Glucocorticoids during fasting contribute to the maintenance of glucose concentrations
- ↑ the release of glucose by the liver
- ↑ gluconeogenesis and glycogen synthase
Gluconeogenic precursors
→ amino acids and glycerol
Describe the effects of glucocorticoids on the development of pulmonary surfactant in the near-term fetus (lung maturation)
→ GCs stimulate the synthesis of surfactant proteins
→ Glucocorticoid receptor (GR) knockout mice do not survive because of lung atelectasis (partial/complete collapse of the lung)
→ prematurity with delayed development of the adrenal axis in foals has been suspected as a cause of neonatal respiratory distress syndrome
GCs have an ________ effect to that of insulin: ___ glucose production from amino acids (___________)
antagonistic, ↑, gluconeogenesis
GCs enhance lipolysis. GC excess may cause redistribution of ____ → stimulation of ____
and thus stimulating __________, which results in ___________.
fat, appetite, hyperinsulinemia, lipogenesis
➢ GCs inhibit bone formation by inhibiting _________ proliferation and the synthesis of bone _____ while stimulating _________ activity.
osteoblast, matrix, osteoclast
In adult dogs, 2 mg/kg __________ for 30 days reduced bone mineral density by 14%
Costa et al. 2010
prednisone
What are the cardiorespiratory effects of glucocorticoids?
➢ GCs have direct positive ___________ and ____________ actions on the heart
➢ They may induce __________ in animals and humans
➢ Increase the number and affinity of _____-___________ receptors
➢ They also increase the expression of ______-________ receptors in the vascular smooth muscle
➢ GCs have direct positive chronotropic and inotropic actions on the heart
➢ They may induce hypertension in animals and humans
➢ Increase the number and affinity of beta-adrenergic receptors
➢ They also increase the expression of alpha-adrenergic receptors in the vascular smooth muscle
How do glucocorticoids affect water and electrolyte balance?
GC use –> PU/PD –> Inhibition of ADH release (vasopressin, antidiuretic hormone)
GCs increase the glomerular filtration
Pharmacological doses of GCs stimulate the excessive production of _____ and _____ in the stomach and may cause _____ _____.
Consider also:
→Patients under ____ or
→receiving other drugs that contribute to GI damage (______)
acid, pepsin, peptic ulcer
stress, NSAIDs
GCs facilitate ____ absorption.
GCs ________ the effect of vitamin D on calcium absorption.
fat
antagonize
Pharmacological use of GCs can have what effect on the liver? Are these effects reversible?
Hepatomegaly and elevated liver enzyme activity.
The effects of GCs are slowly reversible
(1 to 1.5 months after therapy is discontinued)
Immune and hematological effects
➢ GCs results in alterations in the concentration, distribution and function of peripheral _________.
➢ ___________ production is generally unaffected by moderate dosages of GCs. An inhibition is caused only at _____ dosages and with _______-term therapy
➢ GCs inhibit ______-induced interferon synthesis
➢ GCs can induce _________ on normal lymphoid cells
➢ GCs inhibit monocyte differentiation into _________ and ___________ _________
➢ GCs results in alterations in the concentration, distribution and function of peripheral leukocytes
➢ AB production is generally unaffected by moderate dosages of GCs. An inhibition is caused only at high dosages and with long-term therapy
➢ GCs inhibit virus-induced interferon synthesis
➢ GCs can induce apoptosis on normal lymphoid cells
➢ GCs inhibit monocyte differentiation into macrophages and macrophage phagocytosis
What are the principles of rational glucocortioid therapy?
What is the physiological replacement therapy of glucocorticoids?
It involves use of GC in amounts like those of the naturally occurring GCs (cortisol) from the adrenal cortex
* Adrenalectomized and Addisonian dogs and cats
* It is rarely indicated in large animals
Hydrocortisone or cortisone at 0.2-1 mg/Kg day
Prednisolone or prednisone at 0.1-0.2 mg/Kg day
As a rule, animals produce approximately 1 mg/Kg of cortisol (hydrocortisone) every day
The effect of GC in all forms of shock may be controversial
➢ Evidence suggests GCs may lead to increased survival in _______ and _____ _______
➢ Therapy for shock should also include _____ therapy
➢ Suspected endotoxic shock should be treated with a (2)?
➢ Proponents of GCs therapy for shock point out → _____-term ( ͂ ___ h) therapy has few negative effects, and the positive effects outweigh the risks
➢ The __________ effects of GCs make their use contraindicated during chronic sepsis!
The effect of GC in all forms of shock may be controversial
➢ Evidence suggests GCs may lead to increased survival in hemorrhagic and septic shock
➢ Therapy for shock should also include fluid therapy
➢ Suspected endotoxic shock should be treated with a broad-spectrum antimicrobial and
fluid therapy
➢ Proponents of GCs therapy for shock point out → short-term ( ͂ 48 h) therapy has few
negative effects, and the positive effects outweigh the risks
The immunosuppressive effects of GCs make their use contraindicated during chronic sepsis!
What are the concerns with using GCs as anti-inflammatory and anti-allergenic therapy? List examples.
Concerns:
→ such diseases are difficult to definitively diagnose
→ misuse of GCs is not uncommon
Examples of these uses are:
* Symptomatic treatment of pruritic dermatoses
* Allergic pulmonary disease
* Allergic gastroenteritis
➢ Prednisolone or prednisone is most used in ______ animals
→ Induction: at 0.55 mg/Kg q 12 h given orally
→ and then maintenance: 0.55 - 2.2 mg/Kg every other (EOD)
All the dosages should be adjusted according to effect
➢ Prednisolone or prednisone is most used in small animals
→ Induction: at 0.55 mg/Kg q 12 h given orally
→ and then maintenance: 0.55 - 2.2 mg/Kg every other (EOD)
All the dosages should be adjusted according to effect
What is the disadvantage of using depot products?
Drug dosage cannot be stopped or reduced
List the long-acting injectable GC products.
Some long-acting injectable products
* Prednisolone acetate → 1 – 2 days
* Dexamethasone in propylene glycol → 1 – 7 days
* Triamcinolone → 3 – 7 days
Immune dysregulation is likely caused by?
➢ Immune dysregulation: It is likely multifactorial
* Genetic factors
* Environmental triggers
Environmental triggers:
* Infectious agents
* Drugs
* Vaccines
* Neoplasia
