Lect 19

• The physiological effect of glucocorticoids (GCs) is to protect glucose-dependent cerebral functions by stimulating the formation of glucose by the liver, decreasing the peripheral utilization of glucose, and promoting its storage as glycogen.
• The pharmacological effects of glucocorticoids (GCs) include stimulating the production of lipocortin, which inhibits the activity of phospholipase 2 (PLA2) enzyme, and inhibiting bone formation.
• In most domestic animals, the major glucocorticoid (GC) is cortisol.
• In the rat, corticosterone is the most important glucocorticoid.
• Glucocorticoids (GCs) are synthesized in the adrenal gland, with the majority being produced in the cortex.
• Glucocorticoids (GCs) stimulate the production of lipocortin, which inhibits the activity of phospholipase 2 (PLA2) enzyme, and inhibit bone formation.
• Administration of glucocorticoids to dogs for longer than 2 weeks results in significant loss of adrenal functional reserve.
• Administration of greater than 0.5 mg/Kg/day of prednisolone or an equipotent dosage of a more potent drug for longer than 2 weeks should be considered chronic therapy.
• A gradually reduction of the dosage is indicated for glucocorticoid therapy.
• Some of the common systemic inflammatory diseases with an immune-mediated etiology in dogs and cats include Inflammatory bowel disease (IBD), Immune-mediated hemolytic anemia (IMHA), Immune-mediated thrombocytopenia (IMT), and Immune-mediated polyarthritis (IMPA).
• During acute illness, immunosuppressive therapy should not be discontinued until the autoimmune disease is in remission for 2-3 months (recurrence of signs).
• Immunosuppressive therapy is recommended for these diseases, and it is high recommended to use a glucocorticoid with well-documented side effects.
• If glucocorticoids provide incomplete remission, other immunosuppressant agents such as the alkylating agent cyclophosphamide may be added.
• The treatment goals for these diseases are to induce disease remission by inhibiting inflammation and modulating lymphocyte function while minimizing adverse drugs effects.
• The physiological function of glucocorticoids (GCs) is to protect glucose-dependent cerebral functions by stimulating the formation of glucose by the liver, decreasing the peripheral utilization of glucose, and promoting its storage as glycogen.
• Patients under stress and other drugs that contribute to GI damage, such as NSAIDs, can exacerbate the effects of GCs on the gastrointestinal system.
• GCs inhibit virus-induced interferon synthesis.
• GCs result in changes in the concentration, distribution and function of peripheral leukocytes.
• GCs have direct positive chronotropic and inotropic actions on the heart.
• GCs may induce hypertension in animals and humans.
• GCs increase the expression of alpha-adrenergic receptors in the vascular smooth muscle.
• GCs can induce apoptosis on normal lymphoid cells.
• GCs invariably lead to polyuria and polydipsia.
• GCs can cause hepatomegaly and elevated liver enzyme activity.
• The effects of GCs are slowly reversible, with changes returning to normal within 1 to 1.5 months after therapy is discontinued.
• AB production is generally unaffected by moderate dosages of GCs.
• An inhibition is caused only at high dosages and with long-term therapy.
• GCs facilitate fat absorption.
• Pharmacological doses of GCs stimulate the excessive production of acid and pepsin in the stomach and may cause peptic ulcer.
• GCs antagonize the effect of vitamin D on calcium absorption.
• GCs inhibit monocyte differentiation into macrophages and macrophage phagocytosis.
• GCs increase the number and affinity of beta-adrenergic receptors.
• GCs increase the glomerular filtration.
• Physiological replacement therapy involves the use of glucocorticoids in amounts like those of the naturally occurring cortisol from the adrenal gland.
• Lymphocyte dysfunction can lead to failure of lymphocyte selection and generation of antibodies or T cells toward self-antigens.
• Anti-inflammatory and antiallergic therapy involves the use of glucocorticoids for symptomatic treatment of pruritic dermatoses, allergic pulmonary disease, and allergic gastroenteritis.
• Inhibition of ADH release (vasopressin) is a mechanism of action of glucocorticoids.
• Immune dysregulation is likely multifactorial, involving genetic factors and environmental triggers such as infectious agents, drugs, vaccines, and neoplasia.
• The purpose of rational glucocorticoid therapy is to suppress clinical signs, presumptive diagnosis, define specific objectives, and to raise the hematocrit from 10% to 25% in a dog with autoimmune hemolytic anemia.
• Glucocorticoids remain the mainstay of first line treatment of inflammatory and immune-mediated diseases in dogs and cats despite their long list of clinically limiting side effects.