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What is a derivative of anthranilic acid, an analogue of salicyclic acid, has a slow onset of action, thus clinical efficacy requires 2-4 days?
What is a proprionic acid NSAID approved for use in humans, horses, and small animals, it is a strong inhibitor of COX, so has powerful anti-inflammatory, analgesic and antipyretic properties.
How does ketoprofen interfere with the formation of leukotrienes?
What are side effects of ketoprofen (3)?
- GI upset
- CNS reactions
When is piroxicam used(3)?
- Osteoarthritis in dogs
- Transitional cell tumors in dogs (reduce size)
- Anti-inflammatory for musculoskeletal conditions
What is an effective analgesic and antipyretic agent, but has weak anti-inflammatory activity, does not inhibit COX, but interferes with endoperoxidase intermediates formed during the arachidonic acid metabolism?
For what animal is acetaminophen toxic?
What are the adverse effects of acetaminophen (2)?
How do you treat acetaminophen toxicity?
- Precursors of glutathione and ascorbic acid
What are the most widely used anti-inflammatory drug, their anti-inflammatory effects are reflection of their capacity to emulate the action of endogenous corticosteroids?
What are the principal endogenous glucocorticoids that are produced by most mammalian species?
Cortisol is the predominant glucocorticoid in what?
Most domestic species and man
What animals produce mainly corticosterone?
Cortisol is synthesized from where?
Cholesterol in the cells of the zona fasciculata and zona reticularis of the adrenal cortex
How is Cortisol released into the systemic circulation?
Pulsitile release and pulse amplitude varies according to a distinct ciradian pattern
Serum glucocorticoids show what kind of change over a 24 hour period
- 3-5 fold change
- Maximal in the early morning
- Low level early in the sleep phase
Glucocorticoids are released in response to what, and what is it governed by?
- Physical and/or emotional trauma
- Governed by hypothalamus-pituitary-adrenocortical axis (HPAA)
What is the first step of the HPAA and where does it go next?
Release of corticotrophin-releasing hormone from the hypothalmus which travels to the anterior pituitary
When the CRH reaches the anterior pituitary this triggers the release of what?
Adrenocorticotrophic hormone (corticotrophin, ACTH) from the corticotrophs into systemic circulation
What does ACTH do once it is released from the corticotrophs?
Acts on the adrenal cortex, initiating synthesis of cortisol
The sensitivity of the hypothalamus-pituitary-adrenocortical axis is regulated by what?
Negative feedback system, through which the release of CRH and ACTH from hypothalamus and anterior pituitary gland is suppressed by glucocorticoids in circulation
How do glucocorticoids act as transcription factors?
Induce/Repress the expression of target genes by direct interaction with specific glucocorticoid response elements in the promotor region
Glucocorticoid increases the expression of lipocotin which can do what?
- Inhibit phospholipase A2 enzyme activity and thereby production of PGs
- Platelet activating factor
Another mechanism of glucocorticoid action is mediated by interaction of GRC with other transcription factors, such as nuclear factor KappaB and activating protein-1, inconsquence translocation to the nucleus is abolished, this leads to what?
Interference in the production/release of cytokines such as IL-1 and TNF
How do glucocorticoids effect the energy metabolism (5)?
- Increases in glycogenolysis
- Protein catabolism
- Reduction of peripheral use of glucose
How do glucocorticoids effect the central nervous system (2)?
- Reduce excitation threshold
How do glucocorticoids effect the CVS (4)?
- Increase plasma volume and catecholamine tissue sensitvity
- Direct positive inotropic and chronotropic actions
- Increases number and affinity of beta-adrenergic receptors on bronchial smooth muscle
How do glucocorticoids effect the GIT (4)?
- Increase fat absorption
- Increase secretion of gastric acid, pepsin, and trypsin
- Thinning of gastric mucosa
- Decrease in Ca and iron absorption
How do glucocorticoids effect the water and electrolyte balance (2)?
- Sodium retention
- Potassium loss
- ( => PU/PD)
What are some immune and hematologic effects of glucocorticoids (5)?
- Reduction of lymphoid tissue
- Suppression of cell mediated immunity
- Increase erythropoiesis and platelet synthesis, lymphopenia and eosinopenia, neutrophilia
- Suppression of capillary growth
- Fibroblast proliferation
Corticosteroids base determines what (3)?
- Anti-inflammatory Potentcy
- Na retaining potency
- Duration of action
Endogenous glucocorticoids in the circulation are bound to ______, while exogenous glucocorticoids are bound to _______? Carrier Protein
The ester moiety of glucocorticoids is metabolized by what?
- Hydrolysis in blood, tissues, or liver
- (Necessary to activate drug)
Prednisone should be metabolized in the liver to the active compound _______
Cortisone should be metabolized in the liver to the active compound ________.
Glucocorticoids are excreted mainly in what?
What is the most rapid route of administration of glucocorticoids?
The major problem of glucocorticoid therapy is related to the ___________ not to the __________
- Length of treatment
- Administered dose
Replacement therapy involves the use of glucocorticoids in what amounts?
Similar to those of the naturally secreted glucocorticoids from the adrenal gland
Physiological replacement therapy is rarely indicated in what?
When should the dosage of physiological replacent therapy glucocorticoids be increased?
What are examples of anti-inflammatory and anti-allergic use of glucocorticoids (3)?
- Symptomatic relief of pruritic dermatoses
- Allergic pulmonary diseases
- Allergic gastroenteritis
Prednisone or prednisolone is most commonly used in?
Dexamethasone is most commonly used in?
Unlike other immunosuppressants, glucocorticoids, do not significantly inhibit what?
Ab production by B lymphocytes
Glucocorticoids are commonly used with NSAIDs for treating what?
- Hip dysplasia
- (Chronic conditions)
When should glucocorticoids be used (4)?
- Hypercitaminosis D
- Parturition induction
- Metabolic imbalances (ruminants)
When should glucocorticoids NOT be used (6)?
- Systemic fungal infections
- Viral infections
- Eye ulcers
What are Metabolic/endocrine side effects of glucocorticoids (6)?
- Iatrogenic cushings Dz
- Elevate insulin levels? (increase BG)
- Carbohydrate intolerance
- Reduced vitamin D
- Reduces T4/FT4
- Sex steroid levels
What are gastrointestinal and hepatic side effects of glucocorticoids (6)?
- Increased gastric acid secretion
What are musculoskeletal side effects of glucocorticoids (4)?
- Muscle atrophy
- Exercise intolerance
What are dermatologic side effects of glucocorticoids (4)?
- Calcinosis cutis
- Thin skin
- Bilateral hair loss
- Increased bruising
What are immunologic side effects of glucocorticoids?
Exacerbation of clinical or laten infectious disease processes
What are reproductive side effects of glucocorticoids (3)?
- High doses induce parturition during the last part of pregnancy
- Teratogenic effects during early pregnancy
What are CNS side effects of glucocorticoids(4)?
- Increased irritability
What are renal side effects of glucocorticoids (2)?
- Increased urinary Ca excretion
What drugs can be used topical and intralesional (3)?
What drugs can be used topically of subconjunctivally to treat inflammatory conditions such as retinitis, choroiditis, optic neuritis, and orbital cellulitis (3)
- Alcoholic forms of cortisone
When are glucocorticoids contraindicated?