Term
| What are the issues relating the hypersensitivity? |
|
Definition
-atopy
-food allergy
-flea allergic dermatitis
-feline eosinophilic erythematosus |
|
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Term
| What are the issues associated with autoimmune disease? |
|
Definition
-IMHA/ IMT
-Lupoid diseases
-pemphigus |
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Term
| What is the cornerstone of immune-modifying therapy? |
|
Definition
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Term
| Describe the actions of corticosteroids. |
|
Definition
-inhibit action of phospholipase A2
-this inhibits chemotaxis, stabilizes lysosomal and leukocyte membranes, inc capillary selective permeability, inhibit fibroblast activity, suppress T-lymphocyte/macrophage activity and IG production |
|
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Term
| What is/are the short-acting (8-12h)corticosteroid(s)? |
|
Definition
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Term
| What are the intermediate-acting (12-36h) corticosteroids? |
|
Definition
-prednisone
-prednisolone
-methylprednisolone
-triamcinolone
-isoflupredone |
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Term
| What are the long-acting (36-72h) corticosteroids? |
|
Definition
-dexamethasone
-flumethasone |
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Term
| What are the two types of injectable corticosteroid preparations? |
|
Definition
-sodium phosphate & sodium succinate
-acetate |
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Term
| Describe sodium phosphate & sodium succinate corticosteroid preparations. Which acts more rapidly? Give some other samples similar to these. |
|
Definition
-they are water soluble corticosteroids suitable for IV administration
-Sodium succinate is more rapid-acting
-ex: dexamethasone sodium phosphate & prednisolone sodium succinate |
|
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Term
| Describe acetates as injectable corticosteroid preparations. How are they administered? Give some examples. |
|
Definition
-relatively insoluble in water and absorbed slowly
-admin IV
-ex: methylprednisolone acetate & prenisolone acetate |
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Term
| What are the precautions and contraindications associated with corticosteroid use? |
|
Definition
-do not combine high doses of corticosteroids with antibacterial agents in the treatment of infections, unless justified
-do not combine corticosteroids with NSAIDs
-glucocorticoids are contraindicated in the initial treatment of corneal ulcers |
|
|
Term
| What are the common toxicities associated with corticosteroid use? |
|
Definition
-fluid balance: PU/PD (du e4ot inhibition of ADH)
-Mineralcorticoid effects: sodium retention, edema, potassium loss, metabolic alkalosis
-prolonged therapy may suppress the hypothalamic-pituitary-adrenal axis with atrophy of the adrenal cortex
-muscle weakness, wasting
-depression of host defenses |
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|
Term
| Prednisone is an orally administered ______ that is metabolized to ______. In which species is it poorly absorbed compared to prednisolone? |
|
Definition
-prodrug
-prednisolone
-cats and horses |
|
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Term
| What are the important characteristics of budesonide? |
|
Definition
-non-halogenated corticosteroid, highly lipophilic good tissue penetration
-9x greater receptor binding than dexamethasone
-rapidly absorbed in GI tract
-metabolites are almost inactive
-terminal half life about 3 hours |
|
|
Term
| What is the one draw back of budesonide? |
|
Definition
| -needs a specifically designed release system |
|
|
Term
|
Definition
| -a steroid with high affinity for glucocorticoid receptor |
|
|
Term
| Is Budesonide designed to dissolve at a high or low pH? |
|
Definition
|
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Term
| True or False: Because Budesonide is rapidly degraded to inactive metabolites, it does not suppress HPA. |
|
Definition
| -FALSE, it may still suppress HPA |
|
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Term
| Dogs with which syndrome showed an adequate response to Budesonide therapy? |
|
Definition
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|
Term
| What are the three calcineurin inhibitors used to treat atopy? |
|
Definition
-Cyclosporine
-Tacrolimus
-Pimecrolimus |
|
|
Term
| Name a few examples that support the statement "T helper cells are th central orchestrator of the immune system" |
|
Definition
| -They influence: Cytotoxic T lymphocyte function, B cell function, Ab production, NK cell function Ag presenting cell function, cytokine pdn |
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Term
| What is cyclosporine used for in vet med? |
|
Definition
-it is called Atopica
-approved for use in dogs with atopic dermatitis
-also used as an opthalmic preparation for the treatment of keratoconjunctivitis sicca |
|
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Term
| Describe the oral bioavailability of cyclosporine and how it affects administration. |
|
Definition
-the high lipophilicity of cyclsoporine reduces oral bioavailability, which is partially overcome by formulations, such as microemulsions
-products are not equally bioavailabl and hsould be substituted carefully |
|
|
Term
| What is the MOA of cyclosporine? |
|
Definition
| -decreases cell-mediated immune response by decreasing IL-2 production, thus inhibiting the cell signaling system of T-helper lymphocytes |
|
|
Term
| What are the possible adverse effects of cyclosporine? |
|
Definition
| -GIT upset, renal toxicity, hepatotoxifcity (severe toxicity is unusual at therapeutic blood concentrations) |
|
|
Term
| Do we usually use therapeutic drug monitoring with cyclosporine? Why or why not? |
|
Definition
-no usually at low doses used to treat atopy b/c side effects are rare at low doses
-used at higher doses due to both the potential for adverse effects and the high cost of treatment |
|
|
Term
| What are the concerning drug interactions with cyclosporine? |
|
Definition
| -cyclosporine is metabolized by P450 enzymes that can be inhibited by the coadministration of numerous drugs (ex: cimetidine, digoxin, macrolie antibiotics, ketoconazole) |
|
|
Term
| Why would we want to use cyclosporine and ketoconazole in combination? Is this or is this not suggested? |
|
Definition
-slows cyclosprine metabolism and decreases the cost of therapy
-not particularly, attempt with caution as toxicity can occur |
|
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Term
| Why would you co-administer prednisone with cyclosporine? |
|
Definition
-prednisone makes up for the fact that cyclosporine takes a long time to come into effect
-less GI irritation when in combination |
|
|
Term
| What is Tacrolimus used for? |
|
Definition
| -localized topical treatment of atopic dermatitis and to treat perianal sinuses |
|
|
Term
| What is Pimecrolimus used for? |
|
Definition
| -possibly superior to ophthalmic cyclosporine for the treatment of keratoconjunctivitis sicca (KCS) in dogs |
|
|
Term
| What is the JAK STAT inhibitor that we are concerned with? How does it work and what is it used to treat? |
|
Definition
-Oclacitinib (Apoquel)
-inhibits Janus Kinase 1 pathway
-new anti-hypersensitivity cytokine inhibitor in dogs with atopic dermatitis |
|
|
Term
| Does Oclacitinib (Apoquel) have good or poor oral absorbtion? |
|
Definition
-good
-not affected by feeding, sex, or breed |
|
|
Term
| What advantages does Oclacitinib/Apoquel have over Cyclosporine/Atopica? |
|
Definition
| -Apoquel has lese GI side effects, breater bioavailability, you can slit pills, drastically shorter onset of action, way way cheaper, high predictability |
|
|
Term
| What advantages does Atopica have over Apoquel? |
|
Definition
| -greater supply while Apoquel has been on back order for months |
|
|
Term
| Discuss the safety of Apoquel. |
|
Definition
-minimal side effects: GI signs, decreased leukocytes and globulins
-toicity (interdigital furunculosis, lymphadenopathy, bone marrow and GALT suppression, mild interstitial pneumonia) in puppies |
|
|
Term
| What are the 4 cytotoxic agents used to treat autoimmune diseases that we are concerned with? |
|
Definition
-Azathioprine
-Mycophenolate mofetil
-Leflunomide
-chlorambucil |
|
|
Term
| What are the side effects of concern with cytotoxic agents? |
|
Definition
-anemia and thrombocytoenia
-neutropenia: most significant adverse effect = dose limiting
-severe neutropenia = hospitalization + IV antibiotics
-alopecia
-GI toxicity is common: anorexia, vomiting, diarrhea, nausea |
|
|
Term
| Describe dosing based on BSA. |
|
Definition
-it was though to standardize drub exposure based on body surface area better than weight-normalized dosing
-however, smaller animals receive proportionally more drug than large patients so it is a bad idea |
|
|
Term
| How does Azatioprine work? What is it used for? |
|
Definition
-it is a purine analog that ultimately inhibits DNA sythesis
-an antimetabolite that is used as a second or third-line immunosuppressant in dogs
-usually combined with corticosteroids or syclosporine |
|
|
Term
| What are the possible toxic side effects of azatioprine? |
|
Definition
-bone marrow suppression (common to all antineoplastic drugs): worse in cats than in dogs
-GI distrubances
-hepatotoxicity |
|
|
Term
| What is Mycophenolate used to treat? How is it administered? |
|
Definition
-IMHA
-tablet and injectable formulations |
|
|
Term
| Describe the bioavailability of mycophenolate and its adverse effects. |
|
Definition
-oral bioavailability about 55-85%
-GI signs, weight loss, papillomas, hypersensitivity possible in dogs |
|
|
Term
| What are the possible side effects of chronic immunosuppression? |
|
Definition
-increase suscepbility to infections
-increased incideence of neoplasia |
|
|
Term
| Why do we use immunostimulant drugs? |
|
Definition
| -indicated for use in immunosuppressed animals and as an adjunct therapy for neplastic diseases |
|
|
Term
| What are some examples of specific immunostimulant drugs? |
|
Definition
-Microbial immunostimulants: Proprionibacterium acnes infection (canine pyoderma and prevention of resp infections in horses)
-tumor cell vaccines
-levamisole (antiparasitic agent)
-cytokines (interferons, interleukins, etc) |
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