II - Immunosuppressants Flashcards
Glucocorticoids
Prednisone
Prednisilone
Dexamethasone
Calcineurin inhibitors
Cyclosporine
Tacrolimus
Janus kinase inhibitor
Apoquel
Oclacitinib
Caninized monoclonal antibody against IL-31
Cytopoint
Antimetabolite
Azathioprene
Alkylating agents
Cyclophosphamide
Chlorambucil
2nd/3rd line/new
Mycophenolate mofetil
Antihistamine
Diphenhydramine
What are the goals of immunosuppressant therapy?
- Decrease inflammation
- Modulate/suppress lymphocyte function
- Minimize adverse drug effects
What drugs are the first line of treatment in dogs and cats for inflammatory and immune-mediated disease?
Glucocorticoids
- prednisone
- prednisilone
- dexamethasone
What bloodwork changes are seen with glucocorticoid administration?
Increase: erythrocytes, platelets, neutrophils (EPN)
Decrease: eosinophils, macrophages, T-lymphocytes (EMT)
Low doses of glucocorticoids are ____________ and high doses are ____________.
Anti-inflammatory
Immunosuppressive
Glucocorticoids have a systemic impact on ________ and ________ immunity.
Innate and adaptive
Glucocorticoids inhibit release of ______, which decreases recruitment of inflammatory cells.
Cell adhesion molecules
Glucocorticoids prevent release of:
Cytokines: IL-1, IL-2, TNFa
Histamine
Serotonin
Lysosomal enzymes
Which glucocorticoids are shorter acting?
Prednisone and prednisilone
8 side effects of glucocorticoids
GI ulceration
Iatrogenic hyperadrenocorticism
Adrenal gland suppression
Insulin resistance and secondary diabetes mellitus
Muscle catabolism
Delayed wound healing
Opportunistic infections
Behavior changes
________ is a prodrug metabolized to ________ and used in dogs.
Prednisone, prednisilone
Which shorter acting glucocorticoid has better bioavailability in cats?
Prednisilone
Which glucocorticoid lacks mineralocorticoid activity (minimizing sodium and water retention) and is better for patients with underlying cardiovascular disease or diseases associated with fluid retention (hypoalbuminemia, portal hypertension)?
Dexamethasone
What drugs are the first line of treatment for perianal fistulas and keratoconjunctivitis?
Calcineurin inhibitors
- cyclosporine
- Tacrolimus
What drug is a substrate of the cytochrome P450 enzyme CYP3A?
Cyclosporine
What are two drugs that interact with Calcineurin inhibitors to decrease efficacy?
Azole antifungals
phenobarbital (cats)
Which immunosuppressant has a narrow therapeutic window?
Calcineurin inhibitor
- cyclosporine
Which immunosuppressant drug has a patient response that is difficult to predict (due to individual gastric contents, liver function, other meds)?
Calcineurin inhibitor
- cyclosporine
With which immunosuppressant drug should generic/compounded formulas especially be avoided?
Calcineurin inhibitor
- cyclosporine
__________ are frequently used as add-on drugs for IMHA and IBD.
Calcineurin inhibitors
- cyclosporine
- Tacrolimus
5 side effects of Calcineurin inhibitors
- Self-limiting GI upset; can give maropitant or frozen
Immunosuppressive
Gingival hyperplasia
Hepatotoxicity
Thromboembolism
MOA: Binds to a cytoplasmic receptor protein; the complex then binds and inhibits Calcineurin, decreasing expression of IL-2 and other cytokines necessary for T-cell activation.
Calcineurin inhibitors
- cyclosporine
- Tacrolimus
MOA: Inhibits activity of pro-inflammatory cytokines (IL-1, 4, 6, 13, 31)
Janus kinase inhibitor
- Apoquel (Oclacitinib)
First choice drugs for fast relief of hypersensitivity-induced cutaneous pruritis.
Janus kinase inhibitor
- Apoquel
- Oclacitinib
Side effects of these immunosuppressants include vomiting, diarrhea, lethargy, anorexia, and bloodwork changes.
Janus kinase inhibitors
- Apoquel
- Oclacitinib
What populations of dogs should not use Apoquel?
- severe infection
- breeding/pregnant/lactating
Is it ok to use Janus kinase inhibitors with vaccines, nsaids, and allergy shots?
Yes
What drug is used to manage allergic pruritic flares?
How long does it last?
Cytopoint
4-8 weeks
MOA: Interferes with incorporation of purines/pyrimidines into DNA; prodrug metabolized to a purine analog (6-Mercapto purine); decreases synthesis of WBC
Antimetabolites
- azathioprene
What drug is used to treat IBD, IMHA, or to decrease dose of glucocorticoids?
Antimetabolites
- azathioprene
Toxicities for this drug include bone marrow suppression, hepatotoxicity, and GI
Antimetabolites
- Azathioprene
Efficacy of this immunosuppressant is delayed for days to weeks, so should be used in conjunction with another drug initially.
Antimetabolites
- Azathioprene
Where is Azathioprene oxidized?
In the liver and peripheral tissues via TPMT to an inactive metabolite
This drug is oxidized by TPMT, which increases risk for suppression of bone marrow (due to decreased TPMT).
Antimetabolites
- Azathioprene
Azathioprene is contraindicated in which species?
Cats and horses
MOA: Alkylates DNA causing chemical cross-links to occur - interfering with DNA replication
Alkylating agents
- cyclophosphamide
- Chlorambucil
High doses of alkylating agents deplete ______.
T-cells
Low doses of alkylating agents enhance _______.
T-cell memory
This drug is used in cats in lieu of azathioprene.
Chlorambucil
Side effects of this drug include sterile hemorrhagic cystitis.
Cyclophosphamide
*prednisone/furosemide to ensure frequent urination
*monitor for Hematuria
This drug is used in cats as a second line of treatment for IBD and for those who do not respond to prednisilone.
Chlorambucil (Alkylating agent)
MOA: Mycophenolic acid inhibits the type II isoform of inosine-5’-monophosphate dehydrogenase; this enzyme is present in abundance in activated lymphocytes and is critical for the synthesis of guanosine nucleotides.
Mycophenolate mofetil
Indications for this drug include treatment of dogs for:
- IMHA
- IMPT
- IMPA
- IM skin disease
- IM glomerulonephritis
- myasthenia gravis
- meningoencephalomyelitis
Mycophenolate mofetil
Side effects/cautions for Mycophenolate mofetil
GI upset
Avoid use in pregnant patients (+ risk to owner)
Increased susceptibility to infection/neoplasia
Allergic reactions
MOA: inverse agonist (H1) - reverses effects of histamine on capillaries reducing allergic reaction symptoms
Antihistamines
- diphenhydramine
