Immunosuppressive Therapy Flashcards
What is the primary immunosuppressive? What are 5 other secondary ones that can be added on?
glucocorticoids - Prednisolone, Dexamethasone
- Azathioprine
- Cyclosporine
- Chlorambucil
- Leflunomide
- Mycophenolate mofetil
What adjunctive and supportive therapies can be added for immunosuppressive therapy?
ADJUVANT = human IVIg, Vincristine, Melatonin
SUPPORTIVE = blood products, antiplatelet therapy
How are immunosuppressive therapies picked?
- expected course and prognosis of disease
- concurrent diseases
- safety and efficacy
- ease of administration and monitoring
- cost
Why are glucocorticoids a first-line therapy for immunosuppression?
- effective
- relatively rapid onset
- cheap
What are 4 immunosuppressive mechanisms of action of glucocorticoids?
- decreased inflammatory cytokines
- decrease antigen presenting
- down-regulate Fc receptor expression on macrophages
- suppression of T-cell function
What are 7 side effects associated with glucocorticoids?
- PU/PD, panting, polyphagia
- muscle atrophy and weakness
- iatrogenic hyperadrenocorticism
- vacuolar hepatopathy
- infections, sepsis
- GI ulceration
- hypercoagulability
What are 4 contraindications for the use of glucocorticoids for immunosuppression?
- diabetes mellitus
- infections
- hyperadrenocorticism
- NSAID therapy —> needs a washout period
How do the doses of Prednisolone and Dexamethasone compare?
PREDNISOLONE - 2 mg/kg/day, 50 mg/m^2, dose cap at 50-80 mg/day
DEXAMETHASONE - 7-10x more potent than Prednisone, 0.2-0.3 mg/kg/day (SP = 3 mg/mL)
How are glucocorticoid doses altered once remission is reached? What is done is a patient relapses?
decrease 25% every 2-4 weeks for 4-6 months with the goal of discontinuing or getting to the lowest effective dose
return to the original effective dose
What is avoided when decreasing glucocorticoid doses?
decreasing other medications
In what 4 situations should other therapies be considered when using glucocorticoids?
- no or poor response
- excessive side effects
- long duration of therapy anticipated
- corticosteroids contraindiccated
(consider drug availability, patient size, cost, adverse effects, and efficacy —> little to no evidence to support one over the other)
What are 3 mechanisms of actions of Azathioprine?
- inhibits purine synthesis, which disrupts lymphocyte proliferation
- blocks T-cell activation and promotes T-cell apoptosis
- decreases antibody synthesis
Is Azathioprine used in cats?
not usually —> metabolism relies on thiopurine methyltransferase, which is low in cats
What are the 4 most common side effects associated with Azathioprine? What is commoly monitored?
- cytopenias - 2-3 months
- hepatotoxicity - 1-4 weeks
- GI signs - mild and self-limiting
- CHRONIC - subclinical anemia (PCV >25-30%)
CBC/Chem
When is Azathioprine hepatotoxicity seen? What. isthe most common sign? How is it solved?
concurrent prednisone administration
discordant ALT > ALP, increased BILI
- dose reduction by 50% —> discontinuing can cause hyperbilirubinemia
- SAMe can prevent and/or reverse
Why is Azathioprine commonly used? What is it the proposed second-line agent of choice for?
has glucocorticoid-sparing effects
IMHA
What onset of Azathioprine have? How is it tapered?
slow, takes around 3 weeks
after prednisone, over 2-3 months - 2 mg/kg/day q 48 hr —> 1 mg/kg/day q 48 —> 1 mg/kg twice weekly
What are the 2 mechanisms of action of Cyclosporine? How is it unique?
- calcineurin inhibitor that decreases IL-2 synthesis
- impairs function of T-cells and blunts immune response specific for lymphocytes
NOT CYTOTOXIC = no bone marrow suppression
Cyclosporine drug interactions:
What is the most common side effect of Cyclosporine? What else is seen? What is not seen?
GI signs
- hepato/nephrotoxicity
- gingival hyperplasia
- hypertrichosis, excessive shedding, papillomatosis
- opportunistic infections (significant fungal infections)
- platelet activation - avoid with IMHA?
myelosuppression
What onset does Cyclosporine have?
days
How is therapeutic drug monitoring used for Cyclosporine?
- measurement of blood drug levels - measures build-up
- pharmacodynamic assays - drug effect on target cells assesses T-cell function and immune response (IL-2)
What administrations of Cyclosporine are available? What is not recommended?
- oral microemulsion improves bioavailability - Atopica —> expensive for large dogs
- injectable, IV - Sandimmune
oil-based, caution with generics
What is the mechanism of action of Cyclophosphamide? What is it used for?
alkylating agent
IMHA —> fallen out of fever for immunosuppression, mostly used for chemotherapy
