Immunosuppressants Flashcards
What are some diseases that would need to be treated with immunosuppressants?
Immune Mediated hemolytic anemia (IMHA)
Immune mediated thrombocytopenia (IMTP)
Evans Syndrome (IMHA + IMTP)
Immune Mediated Polyarthritis (IMPA)
Inflammatory Bowel Disease (IBD)
Chronic Hepatitis (CH)
Glomerulonephritis (GN)
What are some immunosuppressive Therapies?
Glucocorticoids, azathioprine, cyclosporine, chlorambucil, leflunomide, mycophenolate mofetil
Human IVIG
Vincristine
Blood, antiplatelet, anticoagulant
How do you select the right immunosuppressive therapy?
Expected course and prognosis
Concurrent Disease
Safety and Efficacy
Ease administration and monitoring client compliance
Cost
Which immunosuppressant is the first line of therapy, effective, rapid, cheap, decreased cytokines, antigen processing, Fc receptor, T-cell function?
Glucocorticoids
Which drugs are commonly used glucocorticoids?
Prednisolone (no more
mg/day)
Dexamethasone
What are some side effects of glucocorticoids?
PU/PD
Panting
Polyphagia
Muscle atrophy and weakness
Hyperadrenocorticism
Vacuolar hepatopathy
Infection, sepsis
GI ulceration
Hypercoagulability
Diabetes and CHF
Calcinosis Cutis
What changes in bloodwork are normal when steroids are being administered?
ALP much higher than ALT
ALP and GGT very high
Total bilirubin NEVER high
Indirect liver function normal
When are steroids contradicted?
Diabetes mellitus
Infection
Hyperadrenocorticism
NSAID therapy (Wash out 24-48hr)
When can glucocorticoids be discontinued?
Clinical remission
Reduce by 25% every 2-4 weeks
Discontinue or lowest effective dose
Avoid decreaseing other meds at same time
Relapse - immunosuppressive
Keep at starting dose until 1-2 weeks beyond resolution of abnormal parameter
-Can discontinue at low dose 0.25mg/kg/day
When should you consider other therapies when using a steroid?
No or poor response
Relapse
Excessive side effect
Long duration therapy anticipated
Corticosteroids contraindicated
Drug availability, patient size, cost, adverse effect, efficacy
What is a drug that is a good second line therapy that inhibits purine synthesis and lymphocyte proliferation and shoud not be used in cats due to myelosuppresion?
Azathioprine
What are some side effects to azathioprine?
Cytopenia’s, hepatotoxicity, chronic subclinical anemia, GI signs
Why may it be hard to monitor hepatotoxicity in animals on azathioprine?
They are probably concurrently on prednisone which will affect those values
-Increased ALT and bilirubin
Need to taper off
SAM E may prevent or reverse hepatotoxicity
What is a second line immunosuppressant that can be used for IMHA, ITP, IBD, IMPA, hepatitis, meningoencephalitis, pemhpagus. It is a calcineurin inhibitor (decrease IL-2 synthesis). Impairs function of T-cell and blunt immune response. It is specific for lymphocytes.
Cyclosporine
What is the onset of cyclosporine?
Days to months
What are some down sides to atopica (cyclosporine)?
Microemulsion improve bioavailability
Expensive
Generics not as good
Metabolize cytochrome P450
GI side effect
Gingival hyperplasia, hypertrichosis, shedding, papillomatosis, hepatotoxicity, nephrotocity
NOT Myelosuppressive
Opportunistic fungal infections
What is another second line treatment more commonly used in cats and for chronic protein losing enteropathies in dogs?
Chlorambucil
What is the MOA of Chlorambcuil and what’s the onset of action?
Alkylating agent antineoplastic
Immunosuppressive
Low onset of action (2-4 weeks)
What are the downsides to chlorambucil?
Expensive
GI
Myelosuppressive
Alopecia, poor hair growth (poodle)
Neuro in cat
What is another second line treatment or stand alone?I It inhibits de novo pyrimidine synthesis, reduced lymphocyte proliferation
Leflunomide
What are the negatives of leflunomide?
Well tolerated
GI in appetence, vomiting
Myelosuppression
Cutaneous drug reaction
Hepatotoxicity
What is a drug that could stand alone in stable disease or in combo with prednisone? It is reversible inhibitor of inosine monphospate dehydrogenase that inhibits purine sythesis and lymhpocyte proliferation
Mycophenolate mofetil
What are some negatives to mycophenolate mofetil?
GI - diarre, vomit poor appetitie, myelosuppression and lymphoma (human)
2-3 week to start working
What are some pros of mycophenolate?
Low toxicity
Tablet size
Compounding
Can stand alone
How do you monitor response to these drugs?
Improvement in signs and clinicopathologic abnormalities
Initiate prednisone taper 25% 2-4 week
Acceptable Maintenace dose or discontinue
2nd line drug tapered in similar manner (after)
What is human IVIG?
Adjutant therapy
IV immunoglobulins
IgG from human plasma
What is the MOA of IVIG?
?
Block Fc receptor, eliminate pathogenic antibodies, inhibit complement, modulates cytokine synthesis
What can IVIG be used to help treat?
IMHA and ITP
What is vincristine?
Vinca Alkaloid
Disrupt intracellular muctoubules
Platelet carriers
reduce platelet destrucito, increase platelet 3-5 days
Shorten hospitalization
What are side effects of vincristine?
Minimal myelotoxic
perivascular extravasation
Neurotoxicity
GI
What are some other supportive therapies?
Transfusions - RBC, Fresh whole blood, plasma, platelet
What types of drugs are used for thromboprophylaxis?
Antiplatelet
Anticoagulant
What are some antiplatelet drugs?
Asprin and clopidogrel
What are some anticoagulants?
Herpin
What may cause poor response to therapy?
Misdiagnosis
Underlying disease
Patience
Incorrect duration
Side effects vs disease
