Immunosuppressive Therapies Flashcards
what are the 6 immunosuppressive drugs used in vet med?
- glucocorticoids
- azathioprine
- cyclosporine
- chlorambucil
- leflunomide
- mycophenolate mofetil
what are adjunctive therapies that can be added onto immunosuppressive therapy to help control the disease?
- human IVIG
- vincristine
- melatonin
other supportive treatments – blood products, antiplatelet therapy.
what are the 5 criteria to consider when choosing an immunosuppressive therapy?
- expected course and prognosis of disease
- concurrent diseases
- safety and efficacy
- ease of admin and monitoring
- cost
which of the following is FALSE about glucocorticoids?
A. effective
B. slow onset
C. cheap
D. mechanism of action if to quiet the immune system by downregulating inflammatory cytokines etc.
B. slow onset
these drugs have a rapid onset
what are the side effects associated with glucocorticoids?
- PU/PD, polyphagia, panting
- muscle atrphy and weakness
- iatrogenic cushings
- vacuolar hepatopathy (large liver; inc liver enzymes ALKP>ALT)
- infection, sepsis
- GI ulcers
- hypercoagulability
what are contraindications for glucocorticoids?
- diabetes mellitus
- infection
- hyperadrenocorticism
- NSAID therapy (GI ulceration)
what are the 2 common glucocorticoids used in vet med?
prednisone
dexamethasone
when and how should you wean a patient off of glucocorticoids?
when there is clinical remission for atleast 2 consecutive weeks (specific signs controlled will depend on the disease), then you can reduce the dose 25% every 2-4 weeks.
This will take 4-6 months.
Discontinue it completeley if possible or go to lowest effective dose.
if the patient relapses, return to the original effective dose.
when should you consider OTHER therapies with a patient currently on glucocorticoids?
- no-to-poor response
- excessive side effects
- long-duration therapy anticipated
- corticosteroids are contraindicated (diabetes, hyperadrenocorticism, infection, NSAIDs)
What factor limits the use of azathioprine in cats?
metabolism ot thiopurine methyltransferase
what are the side effects associated with azathioprine?
- cytopenias
- hepatotoxicity
- chronic subclinical anemia (PCV 25-30%; nonregenerative)
- GI signs (mild and self-limiting)
you should monitor CBC and chemistry
How can you identify azathioprine induced hepatotoxicity?
ALT > ALP and increased bilirubin
reduce the dose (can reverse it) or discontinue (if hyperbilirubinemia bc indicates liver failure)
what drug can you add on to azathioprine to protect the liver and prevent/reverse hepatotoxicity?
SAM-e (denamarin)
What is the primary use of azathioprine?
Used as a 2nd line therapy in cases of IMTP, IMHA, IMPA, IBD, or SLE
used for glucocorticoid-sparing effects
Which of the following is FALSE regarding azathioprine?
A. requires loading dose
B. administered every 24 hours
C. slow onset
D. cheap
E. tapered after prednisone over 2-3 months.
B. administered every 24 hours
admin every 48 hrs
which immunosuppressive drug(s) is/are NOT myelosuppressive?
- glucocorticoids
- cyclosporine
what is the MOA of cyclosporine?
impairs T cell function and blunts the immune response
therefore is NOT myelosuppressive
what are the biggest downsides to cyclosporine?
LOTS of drug interactions
primarily GI side effects (v/d)
opportunistic infections
others: hepatotoxicity, nephrotoxicity, gingival hyperplasia, hypertrichosis, excessive shedding, papillomatosis, platelet activation
what are common conditions that cyclosporine is used to treat?
IMHA, ITP, IBD, MG, MUE, GN, anal furunculosis, pemphigus foliaceous
what is the onset for cyclosporine?
days to months
How do we determine doses for cyclosporine in patients?
there are chronic inflammatory doses – 5 mg/kg/day, there are acute life-threatening doses 5-10 mg/kg/day
but each patient is different and the dose will likely better be determined by therapeutic drug monitoring.
T/F: oil-based cyclosporine is the recommended over water-based because the bioavailability is higher
FALSE
microemulsion (atopica) improves bioavailability. The oil-based is NOT recommended because the bioavailability is too variable. Caution with generic versions of this drug.
Which of the following is TRUE about chlorambucil (leukeran)?
A. targets B cells and can lead to myelosuppression
B. fast onset (24 hours)
C. nephrotoxicity is most common side effect
D. used more commonly in dogs than cats
E. cheap
A. targets B cells and can lead to myelosuppression
it has a slow onset (2 weeks), causes GI side effects, myelosuppression, alopecia/poor hair growth, and neuro signs (in cats). Can cause chronic protein losing enteropathies in dogs.
This drug is used more commonly in cats as a 2nd line therapy for IBD, PLE, and glomerulonephritis
The drug is expensive
what are the side effects associated with leflunomide?
GI (inappetance, vomiting)
Myelosuppression
cutaneous drug reactions
hepatotoxicity
monitor CBC and chem
T/F: you should start patients at a higher dose of leflunomide and then decrease to lowest effective dose similar to prednisone or dexamethasone
false – start at a lower dose and increase if needed. this lowers the incidence of side effects.
what are the MOST common side effects associated with mycophenolate mofetil?
GI – diarrhea, vomiting, hyporexia
also can cause myelosuppression and lymphoma (rare)
monitor CBC/Chem
which drugs DECREASE the bioavailability of mycophenolate mofetil?
fluoroquinolones
metronidazole
PPIs
glucocorticoids
cyclosporine
which drug should NOT be used concurrently with mycophenolate mofetil due to similar MOAs?
azathioprine
T/F: mycophenolate mofetil can be used as a stand alone drug in stable disease or in combination with prednisone
true
T/F: mycophenolate mofetil is a more cost-effective immunosuppressive agent to choose for large breed dogs
true
What is the biggest downside to mycophenolate mofetil?
takes 2-3 weeks to work.
Vincristine is an adjunctive treatment for which condition?
ITP
