Immunosuppressive Therapy Flashcards
What are the main indications for starting immunosuppressive therapy?
For primary/idiopathic immune mediated disease
- for secondary, may or may not use it depending on underlying disease pathology
What is the mainstay of therapy for immune mediated disease? What are the secondary drugs used?
Primary: Glucocorticoids- prednisone, dexamethasone
Secondary: azathioprine, cyclosporine, chlorambucil, leflunomide, mycophenolate mofetil
What adjunctive therapies may be used in cases of immune mediated disease?
Human IVIG, Vincristine, Melatonin
Supportive: blood products, antiplatelet therapy
What are the factors that impact the selection of immunosuppressive therapy?
- Expected course and prognosis of disease
- Concurrent diseases
- Safety and efficacy
- Ease of administration- client compliance
- Cost
Describe the use of glucocorticoids for immunosuppression
They are a first line therapy: effective, relatively rapid onset (7-10 days) and cheap
What are the major side effects seen with glucocorticoids?
- PUPD, panting, polyphagia (will see this decreased with dose decreases)
- muscle atrophy and weakness
- iatrogenic hyperadrenocorticism
- vacuolar hepatopathy (cholestatic liver pattern- with ALP elevations much higher than ALT)
- infections, sepsis
- GI ulceration (rare)
- hypercoagulability (unsure of mechanism)
What are some contraindications for glucocorticoids?
- Diabetes mellitus (better to use combo therapies)
- Infections
- Hyperadrenocorticism
- NSAID therapy (if steroids- NSAID use 2 day washout, if NSAID- steroid wait 5-7 days)
How should you dose prednisone and dexamethasone?
Prednisone:
-2 mg/kg/day
-dose cap of 60-80 mg/day in large breeds
Dexamethasone: much more potent (10X)
- 0.2-0.3 mg/kg/day (initially)
- dex SP- 3 mg/mL when doing low dose dex test
What is the goal for steroid treatment?
Clinical remission (clinical and pathologic signs) at the lowest effective dose
- taper by 25% every 2-4 weeks (with 2 weeks of stability on BW/signs) over 4-6 months
- discontinue or lowest effective dose (once at lowest dose, move to every other day)
- avoid decreasing other medications at the same time
- if relapse, return to original effective dose
When should you consider switching to another therapy when treating immune mediated disease?
- no or poor response
- excessive side effects
- long duration of therapy indicated
- corticosteroids contraindicated
Describe the mechanism of action of azathiaprine
Inhibits purine synthesis (DNA) which disrupts lymphocyte proliferation, blocks T cell activation and promotes T cell apoptosis, decreases antibody synthesis
Metabolism limits its use in cats- can lead to very severe myelosuppression
What are the main side effects seen with azathiaprine?
-Cytopenias (develop over 2-3 months)
-hepatotoxicity (develops in 1-4 weeks)
-chronic subclinical anemia (PCV >25-30%)
-GI signs- mild and self limiting
Monitoring with CBC and chem is crucial
Describe the hepatotoxicity that can be seen with azathioprine
-increases are hard to interpret as patients are also often on concurrent prednisone
-if you start to see more increases in ALT over ALP and increased bilirubin, this is more of a concern that this drug is causing liver toxicity
-most cases are reversible with dose reduction (50%)
-discontinue when you see hyperbilirubinemia
-SAM-e can help prevent and/or reverse hepatotoxicity
What are the main indications for azathioprine?
Second line therapy for IMTP, IMHA, IMPA, IBD, SLE
- has glucocorticoid sparing effects (decreases steroid side effects)
- previously was second line agent of choice for IMHA (has been determined that any second line drug is ok)
How do you dose azathioprine?
Dose 2 mg/kg q24 hours for 2 weeks
- then decrease to 2 mg/kg q 48 hours
- slow onset
- cheap
- taper after prednisone has been tapered over 2-3 months
How is the mechanism of action of cyclosporine different than other immunosuppressives?
It does not interfere with lymphocyte proliferation, but instead impairs the function of the T cells, thus blunting the immune response
- aka no myelosuppression
What is one of the main things you need to consider if reaching for cyclosporine in a case?
It has LOTS of drug interactions
- need to check that there are no interactions with any other drug the patient is taking
- antifungals are a big one that interacts with this drug
What are the main side effects seen with cyclosporine?
-primarily GI side effects
- can see hepatotoxicity and nephrotoxicity
-gingival hyperplasia, hypertrichosis, excessive shedding, papillomatous, opportunistic infection (especially fungal infections- often very severe)
-can activate platelets (avoid in IMHA)
NO MYELOSUPPRESSION
What should you do if you see a skin lesion form on a patient on cyclosporine?
Do cytology or biopsy to determine if fungal infection
- if so, stop med entirely or switch to something else
What are some indications for cyclosporine?
IMHA< ITP, IBD, MG, MUE< GN, anal furunculosis, pemphigus foliaceous
-onset of action over days to months
-chronic inflammatory dose 5 mg/kg/day
-acute life-threatening dose: 5-10 mg/kg q 12 h
Why is therapeutic drug monitoring often necessary when on cyclosporine?
The same dose may have different effects in different patients
What is the recommended formulation of cyclosporine?
Microemulsion form- improves bioavailability
- oil based is not recommended- high variability in bioavailability
- be cautious with generics
ATOPICA is the common name brand used- comes in capsules and oral suspension
Describe the use of chlorambucil in vet med
- it is an alkylating antineoplastic agent
- targets B cells (stops proliferation)
- slow onset of action (about 2 weeks)
-can be very expensive (often need to get compounded) - Used mostly in cats for IBD, PLE or glomerulonephritis
- used for chronic protein losing enteropathies in dogs
What are the main side effects associated with chlorambucil?
GI effects in cats, myelosuppression (dose dependent- monitor CBC), alopecia and poor hair growth (especially in beagles), neuro signs in cats
Describe the use of leflunomide in vet med
-it inhibits B and T cell function and proliferation and suppresses antibody production
-well tolerated
-side effects: GI, myelosuppression, cutaneous drug reactions, hepatotoxicity
-must monitor CBC and chem over time (specifically ALT)
-main uses are for add on or stand-alone therapy for immune mediated polyarthritis, IMHA, ITP, MUE, histiocytosis, pemphigus, colorectal polyps
- dose 2 mg/kg PO q 24h
Why is mycophenolate mofetil considered the “more friendly” azathioprine?
Same mechanism of action with less side effects
- still can see GI upset at very high doses
- there are some drug interactions with fluroquinolones, metronidazole, PPIs, glucocorticoids, cyclosporine and azathioprine
When has mycophenolate been used successfully as a standalone therapy?
ITP, IMHA
What are some of the main considerations when using mycophenolate?
- dosed at 10 mg/kg PO BID
- dosing is easier and cheaper for large breed dogs
- there is an oral suspension and IV formulation
- can take 2-3 weeks to start working
- can be used stand alone or in refractory/relapsing disease
