Immunotherapeutics Flashcards
what actions do corticosteroids have?
glucocorticoid and mineralocorticoid actions
how does the dose of dexamethasone compare to that of prednisone?
dex 7x pred
what is the anti-inflammatory dose of prednisone?
0.5-1 mg/kg
what is the physiologic dose of prednisone?
0.2 mg/kg
what is the mechanism of action of cyclosporin?
inhibits calcineurin which reduces cytokines needed for T cell function
what is bioavailability like of cyclosporin?
variable: need to do therapeutic drug monitoring for life-threatening states like transplantation
what is the mechanism of action of mycophenolate?
inhibits enzyme needed for purine synthesis
what is the mechanism of action of azathioprine?
antimetabolite purine antagonist
what are the adverse effects of chlorambucil?
myelosuppression
gastrointestinal upset
in whom is chlorambucil more commonly used in?
cats: blood disorders and IBD, small cell
dogs: PLE
what are the pros of using two drugs?
potentially more rapid/complete immunosuppression
may be able to taper steroid faster
what are the adverse effects of mycophenolate?
hemorrhagic diarrhea
anorexia
what drugs are often used as second drugs in dogs?
azathioprine
mycophenolate
cyclosporine
is there evidence to suggest that one drug is better for a second drug than others?
no
which drugs are used as second drugs in cats?
usually cyclosporine or chlorambucil
what second drug cannot be used in cats?
azathioprine
which second drug has the fastest speed of onset?
cyclosporine
how do the costs of cyclosporine, mycophenolate, and azathioprine compare?
cyclosporine»mycophenolate~azathioprine
which second drug needs to be monitored with CBC and chem?
azathioprine
mycophenolate sometimes CBC
how long are you treating with immunosuppressive tapering?
months
do life-threatening diseases need longer treatment than non-life-threatening diseases?
not always
how long does clinical remission of a systemic immune-mediated disease take?
usually 1-4 weeks
if an animal is on two drugs, what do you taper first?
prednisone usually
how do you taper?
~25% every 2-4 weeks
how do you taper the second drug?
some taper following a similar schedule as for prednisone
what should you check before commencing tapering and every time you reduce the dose?
parameter of interest: platelets, red blood cells
what does the total treatment time depend on?
the disease
what is the treatment time for many conditions?
4-8 months timeframe
why should you not continue drugs at full doses forever without attempting a taper?
prednisone side effects can lead to euthanasia
excessive immunosuppression increases the risk for infections and malignancies
which secondary agent is used in horses?
azathioprine mostly
what is the immunosuppressive dose of pred?
2 mg/kg
what are some side effects of glucocorticoids?
pu/pd
alopecia
thin skin
what are the adverse effects of cyclosporin?
GI upset
gingival hyperplasia
weird infections
what are the adverse effects of azathioprine?
hepatotoxicity
myelosuppression
what are the adverse effects of mycophenolate?
hemorrhagic diarrhea
anorexia
what makes using chlorambucil difficult?
expensive
need to compound
risks to household
must monitor CBC
what are the cons of using two drugs?
increased cost
may need more monitoring
potential for side effects from second drug
may be more immunosuppressed than necessary
no proof superior response/outcome than just using pred
what is usually prescribed for perianal fistulas?
calcineurin inhibitor
how does GI tolerance compare for the three second drugs?
azathioprine>mycophenolate>cyclosporine
how can you taper pred if a second drug is used in IMHA?
25-33% every 3 weeks or 25% every 2 weeks
can taper 25-50%
what diseases are likely lifelong treatment?
atopic dermatitis
IBD
how long should you treat IMHA?
glucocorticoid: 3-6 months
all immunosuppressive therapy: 4-8 months
what should you do if there is a relapse?
confirm relapse
assess for trigger or missed diagnosis
add second drug if relapse was not during taper
if during taper: return to previous dose/effective dose
double time to initial taper and between subsequent tapers
what secondary agents are used in equine?
azathioprine
cyclophosphamide
local cyclosporine