Immunosuppressive Drug Therapies Flashcards
clinical approach to immune mediated disease
- confirm diagnosis of immune mediated disease (primary vs secondary)
- client education and communication
- rational application of immunosuppressive therapy
- active monitoring
why is confirmation of diagnosis important prior to treatment
therapy is immunosuppressive - if animal has an infection then disease will get worse
must differentiate primary vs secondary because need to treat underlying disease
why is client education important
long term treatment required
can be expensive
medications have side effects
risk if underlying cause is infectious or neoplasia
guidelines for immunosuppressive therapy
- avoid excessive immunosuppression
- never use more than 2 immunosuppressive drugs at a time
- want to pulse immunosuppression
goal of active monitoring
assess remission using an objective measure
balance efficacy of drug with adverse side effects
goal for duration of treatment
<6 months
taper by 25% at each check in
what is considered successful therapy
remission of disease with gradual taper of medications over 3 months with minimal adverse effects
if starting to show signs of disease during tapering - go back up and stay at therapeutic dosing for longer
what is considered a therapeutic failure
- inadequate response to treatment
- multiple relapses
- drug adverse reactions
- opportunistic infections
types of immunosuppressive drugs
- glucocorticoids
- cyclosporine A
- azathioprine
- chloramphenicol
- mycophenolate
- leflunomide
glucocorticoids
VERY effective - 1st choice
has HIGH adverse effects that WILL happen
glucocorticoid drugs
prednisone
prednisolone
dexamethasone
glucocorticoid dosing
depends on drug and disease being treated
1. physiologic - low dose
2. anti-inflammatory - medium dose
3. immunosuppressive - extremely high dose
what is the maximum dose for glucocorticoids
60-80 mg total per day REGARDLESS of dog size
glucocorticoid MOA
inhibits phospholipase A2 –> decreases prostaglandin, leukotriene, and thromboxane production
BROAD immunosuppression - inhibits many parts of the immune response (innate and adaptive)
what should glucocorticoids never be used in combination with
NSAIDs
will completely inhibit prostaglandin pathway –> damage to mucosa –> GI ulceration and perforation
glucocorticoid adverse effects
- PU/PD/PP
- panting
- muscle wasting
- GI ulceration
- potbelly appearance
- “pred head”
- alopecia
- thin skin
- decreased hair growth
- calcinosis cutis
- behavioral changes
- opportunistic infections
cyclosporine A
2nd most common immunosuppressant
cyclosporine A dosing
increased dose beyond that labeled for atopic dermatitis
cyclosporine A MOA
calcineurin inhibitor
interacts with cyclophilins in lymphocytes –> blocks transcription factors for interleukin 2 –> down regulation of T cell proliferation and activation
SPECIFIC immunosuppressant - inhibits T cell expansion
cyclosporine A adverse effects
GI signs - vomiting, diarrhea
gingival hyperplasia
dermatopathies
hepato and nephrotoxicity
cyclosporine A drug interactions
cyclosporine A is a p450 enzyme substrate
concentration increased by azole antifungals, metocomplramide, macrolides, fluoroquinolones, omeprazole
azathioprine MOA
targets rapidly dividing cells - T cells, B cells, intestinal epithelial cells, bone marrow
delayed onset of action - often used in conjunction with glucocorticoids
azathioprine adverse effects
dogs: BM suppression, hepatotoxicity
cats: do NOT use in cats
chlorambucil
used in CATS
very safe - few adverse effects
mycophenolate
first choice for immune mediated glomerulonephritis
second choice for refractory IMHA, IMPA
mycophenolate MOA
inhibits purine synthesis
targets rapidly dividing cells (lymphocytes)
mycophenolate adverse effects
profound GI toxicity
leflunomide
backup drug for refractory IMPA
inhibits pyrimidine synthesis
targets rapidly dividing cells
therapeutic plasma exchange
removes serum of dogs with immune disease –> replacing with donor serum that lacks autoantibodies
used for severe, life threatening conditions (ex. IMHA)
immune mediated hemolytic anemia (IMHA)
type 2 hypersensitivity - antibody mediated destruction of red blood cells
characteristics of IMHA
regenerative anemia
agglutination of RBCs
spherocytosis
hemolysis - hyperbilirubinemia, hemolyzed serum
coomb’s test - detects antibodies against RBCs
treatment of IMHA
prednisone
clopidogrel - thromboprophylaxis
immune mediated glomerulonephritis
immune complex (IgG) deposition within nephrons
IMG characteristics
profound proteinuria
- protein losing nephropathy
renal azotemia
hypoalbuminemia
IMG treatment
plasma exchange
hemodialysis
corticosteroids
mycophenolate
immune mediated polyarthritis (IMPA)
type III hypersensitivity reaction - immune complex deposition into the joint space –> activates complement –> local inflammation
diagnosis of IMPA
arthrocentesis in 3+ joints
carpus, tarsus, stifle
IMPA treatment
prednisone
polyarthritis syndromes
IMPA + additional immune disease
polymyositis, meningitis
immune mediated thrombocytopenia (IMTP)
antibody mediated destruction of platelets
primary coagulopathy
severe thrombocytopenia
tx: prednisone
