Immunosuppressive Drugs Flashcards
what are immunosuppressants characterized by?
narrow therapeutic window requiring precise dosing and close side-effect monitoring
what are some things that we will treat immunosuppressive drugs with?
IMHA
ITP
IBD
IMPA
allergic/autoimmune dermatitis
glomerulonephritis
canine chronic hepatitis
SLE
immune-mediated neutropenia
what do you need to think about with secondary immune deviation?
treat underlying disease if possible
immunosuppression often not indicated if infection present
identified disease may influence prognosis and owners’ willingness to pursue treatment
which group of drugs has the most wide-ranging immune effects?
glucocorticoids
what is the glucocorticoid mechanism of action?
inhibit phospholipase A2 and arachidonic acid cascade
inhibit NF-kB decreasing cytokine production
decrease macrophage phagocytosis
inhibit complement
who is azathioprine used in?
dogs
horses
what is azathioprine?
purine antagonist
how is azathioprine ingested/metabolized?
antimetabolite converted to active metabolite: 6-mercaptopurine
what are the main adverse effects of azathiopurine?
myelosuppression
hepatotoxicity
why is azathiopurine not safe in cats?
low thiopurine methyltransferase activity: low safety margin
what is cyclosporine?
calcineurin inhibitor
how do we do therapeutic drug monitoring with cyclosporine (and other drugs usually)?
measure PK: blood concentrations
true/false: there is a standard dose of cyclosporine to use for immunosuppression regardless of the presentation of the immune deviation
false: different degrees of immune suppression needed for different conditions
what are the main adverse effects of cyclosporine?
gastrointestinal upset
gingival hyperplasia
what are the main reported uses of cyclosporine?
transplantation
perianal fistulas
what are some adverse effects that cyclosporine does not have?
not nephrotoxic
not myelotoxic
what can you combine cyclosporine with to reduce drug requirements for perianal fistulas?
ketoconazole: CYP3A inhibitor
what is inosine monophosphate dehydrogenase needed for?
de novo synthesis of purines
what are the main adverse effects of mycophenolate?
dose limiting GI toxicity
anorexia
diarrhea
hematochezia
what is the cytotoxic drug of choice in cats?
chlorambucil
_______________ is the slowest acting and least toxic alkylating agent
chlorambucil
what is chlorambucil used to treat mainly in cats?
inflammatory bowel disease
lymphoma
what is the main adverse effect of chlorambucil?
myelosuppression
reversible, dose dependent
what is oclacitinib (apoquel)?
janus kinase inhibitor
decreases inflammatory cytokines like IL-2, IL-4, IL-6, IL-13, IL-31
what is oclacitinib approved for?
treatment of inflammatory skin disease in dogs
what does cytopoint do?
neutralizes soluble IL-31 and stops its role in causing inflammation and itch
who, if anyone, is cytopoint approved by?
USDA: not FDA
biologic, not a drug
what is cytopoint?
caninized anti-IL-31 monoclonal antibody
what cells are potentially involved in immune diseases?
mast cells
phagocytes
complement
T lymphocytes
B lymphocytes
what cells does cyclosporine immunosuppress?
T cells
what is the prednisone dosing for dogs for anti-inflammatory and immunsuppressive?
anti-inflammatory: 1 mg/kg
immunosuppressive: 2 mg/kg
what are the adverse effects associated with glucocorticoids?
pu/pd
muscle weakness/atrophy
polyphagia
hepatic effects
hypercoagulability
behavioral changes
calcinosis cutis
diabetogenic
risk of CHF (more in cats)
what enzyme converts azathioprine to its inactive metabolites?
thiopurine methyltransferase (TPMT)
what are the adverse effects of azathiopurine?
myelosuppression
GI upset
pancreatitis
hepatotoxicity
neuromuscular blockade: cats
how is cyclosporine given? modified or not?
modified
is cyclosporine used for glomerulonephritis?
no
what does mycophenolate mofetil inhibit?
inosine monophosphate dehydrogenase: IMPDH
who is mycophenolate mofetil primarily used in?
dogs
what is mycophenolate mofetil used in?
glomerulonephritis
IMHA
ITP
IMPA
MUE
myasthenia gravis
what cells does mycophenolatem azathioprine, and chlorambucil target?
lymphocytes
what is the greater effect of azathioprine?
T cell mediated responses than humoral immunity
what does decreased function of thiopurine methyltransferase lead to?
increased myelosuppression
what are the adverse effects of chlorambucil?
myelosuppression
GI upset
neurologic signs
Fanconi syndrome
