Immunosuppressive Drugs

Question 1

what are immunosuppressants characterized by?

Answer 1

narrow therapeutic window requiring precise dosing and close side-effect monitoring

Question 2

what are some things that we will treat immunosuppressive drugs with?

Answer 2

IMHA
ITP
IBD
IMPA
allergic/autoimmune dermatitis
glomerulonephritis
canine chronic hepatitis
SLE
immune-mediated neutropenia

Question 3

what do you need to think about with secondary immune deviation?

Answer 3

treat underlying disease if possible
immunosuppression often not indicated if infection present
identified disease may influence prognosis and owners’ willingness to pursue treatment

Question 4

which group of drugs has the most wide-ranging immune effects?

Answer 4

glucocorticoids

Question 5

what is the glucocorticoid mechanism of action?

Answer 5

inhibit phospholipase A2 and arachidonic acid cascade
inhibit NF-kB decreasing cytokine production
decrease macrophage phagocytosis
inhibit complement

Question 6

who is azathioprine used in?

Answer 6

dogs
horses

Question 7

what is azathioprine?

Answer 7

purine antagonist

Question 8

how is azathioprine ingested/metabolized?

Answer 8

antimetabolite converted to active metabolite: 6-mercaptopurine

Question 9

what are the main adverse effects of azathiopurine?

Answer 9

myelosuppression
hepatotoxicity

Question 10

why is azathiopurine not safe in cats?

Answer 10

low thiopurine methyltransferase activity: low safety margin

Question 11

what is cyclosporine?

Answer 11

calcineurin inhibitor

Question 12

how do we do therapeutic drug monitoring with cyclosporine (and other drugs usually)?

Answer 12

measure PK: blood concentrations

Question 13

true/false: there is a standard dose of cyclosporine to use for immunosuppression regardless of the presentation of the immune deviation

Answer 13

false: different degrees of immune suppression needed for different conditions

Question 14

what are the main adverse effects of cyclosporine?

Answer 14

gastrointestinal upset
gingival hyperplasia

Question 15

what are the main reported uses of cyclosporine?

Answer 15

transplantation
perianal fistulas

Question 16

what are some adverse effects that cyclosporine does not have?

Answer 16

not nephrotoxic
not myelotoxic

Question 17

what can you combine cyclosporine with to reduce drug requirements for perianal fistulas?

Answer 17

ketoconazole: CYP3A inhibitor

Question 18

what is inosine monophosphate dehydrogenase needed for?

Answer 18

de novo synthesis of purines

Question 19

what are the main adverse effects of mycophenolate?

Answer 19

dose limiting GI toxicity
anorexia
diarrhea
hematochezia

Question 20

what is the cytotoxic drug of choice in cats?

Answer 20

chlorambucil

Question 21

_______________ is the slowest acting and least toxic alkylating agent

Answer 21

chlorambucil

Question 22

what is chlorambucil used to treat mainly in cats?

Answer 22

inflammatory bowel disease
lymphoma

Question 23

what is the main adverse effect of chlorambucil?

Answer 23

myelosuppression
reversible, dose dependent

Question 24

what is oclacitinib (apoquel)?

Answer 24

janus kinase inhibitor
decreases inflammatory cytokines like IL-2, IL-4, IL-6, IL-13, IL-31

Question 25

what is oclacitinib approved for?

Answer 25

treatment of inflammatory skin disease in dogs

Question 26

what does cytopoint do?

Answer 26

neutralizes soluble IL-31 and stops its role in causing inflammation and itch

Question 27

who, if anyone, is cytopoint approved by?

Answer 27

USDA: not FDA biologic, not a drug

Question 28

what is cytopoint?

Answer 28

caninized anti-IL-31 monoclonal antibody

Question 29

what cells are potentially involved in immune diseases?

Answer 29

mast cells phagocytes complement T lymphocytes B lymphocytes

Question 30

what cells does cyclosporine immunosuppress?

Answer 30

T cells

Question 31

what is the prednisone dosing for dogs for anti-inflammatory and immunsuppressive?

Answer 31

anti-inflammatory: 1 mg/kg immunosuppressive: 2 mg/kg

Question 32

what are the adverse effects associated with glucocorticoids?

Answer 32

pu/pd muscle weakness/atrophy polyphagia hepatic effects hypercoagulability behavioral changes calcinosis cutis diabetogenic risk of CHF (more in cats)

Question 33

what enzyme converts azathioprine to its inactive metabolites?

Answer 33

thiopurine methyltransferase (TPMT)

Question 34

what are the adverse effects of azathiopurine?

Answer 34

myelosuppression GI upset pancreatitis hepatotoxicity neuromuscular blockade: cats

Question 35

how is cyclosporine given? modified or not?

Answer 35

modified

Question 36

is cyclosporine used for glomerulonephritis?

Answer 36

no

Question 37

what does mycophenolate mofetil inhibit?

Answer 37

inosine monophosphate dehydrogenase: IMPDH

Question 38

who is mycophenolate mofetil primarily used in?

Answer 38

dogs

Question 39

what is mycophenolate mofetil used in?

Answer 39

glomerulonephritis IMHA ITP IMPA MUE myasthenia gravis

Question 40

what cells does mycophenolatem azathioprine, and chlorambucil target?

Answer 40

lymphocytes

Question 41

what is the greater effect of azathioprine?

Answer 41

T cell mediated responses than humoral immunity

Question 42

what does decreased function of thiopurine methyltransferase lead to?

Answer 42

increased myelosuppression

Question 43

what are the adverse effects of chlorambucil?

Answer 43

myelosuppression GI upset neurologic signs Fanconi syndrome