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Pharmacology > Immunosuppressives > Flashcards

Immunosuppressives Flashcards

1
Q

MOA of oclacitinib

A

Inhibits Janus-kinase 1 and 3-dependent cytokines

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2
Q

Which cytokines does oclacitinib inhibit?

A

IL-2/IL-6 (inflammatory cytokines)
IL-4/IL-13 (allergic cytokines)
IL-31 (pruritogenic cytokine)

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3
Q

Side effects of oclacitinib

A

GI- V/D/anorexia

infections- demodicosis, pneumonia, pyoderma

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4
Q

MOA of lokivetmab

A

Binds to and neutralizes IL-31

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5
Q

How is lokivetmab metabolized?

A

Via protein degradation pathways

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6
Q

Side effects of lokivetmab

A 
lethargy
vomiting
hyperexcitability
pain at injection site
urinary incontinence
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7
Q

What is lokivetmab?

A

caninized monoclonal Ab against IL-31

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8
Q

Definition of immunosuppression

A

to reduce the activation or efficacy of the immune system

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9
Q

Definition of immunomodulation

A

to modify the immune system

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10
Q

Name 3 categories of cytotoxic drugs

A
  1. cycle specific: more toxic to cells actively cycling than in G0 phase
  2. phase specific: active during specific cycle
  3. cycle non-specific: toxic to proliferating and intermitotic cells
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11
Q

Which category of cytotoxic drugs are alkylating agents?

A

“cycle non-specific”; most active during G1 and S phases

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12
Q

MOA for cyclosphosphamide

A

creates DNA crosslinkages interfering with DNA and RNA replication and function

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13
Q

Which metabolite of cyclophosphamide is responsible for hemorrhagic cystitis?

A

acrolein

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14
Q

Side effects of cyclophosphamide

A 
myelosuppression
loss of vibrissae (cats)
hemorrhagic cystitis
decreased wound healing
alopecia (poodles, OES)
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15
Q

MOA of chlorambucil

A

creates DNA crosslinkages disrupting DNA synthesis

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16
Q

Side effects of chlorambucil

A

myelosuppression (thrombocytopenia)
GI- V/D/anorexia
alopecia (poodles, Kerry blue terriers)

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17
Q

MOA of lomustine

A

not fully understood….inhibit DNA/RNA synthesis

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18
Q

Which type of cutaneous cancer is lomustine commonly used to treat?

A

cutaneous T cell lymphoma

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19
Q

Name two subclasses of alkylating agents.

A
  1. nitrogen mustards (cyclophosphamide & chlorambucil)

2. nitrosoureas (lomustine)

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20
Q

Side effects of lomustine

A

myelosuppression (neutropenia/thrombocytopenia)
hepatotoxicity
GI effects (V/D/anorexia)

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21
Q

Name 3 subclasses of antimetabolites.

A
  1. purine analogs (azathioprine, mycophenolate)
  2. pyrimidine analogs (5-fluorouracil, leflunomide)
  3. Antifolates (methotrexate)
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22
Q

Which category of cytotoxic drugs are antimetabolites?

A

Most are “phase specific”; usually active in S phase

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23
Q

MOA of azathioprine

A

interferes w/ purine nucleic acid base production–> inhibits DNA/RNA synthesis

24
Q

What is the prodrug of azathioprine responsible for its effects?

A

6-mercaptopurine

25
Q

What is the enzyme mainly responsible for metabolism of 6-mercaptopurine?
Which species or breeds have a decrease or increase in the activity of this enzyme?

A

thiopurine methyl-transferase (TPMT)

Low TPMT activity: cats, Giant Schnauzers

Elevated TPMT activity: Alaskan malamute

26
Q

Side effects of azathioprine

A

Myelosuppression (thrombocytopenia)….NOT for cats
vomiting
hepatotoxicity….monitor enzymes q 2 weeks for first 2 months
pancreatitis

27
Q

MOA of mycophenolate

A

inhibits de novo purine synthesis via its prodrug mycophenolic acid

more specifically: reversibly binds to inosine monophosphate dehydrogenase (IMPDH)…rate limiting step in de novo guanine synthesis

28
Q

Side effects of mycophenolate

A

myelosuppression
V/D/nausea
increased risk of opportunistic infections
leukocytosis

29
Q

MOA of 5-fluorouracil

A

converted to fluoruridine monophosphate (FUMP) and fluoruridine triphosphate (FUTP)…these interfere with DNA and RNA synthesis respectively

30
Q

Which species should 5-fluorouracil NOT be used in?

A

CATS!

Neuro and hepatotoxic

31
Q

Side effects of 5-fluorouracil

A

myelosuppression
GI toxicity
neurotoxicity (seizures)

32
Q

MOA of leflunomide

A

inhibits dihydroorotate dehydrogenase enzyme, thus preventing formation of ribonucleotide uridine monophosphate (rUMP)–> decreased DNA/RNA synthesis

33
Q

Side effects of leflunomide

A

hepatotoxicity
vomiting
myelosuppression (lymphopenia, anemia)
TEN/SJS in people

34
Q

MOA of methotrexate

A

binds and inhibits dihydrofolate reductase needed for purine and pyrimidine synthesis

S-phase specific

35
Q

Side effects of methotrexate

A 
GI (V/D/inappetence)
myelosuppression
hepatopathy
renal tubular necrosis
Alopecia and depigmentation
36
Q

MOA of cyclosporine

A

calcineurin inhibitor

binds to cyclophilin–> CsA/cyclophilin bind to calcineurin–> inhibits signal transmission–> inhibits T cell activation and production of IL-2, -3, -4

37
Q

Name 10 drugs which increase CsA levels

A 
cytochrome P450 INHIBITORS--> increase CsA
acetazolamide
allopurinol
amlodipine
azithromycin
azoles
bromocriptine
diltiazem
carvedilol
cimetidine
chloramphenicol
cipro/enrofloxacin
cisapride
clarithromycin
clopidogrel
colchicine
corticosteroids- NOT methylprednisolone
danazol
digoxin
estrogens
fluvoxamine
glipizide
grapefruit juice (flavonoids)
imipenem
losartan
medroxyprogesterone
metronidazole
omeprazole
sertraline
tinidazole
38
Q

Name 10 drugs which decrease CsA levels

A 
Cytochrome P450 INDUCERS--> decrease CsA levels
azathioprine
carbamazepine
clindamycin
cyclophosphamide
famotidine
griseofulvin
octreotide
rifampin
phenobarbital
phenytoin
St. John's wart
sulfadiazine
sulfasalazine
terbinafine
trimethoprim
warfarin
39
Q

Side effects of cyclosporine

A 
GI- V/D/anorexia
benign gingival hyperplasia
papillomatosis/histiocytomas
hirsutism
fatal systemic toxoplasmosis in cats
40
Q

MOA of tetracycline and niacinamide

A

Exact MOA unknown
tetracycline: anti-inflammatory, affects complement and Ab production, inhibits leukocyte chemotaxis, PG synthesis

niacinamide: blocks Ag specific IgE induced histamine release, inhibits mast cell degranulation

41
Q

Side effects of tetracycline/niacinamide

A

V/D/anorexia
elevated liver enzymes (niacinamide)
enamel hypoplasia and esophageal erosions/ulcerations (tetracycline)

42
Q

MOA of pentoxifylline

A

methylxanthine derivative

increases microcirculation via increased RBC flexibility
decreases platelet aggregation
decreases leukocyte response to IL-1/TNF-alpha
decreased production of IL-1, -4, -12, TNF-alpha

43
Q

Side effects of pentoxifylline

A

V/D
dizziness in people
EM- 2 cases reported

44
Q

MOA of dapsone

A

interferes w/ myeloperoxidase activity

decreases complement activity, mast cell degranulation, Ab production

45
Q

Side effects of dapsone

A

myelosuppression (anemia, neutropenia, thrombocytopenia)
hepatotoxicity
GI
CADR

46
Q

MOA of human IVIG

A

interferes w/ Fas-Fas ligand apoptosis
inhibits T cell proliferation
eliminates circulating immune complexes

47
Q

Side effects of IVIG

A

anaphylaxis during infusion

acute renal failure

48
Q

MOA of gold salts (chrysotherapy)

A

inhibit lysosomal enzymes, complement, chemotaxis, DNA/RNA synthesis, Ig synthesis
suppresses inflammatory mediator release, suppressor T cells

49
Q

Side effects of gold salts

A

myelosuppression
oral ulceration
glomerulonephropathy
fatal TEN

50
Q

MOA of colchicine

A

suppresses neutrophil chemotaxis

inhibits lysosomal degranulation, Ig secretion, IL-1 production, histamine release, cell division

51
Q

Side effects of colchicine

A

GI

myelosuppression (when given w/ NSAIDs)

52
Q

Which drugs should colchicine NOT be used with?

A

azathioprine and chlorambucil

53
Q

Which diseases is colchicine commonly used for?

A

Shar Pei fever, amyloidosis, EBA, JEB

54
Q

MOA of imiquimod

A

activation of TLR7–> IFN-alpha, IL-12, TNF-alpha secretion–> Th1 response and cell-mediated immunity

55
Q

Side effects of imiquimod

A

local irritation- burning, erythema, pain, erosion, oozing

depigmentation/hair loss after use

Pharmacology (2 decks)

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