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Veterinary Clinical Pharmacology > Immunsuppressants Pharm > Flashcards

Immunsuppressants Pharm Flashcards

1
Q

Classes of immunsuppressants? (6)

A 
Glucocorticoids
Calcineurin Inhibitors
Purine Interferants
Pyrimidine interferants
JAK 1&3 inhibitors
Alkylating agents
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2
Q

define molecular mimicry

A

Similarity between foreign and self peptides resulting in cross-reactivity of B and T lymphocytes.

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3
Q

Conditions that could potentially lead to molecular mimicry & autoimmune disease in animals? (3)

A

Infection
Neoplasia
Immunization

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4
Q

list the 4 glucocorticoids in order from least potent to most potent

A

hydrocortisone
prednisone/olone
dexamethasone
budesonide

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5
Q

True or False?

Glucocorticoid receptors are present in almost every cell in the body?

A

true

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6
Q

anti-inflammatory dose of prednisone/olone (in mg/kg and dosing duration)

A

Anti-inflammatory
- 0.5-1 mg/kg SID

others...
Physiologic
   - 0.25-0.5 mg/kg SID
Immunosuppressive
   - 1-2 mg/kg SID
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7
Q

Half-life of Prednisone/olone?

A

24 hr

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8
Q

Maximum dose of pred per day?

A

60-80 mg regardless of body weight

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9
Q

_____ (a calcineurin inhibitor) is FDA approved for alleric dermatitis in dogs and cats.

A

cyclosporine

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10
Q

True or False?

Generic cyclosporines have decreased bioavailability.

A

True. Need unmodified form.

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11
Q

True or false?

Cyclosporine is an inexpensive drug.

A

False! Super spendy.

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12
Q

Cyclosporine can be combined with ____ (an anti-fungal drug) to increase it’s bioavailability.

A

ketoconazole 2.5 mg/kg BID

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13
Q

Mycophenolate mofetil can be administered by what routes?

A

PO, IV

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14
Q

True or false?

Mycophenolate mofetil is expensive.

A

False. Cheaper option for big dogs.

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15
Q

True or false?

Mycophenolate mofetil is toxic to cats.

A

False! Azathioprine is.

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16
Q

True or false? The active metabolite of leflunomide is highly protein bound.

A

True

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17
Q

True or false?

Leflunomide is the active form of the drug?

A

False. It is the prodrug form.

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18
Q

Mechanism of action/effects of:

Apoquel

A

JAK 1&3 inhibitor -> decreased synthesis of inflammatory cytokines ESPECIALLY IL-31 -> decreased pruritis in dogs

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19
Q

What are some DDX for allergic Dz with regaurds to immunosuppressant therapy

A
  • anti-inflammatory
  • RAD (reactive airway Dz)
  • atopy
  • mild IBD
  • mild CNS noninfectious inflammatory Dz
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20
Q

What are some immune mediated and autoimmune DDX with regards to immunosuppressant therapy

A
  • IMHA
  • ITP
  • severe IBD
  • Pemphigous
  • SLE
  • Severe CNS non infectious inflammatory Dz
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21
Q

T or F

in cats you should always use prednisolone as they don’t readily convert prednisone to it’s active form

A

TRUE

22
Q

Mechanism of action/effects of:

Alkylating agents: (____ & ____)

A

Chlorambucil & cyclophasphamide

Cross-link DNA resulting in altered protein synthesis. and Cytotoxic to proliferating leukocytes.

23
Q

Mechanism of action/effects of:

Leflunomide & Arava (human product)

A

Pyrimidine interferant -> decreased DNA and RNA synthesis -> specifically affects B&T lymphocytes because they lack a salvage pathway.

24
Q

Mechanism of action/effects of:

mycophenolate mofetil

A

non-competitive, reversible inhibitor of inosine-5-monophosphate dehydrogenase (IMPDH) -> decreased synthesis of DNA, RNA, & glycoproteins

25
Q

Mechanism of action/effects of:

Azathioprine

A

purine interferant -> inhibits incorporation of purines into DNA -> decreased proliferation of lymphocytes

26
Q

what are common clinical uses for calcineurin inhibitors

A
  • allergic dermatitis
  • perianal fistulas
  • KCS (ophthalmic drops)
  • IMHA
  • ITP
  • IMPA
27
Q

Mechanism of action/effects of:

glucocorticoids (4 main effects with respect to the immune system)

A

o decreased capillary permeability ->decreased migration of neutrophils.
o decreased lymphocyte production
o decreased cytokine release
o Stabilization of lysosomes (decreased release of free radicals?)

28
Q

clinical uses for:

apoquel

A

atopic dermatitis in dogs

IBD?

29
Q 
clinical uses for: 
Alkylating agents (chlorambucil & Cyclophosphamide)
A

Chlorambucil:

  • Feline
    • IBD
    • GI lymphoma
  • K9
    • IBD
    • oncology

Cyclophosphamide: oncology (k9 and feline)

30
Q

clinical uses for:

leflunomide

A

immune mediated polyarthropathy (IMPA)
ITP (immune mediated thrombocytopenia maybe)
IMHA
+/- colorectal polyps

31
Q

clinical uses for:

mycophenolate mofetil

A

IMHA
ITP
Derm conditions
IBD?

32
Q

true or false?

azathioprine is FDA approved for use in dogs and cats.

A

false. FDA approved in humans. TOXIC IN CATS!

33
Q

clinical uses for:

azathioprine

A

Dogs only!
IBD, IMHA, ITP
can use with glucocorticoids to reduce dose.

34
Q

calcineurin inhibitors:
____ is used for systemic disease;
____ is used for focal disease

A

cyclosporine for systemic,

tacrolimus for focal (topical)

35
Q

adverse effects of:

apoquel

A
  • can develop serious infections
  • NOT sufficient studies done on concurrent use with other immune suppressants
  • GI signs - vomiting, diarrhea
36
Q 
adverse effects of: 
alkylating agents (chlorambucil and cyclophosphamide)
A
  • GI - vomiting, diarrhea, anorexia
  • bone marrow suppression
  • neurotoxicity (rare)
37
Q

adverse effects of:

leflunomide

A
  • **Bone marrow suppression!!!
  • GI: vomiting, diarrhea
  • Severe idiosyncratic reactions: seen in dogs with poor liver function or skin issues
    • hepatotoxicity
    • ***toxic epidermal necrolysis
38
Q

adverse effects of:

mycophenolate mofetil

A

GI - diarrhea, anorexia, vomiting

bone marrow suppression

39
Q

adverse effects of:

azathioprine

A
  • ** ACUTE hepatotoxicity - monitor liver enz. frequently!
  • bone marrow suppression - delayed, reversible
  • GI - vomiting, diarrhea
  • immune suppression
40
Q

Never use azathioprine in what species?!

A

MEE-MOWS

41
Q

adverse effects of:

glucocorticoids

A 
PUPD
polyphagia?
panting
immune suppression
dysregulation of glucose 
alopecia
weakness
muscle wasting
suppression of HPA axis
42
Q 
adverse effects of: 
calcineurin inhibitors (5 things)
A

immune suppression -> give killed vaccines
hepatotoxicity -> monitor!
thromboembolism
***Gingival hyperplasia
drug interactions! inhibition of CYP450 and P-gp!

43
Q

how does the dosing interval of dexamethasone differ from other glucocorticoids and why?

A

Dexamethasone is ~7 x’s as potent as pred and the half life is ~48 hours!

44
Q

What is the max dose of pred per day?

A

60-80 mg

45
Q

what are some adverse effects of glucocorticoid administration

A
  • muscle catabolism
  • PU/PD
  • Panting
  • Weakness
  • Alopecia
  • Suppression of HPA axis
  • immune suppression
  • dysregulation of glucose
46
Q

what clinical scenero would be a good use for tacrolimus

A
  • it is a calcineurin inhibitor which is an enzyme crucial for T cell activation.
  • it is generally used for peri-anal fistulas
47
Q

what are common clinical uses for calcineurin inhibitors

A
  • allergic dermatitis
  • perianal fistulas
  • KCS (ophthalmic drops)
  • IMHA
  • ITP
  • IMPA
48
Q

what advantage would you get from combinding a Cyclosporine, a calcineurin inhibitor with ketoconazole

A

it increases the oral bioavailability of the cyclosporine by inhibiting CYP 450 thereby increasing efficacy of the drug, and lowering cost.

49
Q

what are some adverse effects of calcineurin inhibitors

A
  • gingival hyperplasia
  • immunosuppression
  • hepatotoxicity
  • thromboembolism
  • drug interactions
    • inhibits CYP 450
    • inhibits P-glp
50
Q

why should you NEVER used mycophenolate mofetil concurrently with azathioprine?

A

they both inhibit purine synthesis!

Veterinary Clinical Pharmacology (6 decks)

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