Immunsuppressants Pharm Flashcards
Classes of immunsuppressants? (6)
Glucocorticoids Calcineurin Inhibitors Purine Interferants Pyrimidine interferants JAK 1&3 inhibitors Alkylating agents
define molecular mimicry
Similarity between foreign and self peptides resulting in cross-reactivity of B and T lymphocytes.
Conditions that could potentially lead to molecular mimicry & autoimmune disease in animals? (3)
Infection
Neoplasia
Immunization
list the 4 glucocorticoids in order from least potent to most potent
hydrocortisone
prednisone/olone
dexamethasone
budesonide
True or False?
Glucocorticoid receptors are present in almost every cell in the body?
true
anti-inflammatory dose of prednisone/olone (in mg/kg and dosing duration)
Anti-inflammatory
- 0.5-1 mg/kg SID
others... Physiologic - 0.25-0.5 mg/kg SID Immunosuppressive - 1-2 mg/kg SID
Half-life of Prednisone/olone?
24 hr
Maximum dose of pred per day?
60-80 mg regardless of body weight
_____ (a calcineurin inhibitor) is FDA approved for alleric dermatitis in dogs and cats.
cyclosporine
True or False?
Generic cyclosporines have decreased bioavailability.
True. Need unmodified form.
True or false?
Cyclosporine is an inexpensive drug.
False! Super spendy.
Cyclosporine can be combined with ____ (an anti-fungal drug) to increase it’s bioavailability.
ketoconazole 2.5 mg/kg BID
Mycophenolate mofetil can be administered by what routes?
PO, IV
True or false?
Mycophenolate mofetil is expensive.
False. Cheaper option for big dogs.
True or false?
Mycophenolate mofetil is toxic to cats.
False! Azathioprine is.
True or false? The active metabolite of leflunomide is highly protein bound.
True
True or false?
Leflunomide is the active form of the drug?
False. It is the prodrug form.
Mechanism of action/effects of:
Apoquel
JAK 1&3 inhibitor -> decreased synthesis of inflammatory cytokines ESPECIALLY IL-31 -> decreased pruritis in dogs
What are some DDX for allergic Dz with regaurds to immunosuppressant therapy
- anti-inflammatory
- RAD (reactive airway Dz)
- atopy
- mild IBD
- mild CNS noninfectious inflammatory Dz
What are some immune mediated and autoimmune DDX with regards to immunosuppressant therapy
- IMHA
- ITP
- severe IBD
- Pemphigous
- SLE
- Severe CNS non infectious inflammatory Dz
T or F
in cats you should always use prednisolone as they don’t readily convert prednisone to it’s active form
TRUE
Mechanism of action/effects of:
Alkylating agents: (____ & ____)
Chlorambucil & cyclophasphamide
Cross-link DNA resulting in altered protein synthesis. and Cytotoxic to proliferating leukocytes.
Mechanism of action/effects of:
Leflunomide & Arava (human product)
Pyrimidine interferant -> decreased DNA and RNA synthesis -> specifically affects B&T lymphocytes because they lack a salvage pathway.
Mechanism of action/effects of:
mycophenolate mofetil
non-competitive, reversible inhibitor of inosine-5-monophosphate dehydrogenase (IMPDH) -> decreased synthesis of DNA, RNA, & glycoproteins
Mechanism of action/effects of:
Azathioprine
purine interferant -> inhibits incorporation of purines into DNA -> decreased proliferation of lymphocytes
what are common clinical uses for calcineurin inhibitors
- allergic dermatitis
- perianal fistulas
- KCS (ophthalmic drops)
- IMHA
- ITP
- IMPA
Mechanism of action/effects of:
glucocorticoids (4 main effects with respect to the immune system)
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?)
clinical uses for:
apoquel
atopic dermatitis in dogs
IBD?
clinical uses for: Alkylating agents (chlorambucil & Cyclophosphamide)
Chlorambucil:
- Feline
- IBD
- GI lymphoma
- K9
- IBD
- oncology
Cyclophosphamide: oncology (k9 and feline)
clinical uses for:
leflunomide
immune mediated polyarthropathy (IMPA)
ITP (immune mediated thrombocytopenia maybe)
IMHA
+/- colorectal polyps
clinical uses for:
mycophenolate mofetil
IMHA
ITP
Derm conditions
IBD?
true or false?
azathioprine is FDA approved for use in dogs and cats.
false. FDA approved in humans. TOXIC IN CATS!
clinical uses for:
azathioprine
Dogs only!
IBD, IMHA, ITP
can use with glucocorticoids to reduce dose.
calcineurin inhibitors:
____ is used for systemic disease;
____ is used for focal disease
cyclosporine for systemic,
tacrolimus for focal (topical)
adverse effects of:
apoquel
- can develop serious infections
- NOT sufficient studies done on concurrent use with other immune suppressants
- GI signs - vomiting, diarrhea
adverse effects of: alkylating agents (chlorambucil and cyclophosphamide)
- GI - vomiting, diarrhea, anorexia
- bone marrow suppression
- neurotoxicity (rare)
adverse effects of:
leflunomide
- **Bone marrow suppression!!!
- GI: vomiting, diarrhea
- Severe idiosyncratic reactions: seen in dogs with poor liver function or skin issues
- hepatotoxicity
- ***toxic epidermal necrolysis
adverse effects of:
mycophenolate mofetil
GI - diarrhea, anorexia, vomiting
bone marrow suppression
adverse effects of:
azathioprine
- ** ACUTE hepatotoxicity - monitor liver enz. frequently!
- bone marrow suppression - delayed, reversible
- GI - vomiting, diarrhea
- immune suppression
Never use azathioprine in what species?!
MEE-MOWS
adverse effects of:
glucocorticoids
PUPD polyphagia? panting immune suppression dysregulation of glucose alopecia weakness muscle wasting suppression of HPA axis
adverse effects of: calcineurin inhibitors (5 things)
immune suppression -> give killed vaccines
hepatotoxicity -> monitor!
thromboembolism
***Gingival hyperplasia
drug interactions! inhibition of CYP450 and P-gp!
how does the dosing interval of dexamethasone differ from other glucocorticoids and why?
Dexamethasone is ~7 x’s as potent as pred and the half life is ~48 hours!
What is the max dose of pred per day?
60-80 mg
what are some adverse effects of glucocorticoid administration
- muscle catabolism
- PU/PD
- Panting
- Weakness
- Alopecia
- Suppression of HPA axis
- immune suppression
- dysregulation of glucose
what clinical scenero would be a good use for tacrolimus
- it is a calcineurin inhibitor which is an enzyme crucial for T cell activation.
- it is generally used for peri-anal fistulas
what are common clinical uses for calcineurin inhibitors
- allergic dermatitis
- perianal fistulas
- KCS (ophthalmic drops)
- IMHA
- ITP
- IMPA
what advantage would you get from combinding a Cyclosporine, a calcineurin inhibitor with ketoconazole
it increases the oral bioavailability of the cyclosporine by inhibiting CYP 450 thereby increasing efficacy of the drug, and lowering cost.
what are some adverse effects of calcineurin inhibitors
- gingival hyperplasia
- immunosuppression
- hepatotoxicity
- thromboembolism
- drug interactions
- inhibits CYP 450
- inhibits P-glp
why should you NEVER used mycophenolate mofetil concurrently with azathioprine?
they both inhibit purine synthesis!
