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Pharmacology > Immunosuppressive Drugs therapy > Flashcards

Immunosuppressive Drugs therapy Flashcards

1
Q

Why use immunosuppressive drugs?

A

-treat immune mediated disease
TO TREAT CLINICAL SIGNS

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2
Q

Balance of immune mediated disease treatment

A

All about risk management; no cure
-balance between adverse effects and the disease itself

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3
Q

Examples of immune mediated diseases

A

-immune mediated hemolytic anemia or thrombocytopenia
-systemic lupus erythematosus
-inflammatory bowel disease
-immune mediated polyarthritis
-immune mediated glomerulonephritis
-myasthenia gravis
-immune mediated derm diseases: atopic dermatitis

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4
Q

Immunomodulating

A

-favour one immune response while minimizing another
*mild changes

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5
Q

Dosing for severe immunosuppression

A

-high dose results in prolonged duration and leads to severe immunosuppression

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6
Q

Timing of immunosuppressive effects

A

-typically take a few weeks before clinical efficacy is observed

-steroid induced immunosuppression occurs faster (5-10 days)

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7
Q

Glucocorticoids

A

Most basic immunosuppressive
-non specific response- does not target specific tissues or pathways

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8
Q

Anti inflammatory vs. immunosuppressive effects of Glucocorticoids

A

-depends on the dose
-higher dose=immunosuppressive
-lower dose=anti-inflammatory

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9
Q

Immunosuppressive effects of Glucocorticoids

A

1.Decreased function of monocytes and macrophages
-decrease in Ig receptors, impaired phagocytosis

  1. Decreased lymphocyte function
    -cell mediated immunity decreased
    -decreased antibody production at high dose
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10
Q

Steroid general inhibition

A

-inhibits prostaglandins, prostacyclin, thromboxanes
AND leukotrienes

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11
Q

Types of glucocorticoids

A

-prednisone, prednisolone (horses and cats for sure)
-dexmethasone

**dex more potent, but can interchange between them in most patients)

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12
Q

Short acting and long acting formulations

A

Long acting: acetate (prednisolone or methylprednisolone)
*dont start with this

Short acting= succinate (dexmethasone)

**put typically start parenteral in clinic, and then continue orally

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13
Q

Immunosuppressive treatment pattern

A

-start aggressively and then taper slowly
*Because if you need it then you need it!

-unknown whether best to do once a day, split dose over twice a day or what

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14
Q

Cyclosporine (Atopica)

A

-1st or 2nd line immunosuppressive drug
(can do this before glucocorticoids or after; atopica more expensive)

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15
Q

Mechanism of Cyclosporine

A

**specific mechanism of action unlike glucocorticoids
Inhibits enzyme that prevents induction of genes coding for cytokines and their receptors

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16
Q

What does cyclosporin reduction of cytokines result in?

A

Inhibition of:
-T cell activation, chemotaxis
-antigen presenting cells
-mast cell and eosinophil infiltration

17
Q

Vet licensed oral forms

A

-Capsules (dogs)= atopica dermatitis

-solution (cats)= various derm conditions

-Extralabel for other immune mediated disease

18
Q

Cyclosporine pharmacokinetics

A

-oral bioavailability is highly variable and depends on formulation

-plasma concentrations do not correlated with efficacy/safety

-can monitor IL-2 assays to monitor drug- but rare and only in one lab in USA

19
Q

Topical cyclosporine

A

Optimmune
-ophthalmic
-used for keratoconjunctivitis sicca (dry eye) and chronic superficial keratitis in dogs

20
Q

Compounded cyclosporine

A

Capsule potency was found to be relatively the same

Solution potency- not good, many too high or too low
**things in solution are harder to compound because stability and expiry poor compared to capsules

21
Q

Adverse effects of cyclosporine

A

-vomiting

-GI disorder/diarrhea
*few actually have to stop the drug

-gingival hyperplasia

-immunosuppresions
*secondary infections are uncommon but can occur

-drug interactions (P-gp/CYP substrates)

22
Q

Use of Atopical oral solution for cats

A

Used to control feline allergic dermatitis
-also used for eosinophilic granuloma/indolent ulcer AND plasmacytic stomatitis

23
Q

Azathioprine (Imuran)

A

-2nd line systemic immunosuppressive
-oral or injectable products available (ALL HUMAN, NO VET)

24
Q

Mechanism of Azathioprine

A

Purine anti-metabolite
-interferes with DNA synthesis

25
Q

Metabolism of Azathioprine

A

-metabolized in liver to a variety of active metabolites and inactive metabolites
*but variety between animals

26
Q

Azathioprine uses in dogs

A

Immunosuppressive
-lymphocytes have to make their own purines so more susceptible to azathioprine than other cell types

27
Q

Azathioprine adverse effects

A
  1. Myelosuppression
    -especially in cats because they dont clear well in liver and increase their drug exposure SO DONT USE
    -anemia
  2. Increased liver enzymes
  3. Pancreatitis
  4. Rebound hyper immune response possible if drug rapidly discontinued so taper slowly
28
Q

Chlorambucil (Leukeran)

A

-2nd line systemic immunosuppressive
-Alkylating agent which cross links DNA
-no vet product
-less potent/toxic version of chemotherapy drugs
-expensive, used for cats and small dogs= considered steroid sparing

29
Q

Side effects of Chlorambucil

A

-Myelosuppression
-vomiting
-Rare: Fanconi’s syndrome and neurological signs reported

30
Q

Uses of Chlorambucil

A

-lymphocytic/plamacytic infiltrative diseases
>inflammatory bowel disease

-indolent ulcers

-pemphigus

-atopy

31
Q

IMHA possible drugs

A

-Leflunomide
-Mycophenolate Mofetil

**be aware that they exist but know that other drugs are likely better

32
Q

Tacrolimus (Protopic)

A

-human ointment; similar function to cyclosporine

-can be used for atopy but expensive!

33
Q

Apoquel (oclacitinib)

A

-derm specific immunosuppresive drugs

-used for control of pruritus associated with allergic dermatitis and for control of atopic dermatitis in dogs at least 12 mths of age

-rapid effect

-BID dosing, for 14 days (may need recurring doses)

34
Q

Mechanism of Apoquel

A

Janus kinase inhibitors
-blocks the intra cellular communication
-inhibits pruritic and pro inflammatory cytokines (IL-31) because they depend on JAK1 and JAK 3 enzyme activity
-minimal effet on JAK2 hematopoiesis

35
Q

Adverse events of Apoquel

A

-immunosuppression= secondary infection, demodecosis

-low incidence of vomit/diarrhea

36
Q

Cytopoint

A

-Canine monoclonal antibody against interleukin-31
*same target as Apoquel but different method

37
Q

Indication for Cytopoint

A

Aids in the reduction of clinical signs associated with atopic dermatitis in dogs
-reduce pruritis

38
Q

Cytopoint administration

A

-SQ injection
-long duration of effect (>30days)

-can be used concurrently with other atopic derm therapy (trial and error approach…see what works)

39
Q

Cytopoint efficacy

A

-effects decreasing overtime but some cases may not need it monthly
-stop clinical signs/dermatitis but does not solve the whole problem

Pharmacology (33 decks)

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