Immunosuppressants Flashcards
Allergic Disease
- Hypersensitivity
- Use an anti-inflammatory NOT an immunosuppressant dose
- Common antigens that most individuals do not respond to lead to inflammation and tissue damage
Immune-mediated disease
- Self antigens
- Foreign antigens
- Failure of tolerance
- Host tissues become 1° or 2° target –> inflammation, tissue damage
Autoimmune disease
- A type of immune-mediated disease
- Self-antigens lead to inflammation and tissue damage
Molecular mimicry
- Similarity between foreign and self peptides results in cross-activation of T or B cells
Hemolytic anemia example of molecular mimicry
- Myocplasma pneumonia
Rheumatic fever after Streptococcus pyogenes infection example of molecular mimicry
- M protein (virulence factor) of Streptococcus pyogenes cross-react with glycoproteins
- Heart, joints, kidney
Immune stimulation and molecular mimicry
- Immunization
- Infection (e.g. Anaplasma, Rickettsia, etc.)
- Neoplasia
- Goal of treatment is to identify and eliminate underlying cause
What is the goal of treatment if you can’t determine the underlying cause?
- Treat clinical signs
- Adverse effects
- Have to use immunosuppressants
Allergic diseases and immunosuppressants
- USE ANTI-INFLAMMATORY DOSES**
e. g. Reactive airway disease, atopy, mild IBD, mild CNS noninfectious inflammatory diseases
Immune-mediated and autoimmune Immunosuppressant philsophy
- Use Immunosuppressive > anti-inflammatory doses
- e.g. IMHA, ITP, Severe IBD, Pemphigus, SLE, Severe CNS non-infectious inflammatory diseases
- These are usually life threatening, and we have to be very agressive
Glucocorticoids Overview
- 1° medication used clinically
- Best, fastest, and cheapest drug
- Mis-used regularly
Relative potencies of glucocorticoids
- Budesonide > Dexamethasone > Prednisone/nisolone > Hydrocortisone
From most potent to least potent
Which steroid (prednisone/prednisolone) do you use in cats and why?
- Cats you use prednisolone because they have decreased conversion from prednisone to prednisolone
- Some subpopulations of dogs that also don’t make this conversion
Mechanism of action of Glucocorticoids in Immunosuppression
- Decreased capillary permeability (decreases extravasation)
- Decreases lymphocyte production
- Decreases cytokine release
- Stabilizes lysosomes (recycling center)
Where are glucocorticoid receptors located?
- EVERY vertebrate animal cell
- However, every individual may have different expression of glucocorticoid receptors
- Because they are merely in every cell, does not mean that they will all react the same
- If we start an an appropriate dose
- Receptors expressed a little differently in every individual
- Other options too
Physiologic dose for Prednisolone/Prednisone
- e.g. dog with Addison’s
- 0.25-0.5 mg/kg SID
- with Dr. Haines we said 0.15-0.3 mg/kg
Anti-inflammatory dose for Prednisone/prednisolone
- 0.5-1 mg/kg SID
Immunosuppressive dose for prednisolone/prednisone
- 2 mg/kg SID
Half life of prednisone/nisolone
- 24 hours approximately
- Therefore we can usually do SID instead of BID
Dexamethasone relative potency to prednisone and half life
- 7 times as potent as pred (divide pred dose by 7)
- Half life ~48 hours
Maximum dose of Prednisone/Prednisolone per day
- 60-80 mg per DAY
- Sensitivity of larger animals tends to be increased with glucocorticoids
- Metered squared dosing
Adverse effects of glucocorticoids
- Muscle catabolism
- PU/PD
- Panting
- Weakness
- SUppression of HPA axis
- Immune suppression
- Dysregulation of glucose
- Basically start looking like a Cushingoid dog
Calcineurin Inhibitors Examples
- Cyclosporine (Atopica)
- FDA approved for allergic dermatitis in dogs and cats
- Tacrolimus used for perianal fistulas as a topical in veterinary medicine
Mechanism of action of Calcineurin inhibitors
- Inhibits enzyme critical for T cell activation
- Calcineurin enzyme helps to import/induce nuclear factor of activated T cells (NFAT) –> this stimulates IL2 which helps to regulate WBC, especially T lymphocytes