immune modulating and hematology drugs Flashcards
goal of immunosuppressive drugs
-treat immune-mediated diseases (reduce clinical signs, “cure”)
-immune system is overactive and is attacking normal host cells.
-immunomodulation: favoring one immune response while minimizing another happens.
glucocorticoids as immune suppressing drugs
-non-specific response, most common treatment of immune mediated conditions.
* Anti-inflammatory vs immunosuppressive effect
– Depends on dose used
* Immunosuppression: typically ≥ 2 mg/kg/day (prednisolone)
-mechanism: altered leukocyte migration & function- decreasing antibody production at a high dose.
glucocorticoid mechanism as immune suppressing drug
- Altered leukocyte migration & function:
- ↓ function of monocytes and macrophages
– ↓ Ig receptors, impaired phagocytosis - ↓ lymphocyte function
– Cell-mediated immunity decreased most
– ↓ antibody production at high dose.
1st line systemic immunosuppressive:
Glucocorticoids
-Prednisone, prednisolone
– Dexamethasone
-interchangeable in patients.
-short acting or long acting injectable formulations.
– Acetate = long-acting (prednisolone or methylprednisolone)
– Succinate = short-acting (dexamethasone)
-start in clinic then send home orally, taper slowly.
1st or 2nd line systemic immunosuppressive:
Cyclosporine (AtopicaTM) mechanism of action
-ciclosporine, cyclosporin A:
* Inhibits the enzyme which will Prevent induction of genes coding for cytokines & their receptors (hence “immunomodulating”)
– End result: ↓ IL-2 production.
* ↓ cytokines leads to inhibition of:
– T-lymphocyte activation, chemotaxis
– Antigen-presenting cells (Langerhans)
– Mast cell and eosinophil infiltration
Cyclosporine (AtopicaTM)
-types matter know the different formulations.
-Capsules (dogs) – atopic dermatitis
* Solution (cats) – various derm conditions.
-topical (opthalmic) optimmune formulation for eyes.
* Used extralabel for other imm-med dz
-plasma [ ] doesn’t correlate well with efficacy or safety.
-use PD monitoring activity of drug. with IL-2 essay.
-very variable between animals and formulation, compounded is difficult.
Adverse effects of cyclosporine (atopica)
-vomiting 31%
-GI disorder/ diarrhea 18%
-gingival hyperplasia 2%
-***immunosuppression: 2 degree infections rare. but big AE. with high dose and long term therapy.
-drug interactions p-Gp and CYP substrates.
Cyclosporine in cats
-AtopicaTM oral solution for cats:
* Indication: Control of feline allergic dermatitis
* Used for other feline immune-mediated dermatoses:
– Eosinophilic granuloma/indolent ulcer
– Plasmacytic stomatitis
-improvement in most cats, work great.
Azathioprine (Imuran®)
2nd line systemic immunosuppressive
-oral or injectable human products only
-mechanism: purine anit-metabolite interfers with DNA synthesis.
-metabolized in liver has active metabolites.
- Variety of immunosuppressive uses in dogs
– Lymphocytes have to make their own purines so susceptible to drug compared to other cells.
Azathioprine (Imuran®)
Azathioprine adverse effects
- Myelosuppression:
– Especially cats (↓ hepatic clearance = ↑ drug exposure)
-don’t use in CATS
– Anemia (common, but not severe) - ↑ liver enzymes (~15% of dogs, dose-dependent)
- Pancreatitis
- Rebound “hyper-immune”
response possible if drug
rapidly discontinued, so
taper slowly
2nd-line systemic immunosuppressive:
Chlorambucil (Leukeran®)
- Alkylating agent which cross-links DNA.
- Myelosuppression / vomiting are common: Fanconi’s syndrome (defective renal tubular reabsorption) &
neurologic signs have been reported, but are very rare - Expensive, so used for cats
and small dogs - considered “steroid-sparing”
-used for * Lymphocytic/plasmacytic infiltrative diseases
– Inflammatory bowel disease - Indolent ulcers
- Pemphigus
- Atopy
ApoquelTM (oclacitinib) – mechanism veterinary formulation
-derm specific immunosuppresive drug
Janus kinase (JAK) inhibitors:
* Blocks intra-cellular communication
* Inhibits pruritic & pro-inflammatory cytokines (IL-31) which is (JAK1 or JAK3 dependent)
-decreases IL -31 which is the pruritic cytokine related to being itchy.
-indication: control of pruritus associated with allergic dermatitis, and for the control of atopic dermatitis in dogs at least 12 months of age.
ApoquelTM (oclacitinib) AE
-derm specific immunosuppresive drug
Rapid effect is typical
* Faster than cyclosporine
Adverse events:
* Immunosuppression (2⁰ infection, demodecosis)
* Low incidence of vomit / diarrhea Derm-specific immunosuppressive drugs
cytopoint
-derm specific immunosuppressive drug.
* Not actually a drug: canine monoclonal antibody against interleukin-31
– Same target compound as Apoquel – but different method.
* Indication: “Aids in the reduction of clinical signs associated with atopic dermatitis in dogs”
-dose not solve the underlying allergy problem.
– Reduces pruritis in dogs with atopic dermatitis.
-long term SQ injection >30 d.
Drugs affecting coagulation
- Heparin
- Calcium chelators
- Vit K antag. (warfarin, dicoumarol
