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 () mechanism of action
-ciclosporine, cyclosporin A: AtopicaTM**
* 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 (
2nd line systemic immunosuppressive
-Imuran®)
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 () – mechanism/ veterinary formulation/ uses
-oclacitinib active ingredient
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
Drugs affecting clot formation
-Streptokinase, tPA
Drugs affecting platelets:
- Aspirin (ASA)
- clopidogrel
Drugs affecting RBCs
- Erythropoietin & variants (RBC stimulation)
- NEW: molidustat (stimulation)
Drugs affecting WBCs
- Goal: ↑ WBC numbers & function
- Recombinant granulocyte colony-
stimulating factors (g-CSF) - Drugs: Neupogen, Neulasta
Immune “stimulants
- exogenous Granulocyte-Colony Stimulating Factor (G-CSF)
- Uses:
– ↑ circulating neutrophil counts
– activate neutrophil function (phagocytosis) - Filgrastim is CSF molecule =pegfilgrastim human products are (Neupogen, Neulasta) =
recombinant form of human G-CSF. you can give human form to dogs to increase WBC count.
– Used for neutropenic patients during chemotherapy
– Occasionally used in canine oncology patients
Erythropoietin (EPO, “Epoetin”) uses
-Red blood cell stimulation (erythropoietics)
– Produced by kidney peritubular interstitial cells, goes to blood then BM increases RBC.
-neg feedback in kidneys.
– Injectable formulations only: peptide hormone
– Uses:
* Anemia due to chronic kidney disease
* Myelodysplasia
* Performance-enhancing drug
-could get immune response with repeated use
antithrombotic drugs what do they prevent
-prevent thrombosis (formation of a solid blood clot in vessel)
-arterial or venous
-pulmonary or DIC
-clot is formed by subendo tissue exposed, coagulation of platelets, broken down by fibrinolysis.
calcium chelators
– Sodium citrate, sodium oxalate, EDTA, sodium fluoride
– good for blood collection, blood storage
– But NOT used as anticoagulant drugs
-calcium chelation could impact fibrin clot formation, is a co factor in many steps of coagulation pathway.
Anticoagulants = heparin
- Produced in mast cells (proteoglycan)
- Inactivates Factors IX, X, XI, XII (along with antithrombin)
- Prevents conversion of prothrombin to thrombin
- Prevents conversion of fibrinogen to fibrin
- Prevents stabilization of fibrin clots (inhibition of factor XIII)
- Heparin used in multiple types of antithrombotic drugs
- Given i.v. or s.c
anticoagulant= coumarin derivatives
– dicoumarol, warfarin
– Interfere with vitamin K-dependent coagulation factors
– Long-term oral administration may be required
– Dose modification based on observed Prothrombin Time (PT)
-treat toxicity with vitamin K injection
Thrombolytics
- Enhance clot breakdown (fibrinolysis) by stimulating
conversion of plasminogen to plasmin
1. Streptokinase
2. tissue-type plasminogen activator (tPA)
Drugs affecting platelet activation and how
-clopidogrel, aspirin
-stops thromboxane
-decreases aggregation and plug formation.
-used in DIC
