Treatment Options for Immune-Mediated Disease Flashcards
What does treatment of immune-mediated disease rely on?
Halting ongoing damage whilst satisfying nutritional and nursing requirements
What form the mainstay of immune-mediated disease therapy?
Steroids
What are the potential adjunctive therapies for immune-mediated disease?
Topical therapy/GI barrier protection Blood products/Darbepoietin Diet Danaxol?/plasmapheresis? Splenectomy?
What nursing tasks are vital to patient treatment?
If recumbent then urination/defaecation/hygiene/exercise
Physical signs of clinical deterioration
Analgesia and general comfort of the patient
Nutrition - feeding tube needed?
Proper access to water and ability to drink
IV catheter care and IVFT
Diagnostic samples
How do corticosteroids exert their effects?
Associate with binding proteins transcortin and albumin
Following dissociation from binding proteins passively diffuse into cell and bind to cytoplasmic receptor
Conformational change of receptor unmasks DNA binding domain, associates with GREs following nuclear translocation
Which inflammatory cells are the target for corticosteroids?
Eosinophils, T cells, Mast cells, Macrophage, Dendritic cells
What structural cells are the target for corticosteroids?
Epithelium, endothelium, airway smooth muscle, mucous glands
What are the differences in potency and DOA of most commonly used corticosteroids?
Prednisolone - potency=1.00, dose=2-4mg/kg/d, DOA=12-36h
Methylpred - potency=1.25, dose=2-4mg/kg/d, DOA=12-36h
Dexamethasone - potency=7-10, dose=0.2-0.5mg/kg/d, DOA=>48h
What are the potential adverse effects of corticosteroids?
Have effects on CNS, musculoskeletal system, GIT, fluid and electrolyte balance, metabolic, endocrine and immune system
Which drug acts at the mitotic stage of the cell cycle?
Vinca alkaloids
Which drugs act at G1 stage of the cell cycle?
Calcineurin inhibitors
Leflunomide
What drug acts between G1 and S stages of the cell cycle?
Rapamycin
Which drugs act as the S stage of the cell cycle?
Corticosteroids
Antimetabolites
Mycophenolate mofetil
What is the mechanism of action of alkylating agents?
Alkynate DNA causing breaks in molecule and cross-linking of twin strands
Inhibit protein synthesis in resting cells, prevent mitosis and kill dividing cells
What are some examples of alkylating agents
Cyclophosphamide, ifosfamide, chlorambucil
Melphalan, mechlorethmine, nitrosoureas
Procarbazin, dacarbazine
What are the characteristics of chlorambucil?
Rapidly metabolised to phenylacetic acid mustard
Slowest acting, least toxic of all alkylating agents
Myelosuppression generally not observed until administered for > 1 month
Urinary and faecal excretion
Administered without food
What are two examples of antimetabolites?
Azathioprine
Methotrexate
What are the characteristics of antimetabolites?
Greater decrease of cellular than humoral immunity
Hepatic metabolism through several stages to thiouric acids
Compete with endogenous adenine and guanine resulting in non-functional DNA strands
Slow immunosuppressive effect?
Haematological, GI, hepatic +/- neuromuscular side effects
What are vinca alkaloids?
Originally extracted from the common periwinkle plant
Vincristine and vinblastine are the most commonly used
What are the characteristics of vincristine and vinblastine?
Bind to tubulin, blocking polymerisation, also break down pre-formed microtubles - increased release of PLTs from megakaryocytes
Can be fiven as bolus IV or to pre-load PLTs
Severe extra-vascular vesicants
Haematological, GI, neurological toxicity
What are two examples of calcineurin inhibitors?
Ciclosporin
Tacrolimus
What are the characteristics of ciclosporin?
IV and oral forms
Large volume of distribution with primary hepatic metabolism
Therapeutic drug monitoring crucial acutely and chronically
GI, renal, hepatic toxicity also hirtsutism, gingival hyperplasia, papillomatosis =/- diabetogenic
What is human IVIG?
Polyspecific IgG derived from healthy donor plasma
Primary use in human medicine is in the treatment of immunodeficiency
How does human IVIG work?
Blockade of Fc receptors on mononuclear phagocytic cells accounts for rapid response
Inhibits phagocytosis of Ab-coated RCs
What can human IVIG be used to treat?
Acute IMHA, immune-mediated non-regenerative anaemia, pure red cell aplasia, ITP, EM, TEN and SARDS
What are the disadvantages of human IVIG?
Thromboembolism, hypersensitivity possible
High cost, limited availability
What other agents are also used to treat immune-mediated disease?
Mycophenolate mofetil Leflunomide Chrysotherapy Levamisole Rapamycin Melatonin
How should treatment for immune-mediated disease start?
With prednisone/prednisolone at 3-4mg/kg/d PO
What risks need to be considered when starting treatment for immune-mediated disease?
Use maximum dose of preds in dogs >30kg
Occult rickettsial/protozoal infection = doxycycline
If IMHA or aggressive I-M disease consider adjunctive agent from the beginning
Always consider co-morbidities
How soon should a clinical response be assessed?
Over 7 days
What should be done if there is a poor response to treatment?
Add adjunctive immuno-suppressants if not already being administered
What factors need to be monitored in treatment of immune-mediated disease?
CBA and UA every 7-14d
+/- synovial fluid monitoring
How should treatment for immune-mediated disease be terminated?
Taper corticosteroid over 3-4 month period following initial remission with a 20-25% decrease in dose every 4-6 weeks
