Immune-Mediated Dz Tx Flashcards
(38 cards)
Necessary adjunctive therapies for IMD?
- diet
- topical tx and gastrointestinal barrier protection for steroid (only if indicated w/ concurrent liver/spleen dz etc. or thrombocytopenia d/t ^ risk of bleeding from ulcer)
- blood products (esp anaemia) Darbopoietin (erythropoetin substitute)
- ? Danazol (androgen, not used much now, min evidence)
- ? Plasmapheresis (high level establishments, emergency only with intractable haemolysis etc)
What should be cautioned with steroids and nutrition?
- PEG tube risks
- v fibrous tissue formation so when removed septic peritonitis will ensue
Outline nursing care needed for IMD. LOOK UP
> recumbency - UD, hygeine, excercie > physical signs of deterioration - analgesia, comfort > nutrition - naso-oesophageal, oeseophageal, PEG > water > IV catheter care and fluid tx > diagnostic samples > client comms
How do corticosteroids function on a cellular level?
- associate with binding proteins (transcortin and albumin)
- dissociate, passively diffuse into cell
- bind to cytoplasmic receptors (>3)
- conformational change of R unmasks DNA binding domains
- associates with GREs following nuclear translocation
CEellular targets of corticosteroids?
> inflam cells - eosinophils - T cells - mast cells - macrophages - denritic cells > structural cells - epithelium - endothelium - airway smooth muscle - mucous glands
How do different corticosteroids differ?
- GC and MC activity
> dexamethasone NO MC activity, potent GC
> prednisone/prednisolone GC and MC
How do seroids in US and UK differ?
- Prednisolone used for everything UK
- PrednisONE USA
How does potency, duration or action and dose of the 3 main corticosteroids differ? LOOK UP
> prednisolone - potency 1 - dose 2-4mg/kg/d - DOA 12-36 > methylpred - 1.25 - 2-4 - 12-36 > dex - 7-10 - -
Potential adverse effects of immunosuppressive doses of steroids?
> worse in dogs, WARN OWNERS!!!
- sarcopenia (muscle melt away)
- GIT (esp ulceration)
- MC activity -> fluid retention etc. (pred and methyl pred) contraindicated for CHF
- metabolic effects (bone density)
- Cushingoid appearance after 2-3weeks
- immune vulnerability
What other immunosuppressive drugs (other than steroids) can be used for IMD? What stages of the cell cycle do they act at?
> Mitosis phase - Vinca alkaloids (eg. vinblastine) > GI - calcinuerin inhibitors (eg. cyclosporine) - leflunomide ~ G1-S rapamycin (not used vet) > S - steroids - antimetabolites - mycophenolate mofetil
How do alkylating agents work? LOOK UP
- cross-links twin strands
- inhibits protein synthesis in resting cells, prevents mitosis, kills dividing cells
Egs of alkylating agents?
> cyclophosphamide
- now no longer advocated, only for CHOP lymphoma
ifosphamide
chlorambucil
- minimally toxic, min side effects (myelosuppression)
melhalen, mechlorethamine, nitrosoureas
procarbazine, decarbazine
Outline cyclophospmahde
- dont use
Overview of chlorambucil
- rapidly metabolised (mustard thing)
- slowest acting and least toxic of all alkylating agents
- myelosupression only when admin >1 month
- urinary and feacal excretion
- administer without food
Which immunosuppressive drug is contraindicated in cats?
Azathioprene (irreversiple BM suppression)
Overview of azathioprene
- greater effeect on cellular than humoral immunity
- hepatic metabolism
- competes with endogenous A and G nucleotides -> non-fucntional nucleic aid strands
- slow immunosuppressive effect
- haaem, GIT, hepatic +- neuromuscular toxicity (can exacerbate MG)
What can azathioprene be used alongside?
Steroids
Where are vinca alkyloids derived from? Whih are the 2 most common?
> common periwinkle plant!
- vincristine and vinblastine (though blastine not used for IMD)
How do vinca alkaloids work? ROA?
- bind tubulin, block polymerisation
- breakdown preformed microtubules and ^ rate of PLT release from megakaryocytes
> esp good for IM thrombocytopenia (^no. platlets) - bolus IV, or to preload PLTs
- severe extra-vascular vesicants (get it in the vein!!)
How must vinca- alkaloids be given? Side effects?
- IV
- severe extra-vascualr irritation and sloughing
> warm compress and flush saline if injected wrong
> side effects: - haem
- GIT
- neurological tox (megacolon/megaoesophagus w/ repeated dosing)
Vincristine and vinblastine. ALternative drug that is not used d/t severe neutropenia?
> Vinorelbine
- Semi-synthetic derivative of vinblastine, neutropenia
Lic calcineurin inhibitiros?
- Atopica for atopic derm (Ciclosporin)
- Tacrolimus (Anal furunculosis topically)
Cilosporin and dosing
- IV and oral forms
- large volume of distribution and 1* hepatic metabolism
- should probably monitor drug conc (peak @ 2hrs post administration, acute and chronic)
How can dose of ciclosporin be decresed? Side effects?
> Give ketoconazole to inhibit hepatic metabolism
SIde effects
- renal, GI, heptic
- hirsuitism, gingival hyperplasia, paillomatosis
+- diabetogenic (CI in diabetic patients)
