Immunosuppressive therapy (Proceedings)

Glucocorticoids

• Effective

• Many routes of administration

Actions

• Redistribution of white blood cells

     o Lymphopenia

     o Neutrophilia

• Decreased vascular permeability

• Monocyte/macrophage function modulation

     o Reduced cytokine production

     o Phagocytosis inhibited

• Antibody production only reduced with long-term aggressive therapy

Side effects

• Most side effects are bothersome, but not dangerous to the patient

     o Panting

     o Thin skin

     o Liver value elevation

     o Polyphagia

     o Pot belly

• PU/PD one of the most bothersome for the owners, consider DDAVP (1-2 drops BID, adjust dose to control signs)

• When serious side effects occur they are bad

     o Colonic ulcers with spinal disease

     o Although gastric changes are common with high dose therapy it does not seem to be a clinical problem

• PTE

• Pancreatitis

Cyclophosphamide

• Nitrogen mustard derivative

• Alkylating agent

     o Cytoxic to resting and dividing cells

     o Also chemo drug

• Inexpensive

• Commonly used as adjunctive therapy

Actions

• Cross links DNA to prevent replication of cells

• More pronounced in B lymphocytes (AB producers)

• Phagocytosis may also be inhibited

• Some question efficacy in immune-mediated disease, especially IMHA

Side effects

• Relatively rare, but when they occur they can be serious

•GI signs (rare)

• Bone marrow suppression (rare, but monitor CBCs regularly)

• Sterile cystitis (monitor UAs)

     o Make sure patient is drinking lots and urinating frequently (usually not a problem since many are on glucocorticoids concurrently, if it does occur it is a tough one to deal with

Dosage

• Usually 50 mg/M2 is used daily for 4 days, stop 3 days and then repeat therapy

• Every other day therapy is also possible

• I rarely use long term and now use it mainly for chemo

• Can be used in cats, not very safe though

Azathioprine

• Relatively inexpensive

• Used as an adjunctive therapy (cut pred faster)

• Side effects very rare, but when they happen they are bad

• My favorite adjunctive therapy with immune-mediated disease

Actions

• Antimetabolite, mainly effects proliferating T-cells

• Antibody production reduced, however not by influencing the B-cells, seems to be a reduction in T-helper cells

Side effects

• Quite rare

• Bone marrow suppression can occur (may be a genetic thing, it is in humans)

     o Monitor CBCs

• Pancreatitis can occur

• Hepatopathies can occur as well

     o Monitor chemistry panels

Dosage

• Start at 2 mg/kg initially daily for 7 days

• Reduce to 0.5 to 1 mg/kg every other day

• Use in conjunction with other medications, especially glucocorticoids

• Effect may take 2 to 4 weeks to set in

• May be a very good drug in IMHA

• Avoid in cats

Cyclosporine

• Can be used in dogs and cats

• Expensive

• Effective and potent

Actions

• Predominantly influences T-lymphocytes

• Reduces cytokine production

• Reduces the amplification signals that activate macrophages

• Mainly used for transplant patients in humans

• In veterinary medicine has shown benefit in KCS, perianal fistulas, IMHA and preventing transplant rejection

Side effects

• Gingival hyperplasia

• Renal disease not an issue in small animals unless overdosed

• GI upset especially with liquid

• Potent enough to allow secondary infections to occur

Dosage

• Every patient is different, monitoring trough levels recommended though at least in dogs with pruritus drug levels do not correlate with response

• Neoral better than Sandimmune (variable, but up to 10 times the blood levels)

• 10 to 20 mg/kg/day (regular cyclosporine) effective for perianal fistulas

• Usually use Neoral in dogs at 5 mg/kg BID initially, monitor trough 24 to 48 hours after starting therapy

• Ketoconazole at 10 mg/kg SID reduces amount of cyclosporine needed

• In cats the dosage is 0.5 to 2.5 mg/kg Neoral BID, also check trough after 24 to 48 hours of therapy

• Since there are various ways to measure cyclosporine check with the lab as to what levels are desirable

Human Ivigg

• Cool drug, amazing efficacy with IMT and IMHA

• In IMHA mortality unchanged or possibly even worse

• Extremely expensive and often impossible to get a hold of

• Dose is 0.5 to 1 gram/kg in dogs

Danazol

• Anabolic steroid

• May have some questionable efficacy in immune-mediated blood dyscrasias

• Long onset of action

• Expensive