Lecture: Immunosuppressive TX

Question 1

Most immunosuppressive agents have a …….

Answer 1

lag phase before reaching full efficacy

Question 2

immunosuppressive guidelines (carefully monitor…..)

Answer 2

• careful monitoring of CBC and platelet counts during therapy
• antibiotic therapy necessary in the first few months of therapy

Question 3

If worsening of skin lesions with steroids, consider:_____

before increasing dose

Answer 3

• demodecosis
• dermatophytosis
• bacterial infection
• calcinosis cutis (dogs)

Question 4

After relapse of autoimmune dz …..

Answer 4

resistance to previously used glucocorticoids may be observed

Question 5

most animals require therapy for

Answer 5

life

Question 6

DLE (discoid lupus erythematous) and PE usually managed with

Answer 6

• topical glucocorticoid
• topical tacrolimus
• tetracycline and niacinamide

Question 7

PF usually requires a combo of

Answer 7

glucocorticoids and another immunosuppressive agent

Question 8

PV and BP usually require

Answer 8

very high doses that are rarely tolerated

Question 9

High dose steroids can kill a patient due to

Answer 9

GI ulceration

Question 10

SLE usually requires combo of

Answer 10

• glucocorticoids and another immunosuppressive agent

*Gold salts are contraindicated due to potential for renal toxicity

Question 11

Glucocorticoids

Answer 11

• used for management of autoimmune diseases due to anti-inflammatory properties
  
  • inhibits macrophages chemotaxis
  • Phospholipase A₂
  • Reduce compliment levels
  • Decrease capillary permeability
  • Inhibit PMN chemotaxis and phagocytosis
  • Stabilize lysosomal membranes

Question 12

Rules for steroid therapy

Answer 12

• oral steroids
• alternate days to minimize adrenal suppression
  
  • prednisone
  • prednisolone
  • methylprednisolone
• use lowest effective dose

Question 13

Induction of steroid therapy

Answer 13

• lasts 10-14 days
• once no new lesions, tapering is started
• maintenance dose achieved in 8-10 weeks

Question 14

Prednisone

immunosuppressive doses

Answer 14

• Dogs
  
  • induction: 2.2-3.3 mg/kg q 12hr
  • maintenance: 0.5-1 mg/kg q 48hr
• Cats
  
  • induction: 3.3-4.4 mg/kg q 12hr
  • maintenance: 1-2 mg/kg q 48hr

Question 15

Immunosuppressive doses

Methylprednisolone

Answer 15

• Dogs
  
  • Induction: 0.8-1.5 mg/kg q 12hrs
  • Maintenance: 0.3-0.8 mg/kg q 48hrs
• Cats
  
  • Induction: 1.5-3 mg/kg q 12hrs
  • Maintenance: 0.6-1.5 mg/kg q 48hrs

*Less PUPD

Question 16

Immunosuppressive doses

dexamethasone

Answer 16

• Dogs
  
  • Induction: 0.1-0.2 mg/kg q 12hrs
  • maintenance: 0.05-0.1 mg/kg q 48-72hrs
• Cats
  
  • Induction: 0.2-0.4 mg/kg q 12hrs
  • Maintenance: 0.1-0.2 mg/kg q 48-72hrs

Question 17

Side effects of steroid therapy

Answer 17

• GI ulcers
• PU/PD
• Polyphagia
• Panting
• Behavioral changes
• Diabetes
• Steroid hepatopathy

Question 18

Other side effect of steroid therapy

Answer 18

• Muscle weakness
• Osteoporosis
• Redistribution of body fat
• Decreased synthesis of thyroid hormones
• Inc risk of infections
  
  • skin
  • urinary tract

Question 19

Side effects on skin of steroid therapy

Answer 19

• thin skin
• comedones
• demodicosis
• calcinosis cutis (dogs)
• skin fragility (cats)

Question 20

Azathioprine metabolism

Answer 20

• TPMT deficiency leads to inc production of active metabolites => inc toxicity
• Some dogs have genetic deficiency in TPMT

Question 21

Side effects of Azathioprine

Answer 21

• bone marrow suppression
  
  • anemia
  • leukopenia
  • Thrombocytopenia
• pancreatitis
• Hepatitis
• Vomiting
• Hemorrhagic diarrhea

Question 22

Azathioprine

Answer 22

• 2.2 mg/kg q 48hrs (50 mg tab)
• Lag phase of 4-6 weeks
• Dose should be reduced when used with xanthine oxidase inhibitor
• monitor CBC and platelet counts q 2 weeks
• DO NOT USE IN CATS

Question 23

Chlorambucil

Answer 23

• used for cats
• Cytotoxic
• alkylating agent: causes DNA breaks and cross-links
• Toxic for B cells
• Lag phase
• Liver metabolism
• bone marrow suppression
• V/D

Question 24

Chlorambucil

Dose

Answer 24

• 0.1-0.2 mg/kg q 48hrs (2 mg tab)
• Lag phase: 6 weeks
• monitor CBC and platelet counts q 2 weeks
• Safe for cats

Question 25

Gold salts

Answer 25

• injectible
• 1 mg/kg IM q 1 week until remission
• lag phase 6-12 weeks
• side effects
  
  • bone marrow suppression
  • nephrotoxicity
  • hepatic necrosis
  • drug eruption (EM, TEN)
• don’t use for dogs

Question 28

Cyclophosphamide

Answer 28

• alkylating agent
• Interference with DNA replication
• side effects
  
  • bone marrow suppression
  • hemorrhagic cystitis
  • bladder fibrosis
  • teratogenesis

Question 29

Tetracycline and Niacinamide together

Answer 29

• Dosing regimen is 3 X a day
• Tetracycline
  
  • inhibits PMN chemotaxis
  • Inhibits complement and PG synthesis
• Niacinamide
  
  • Inhibits mast cell degranulation
  • Inhibits PDE thus stabilizes cells

Question 30

Tetracycline and Niacinamide

doses

Answer 30

• dogs > 10 kg : 500 mg each TID
• Dogs < 10 kg : 250 mg each TID

*70% effective for DLE

*15% effective for PF

• Adverse effects
  
  • V/D
  • anorexia
  • inc liver enzymes
  • seizures

Question 31

Cyclosporine

Answer 31

• Adjunctive therapy
• dec nec dose of glucocorticoids
• suppresses T cell proliferation and activation
• metabolized by cytochrome P450
• delayed metabolism in patients with liver dz

Question 32

Cyclosporine doses

Answer 32

• Induction: 20 mg/kg a 24 hrs
• Maintenance: 10 mg/kg q 48 hrs
• as adjuctive therapy: 5 mg/kg SID to EOD

Question 33

Cyclosporin adverse effects

Answer 33

• GI upset
• nephrotoxicity
• papillomatous dermatitis
• gingival hyperplasia

Question 34

Dapsone

Answer 34

• used in conjuction with glucocorticoids
• lag phase 4-6 weeks
• decreases
  
  • complement
  • antibody production
  • PMN chemotaxis
• I mg/kg TID