Immunosuppressants

Question 1

Mycophenolate?

Answer 1

• *Mike cooking chicken bones on BBQ - everyone gets gastro Sx, and can see bones (bone marrow suppression)
• Depletes guanine nucleotides in T and B cell lymphocytes, inhibits proliferation - stops cell mediated response and antibody formation
• Side effects:
• GI upset - diarrhoea and vomiting
• Leucopenia (low WCC) - (bone marrow suppression)
• Anaemia
  Infectious

Question 2

Tacrolimus?

Answer 2

• Calcineurin inhibitor - inhibit calcineurin, impair transcription IL2 and others for T cells –> suppress T cells and T cell dependent B cell activation
• Side effects:
• Hyperglycemia/diabetes
• Hypomagnesium
• Neurotoxicity (seizures, tremors)
• CYP450
  Does not increase cholesterol, ?UTD dyslipidemia

Question 3

Tacro and cyclosporin?

Answer 3

Calcineurin inhibitors
* Triple M - metabolic syndrome (HTN, diabetes, hyperlipidemia)
* + cyclo (psycho - calling gorilla) - hyperplasia gingiva, hair

Both - Tacro and Cyclosporin
* Nephrotoxicity
* Hypertension
* Diabetes (more with tacro)
* Neurotoxicity
* Hyperkalemia
* Hypomagnesium
Dyslipidemia

Question 4

Cyclosporin?

Answer 4

• Acts on T helper cells, increased TGF beta
• Side effects:
• Gingival hyperplasia
• Hirsuitism (most common with long term use)
• Trichosis - hair
  Can cause IgA deficiency

Question 5

Hydroxychloroquine (Plaquenil)?

Answer 5

• Rheum, SLE, malaria
  Increases lysosomal pH in antigen presenting cells
• Retinal toxicity - irreversible
• Corneal toxicity - reversible
• Long QT
• Nausea - not GI ulcers
  Skin - hyperpigmentation

Question 6

Methotrexate?

Answer 6

• Inhibits dihydrofolate reductase leading to low folate and defective DNA synthesis and cell death
• Nausea GI upset 25%
• Liver toxicity 10-20% - dose reduction/with-hold if LFT persistent > 2 x ULN
• Macrocytosis (folate deficiency) and bone marrow suppression
• Stomatitis
• Skin - macular punctate cutaneous eruption
• CNS - headache, fatigue, malaise
• Alopecia
• Fever
• Infection
• Lung fibrosis

Monitoring
* Pre - CXR, PFTs
2 weekly FBE, LFT then reduce to 3 monthly

Question 7

Azathioprine and 6 mercaptopurine?

Answer 7

• 6MP impedes DNA synthesis - purine antagonist -blocks adenine and guanine
• Thiopurines, anti-rejection agents in transplant
• Inhibits proliferations of cells esp lymphocytes, down regulation immune system
• Bone marrow toxicity 4% - dose dependent, occurs early, increased risk if TPMT deficient
• Liver dysfunction 1-3%
• GI upset
• Pancreatitis 2-5%
• Infection risk - VZV, measles, EBV
• Malignancy - 4 x risk of lymphoma, sun related skin damage